A Study of Capecitabine (Xeloda) and Bevacizumab as a Fir... | NCT00069095 | Trialant
NCT00069095
Sponsor
Hoffmann-La Roche
Status
Completed
Last Update Posted
Oct 6, 2016Estimated
Enrollment
2,035Actual
Phase
Phase 3
Conditions
Colorectal Cancer
Interventions
Oxaliplatin 130 mg/m^2
Capecitabine 1000 mg/m^2
Bevacizumab 7.5 mg/kg
Placebo for bevacizumab 7.5 mg/kg
Oxaliplatin 85 mg/m^2
Leucovorin 200 mg/m^2
Fluorouracil 400 mg/m^2
Bevacizumab 5 mg/kg
Placebo for bevacizumab 5 mg/kg
Countries
United States
Australia
Austria
Brazil
Canada
China
Czechia
Denmark
Finland
France
Germany
Guatemala
Hong Kong
Hungary
Ireland
Israel
Italy
Mexico
New Zealand
Norway
Panama
Portugal
Puerto Rico
Russia
South Africa
South Korea
Spain
Sweden
Switzerland
Taiwan
Thailand
Turkey (Türkiye)
United Kingdom
Protocol Section
Identification Module
NCT ID
NCT00069095
Obsolete or Duplicate NCT IDs
Not provided
Organization Study
NO16966
Secondary IDs
Not provided
Brief Title
A Study of Capecitabine (Xeloda) and Bevacizumab as a First-line Therapy in Patients With Metastatic Colorectal Cancer
Official Title
A 2x2 Factorial Randomized Phase III Study of Intermittent Oral Capecitabine in Combination With Intravenous Oxaliplatin (Q3W) ("XELOX") With/Without Intravenous Bevacizumab (Q3W) Versus Bolus and Continuous Infusion Fluorouracil/Intravenous Leucovorin With Intravenous Oxaliplatin (Q2W) ("FOLFOX-4") With/Without Intravenous Bevacizumab (Q2W) as First-line Treatment for Patients With Metastatic Colorectal Cancer
Acronym
Not provided
Organization
Hoffmann-La RocheINDUSTRY
Status Module
Record Verification Date
Aug 2016
Overall Recruitment Status or Expanded Access Status
Completed
Last Known Status
Not provided
Delayed Posting
Not provided
Why Stopped
Not provided
Expanded Access Info
No
Start Date
Jul 2003
Primary Completion Date
Jan 2006Actual
Completion Date
Apr 2009Actual
First Submitted Date
Sep 15, 2003
First Submission Date that Met QC Criteria
Sep 17, 2003
First Posted Date
Sep 18, 2003Estimated
Results Waived
Not provided
Results First Submitted Date
Dec 11, 2015
Results First Submitted that Met QC Criteria
Dec 11, 2015
Results First Posted Date
Jan 22, 2016Estimated
Certification/Extension (aka Delayed Results) First Submitted Date
Not provided
Certification/Extension First Submitted that Passed QC Review
Not provided
Certification/Extension First Posted Date
Not provided
Last Update Submitted Date
Aug 26, 2016
Last Update Posted Date
Oct 6, 2016Estimated
Sponsor/Collaborators Module
Responsible Party, by Official Title
Sponsor
Lead Sponsor
Hoffmann-La RocheINDUSTRY
Collaborators
Not provided
Oversight Module
No data available
No data is available for this block.
Description Module
Brief Summary
This 4 arm study assessed the efficacy and safety of oral capecitabine (Xeloda) or intravenous (iv) fluorouracil/leucovorin, in combination with iv oxaliplatin (Eloxatin) with or without iv bevacizumab (Avastin), as a first-line treatment in patients with metastatic colorectal cancer. Patients were randomized to receive 1) XELOX (Xeloda 1000 mg/m^2 orally [po] twice a day [bid] on Days 1-15 + oxaliplatin in 3 week cycles), 2) FOLFOX-4 (oxaliplatin + leucovorin + fluorouracil [5-FU] in 2 week cycles), 3) XELOX + bevacizumab (7.5 mg iv on Day 1 in 3 week cycles), or 4) FOLFOX-4 + bevacizumab (5 mg iv on Day 1 in 2 week cycles).
Detailed Description
This study was conducted in 2 parts: An initial 2-arm part in which patients were randomized to 1 of 2 different treatment groups (XELOX or FOLFOX-4), and a subsequent 2 x 2 factorial part, added to the study through a protocol amendment, in which additional patients were randomized into one of 4 different treatment groups (XELOX + placebo, FOLFOX-4 + placebo, XELOX + bevacizumab, or FOLFOX-4 + bevacizumab). Due to the comparison of the oral agent capecitabine with bolus and infused fluorouracil, the study was not blinded with respect to these 2 treatments. The study was double-blind with regard to the administration of bevacizumab, ie, there was a placebo control for bevacizumab in the second part of the study.
The study consisted of 3 phases, a Primary Study Treatment Phase, a Post-Study Treatment Phase, and a Follow-Up Phase.
Primary Study Treatment Phase
Patients were to receive up to 16 cycles (2-arm part of the study) or 24 cycles (4-arm part of the study) of treatment during the Primary Study Treatment Phase (48 weeks).
Post-Study Treatment Phase
Patients who completed the 48-week primary study treatment phase without progressive disease were eligible to enter the post-study treatment phase at the discretion of the investigator and the sponsor. Patients who entered this phase were to continue treatment on the same regimen to which they were initially randomized until either progression of disease was documented, unacceptable toxicity occurred, or the patient withdrew consent.
Follow-up Phase
Patients who terminated study treatment during the primary or post-study treatment phase were followed until disease progression or death.
Conditions Module
Conditions
Colorectal Cancer
Keywords
Not provided
Design Module
Study Type
Interventional
Number of References to an Expanded Access Study
Not provided
Expanded Access Types
Not provided
Patient Registry
Not provided
Target Follow-Up Duration
Not provided
Phases
Phase 3
Interventional Study Design
Allocation
Biospecimen
No data available
No data is available for this block.
Enrollment
2,035Actual
Arms/Interventions Module
Arm Groups
Label
Type
Description
Intervention Names
XELOX (oxaliplatin+capecitabine)
Experimental
Patients in the 2-arm part of the study received oxaliplatin 130 mg/m^2 intravenously (iv) on Day 1 of every 3 week cycle + capecitabine 1000 mg/m^2 orally twice a day for the first 2 weeks of every 3 week cycle. Patients in the 4-arm part of the study received the same treatments plus placebo for bevacizumab 7.5 mg/kg iv on Day 1 of every 3 week cycle.
Drug: Oxaliplatin 130 mg/m^2
Drug: Capecitabine 1000 mg/m^2
Drug: Placebo for bevacizumab 7.5 mg/kg
XELOX (oxaliplatin+capecitabine) + bevacizumab
Experimental
Patients in the 4-arm part of the study received oxaliplatin 130 mg/m^2 intravenously (iv) on Day 1 of every 3 week cycle + capecitabine 1000 mg/m^2 orally twice a day for the first 2 weeks of every 3 week cycle + bevacizumab 7.5 mg/kg iv on Day 1 of every 3 week cycle.
Drug: Oxaliplatin 130 mg/m^2
Drug: Capecitabine 1000 mg/m^2
Drug: Bevacizumab 7.5 mg/kg
FOLFOX-4 (oxaliplatin+leucovorin+fluorouracil)
Active Comparator
Patients in the 2-arm part of the study received oxaliplatin 85 mg/m^2 intravenously (iv) + leucovorin 200 mg/m^2 iv on Day 1 of every 2 week cycle + fluorouracil 400 mg/m^2 bolus injection over 2 to 4 min followed by 600 mg/m^2 continuous infusion over 22 h on Days 1 and 2 of every 2 week cycle. Patients in the 4-arm part of the study received the same treatments plus placebo for bevacizumab 5 mg/kg iv on Day 1 of every 2 week cycle.
Oxaliplatin was administered in a 2 h infusion before the first dose of capecitabine.
XELOX (oxaliplatin+capecitabine)
XELOX (oxaliplatin+capecitabine) + bevacizumab
Outcomes Module
Primary Outcomes
Measure
Description
Time Frame
Progression-free Survival (PFS) as Assessed by the Investigator According to Response Evaluation Criteria in Solid Tumors (RECIST) by General Approach (Participants With Curative Surgery Censored): Non-inferiority of XELOX Versus FOLFOX-4
PFS was defined as the time from randomization to progressive disease or death. Participants with neither disease progression nor death were censored at the last date of the last tumor assessment that confirmed that their disease had not progressed. Participants with no tumor assessments after baseline who were alive at the time of clinical cutoff were censored at the date of randomization. Participants who underwent surgical resection with curative intent without prior progression were censored at the date of surgery. PFS was based on tumor assessments made by the investigators according to the RECIST criteria. Non-inferiority analysis that followed the general approach took into account all tumor assessments obtained during the primary study treatment phase, the post-study treatment phase and those obtained during the follow-up phase. Non-inferiority of the XELOX-containing arms compared with the FOLFOX-4- containing arms was investigated.
Baseline until disease progression or death, approximately 2 years 6 months
PFS as Assessed by the Investigator According to Response Evaluation Criteria in Solid Tumors (RECIST) by General Approach (Participants With Curative Surgery Censored) - Superiority of Chemotherapy Plus BV Over Chemotherapy Alone
PFS was defined as the time from randomization to progressive disease or death. Participants with neither disease progression nor death were censored at the last date of the last tumor assessment that confirmed that their disease had not progressed. Participants with no tumor assessments after baseline who were alive at the time of clinical cutoff were censored at the date of randomization. Participants who underwent surgical resection with curative intent without prior progression were censored at the date of surgery. PFS was based on tumor assessments made by the investigators according to the RECIST criteria. Superiority analysis that followed the general approach took into account all tumor assessments obtained during the primary study treatment phase, the post-study treatment phase and those obtained during the follow-up phase. Superiority of the BV-containing arms was compared with the chemotherapy alone arms.
Baseline until disease progression or death, approximately 2 years 6 months
Secondary Outcomes
Measure
Description
Time Frame
PFS as Assessed by the Independent Review Committee (IRC) (General Approach, Participants With Curative Surgery Censored) - Non-inferiority of XELOX Versus FOLFOX-4
PFS is defined as the time from randomization to disease progression (PD) or death due to any cause. Participants with neither disease progression nor death were censored at the last date of the last tumor assessment that confirmed that their disease had not progressed. Participants who underwent surgical resection with curative intent without prior progression were censored at the date of surgery. PFS was analyzed on the basis of the tumor response assessments made by the IRC. Non-inferiority analysis that followed the general approach took into account all tumor assessments obtained during the primary study treatment phase, the post-study treatment phase and those obtained during the follow-up phase. Non-inferiority of the XELOX-containing arms was compared with the FOLFOX-4-containing arms.
Other Outcomes
Not provided
Eligibility Module
Eligibility Criteria
Inclusion Criteria:
Adult patients ≥ 18 years of age.
Metastatic colorectal cancer.
≥ 1 target lesion.
Exclusion Criteria:
Previous treatment with oxaliplatin or bevacizumab.
Previous systemic chemotherapy or immunotherapy for advanced or metastatic disease.
Progressive disease during or within 6 months of completion of previous adjuvant therapy.
Accepts Healthy Volunteers
No
Sex
All
Sex/Gender Based
Not provided
Sex/Gender Description
Not provided
Minimum Age
18 Years
Maximum Age
Not provided
Standard Ages
AdultOlder Adult
Study Population
Not provided
Sampling Method
Not provided
Contacts/Locations Module
Central Contacts
Not provided
Overall Officials
Name
Affiliation
Role
Clinical Trials
Hoffmann-La Roche
Study Director
Locations
Facility
Status
City
State
ZIP
Country
Contacts
Berkeley
California
94704
United States
References Module
No data available
No data is available for this block.
IPD Sharing Statement Module
No data available
No data is available for this block.
Results Section
Participant Flow Module
Pre-assignment Details
A total of 2035 participants were randomized to any one of the treatment groups in the study (634 participants in the initial 2-arm part and 1401 participants in the 2x2 factorial part of the study), but only 2034 received study treatment as 1 participant was enrolled twice in the study at 2 study centers.
Recruitment Details
This study was conducted in 32 countries - Australia, Austria, Brazil, Canada, China, Czech Republic, Denmark, Finland, France, Germany, Great Britain, Guatemala, Hong Kong, Hungary, Ireland, Israel, Italy, Korea, Mexico, New Zealand, Norway, Panama, Portugal, Russia, South Africa, Spain, Sweden, Switzerland, Taiwan, Thailand, Turkey and USA.
Type of Units Analyzed
Not provided
Arm/Group Information
ID
Title
Description
FG000
Xelox
Participants in the 2-arm part of the study received intravenous infusion of oxaliplatin 130 mg/m^2 over 2 hours on Day 1 of every 3 weeks before the first dose of capecitabine. Capecitabine was administered orally within 30 minutes after the end of a meal (breakfast and dinner) at a dose of 1000 mg/m^2 twice-daily (equivalent to a total daily dose of 2000 mg/m^2), for the first 2 weeks of every 3-week cycle. Participants received up to 16 cycles of treatment during the primary study treatment phase (48 weeks). Participants who completed the 48-week primary study treatment phase without progressive disease were eligible to enter the post-study treatment phase at the discretion of the investigator and the sponsor. Participants who entered this phase were to continue treatment on the same regimen to which they were initially randomized until either progression of disease was documented, unacceptable toxicity occurred, or the participant withdrew consent.
Periods
Title
Milestones
Reasons Not Completed
Primary Treatment Phase
Type
Comment
Milestone Data
STARTED
Baseline Characteristics Module
Baseline Analysis Population Description
Outcome Measures Module
Outcome Measures
Adverse Events Module
Frequency Threshold
5
More Info Module
Limitations and Caveats
Not provided
Annotation Section
No data available
No data is available for this block.
Document Section
No data available
No data is available for this block.
Derived Section
Miscellaneous Info Module
Version Holder
Jul 10, 2026
Removed Countries
Greece
Submission Tracking
No data available
No data is available for this block.
Condition Browse Module
MeSH Terms
Intervention Browse Module
MeSH Terms
Randomized
Intervention Model
Factorial Assignment
Intervention Model Description
Not provided
Primary Purpose
Treatment
Observational Model
Not provided
Time Perspective
Not provided
Masking Info
Masking
Double
Masking Description
Not provided
Who Masked
ParticipantInvestigator
Active Comparator
Patients in the 4-arm part of the study received oxaliplatin 85 mg/m^2 intravenously (iv) + leucovorin 200 mg/m^2 iv + bevacizumab 5 mg/kg iv on Day 1 of every 2 week cycle + fluorouracil 400 mg/m^2 bolus injection over 2 to 4 min followed by 600 mg/m^2 continuous infusion over 22 h on Days 1 and 2 of every 2 week cycle.
Drug: Oxaliplatin 85 mg/m^2
Drug: Leucovorin 200 mg/m^2
Drug: Fluorouracil 400 mg/m^2
Drug: Bevacizumab 5 mg/kg
Eloxatin
Capecitabine 1000 mg/m^2
Drug
Capecitabine was taken within 30 min after the end of breakfast and dinner.
XELOX (oxaliplatin+capecitabine)
XELOX (oxaliplatin+capecitabine) + bevacizumab
Xeloda
Bevacizumab 7.5 mg/kg
Drug
Bevacizumab was administered in a 30 to 90 min infusion.
XELOX (oxaliplatin+capecitabine) + bevacizumab
Avastin
Placebo for bevacizumab 7.5 mg/kg
Drug
Placebo control for bevacizumab (volume equivalent to 7.5 mg/kg bevacizumab) was administered in a 30 to 90 min infusion.
XELOX (oxaliplatin+capecitabine)
Oxaliplatin 85 mg/m^2
Drug
Oxaliplatin 85 mg/m^2 was administered simultaneously with leucovorin in a 2 h infusion.
Placebo control for bevacizumab (volume equivalent to 5 mg/kg bevacizumab) was administered in a 30 to 90 min infusion.
FOLFOX-4 (oxaliplatin+leucovorin+fluorouracil)
Baseline until disease progression or death, approximately 2 years 6 months
PFS as Assessed by the Independent Review Committee (IRC) (General Approach, Participants With Curative Surgery Censored) - Superiority of Chemotherapy Plus BV Over Chemotherapy Alone
PFS is defined as the time from randomization to disease progression (PD) or death due to any cause. Participants with neither disease progression nor death were censored at the last date of the last tumor assessment that confirmed that their disease had not progressed. Participants who underwent surgical resection with curative intent without prior progression were censored at the date of surgery. PFS was analyzed on the basis of the tumor response assessments made by the IRC. Superiority analysis that followed the general approach took into account all tumor assessments obtained during the primary study treatment phase, the post-study treatment phase and those obtained during the follow-up phase. Superiority of the bevacizumab-containing arms was compared with the placebo-containing arms.
Baseline until disease progression or death, approximately 2 years 6 months
PFS (On-treatment Approach): Non-inferiority of XELOX Versus FOLFOX-4
PFS is defined as the time from randomization to disease progression (PD) or death due to any cause. The on-treatment analysis included only tumor assessments and death events that occurred no later than 28 days after the last confirmed intake of any study medication in the primary study treatment phase. Participants who did not have an event during this interval were censored at the date of the last tumor assessment within this time window, or on day 1 if no tumor assessment was available after baseline. Participants who underwent surgical resection with curative intent without prior progression within 28 days after the last confirmed intake of any study medication in the primary study treatment phase were censored at the date of surgery. The on-treatment approach excluded the possible impact of other treatments that might have been started before disease progression. Non-inferiority of the XELOX-containing arms was compared with the FOLFOX-4-containing arms.
Baseline until disease progression or death, approximately 2 years 6 months
PFS (On-treatment Approach): Superiority of Chemotherapy Plus BV Over Chemotherapy Alone
PFS is defined as the time from randomization to disease progression (PD) or death due to any cause. The on-treatment analysis included only tumor assessments and death events that occurred no later than 28 days after the last confirmed intake of any study medication in the primary study treatment phase. Participants who did not have an event during this interval were censored at the date of the last tumor assessment within this time window, or on day 1 if no tumor assessment was available after baseline. Participants who underwent surgical resection with curative intent without prior progression within 28 days after the last confirmed intake of any study medication in the primary study treatment phase were censored at the date of surgery. The on-treatment approach excluded the possible impact of other treatments that might have been started before disease progression. Non-inferiority of the XELOX-containing arms was compared with the FOLFOX-4-containing arms.
Baseline until disease progression or death, approximately 2 years 6 months
PFS by General Approach, Participants With Curative Surgery Not Censored: Non-inferiority of XELOX Versus FOLFOX-4
PFS is defined as the time from randomization to disease progression (PD) or death due to any cause. Participants who underwent curative surgery after experiencing a sufficient shrinkage of their tumor were not censored at the date of surgery, but any relapse, new occurrence of colorectal cancer, or death was considered as an event. Non-inferiority analysis that followed the general approach took into account all tumor assessments obtained during the primary study treatment phase, the post-study treatment phase and those obtained during the follow-up phase. Non-inferiority of the XELOX-containing arms was compared with the FOLFOX-4-containing arms.
Baseline until disease progression or death, approximately 2 years 6 months
PFS by General Approach, Participants With Curative Surgery Not Censored: Superiority of Chemotherapy Plus BV Over Chemotherapy Alone
PFS is defined as the time from randomization to disease progression (PD) or death due to any cause. Participants who underwent curative surgery after experiencing a sufficient shrinkage of their tumor were not censored at the date of surgery, but any relapse, new occurrence of colorectal cancer, or death was considered as an event. Superiority analysis that followed the general approach took into account all tumor assessments obtained during the primary study treatment phase, the post-study treatment phase and those obtained during the follow-up phase. Superiority of the BV-containing arms was compared with the chemotherapy alone arms.
Baseline until disease progression or death, approximately 2 years 6 months
Overall Survival: Non-inferiority of XELOX Versus FOLFOX-4
Overall survival was defined as the time from the date of randomization to the date of death. Participants who were not reported to have died at the time of the clinical cut-off date for the analysis were censored using the date they were last known to be alive. Non-inferiority of the XELOX-containing arms was compared with the FOLFOX-4-containing arms.
Baseline until disease progression or death, approximately 2 years 6 months
Overall Survival: Superiority of Chemotherapy Plus BV Over Chemotherapy Alone
Overall survival was defined as the time from the date of randomization to the date of death. Participants who were not reported to have died at the time of the clinical cut-off date for the analysis were censored using the date they were last known to be alive. Superiority of the BV-containing arms was compared with the chemotherapy alone arms.
Baseline until disease progression or death, approximately 2 years 6 months
Best Overall Response (BOR) as Assessed by the Investigator According to Response Evaluation Criteria in Solid Tumors (RECIST): Non-inferiority of XELOX Versus FOLFOX-4
According to the RECIST criteria, BOR in an individual participant was defined as the best response recorded from the start of the treatment until disease progression or recurrence. Only tumor assessments as assessed by the investigator and made up to and including 28 days after last intake of study medication in the primary study treatment phase not later than date of first curative surgery were included in these analyses. Responders were defined as the percentage of participants with a confirmed best overall response of complete response (CR) or partial response (PR). Non-inferiority of the XELOX-containing arms was compared with the FOLFOX-4-containing arms.
From baseline until disease progression/recurrence, approximately 2 years 6 months
Best Overall Response (BOR) as Assessed by the Investigator According to RECIST: Superiority of Chemotherapy Plus BV Over Chemotherapy Alone
According to the RECIST criteria, BOR in an individual participant was defined as the best response recorded from the start of the treatment until disease progression or recurrence. Only tumor assessments as assessed by the investigator and made up to and including 28 days after last intake of study medication in the primary study treatment phase not later than date of first curative surgery were included in these analyses. Responders were defined as the percentage of participants with a confirmed best overall response of complete response (CR) or partial response (PR). Superiority of the BV-containing arms was compared with the chemotherapy alone arms.
From baseline until disease progression/recurrence, approximately 2 years 6 months
BOR as Assessed by the IRC According to RECIST: Non-inferiority of XELOX Versus FOLFOX-4
According to the RECIST criteria, the BOR in an individual participant was the best response recorded from the start of the treatment until disease progression/recurrence (taking the smallest measurements recorded since the baseline assessment as a reference for PD). The BOR as assessed by the IRC was determined based on tumor assessments that were made up to and including 28 days after last intake of study medication in the primary study treatment phase. Responders were defined as the percentage of participants with a complete response (CR) or partial response (PR). Non-inferiority of the XELOX-containing arms was compared with the FOLFOX-4-containing arms.
From baseline until disease progression/recurrence, approximately 2 years 6 months
BOR as Assessed by the IRC According to RECIST: Superiority of Chemotherapy Plus BV Over Chemotherapy Alone
According to the RECIST criteria, the BOR in an individual participant was the best response recorded from the start of the treatment until disease progression/recurrence (taking the smallest measurements recorded since the baseline assessment as a reference for PD). The BOR as assessed by the IRC was determined based on tumor assessments that were made up to and including 28 days after last intake of study medication in the primary study treatment phase. Responders were defined as the percentage of participants with a complete response (CR) or partial response (PR). Superiority of the BV-containing arms was compared with the chemotherapy alone arms.
From baseline until disease progression/recurrence, approximately 2 years 6 months
Time to Treatment Failure (TTF) as Assessed by the Investigator According to RECIST: Non-inferiority of XELOX Versus FOLFOX-4
Time to treatment failure was defined as the time from the date of randomization to the date of discontinuation of the primary study treatment phase due to adverse event/intercurrent illness, insufficient therapeutic response, death, failure to return, refusing treatment/being unwilling to cooperate, or withdrawing consent; discontinuation of the post study treatment phase due to adverse event, progressive disease, death, participant refusal/administrative reasons, or withdrawing consent; documented disease progression; or death due to any cause, whichever occurred first. The general approach took into account all tumor assessments obtained during the primary study treatment phase, the post-study treatment phase and those obtained during the follow-up phase.The on-treatment approach included only tumor assessments and deaths that occurred no later than 28 days after the last confirmed intake of any study medication in the primary study treatment phase only.
From baseline until disease progression/recurrence, approximately 2 years 6 months
Time to Treatment Failure as Assessed by the Investigator According to RECIST: Superiority of Chemotherapy Plus BV Over Chemotherapy Alone
Time to treatment failure was defined as the time from the date of randomization to the date of discontinuation of the primary study treatment phase due to adverse event/intercurrent illness, insufficient therapeutic response, death, failure to return, refusing treatment/being unwilling to cooperate, or withdrawing consent; discontinuation of the post study treatment phase due to adverse event, progressive disease, death, participant refusal/administrative reasons, or withdrawing consent; documented disease progression; or death due to any cause, whichever occurred first. The general approach included all tumor assessments or deaths that occurred during the primary study treatment phase, the post-study treatment phase, or the follow-up phase. The on-treatment approach included only tumor assessments and deaths that occurred no later than 28 days after the last confirmed intake of any study medication in the primary study treatment phase only.
From baseline until disease progression/recurrence, approximately 2 years 6 months
Time to Response as Assessed by the Investigator According to RECIST: Non-inferiority of XELOX Versus FOLFOX-4
For participants whose BOR was CR or PR, time to response was measured as the time from randomization to the first time when the measurement criteria for CR or PR (whichever status was recorded first) was met. It was based on tumor assessments made by the investigators according to the RECIST criteria. Results were reported as the number of participants achieving a response in 8 time categories from Week 1 to Week 54. Non-inferiority of the XELOX-containing arms was compared with the FOLFOX-4-containing arms.
Week 1 to Week 54
Time to Response as Assessed by the Investigator According to RECIST: Superiority of Chemotherapy Plus BV Over Chemotherapy Alone
For participants whose BOR was CR or PR, time to response was measured as the time from randomization to the first time when the measurement criteria for CR or PR (whichever status was recorded first) was met. It was based on tumor assessments made by the investigators according to the RECIST criteria. Results were reported as the number of participants achieving a response in 8 time categories from Week 1 to Week 54. Superiority of the BV-containing arms was compared with the chemotherapy alone arms.
Week 1 to Week 54
Duration of Overall Response as Assessed by the Investigator According to RECIST: Non-inferiority of XELOX Versus FOLFOX-4
Duration of overall response was measured from the time that measurement criteria were first met for CR or PR (whichever status was recorded first) until the first date when progressive disease or death was documented. It was based on tumor assessments made by the investigators according to the RECIST criteria. Participants who neither progressed nor died were censored at the date of the last tumor assessment. Participants undergoing surgical resection with curative intent were censored at the date of surgery. Non-inferiority of the XELOX-containing arms was compared with the FOLFOX-4-containing arms.
From baseline until disease progression/recurrence, approximately 2 years 6 months
Duration of Overall Response as Assessed by the Investigator According to RECIST: Superiority Analysis of Chemotherapy Plus Bevacizumab Versus Chemotherapy Alone
Duration of overall response was measured from the time that measurement criteria were first met for CR or PR (whichever status was recorded first) until the first date when progressive disease or death was documented. It was based on tumor assessments made by the investigators according to the RECIST criteria. Participants who neither progressed nor died were censored at the date of the last tumor assessment. Participants undergoing surgical resection with curative intent were censored at the date of surgery. Superiority of the BV-containing arms was compared with the chemotherapy alone arms.
From baseline until disease progression/recurrence, approximately 2 years 6 months
Duration of Complete Response as Assessed by the Investigator According to RECIST: Non-inferiority of XELOX Versus FOLFOX-4
For complete responders, the duration of complete response was measured from the time measurement criteria were first met for complete response until the date that progressive disease (or death) was documented. Non-inferiority of the XELOX-containing arms was compared with the FOLFOX-4-containing arms.
From baseline until disease progression/recurrence, approximately 2 years 6 months
Duration of Complete Response as Assessed by the Investigator According to RECIST: Superiority of Chemotherapy Plus BV Over Chemotherapy Alone
For complete responders, the duration of complete response was measured from the time measurement criteria were first met for complete response until the date that progressive disease (or death) was documented. Superiority of the BV-containing arms was compared with the chemotherapy alone arms.
From baseline until disease progression/recurrence, approximately 2 years 6 months
Participants in the 2-arm part of the study received intravenous infusion of oxaliplatin 85 mg/m^2 on Day 1 of every 2-week cycle; concomitantly with leucovorin 200 mg/m^2 iv for 2 hours followed by fluorouracil 400 mg/m^2 bolus injection over 2 to 4 min followed by 600 mg/m^2 continuous infusion over 22 h on Days 1 and 2 of every 2-week cycle. Participants received up to 24 cycles of treatment during the primary study treatment phase (48 weeks). Participants who completed the 48-week primary study treatment phase without progressive disease were eligible to enter the post-study treatment phase at the discretion of the investigator and the sponsor. Participants who entered this phase were to continue treatment on the same regimen to which they were initially randomized until either progression of disease was documented, unacceptable toxicity occurred, or the participant withdrew consent.
FG002
Xelox+P
Participants in the 2x2 factorial part of the study received intravenous infusion of placebo control for bevacizumab (BV) [volume equivalent to 7.5 mg/kg BV] over 30 to 90 minutes followed by oxaliplatin 130 mg/m^2 over 2 hours on Day 1 of every 3 weeks in combination with capecitabine, administered orally at a dose of 1000 mg/m^2 twice-daily (equivalent to a total daily dose of 2000 mg/m^2), for the first 2 weeks of every 3-week cycle. Participants received up to 16 cycles of treatment during the primary study treatment phase (48 weeks). Participants who completed the 48-week primary study treatment phase without progressive disease were eligible to enter the post-study treatment phase at the discretion of the investigator and the sponsor. Participants who entered this phase were to continue treatment on the same regimen to which they were initially randomized until either progression of disease was documented, unacceptable toxicity occurred, or the participant withdrew consent.
FG003
Folfox-4+P
Participants in the 2x2 factorial part of the study received intravenous infusion of placebo control for BV (volume equivalent to 5 mg/kg BV) over 30 to 90 minutes followed by oxaliplatin 85 mg/m^2 on Day 1 of every 2-week cycle; concomitantly with leucovorin 200 mg/m^2 iv for 2 hours followed by fluorouracil 400 mg/m^2 bolus injection over 2 to 4 min followed by 600 mg/m^2 continuous infusion over 22 h on Days 1 and 2 of every 2-week cycle. Participants received up to 24 cycles of treatment during the primary study treatment phase (48 weeks). Participants who completed the 48-week primary study treatment phase without progressive disease were eligible to enter the post-study treatment phase at the discretion of the investigator and the sponsor. Participants who entered this phase were to continue treatment on the same regimen to which they were initially randomized until either progression of disease was documented, unacceptable toxicity occurred, or the participant withdrew consent.
FG004
Xelox+BV
Participants in the 2x2 factorial part of the study received intravenous infusion of bevacizumab 7.5 mg/kg over 30 to 90 minutes followed by oxaliplatin 130 mg/m^2 over 2 hours on Day 1 of every 3 weeks in combination with capecitabine, administered orally at a dose of 1000 mg/m^2 twice-daily (equivalent to a total daily dose of 2000 mg/m^2), for the first 2 weeks of every 3-week cycle. Participants received up to 16 cycles of treatment during the primary study treatment phase (48 weeks). Participants who completed the 48-week primary study treatment phase without progressive disease were eligible to enter the post-study treatment phase at the discretion of the investigator and the sponsor. Participants who entered this phase were to continue treatment on the same regimen to which they were initially randomized until either progression of disease was documented, unacceptable toxicity occurred, or the participant withdrew consent.
FG005
Folfox-4+BV
Participants in the 2x2 factorial part of the study received intravenous infusion of bevacizumab 5 mg/kg over 30 to 90 minutes followed by oxaliplatin 85 mg/m^2 on Day 1 of every 2-week cycle; concomitantly with leucovorin 200 mg/m^2 iv for 2 hours followed by fluorouracil 400 mg/m^2 bolus injection over 2 to 4 min followed by 600 mg/m^2 continuous infusion over 22 h on Days 1 and 2 of every 2-week cycle. Participants received up to 24 cycles of treatment during the primary study treatment phase (48 weeks). Participants who completed the 48-week primary study treatment phase without progressive disease were eligible to enter the post-study treatment phase at the discretion of the investigator and the sponsor. Participants who entered this phase were to continue treatment on the same regimen to which they were initially randomized until either progression of disease was documented, unacceptable toxicity occurred, or the participant withdrew consent.
FG000317 subjects
FG001317 subjects
FG002350 subjects
FG003351 subjects
FG004350 subjects
FG005349 subjects
COMPLETED
FG00022 subjects
FG00115 subjects
FG00236 subjects
FG00331 subjects
FG00448 subjects
FG00548 subjects
NOT COMPLETED
FG000295 subjects
FG001302 subjects
FG002314 subjects
FG003320 subjects
FG004302 subjects
FG005301 subjects
Type
Comment
Reasons
Ongoing
FG0000 subjects
FG0010 subjects
FG0025 subjects
FG0037 subjects
FG0047 subjects
FG0054 subjects
Admin/Other
FG00029 subjects
FG00138 subjects
FG00231 subjects
FG00345 subjects
FG004
Adverse Event
FG00099 subjects
FG00192 subjects
FG00271 subjects
FG00372 subjects
FG004
Death
FG00014 subjects
FG0018 subjects
FG0022 subjects
FG0035 subjects
FG004
Failure to return
FG0005 subjects
FG0015 subjects
FG0020 subjects
FG0030 subjects
FG004
Insufficient Therapeutic Response
FG000131 subjects
FG001127 subjects
FG002175 subjects
FG003154 subjects
FG004
Refused treatment
FG00015 subjects
FG00126 subjects
FG00217 subjects
FG00331 subjects
FG004
Withdrew
FG0002 subjects
FG0013 subjects
FG0028 subjects
FG0032 subjects
FG004
Other Violation
FG0000 subjects
FG0011 subjects
FG0021 subjects
FG0031 subjects
FG004
Violation criteria
FG0000 subjects
FG0012 subjects
FG0024 subjects
FG0033 subjects
FG004
Post-study Treatment Phase
Type
Comment
Milestone Data
STARTED
FG0008 subjectsParticipants could enter the follow-up phase even without entering the post-study treatment phase.
FG00113 subjectsParticipants could enter the follow-up phase even without entering the post-study treatment phase.
FG00221 subjectsParticipants could enter the follow-up phase even without entering the post-study treatment phase.
FG00317 subjectsParticipants could enter the follow-up phase even without entering the post-study treatment phase.
FG00436 subjectsParticipants could enter the follow-up phase even without entering the post-study treatment phase.
FG00529 subjectsParticipants could enter the follow-up phase even without entering the post-study treatment phase.
COMPLETED
FG0000 subjects
FG0010 subjects
FG0020 subjects
FG0030 subjects
FG004
NOT COMPLETED
FG0008 subjects
FG00113 subjects
FG00221 subjects
FG00317 subjects
FG004
Type
Comment
Reasons
Missing reason
FG0001 subjects
FG0013 subjects
FG00212 subjects
FG003
Follow-up Phase
Type
Comment
Milestone Data
STARTED
FG000284 subjectsParticipants could enter the follow-up phase even without entering the post-study treatment phase.
FG001299 subjectsParticipants could enter the follow-up phase even without entering the post-study treatment phase.
FG002298 subjectsParticipants could enter the follow-up phase even without entering the post-study treatment phase.
FG003299 subjectsParticipants could enter the follow-up phase even without entering the post-study treatment phase.
FG004278 subjectsParticipants could enter the follow-up phase even without entering the post-study treatment phase.
FG005272 subjectsParticipants could enter the follow-up phase even without entering the post-study treatment phase.
COMPLETED
FG000110 subjects
FG00193 subjects
FG002178 subjects
FG003187 subjects
FG004
NOT COMPLETED
FG000174 subjects
FG001206 subjects
FG002120 subjects
FG003112 subjects
FG004
Type
Comment
Reasons
Death
FG000174 subjects
FG001206 subjects
FG002120 subjects
FG003
Baseline characteristics were described for the Intent-to-treat (ITT) population.This population included all randomized participants who provided written informed consent.
Type of Units Analyzed
Not provided
Arm/Group Information
ID
Title
Description
BG000
Xelox
Participants in the 2-arm part of the study received intravenous infusion of oxaliplatin 130 mg/m^2 over 2 hours on Day 1 of every 3 weeks before the first dose of capecitabine. Capecitabine was administered orally within 30 minutes after the end of a meal (breakfast and dinner) at a dose of 1000 mg/m^2 twice-daily (equivalent to a total daily dose of 2000 mg/m^2), for the first 2 weeks of every 3-week cycle. Participants received up to 16 cycles of treatment during the primary study treatment phase (48 weeks). Participants who completed the 48-week primary study treatment phase without progressive disease were eligible to enter the post-study treatment phase at the discretion of the investigator and the sponsor. Participants who entered this phase were to continue treatment on the same regimen to which they were initially randomized until either progression of disease was documented, unacceptable toxicity occurred, or the participant withdrew consent.
BG001
Folfox-4
Participants in the 2-arm part of the study received intravenous infusion of oxaliplatin 85 mg/m^2 on Day 1 of every 2-week cycle; concomitantly with leucovorin 200 mg/m^2 iv for 2 hours followed by fluorouracil 400 mg/m^2 bolus injection over 2 to 4 min followed by 600 mg/m^2 continuous infusion over 22 h on Days 1 and 2 of every 2-week cycle. Participants received up to 24 cycles of treatment during the primary study treatment phase (48 weeks). Participants who completed the 48-week primary study treatment phase without progressive disease were eligible to enter the post-study treatment phase at the discretion of the investigator and the sponsor. Participants who entered this phase were to continue treatment on the same regimen to which they were initially randomized until either progression of disease was documented, unacceptable toxicity occurred, or the participant withdrew consent.
BG002
Xelox+P
Participants in the 2x2 factorial part of the study received intravenous infusion of placebo control for bevacizumab (BV) [volume equivalent to 7.5 mg/kg BV] over 30 to 90 minutes followed by oxaliplatin 130 mg/m^2 over 2 hours on Day 1 of every 3 weeks in combination with capecitabine, administered orally at a dose of 1000 mg/m^2 twice-daily (equivalent to a total daily dose of 2000 mg/m^2), for the first 2 weeks of every 3-week cycle. Participants received up to 16 cycles of treatment during the primary study treatment phase (48 weeks). Participants who completed the 48-week primary study treatment phase without progressive disease were eligible to enter the post-study treatment phase at the discretion of the investigator and the sponsor. Participants who entered this phase were to continue treatment on the same regimen to which they were initially randomized until either progression of disease was documented, unacceptable toxicity occurred, or the participant withdrew consent.
BG003
Folfox-4+P
Participants in the 2x2 factorial part of the study received intravenous infusion of placebo control for BV (volume equivalent to 5 mg/kg BV) over 30 to 90 minutes followed by oxaliplatin 85 mg/m^2 on Day 1 of every 2-week cycle; concomitantly with leucovorin 200 mg/m^2 iv for 2 hours followed by fluorouracil 400 mg/m^2 bolus injection over 2 to 4 min followed by 600 mg/m^2 continuous infusion over 22 h on Days 1 and 2 of every 2-week cycle. Participants received up to 24 cycles of treatment during the primary study treatment phase (48 weeks). Participants who completed the 48-week primary study treatment phase without progressive disease were eligible to enter the post-study treatment phase at the discretion of the investigator and the sponsor. Participants who entered this phase were to continue treatment on the same regimen to which they were initially randomized until either progression of disease was documented, unacceptable toxicity occurred, or the participant withdrew consent.
BG004
Xelox+BV
Participants in the 2x2 factorial part of the study received intravenous infusion of bevacizumab 7.5 mg/kg over 30 to 90 minutes followed by oxaliplatin 130 mg/m^2 over 2 hours on Day 1 of every 3 weeks in combination with capecitabine, administered orally at a dose of 1000 mg/m^2 twice-daily (equivalent to a total daily dose of 2000 mg/m^2), for the first 2 weeks of every 3-week cycle. Participants received up to 16 cycles of treatment during the primary study treatment phase (48 weeks). Participants who completed the 48-week primary study treatment phase without progressive disease were eligible to enter the post-study treatment phase at the discretion of the investigator and the sponsor. Participants who entered this phase were to continue treatment on the same regimen to which they were initially randomized until either progression of disease was documented, unacceptable toxicity occurred, or the participant withdrew consent.
BG005
Folfox-4+BV
Participants in the 2x2 factorial part of the study received intravenous infusion of bevacizumab 5 mg/kg over 30 to 90 minutes followed by oxaliplatin 85 mg/m^2 on Day 1 of every 2-week cycle; concomitantly with leucovorin 200 mg/m^2 iv for 2 hours followed by fluorouracil 400 mg/m^2 bolus injection over 2 to 4 min followed by 600 mg/m^2 continuous infusion over 22 h on Days 1 and 2 of every 2-week cycle. Participants received up to 24 cycles of treatment during the primary study treatment phase (48 weeks). Participants who completed the 48-week primary study treatment phase without progressive disease were eligible to enter the post-study treatment phase at the discretion of the investigator and the sponsor. Participants who entered this phase were to continue treatment on the same regimen to which they were initially randomized until either progression of disease was documented, unacceptable toxicity occurred, or the participant withdrew consent.
BG006
Total
Total of all reporting groups
Denominators
Units
Counts
Participants
BG000317
BG001317
BG002350
BG003351
BG004350
BG005349
BG0062034
Baseline Measures
Title
Description
Population Description
Parameter Type
Dispersion Type
Unit of Measure
Calculate Percentage
Denominator Units Selected
Denominators
Classes
Age, Continuous
Mean
Standard Deviation
years
Title
Denominators
Categories
Title
Measurements
BG00060.3± 10.76
BG00160.6± 10.94
BG00259.1± 12.14
BG003
Sex: Female, Male
Count of Participants
Participants
Title
Denominators
Categories
Title
Measurements
Female
BG000123
BG001113
BG002
Type
Title
Description
Population Description
Reporting Status
Anticipated Posting Date
Parameter Type
Dispersion Type
Unit of Measure
Calculate Percentage
Time Frame
Units Analyzed
Denominator Units Selected
Arm/Group Information
Denominators
Classes
Analyses
Primary
Progression-free Survival (PFS) as Assessed by the Investigator According to Response Evaluation Criteria in Solid Tumors (RECIST) by General Approach (Participants With Curative Surgery Censored): Non-inferiority of XELOX Versus FOLFOX-4
PFS was defined as the time from randomization to progressive disease or death. Participants with neither disease progression nor death were censored at the last date of the last tumor assessment that confirmed that their disease had not progressed. Participants with no tumor assessments after baseline who were alive at the time of clinical cutoff were censored at the date of randomization. Participants who underwent surgical resection with curative intent without prior progression were censored at the date of surgery. PFS was based on tumor assessments made by the investigators according to the RECIST criteria. Non-inferiority analysis that followed the general approach took into account all tumor assessments obtained during the primary study treatment phase, the post-study treatment phase and those obtained during the follow-up phase. Non-inferiority of the XELOX-containing arms compared with the FOLFOX-4- containing arms was investigated.
The eligible patient population (EPP) excluded participants from the ITT who had violated major protocol inclusion or exclusion criteria or participants who were randomized and did not receive at least one dose of capecitabine, 5-FU, oxaliplatin, or bevacizumab/placebo.
Posted
Median
95% Confidence Interval
days
Baseline until disease progression or death, approximately 2 years 6 months
ID
Title
Description
OG000
FOLFOX-4/FOLFOX-4+P/FOLFOX-4+BV
Participants from the initial 2-arm part and the 2x2 factorial part of the study including the following groups -
Folfox-4: Participants who received 2-week cycles of infused leucovorin, bolus injection fluorouracil and continuous infusion fluorouracil (given on days 1 and 2), combined with intravenous oxaliplatin (given on day 1).
Folfox-4+P: Participants who received 2-week cycles of infused leucovorin, bolus injection fluorouracil and continuous infusion fluorouracil (given on days 1 and 2), combined with intravenous oxaliplatin and placebo control for bevacizumab (both given on day 1 every 2 weeks).
Folfox-4+BV: Participants who received 2-week cycles of infused leucovorin, bolus injection fluorouracil and continuous infusion fluorouracil (given on days 1 and 2), combined with intravenous oxaliplatin and intravenous bevacizumab (both given on day 1 every 2 weeks).
OG001
XELOX/XELOX+P/XELOX+BV
Participants from the initial 2-arm part and the 2x2 factorial part of the study including the following groups -
Xelox: Capecitabine was administered as an oral twice-daily outpatient intermittent treatment (3-week cycles consisting of 2 weeks of treatment followed by 1 week without treatment) combined with intravenous oxaliplatin (given on day 1).
Xelox+P: Capecitabine was administered as an oral twice-daily outpatient intermittent treatment (3-week cycles consisting of 2 weeks of treatment followed by 1 week without treatment) combined with intravenous oxaliplatin and placebo (P) control for bevacizumab (both given on day 1 every 3 weeks).
Xelox+BV: Capecitabine was administered as an oral twice-daily outpatient intermittent treatment (3-week cycles consisting of 2 weeks of treatment followed by 1 week without treatment) combined with intravenous oxaliplatin and intravenous bevacizumab (both given on day 1 every 3 weeks).
Units
Counts
Participants
OG000937
OG001967
Title
Denominators
Categories
Title
Measurements
OG000259(245 to 268)
OG001241(229 to 254)
Group IDs
Group Description
Statistical Method
Statistical Comment
P-Value
P-Value Comment
Parameter Type
Parameter Value
Dispersion Type
Dispersion Value
Confidence Interval Sides
Confidence Interval %
CI Lower Limit
CI Upper Limit
CI Lower Limit Comment
CI Upper Limit Comment
Estimate Comment
Tested Non-Inferiority
Non-Inferiority Type
Non-Inferiority Comment
Other Analysis Description
OG000
OG001
Equivalence of treatment arm A ('XELOX') to treatment arm B ('FOLFOX-4') was tested via the following hypotheses - H0: HRA/B >/= 1.23 versus H1: HRA/B < 1.23. HRA/B denotes the hazard of disease progression or death under treatment A ('XELOX') divided by the hazard of disease progression or death under treatment B ('FOLFOX-4').
Hazard Ratio (HR)
1.05
2-Sided
97.5
0.94
1.18
Yes
Non-Inferiority or Equivalence
Non-inferiority was demonstrated if the upper limit of the 2-sided 97.5% confidence interval (CI) for the hazard ratio (HR) was less than the predefined limit of 1.23 (the non-inferiority margin). A stratified Cox model was used. In order to retain an experiment-wise two-sided type I error of 5%, the non-inferiority analysis for PFS used a two-sided significance level of 2.5%.
Secondary
PFS as Assessed by the Independent Review Committee (IRC) (General Approach, Participants With Curative Surgery Censored) - Non-inferiority of XELOX Versus FOLFOX-4
PFS is defined as the time from randomization to disease progression (PD) or death due to any cause. Participants with neither disease progression nor death were censored at the last date of the last tumor assessment that confirmed that their disease had not progressed. Participants who underwent surgical resection with curative intent without prior progression were censored at the date of surgery. PFS was analyzed on the basis of the tumor response assessments made by the IRC. Non-inferiority analysis that followed the general approach took into account all tumor assessments obtained during the primary study treatment phase, the post-study treatment phase and those obtained during the follow-up phase. Non-inferiority of the XELOX-containing arms was compared with the FOLFOX-4-containing arms.
The EPP excluded participants from the ITT who had violated major protocol inclusion or exclusion criteria or participants who were randomized and did not receive at least one dose of capecitabine, 5-FU, oxaliplatin, or bevacizumab/placebo.
Posted
Median
95% Confidence Interval
days
Baseline until disease progression or death, approximately 2 years 6 months
ID
Title
Description
OG000
FOLFOX-4/FOLFOX-4+P/FOLFOX-4+BV
Participants from the initial 2-arm part and the 2x2 factorial part of the study including the following groups -
Folfox-4: Participants who received 2-week cycles of infused leucovorin, bolus injection fluorouracil and continuous infusion fluorouracil (given on days 1 and 2), combined with intravenous oxaliplatin (given on day 1).
Folfox-4+P: Participants who received 2-week cycles of infused leucovorin, bolus injection fluorouracil and continuous infusion fluorouracil (given on days 1 and 2), combined with intravenous oxaliplatin and placebo control for bevacizumab (both given on day 1 every 2 weeks).
Folfox-4+BV: Participants who received 2-week cycles of infused leucovorin, bolus injection fluorouracil and continuous infusion fluorouracil (given on days 1 and 2), combined with intravenous oxaliplatin and intravenous bevacizumab (both given on day 1 every 2 weeks).
Secondary
PFS as Assessed by the Independent Review Committee (IRC) (General Approach, Participants With Curative Surgery Censored) - Superiority of Chemotherapy Plus BV Over Chemotherapy Alone
PFS is defined as the time from randomization to disease progression (PD) or death due to any cause. Participants with neither disease progression nor death were censored at the last date of the last tumor assessment that confirmed that their disease had not progressed. Participants who underwent surgical resection with curative intent without prior progression were censored at the date of surgery. PFS was analyzed on the basis of the tumor response assessments made by the IRC. Superiority analysis that followed the general approach took into account all tumor assessments obtained during the primary study treatment phase, the post-study treatment phase and those obtained during the follow-up phase. Superiority of the bevacizumab-containing arms was compared with the placebo-containing arms.
The ITT population included all randomized participants who provided written informed consent.
Posted
Median
95% Confidence Interval
days
Baseline until disease progression or death, approximately 2 years 6 months
ID
Title
Description
OG000
FOLFOX-4+P/XELOX+P
Participants from the 2x2 factorial part of the study including the following groups -
Folfox-4+P: Participants received 2-week cycles of infused leucovorin, bolus injection fluorouracil and continuous infusion fluorouracil (given on days 1 and 2), combined with intravenous oxaliplatin and placebo control for bevacizumab (both given on day 1 every 2 weeks).
Xelox+P: Capecitabine was administered as an oral twice-daily outpatient intermittent treatment (3-week cycles consisting of 2 weeks of treatment followed by 1 week without treatment) combined with intravenous oxaliplatin and placebo (P) control for bevacizumab (both given on day 1 every 3 weeks).
Secondary
PFS (On-treatment Approach): Non-inferiority of XELOX Versus FOLFOX-4
PFS is defined as the time from randomization to disease progression (PD) or death due to any cause. The on-treatment analysis included only tumor assessments and death events that occurred no later than 28 days after the last confirmed intake of any study medication in the primary study treatment phase. Participants who did not have an event during this interval were censored at the date of the last tumor assessment within this time window, or on day 1 if no tumor assessment was available after baseline. Participants who underwent surgical resection with curative intent without prior progression within 28 days after the last confirmed intake of any study medication in the primary study treatment phase were censored at the date of surgery. The on-treatment approach excluded the possible impact of other treatments that might have been started before disease progression. Non-inferiority of the XELOX-containing arms was compared with the FOLFOX-4-containing arms.
The EPP excluded participants from the ITT who had violated major protocol inclusion or exclusion criteria or participants who were randomized and did not receive at least one dose of capecitabine, 5-FU, oxaliplatin, or bevacizumab/placebo.
Posted
Median
95% Confidence Interval
days
Baseline until disease progression or death, approximately 2 years 6 months
ID
Title
Description
OG000
FOLFOX-4/FOLFOX-4+P/FOLFOX-4+BV
Participants from the initial 2-arm part and the 2x2 factorial part of the study including the following groups -
Folfox-4: Participants who received 2-week cycles of infused leucovorin, bolus injection fluorouracil and continuous infusion fluorouracil (given on days 1 and 2), combined with intravenous oxaliplatin (given on day 1).
Folfox-4+P: Participants who received 2-week cycles of infused leucovorin, bolus injection fluorouracil and continuous infusion fluorouracil (given on days 1 and 2), combined with intravenous oxaliplatin and placebo control for bevacizumab (both given on day 1 every 2 weeks).
Folfox-4+BV: Participants who received 2-week cycles of infused leucovorin, bolus injection fluorouracil and continuous infusion fluorouracil (given on days 1 and 2), combined with intravenous oxaliplatin and intravenous bevacizumab (both given on day 1 every 2 weeks).
Secondary
PFS (On-treatment Approach): Superiority of Chemotherapy Plus BV Over Chemotherapy Alone
PFS is defined as the time from randomization to disease progression (PD) or death due to any cause. The on-treatment analysis included only tumor assessments and death events that occurred no later than 28 days after the last confirmed intake of any study medication in the primary study treatment phase. Participants who did not have an event during this interval were censored at the date of the last tumor assessment within this time window, or on day 1 if no tumor assessment was available after baseline. Participants who underwent surgical resection with curative intent without prior progression within 28 days after the last confirmed intake of any study medication in the primary study treatment phase were censored at the date of surgery. The on-treatment approach excluded the possible impact of other treatments that might have been started before disease progression. Non-inferiority of the XELOX-containing arms was compared with the FOLFOX-4-containing arms.
The ITT population included all randomized participants who provided written informed consent.
Posted
Median
95% Confidence Interval
days
Baseline until disease progression or death, approximately 2 years 6 months
ID
Title
Description
OG000
FOLFOX-4+P/XELOX+P
Participants from the 2x2 factorial part of the study including the following groups -
Folfox-4+P: Participants received 2-week cycles of infused leucovorin, bolus injection fluorouracil and continuous infusion fluorouracil (given on days 1 and 2), combined with intravenous oxaliplatin and placebo control for bevacizumab (both given on day 1 every 2 weeks).
Xelox+P: Capecitabine was administered as an oral twice-daily outpatient intermittent treatment (3-week cycles consisting of 2 weeks of treatment followed by 1 week without treatment) combined with intravenous oxaliplatin and placebo (P) control for bevacizumab (both given on day 1 every 3 weeks).
Secondary
PFS by General Approach, Participants With Curative Surgery Not Censored: Non-inferiority of XELOX Versus FOLFOX-4
PFS is defined as the time from randomization to disease progression (PD) or death due to any cause. Participants who underwent curative surgery after experiencing a sufficient shrinkage of their tumor were not censored at the date of surgery, but any relapse, new occurrence of colorectal cancer, or death was considered as an event. Non-inferiority analysis that followed the general approach took into account all tumor assessments obtained during the primary study treatment phase, the post-study treatment phase and those obtained during the follow-up phase. Non-inferiority of the XELOX-containing arms was compared with the FOLFOX-4-containing arms.
EPP excluded participants from the ITT who had violated major protocol inclusion or exclusion criteria or participants who were randomized and did not receive at least one dose of capecitabine, 5-FU, oxaliplatin, or bevacizumab/placebo.
Posted
Median
95% Confidence Interval
days
Baseline until disease progression or death, approximately 2 years 6 months
ID
Title
Description
OG000
FOLFOX-4/FOLFOX-4+P/FOLFOX-4+BV
Participants from the initial 2-arm part and the 2x2 factorial part of the study including the following groups -
Folfox-4: Participants who received 2-week cycles of infused leucovorin, bolus injection fluorouracil and continuous infusion fluorouracil (given on days 1 and 2), combined with intravenous oxaliplatin (given on day 1).
Folfox-4+P: Participants who received 2-week cycles of infused leucovorin, bolus injection fluorouracil and continuous infusion fluorouracil (given on days 1 and 2), combined with intravenous oxaliplatin and placebo control for bevacizumab (both given on day 1 every 2 weeks).
Folfox-4+BV: Participants who received 2-week cycles of infused leucovorin, bolus injection fluorouracil and continuous infusion fluorouracil (given on days 1 and 2), combined with intravenous oxaliplatin and intravenous bevacizumab (both given on day 1 every 2 weeks).
Secondary
PFS by General Approach, Participants With Curative Surgery Not Censored: Superiority of Chemotherapy Plus BV Over Chemotherapy Alone
PFS is defined as the time from randomization to disease progression (PD) or death due to any cause. Participants who underwent curative surgery after experiencing a sufficient shrinkage of their tumor were not censored at the date of surgery, but any relapse, new occurrence of colorectal cancer, or death was considered as an event. Superiority analysis that followed the general approach took into account all tumor assessments obtained during the primary study treatment phase, the post-study treatment phase and those obtained during the follow-up phase. Superiority of the BV-containing arms was compared with the chemotherapy alone arms.
The ITT population included all randomized participants who provided written informed consent.
Posted
Median
95% Confidence Interval
days
Baseline until disease progression or death, approximately 2 years 6 months
ID
Title
Description
OG000
FOLFOX-4+P/XELOX+P
Participants from the 2x2 factorial part of the study including the following groups -
Folfox-4+P: Participants received 2-week cycles of infused leucovorin, bolus injection fluorouracil and continuous infusion fluorouracil (given on days 1 and 2), combined with intravenous oxaliplatin and placebo control for bevacizumab (both given on day 1 every 2 weeks).
Xelox+P: Capecitabine was administered as an oral twice-daily outpatient intermittent treatment (3-week cycles consisting of 2 weeks of treatment followed by 1 week without treatment) combined with intravenous oxaliplatin and placebo (P) control for bevacizumab (both given on day 1 every 3 weeks).
Secondary
Overall Survival: Non-inferiority of XELOX Versus FOLFOX-4
Overall survival was defined as the time from the date of randomization to the date of death. Participants who were not reported to have died at the time of the clinical cut-off date for the analysis were censored using the date they were last known to be alive. Non-inferiority of the XELOX-containing arms was compared with the FOLFOX-4-containing arms.
The EPP excluded participants from the ITT who had violated major protocol inclusion or exclusion criteria or participants who were randomized and did not receive at least one dose of capecitabine, 5-FU, oxaliplatin, or bevacizumab/placebo.
Posted
Median
95% Confidence Interval
days
Baseline until disease progression or death, approximately 2 years 6 months
ID
Title
Description
OG000
FOLFOX-4/FOLFOX-4+P/FOLFOX-4+BV
Participants from the initial 2-arm part and the 2x2 factorial part of the study including the following groups -
Folfox-4: Participants who received 2-week cycles of infused leucovorin, bolus injection fluorouracil and continuous infusion fluorouracil (given on days 1 and 2), combined with intravenous oxaliplatin (given on day 1).
Folfox-4+P: Participants who received 2-week cycles of infused leucovorin, bolus injection fluorouracil and continuous infusion fluorouracil (given on days 1 and 2), combined with intravenous oxaliplatin and placebo control for bevacizumab (both given on day 1 every 2 weeks).
Folfox-4+BV: Participants who received 2-week cycles of infused leucovorin, bolus injection fluorouracil and continuous infusion fluorouracil (given on days 1 and 2), combined with intravenous oxaliplatin and intravenous bevacizumab (both given on day 1 every 2 weeks).
Secondary
Overall Survival: Superiority of Chemotherapy Plus BV Over Chemotherapy Alone
Overall survival was defined as the time from the date of randomization to the date of death. Participants who were not reported to have died at the time of the clinical cut-off date for the analysis were censored using the date they were last known to be alive. Superiority of the BV-containing arms was compared with the chemotherapy alone arms.
The ITT population included all randomized participants who provided written informed consent.
Posted
Median
95% Confidence Interval
days
Baseline until disease progression or death, approximately 2 years 6 months
ID
Title
Description
OG000
FOLFOX-4+P/XELOX+P
Participants from the 2x2 factorial part of the study including the following groups -
Folfox-4+P: Participants received 2-week cycles of infused leucovorin, bolus injection fluorouracil and continuous infusion fluorouracil (given on days 1 and 2), combined with intravenous oxaliplatin and placebo control for bevacizumab (both given on day 1 every 2 weeks).
Xelox+P: Capecitabine was administered as an oral twice-daily outpatient intermittent treatment (3-week cycles consisting of 2 weeks of treatment followed by 1 week without treatment) combined with intravenous oxaliplatin and placebo (P) control for bevacizumab (both given on day 1 every 3 weeks).
OG001
FOLFOX-4+BV/XELOX+BV
Participants from the 2x2 factorial part of the study including the following groups -
Folfox-4+BV: Participants who received 2-week cycles of infused leucovorin, bolus injection fluorouracil and continuous infusion fluorouracil (given on days 1 and 2), combined with intravenous oxaliplatin and intravenous bevacizumab (both given on day 1 every 2 weeks).
Xelox+BV: Capecitabine was administered as an oral twice-daily outpatient intermittent treatment (3-week cycles consisting of 2 weeks of treatment followed by 1 week without treatment) combined with intravenous oxaliplatin and intravenous bevacizumab (both given on day 1 every 3 weeks).
Primary
PFS as Assessed by the Investigator According to Response Evaluation Criteria in Solid Tumors (RECIST) by General Approach (Participants With Curative Surgery Censored) - Superiority of Chemotherapy Plus BV Over Chemotherapy Alone
PFS was defined as the time from randomization to progressive disease or death. Participants with neither disease progression nor death were censored at the last date of the last tumor assessment that confirmed that their disease had not progressed. Participants with no tumor assessments after baseline who were alive at the time of clinical cutoff were censored at the date of randomization. Participants who underwent surgical resection with curative intent without prior progression were censored at the date of surgery. PFS was based on tumor assessments made by the investigators according to the RECIST criteria. Superiority analysis that followed the general approach took into account all tumor assessments obtained during the primary study treatment phase, the post-study treatment phase and those obtained during the follow-up phase. Superiority of the BV-containing arms was compared with the chemotherapy alone arms.
The ITT population included all randomized participants who provided written informed consent.
Posted
Median
95% Confidence Interval
days
Baseline until disease progression or death, approximately 2 years 6 months
ID
Title
Description
OG000
FOLFOX-4+P/XELOX+P
Participants from the 2x2 factorial part of the study including the following groups -
Folfox-4+P: Participants received 2-week cycles of infused leucovorin, bolus injection fluorouracil and continuous infusion fluorouracil (given on days 1 and 2), combined with intravenous oxaliplatin and placebo control for bevacizumab (both given on day 1 every 2 weeks).
Xelox+P: Capecitabine was administered as an oral twice-daily outpatient intermittent treatment (3-week cycles consisting of 2 weeks of treatment followed by 1 week without treatment) combined with intravenous oxaliplatin and placebo (P) control for bevacizumab (both given on day 1 every 3 weeks).
Secondary
Best Overall Response (BOR) as Assessed by the Investigator According to Response Evaluation Criteria in Solid Tumors (RECIST): Non-inferiority of XELOX Versus FOLFOX-4
According to the RECIST criteria, BOR in an individual participant was defined as the best response recorded from the start of the treatment until disease progression or recurrence. Only tumor assessments as assessed by the investigator and made up to and including 28 days after last intake of study medication in the primary study treatment phase not later than date of first curative surgery were included in these analyses. Responders were defined as the percentage of participants with a confirmed best overall response of complete response (CR) or partial response (PR). Non-inferiority of the XELOX-containing arms was compared with the FOLFOX-4-containing arms.
The EPP excluded participants from the ITT who had violated major protocol inclusion or exclusion criteria or participants who were randomized and did not receive at least one dose of capecitabine, 5-FU, oxaliplatin, or bevacizumab/placebo.
Posted
Number
Percentage of responders
From baseline until disease progression/recurrence, approximately 2 years 6 months
ID
Title
Description
OG000
FOLFOX-4/FOLFOX-4+P/FOLFOX-4+BV
Participants from the initial 2-arm part and the 2x2 factorial part of the study including the following groups -
Folfox-4: Participants who received 2-week cycles of infused leucovorin, bolus injection fluorouracil and continuous infusion fluorouracil (given on days 1 and 2), combined with intravenous oxaliplatin (given on day 1).
Folfox-4+P: Participants who received 2-week cycles of infused leucovorin, bolus injection fluorouracil and continuous infusion fluorouracil (given on days 1 and 2), combined with intravenous oxaliplatin and placebo control for bevacizumab (both given on day 1 every 2 weeks).
Folfox-4+BV: Participants who received 2-week cycles of infused leucovorin, bolus injection fluorouracil and continuous infusion fluorouracil (given on days 1 and 2), combined with intravenous oxaliplatin and intravenous bevacizumab (both given on day 1 every 2 weeks).
Secondary
Best Overall Response (BOR) as Assessed by the Investigator According to RECIST: Superiority of Chemotherapy Plus BV Over Chemotherapy Alone
According to the RECIST criteria, BOR in an individual participant was defined as the best response recorded from the start of the treatment until disease progression or recurrence. Only tumor assessments as assessed by the investigator and made up to and including 28 days after last intake of study medication in the primary study treatment phase not later than date of first curative surgery were included in these analyses. Responders were defined as the percentage of participants with a confirmed best overall response of complete response (CR) or partial response (PR). Superiority of the BV-containing arms was compared with the chemotherapy alone arms.
The ITT population included all randomized participants who provided written informed consent.
Posted
Number
Percentage of responders
From baseline until disease progression/recurrence, approximately 2 years 6 months
ID
Title
Description
OG000
FOLFOX-4+P/XELOX+P
Participants from the 2x2 factorial part of the study including the following groups -
Folfox-4+P: Participants received 2-week cycles of infused leucovorin, bolus injection fluorouracil and continuous infusion fluorouracil (given on days 1 and 2), combined with intravenous oxaliplatin and placebo control for bevacizumab (both given on day 1 every 2 weeks).
Xelox+P: Capecitabine was administered as an oral twice-daily outpatient intermittent treatment (3-week cycles consisting of 2 weeks of treatment followed by 1 week without treatment) combined with intravenous oxaliplatin and placebo (P) control for bevacizumab (both given on day 1 every 3 weeks).
Secondary
BOR as Assessed by the IRC According to RECIST: Non-inferiority of XELOX Versus FOLFOX-4
According to the RECIST criteria, the BOR in an individual participant was the best response recorded from the start of the treatment until disease progression/recurrence (taking the smallest measurements recorded since the baseline assessment as a reference for PD). The BOR as assessed by the IRC was determined based on tumor assessments that were made up to and including 28 days after last intake of study medication in the primary study treatment phase. Responders were defined as the percentage of participants with a complete response (CR) or partial response (PR). Non-inferiority of the XELOX-containing arms was compared with the FOLFOX-4-containing arms.
The EPP excluded participants from the ITT who had violated major protocol inclusion or exclusion criteria or participants who were randomized and did not receive at least one dose of capecitabine, 5-FU, oxaliplatin, or bevacizumab/placebo.
Posted
Number
Percentage of responders
From baseline until disease progression/recurrence, approximately 2 years 6 months
ID
Title
Description
OG000
FOLFOX-4/FOLFOX-4+P/FOLFOX-4+BV
Participants from the initial 2-arm part and the 2x2 factorial part of the study including the following groups -
Folfox-4: Participants who received 2-week cycles of infused leucovorin, bolus injection fluorouracil and continuous infusion fluorouracil (given on days 1 and 2), combined with intravenous oxaliplatin (given on day 1).
Folfox-4+P: Participants who received 2-week cycles of infused leucovorin, bolus injection fluorouracil and continuous infusion fluorouracil (given on days 1 and 2), combined with intravenous oxaliplatin and placebo control for bevacizumab (both given on day 1 every 2 weeks).
Folfox-4+BV: Participants who received 2-week cycles of infused leucovorin, bolus injection fluorouracil and continuous infusion fluorouracil (given on days 1 and 2), combined with intravenous oxaliplatin and intravenous bevacizumab (both given on day 1 every 2 weeks).
Secondary
BOR as Assessed by the IRC According to RECIST: Superiority of Chemotherapy Plus BV Over Chemotherapy Alone
According to the RECIST criteria, the BOR in an individual participant was the best response recorded from the start of the treatment until disease progression/recurrence (taking the smallest measurements recorded since the baseline assessment as a reference for PD). The BOR as assessed by the IRC was determined based on tumor assessments that were made up to and including 28 days after last intake of study medication in the primary study treatment phase. Responders were defined as the percentage of participants with a complete response (CR) or partial response (PR). Superiority of the BV-containing arms was compared with the chemotherapy alone arms.
The ITT population included all randomized participants who provided written informed consent.
Posted
Number
Percentage of responders
From baseline until disease progression/recurrence, approximately 2 years 6 months
ID
Title
Description
OG000
FOLFOX-4+P/XELOX+P
Participants from the 2x2 factorial part of the study including the following groups -
Folfox-4+P: Participants received 2-week cycles of infused leucovorin, bolus injection fluorouracil and continuous infusion fluorouracil (given on days 1 and 2), combined with intravenous oxaliplatin and placebo control for bevacizumab (both given on day 1 every 2 weeks).
Xelox+P: Capecitabine was administered as an oral twice-daily outpatient intermittent treatment (3-week cycles consisting of 2 weeks of treatment followed by 1 week without treatment) combined with intravenous oxaliplatin and placebo (P) control for bevacizumab (both given on day 1 every 3 weeks).
Secondary
Time to Treatment Failure (TTF) as Assessed by the Investigator According to RECIST: Non-inferiority of XELOX Versus FOLFOX-4
Time to treatment failure was defined as the time from the date of randomization to the date of discontinuation of the primary study treatment phase due to adverse event/intercurrent illness, insufficient therapeutic response, death, failure to return, refusing treatment/being unwilling to cooperate, or withdrawing consent; discontinuation of the post study treatment phase due to adverse event, progressive disease, death, participant refusal/administrative reasons, or withdrawing consent; documented disease progression; or death due to any cause, whichever occurred first. The general approach took into account all tumor assessments obtained during the primary study treatment phase, the post-study treatment phase and those obtained during the follow-up phase.The on-treatment approach included only tumor assessments and deaths that occurred no later than 28 days after the last confirmed intake of any study medication in the primary study treatment phase only.
The safety population included all participants who were randomized and received at least one dose of capecitabine, 5-FU, oxaliplatin, or bevacizumab/placebo.
Posted
Median
95% Confidence Interval
days
From baseline until disease progression/recurrence, approximately 2 years 6 months
ID
Title
Description
OG000
FOLFOX-4/FOLFOX-4+P/FOLFOX-4+BV
Participants from the initial 2-arm part and the 2x2 factorial part of the study including the following groups -
Folfox-4: Participants who received 2-week cycles of infused leucovorin, bolus injection fluorouracil and continuous infusion fluorouracil (given on days 1 and 2), combined with intravenous oxaliplatin (given on day 1).
Folfox-4+P: Participants who received 2-week cycles of infused leucovorin, bolus injection fluorouracil and continuous infusion fluorouracil (given on days 1 and 2), combined with intravenous oxaliplatin and placebo control for bevacizumab (both given on day 1 every 2 weeks).
Folfox-4+BV: Participants who received 2-week cycles of infused leucovorin, bolus injection fluorouracil and continuous infusion fluorouracil (given on days 1 and 2), combined with intravenous oxaliplatin and intravenous bevacizumab (both given on day 1 every 2 weeks).
Secondary
Time to Treatment Failure as Assessed by the Investigator According to RECIST: Superiority of Chemotherapy Plus BV Over Chemotherapy Alone
Time to treatment failure was defined as the time from the date of randomization to the date of discontinuation of the primary study treatment phase due to adverse event/intercurrent illness, insufficient therapeutic response, death, failure to return, refusing treatment/being unwilling to cooperate, or withdrawing consent; discontinuation of the post study treatment phase due to adverse event, progressive disease, death, participant refusal/administrative reasons, or withdrawing consent; documented disease progression; or death due to any cause, whichever occurred first. The general approach included all tumor assessments or deaths that occurred during the primary study treatment phase, the post-study treatment phase, or the follow-up phase. The on-treatment approach included only tumor assessments and deaths that occurred no later than 28 days after the last confirmed intake of any study medication in the primary study treatment phase only.
The safety population included all participants who were randomized and received at least one dose of capecitabine, 5-FU, oxaliplatin, or bevacizumab/placebo.
Posted
Median
95% Confidence Interval
days
From baseline until disease progression/recurrence, approximately 2 years 6 months
ID
Title
Description
OG000
FOLFOX-4+P/XELOX+P
Participants from the 2x2 factorial part of the study including the following groups -
Folfox-4+P: Participants received 2-week cycles of infused leucovorin, bolus injection fluorouracil and continuous infusion fluorouracil (given on days 1 and 2), combined with intravenous oxaliplatin and placebo control for bevacizumab (both given on day 1 every 2 weeks).
Xelox+P: Capecitabine was administered as an oral twice-daily outpatient intermittent treatment (3-week cycles consisting of 2 weeks of treatment followed by 1 week without treatment) combined with intravenous oxaliplatin and placebo (P) control for bevacizumab (both given on day 1 every 3 weeks).
Secondary
Time to Response as Assessed by the Investigator According to RECIST: Non-inferiority of XELOX Versus FOLFOX-4
For participants whose BOR was CR or PR, time to response was measured as the time from randomization to the first time when the measurement criteria for CR or PR (whichever status was recorded first) was met. It was based on tumor assessments made by the investigators according to the RECIST criteria. Results were reported as the number of participants achieving a response in 8 time categories from Week 1 to Week 54. Non-inferiority of the XELOX-containing arms was compared with the FOLFOX-4-containing arms.
The EPP excluded participants from the ITT who had violated major protocol inclusion or exclusion criteria or participants who were randomized and did not receive at least one dose of capecitabine, 5-FU, oxaliplatin, or bevacizumab/placebo.
Posted
Number
Participants
Week 1 to Week 54
ID
Title
Description
OG000
FOLFOX-4/FOLFOX-4+P/FOLFOX-4+BV
Participants from the initial 2-arm part and the 2x2 factorial part of the study including the following groups -
Folfox-4: Participants who received 2-week cycles of infused leucovorin, bolus injection fluorouracil and continuous infusion fluorouracil (given on days 1 and 2), combined with intravenous oxaliplatin (given on day 1).
Folfox-4+P: Participants who received 2-week cycles of infused leucovorin, bolus injection fluorouracil and continuous infusion fluorouracil (given on days 1 and 2), combined with intravenous oxaliplatin and placebo control for bevacizumab (both given on day 1 every 2 weeks).
Folfox-4+BV: Participants who received 2-week cycles of infused leucovorin, bolus injection fluorouracil and continuous infusion fluorouracil (given on days 1 and 2), combined with intravenous oxaliplatin and intravenous bevacizumab (both given on day 1 every 2 weeks).
Secondary
Time to Response as Assessed by the Investigator According to RECIST: Superiority of Chemotherapy Plus BV Over Chemotherapy Alone
For participants whose BOR was CR or PR, time to response was measured as the time from randomization to the first time when the measurement criteria for CR or PR (whichever status was recorded first) was met. It was based on tumor assessments made by the investigators according to the RECIST criteria. Results were reported as the number of participants achieving a response in 8 time categories from Week 1 to Week 54. Superiority of the BV-containing arms was compared with the chemotherapy alone arms.
The ITT population included all randomized participants who provided written informed consent.
Posted
Number
Participants
Week 1 to Week 54
ID
Title
Description
OG000
FOLFOX-4+P/XELOX+P
Participants from the 2x2 factorial part of the study including the following groups -
Folfox-4+P: Participants received 2-week cycles of infused leucovorin, bolus injection fluorouracil and continuous infusion fluorouracil (given on days 1 and 2), combined with intravenous oxaliplatin and placebo control for bevacizumab (both given on day 1 every 2 weeks).
Xelox+P: Capecitabine was administered as an oral twice-daily outpatient intermittent treatment (3-week cycles consisting of 2 weeks of treatment followed by 1 week without treatment) combined with intravenous oxaliplatin and placebo (P) control for bevacizumab (both given on day 1 every 3 weeks).
OG001
XELOX/XELOX+P/XELOX+BV
Secondary
Duration of Overall Response as Assessed by the Investigator According to RECIST: Non-inferiority of XELOX Versus FOLFOX-4
Duration of overall response was measured from the time that measurement criteria were first met for CR or PR (whichever status was recorded first) until the first date when progressive disease or death was documented. It was based on tumor assessments made by the investigators according to the RECIST criteria. Participants who neither progressed nor died were censored at the date of the last tumor assessment. Participants undergoing surgical resection with curative intent were censored at the date of surgery. Non-inferiority of the XELOX-containing arms was compared with the FOLFOX-4-containing arms.
The EPP excluded participants from the ITT who had violated major protocol inclusion or exclusion criteria or participants who were randomized and did not receive at least one dose of capecitabine, 5-FU, oxaliplatin, or bevacizumab/placebo.
Posted
Median
95% Confidence Interval
days
From baseline until disease progression/recurrence, approximately 2 years 6 months
ID
Title
Description
OG000
FOLFOX-4/FOLFOX-4+P/FOLFOX-4+BV
Participants from the initial 2-arm part and the 2x2 factorial part of the study including the following groups -
Folfox-4: Participants who received 2-week cycles of infused leucovorin, bolus injection fluorouracil and continuous infusion fluorouracil (given on days 1 and 2), combined with intravenous oxaliplatin (given on day 1).
Folfox-4+P: Participants who received 2-week cycles of infused leucovorin, bolus injection fluorouracil and continuous infusion fluorouracil (given on days 1 and 2), combined with intravenous oxaliplatin and placebo control for bevacizumab (both given on day 1 every 2 weeks).
Folfox-4+BV: Participants who received 2-week cycles of infused leucovorin, bolus injection fluorouracil and continuous infusion fluorouracil (given on days 1 and 2), combined with intravenous oxaliplatin and intravenous bevacizumab (both given on day 1 every 2 weeks).
Secondary
Duration of Overall Response as Assessed by the Investigator According to RECIST: Superiority Analysis of Chemotherapy Plus Bevacizumab Versus Chemotherapy Alone
Duration of overall response was measured from the time that measurement criteria were first met for CR or PR (whichever status was recorded first) until the first date when progressive disease or death was documented. It was based on tumor assessments made by the investigators according to the RECIST criteria. Participants who neither progressed nor died were censored at the date of the last tumor assessment. Participants undergoing surgical resection with curative intent were censored at the date of surgery. Superiority of the BV-containing arms was compared with the chemotherapy alone arms.
The ITT population included all randomized participants who provided written informed consent.
Posted
Median
95% Confidence Interval
days
From baseline until disease progression/recurrence, approximately 2 years 6 months
ID
Title
Description
OG000
FOLFOX-4+P/XELOX+P
Participants from the 2x2 factorial part of the study including the following groups -
Folfox-4+P: Participants received 2-week cycles of infused leucovorin, bolus injection fluorouracil and continuous infusion fluorouracil (given on days 1 and 2), combined with intravenous oxaliplatin and placebo control for bevacizumab (both given on day 1 every 2 weeks).
Xelox+P: Capecitabine was administered as an oral twice-daily outpatient intermittent treatment (3-week cycles consisting of 2 weeks of treatment followed by 1 week without treatment) combined with intravenous oxaliplatin and placebo (P) control for bevacizumab (both given on day 1 every 3 weeks).
Secondary
Duration of Complete Response as Assessed by the Investigator According to RECIST: Non-inferiority of XELOX Versus FOLFOX-4
For complete responders, the duration of complete response was measured from the time measurement criteria were first met for complete response until the date that progressive disease (or death) was documented. Non-inferiority of the XELOX-containing arms was compared with the FOLFOX-4-containing arms.
The EPP excluded participants from the ITT who had violated major protocol inclusion or exclusion criteria or participants who were randomized and did not receive at least one dose of capecitabine, 5-FU, oxaliplatin, or bevacizumab/placebo.
Posted
Median
95% Confidence Interval
days
From baseline until disease progression/recurrence, approximately 2 years 6 months
ID
Title
Description
OG000
FOLFOX-4/FOLFOX-4+P/FOLFOX-4+BV
Participants from the initial 2-arm part and the 2x2 factorial part of the study including the following groups -
Folfox-4: Participants who received 2-week cycles of infused leucovorin, bolus injection fluorouracil and continuous infusion fluorouracil (given on days 1 and 2), combined with intravenous oxaliplatin (given on day 1).
Folfox-4+P: Participants who received 2-week cycles of infused leucovorin, bolus injection fluorouracil and continuous infusion fluorouracil (given on days 1 and 2), combined with intravenous oxaliplatin and placebo control for bevacizumab (both given on day 1 every 2 weeks).
Folfox-4+BV: Participants who received 2-week cycles of infused leucovorin, bolus injection fluorouracil and continuous infusion fluorouracil (given on days 1 and 2), combined with intravenous oxaliplatin and intravenous bevacizumab (both given on day 1 every 2 weeks).
Secondary
Duration of Complete Response as Assessed by the Investigator According to RECIST: Superiority of Chemotherapy Plus BV Over Chemotherapy Alone
For complete responders, the duration of complete response was measured from the time measurement criteria were first met for complete response until the date that progressive disease (or death) was documented. Superiority of the BV-containing arms was compared with the chemotherapy alone arms.
The ITT population included all randomized participants who provided written informed consent.
Posted
Median
95% Confidence Interval
days
From baseline until disease progression/recurrence, approximately 2 years 6 months
ID
Title
Description
OG000
FOLFOX-4+P/XELOX+P
Participants from the 2x2 factorial part of the study including the following groups -
Folfox-4+P: Participants received 2-week cycles of infused leucovorin, bolus injection fluorouracil and continuous infusion fluorouracil (given on days 1 and 2), combined with intravenous oxaliplatin and placebo control for bevacizumab (both given on day 1 every 2 weeks).
Xelox+P: Capecitabine was administered as an oral twice-daily outpatient intermittent treatment (3-week cycles consisting of 2 weeks of treatment followed by 1 week without treatment) combined with intravenous oxaliplatin and placebo (P) control for bevacizumab (both given on day 1 every 3 weeks).
OG001
FOLFOX-4+BV/XELOX+BV
Participants from the 2x2 factorial part of the study including the following groups -
Folfox-4+BV: Participants who received 2-week cycles of infused leucovorin, bolus injection fluorouracil and continuous infusion fluorouracil (given on days 1 and 2), combined with intravenous oxaliplatin and intravenous bevacizumab (both given on day 1 every 2 weeks).
Xelox+BV: Capecitabine was administered as an oral twice-daily outpatient intermittent treatment (3-week cycles consisting of 2 weeks of treatment followed by 1 week without treatment) combined with intravenous oxaliplatin and intravenous bevacizumab (both given on day 1 every 3 weeks).
Time Frame
Approximately 2 years 6 months
Description
Serious adverse events (SAEs) and non-serious adverse events were reported for members of the safety population, which included all participants were randomized and received at least one dose of capecitabine, 5-FU, oxaliplatin, or bevacizumab/placebo.
All-Cause Mortality Comment
Not provided
Arm/Groups
ID
Title
Description
Deaths (Affected)
Deaths (At Risk)
Serious Events (Affected)
Serious Events (At Risk)
Other Events (Affected)
Other Events (At Risk)
EG000
Xelox
Participants in the 2-arm part of the study received intravenous infusion of oxaliplatin 130 mg/m^2 over 2 hours on Day 1 of every 3 weeks before the first dose of capecitabine. Capecitabine was administered orally within 30 minutes after the end of a meal (breakfast and dinner) at a dose of 1000 mg/m^2 twice-daily (equivalent to a total daily dose of 2000 mg/m^2), for the first 2 weeks of every 3-week cycle. Participants received up to 16 cycles of treatment during the primary study treatment phase (48 weeks). Participants who completed the 48-week primary study treatment phase without progressive disease were eligible to enter the post-study treatment phase at the discretion of the investigator and the sponsor. Participants who entered this phase were to continue treatment on the same regimen to which they were initially randomized until either progression of disease was documented, unacceptable toxicity occurred, or the participant withdrew consent.
117
316
310
316
EG001
Folfox-4
Participants in the 2-arm part of the study received intravenous infusion of oxaliplatin 85 mg/m^2 on Day 1 of every 2-week cycle; concomitantly with leucovorin 200 mg/m^2 iv for 2 hours followed by fluorouracil 400 mg/m^2 bolus injection over 2 to 4 min followed by 600 mg/m^2 continuous infusion over 22 h on Days 1 and 2 of every 2-week cycle. Participants received up to 24 cycles of treatment during the primary study treatment phase (48 weeks). Participants who completed the 48-week primary study treatment phase without progressive disease were eligible to enter the post-study treatment phase at the discretion of the investigator and the sponsor. Participants who entered this phase were to continue treatment on the same regimen to which they were initially randomized until either progression of disease was documented, unacceptable toxicity occurred, or the participant withdrew consent.
120
313
310
313
EG002
Xelox+P
Participants in the 2x2 factorial part of the study received intravenous infusion of placebo control for bevacizumab (BV) [volume equivalent to 7.5 mg/kg BV] over 30 to 90 minutes followed by oxaliplatin 130 mg/m^2 over 2 hours on Day 1 of every 3 weeks in combination with capecitabine, administered orally at a dose of 1000 mg/m^2 twice-daily (equivalent to a total daily dose of 2000 mg/m^2), for the first 2 weeks of every 3-week cycle. Participants received up to 16 cycles of treatment during the primary study treatment phase (48 weeks). Participants who completed the 48-week primary study treatment phase without progressive disease were eligible to enter the post-study treatment phase at the discretion of the investigator and the sponsor. Participants who entered this phase were to continue treatment on the same regimen to which they were initially randomized until either progression of disease was documented, unacceptable toxicity occurred, or the participant withdrew consent.
121
339
330
339
EG003
Folfox-4+P
Participants in the 2x2 factorial part of the study received intravenous infusion of placebo control for BV (volume equivalent to 5 mg/kg BV) over 30 to 90 minutes followed by oxaliplatin 85 mg/m^2 on Day 1 of every 2-week cycle; concomitantly with leucovorin 200 mg/m^2 iv for 2 hours followed by fluorouracil 400 mg/m^2 bolus injection over 2 to 4 min followed by 600 mg/m^2 continuous infusion over 22 h on Days 1 and 2 of every 2-week cycle. Participants received up to 24 cycles of treatment during the primary study treatment phase (48 weeks). Participants who completed the 48-week primary study treatment phase without progressive disease were eligible to enter the post-study treatment phase at the discretion of the investigator and the sponsor. Participants who entered this phase were to continue treatment on the same regimen to which they were initially randomized until either progression of disease was documented, unacceptable toxicity occurred, or the participant withdrew consent.
128
336
331
336
EG004
Xelox+BV
Participants in the 2x2 factorial part of the study received intravenous infusion of bevacizumab 7.5 mg/kg over 30 to 90 minutes followed by oxaliplatin 130 mg/m^2 over 2 hours on Day 1 of every 3 weeks in combination with capecitabine, administered orally at a dose of 1000 mg/m^2 twice-daily (equivalent to a total daily dose of 2000 mg/m^2), for the first 2 weeks of every 3-week cycle. Participants received up to 16 cycles of treatment during the primary study treatment phase (48 weeks). Participants who completed the 48-week primary study treatment phase without progressive disease were eligible to enter the post-study treatment phase at the discretion of the investigator and the sponsor. Participants who entered this phase were to continue treatment on the same regimen to which they were initially randomized until either progression of disease was documented, unacceptable toxicity occurred, or the participant withdrew consent.
131
353
348
353
EG005
Folfox-4+BV
Participants in the 2x2 factorial part of the study received intravenous infusion of bevacizumab 5 mg/kg over 30 to 90 minutes followed by oxaliplatin 85 mg/m^2 on Day 1 of every 2-week cycle; concomitantly with leucovorin 200 mg/m^2 iv for 2 hours followed by fluorouracil 400 mg/m^2 bolus injection over 2 to 4 min followed by 600 mg/m^2 continuous infusion over 22 h on Days 1 and 2 of every 2-week cycle. Participants received up to 24 cycles of treatment during the primary study treatment phase (48 weeks). Participants who completed the 48-week primary study treatment phase without progressive disease were eligible to enter the post-study treatment phase at the discretion of the investigator and the sponsor. Participants who entered this phase were to continue treatment on the same regimen to which they were initially randomized until either progression of disease was documented, unacceptable toxicity occurred, or the participant withdrew consent.
146
341
335
341
Serious Adverse Events
Term
Organ System
Source Vocabulary
Assessment Type
Notes
Statistical Information
Diarrhoea
Gastrointestinal disorders
MedDRA (9.0)
Systematic Assessment
EG00027 affected316 at risk
EG00113 affected313 at risk
EG00225 affected339 at risk
EG0037 affected336 at risk
EG00426 affected353 at risk
EG0058 affected341 at risk
Vomiting
Gastrointestinal disorders
MedDRA (9.0)
Systematic Assessment
EG0007 affected316 at risk
EG0017 affected313 at risk
EG00216 affected339 at risk
EG003
Abdominal pain
Gastrointestinal disorders
MedDRA (9.0)
Systematic Assessment
EG0004 affected316 at risk
EG0017 affected313 at risk
EG0027 affected339 at risk
EG003
Intestinal obstruction
Gastrointestinal disorders
MedDRA (9.0)
Systematic Assessment
EG0004 affected316 at risk
EG0016 affected313 at risk
EG0026 affected339 at risk
EG003
Small intestinal obstruction
Gastrointestinal disorders
MedDRA (9.0)
Systematic Assessment
EG0005 affected316 at risk
EG0013 affected313 at risk
EG0023 affected339 at risk
EG003
Nausea
Gastrointestinal disorders
MedDRA (9.0)
Systematic Assessment
EG0001 affected316 at risk
EG0016 affected313 at risk
EG0024 affected339 at risk
EG003
Constipation
Gastrointestinal disorders
MedDRA (9.0)
Systematic Assessment
EG0001 affected316 at risk
EG0015 affected313 at risk
EG0021 affected339 at risk
EG003
Gastrointestinal haemorrhage
Gastrointestinal disorders
MedDRA (9.0)
Systematic Assessment
EG0001 affected316 at risk
EG0012 affected313 at risk
EG0023 affected339 at risk
EG003
Ascites
Gastrointestinal disorders
MedDRA (9.0)
Systematic Assessment
EG0003 affected316 at risk
EG0010 affected313 at risk
EG0021 affected339 at risk
EG003
Rectal haemorrhage
Gastrointestinal disorders
MedDRA (9.0)
Systematic Assessment
EG0001 affected316 at risk
EG0012 affected313 at risk
EG0022 affected339 at risk
EG003
Stomatitis all
Gastrointestinal disorders
MedDRA (9.0)
Systematic Assessment
EG0002 affected316 at risk
EG0010 affected313 at risk
EG0020 affected339 at risk
EG003
Enteritis
Gastrointestinal disorders
MedDRA (9.0)
Systematic Assessment
EG0003 affected316 at risk
EG0010 affected313 at risk
EG0021 affected339 at risk
EG003
Intestinal perforation
Gastrointestinal disorders
MedDRA (9.0)
Systematic Assessment
EG0001 affected316 at risk
EG0011 affected313 at risk
EG0021 affected339 at risk
EG003
Abdominal pain upper
Gastrointestinal disorders
MedDRA (9.0)
Systematic Assessment
EG0001 affected316 at risk
EG0011 affected313 at risk
EG0021 affected339 at risk
EG003
Ileus
Gastrointestinal disorders
MedDRA (9.0)
Systematic Assessment
EG0000 affected316 at risk
EG0011 affected313 at risk
EG0022 affected339 at risk
EG003
Colitis
Gastrointestinal disorders
MedDRA (9.0)
Systematic Assessment
EG0001 affected316 at risk
EG0010 affected313 at risk
EG0020 affected339 at risk
EG003
Haematemesis
Gastrointestinal disorders
MedDRA (9.0)
Systematic Assessment
EG0000 affected316 at risk
EG0010 affected313 at risk
EG0021 affected339 at risk
EG003
Large intestinal obstruction
Gastrointestinal disorders
MedDRA (9.0)
Systematic Assessment
EG0001 affected316 at risk
EG0011 affected313 at risk
EG0021 affected339 at risk
EG003
Mechanical ileus
Gastrointestinal disorders
MedDRA (9.0)
Systematic Assessment
EG0000 affected316 at risk
EG0010 affected313 at risk
EG0021 affected339 at risk
EG003
Pancreatitis
Gastrointestinal disorders
MedDRA (9.0)
Systematic Assessment
EG0001 affected316 at risk
EG0010 affected313 at risk
EG0021 affected339 at risk
EG003
Gastrointestinal toxicity
Gastrointestinal disorders
MedDRA (9.0)
Systematic Assessment
EG0000 affected316 at risk
EG0010 affected313 at risk
EG0022 affected339 at risk
EG003
Intestinal functional disorder
Gastrointestinal disorders
MedDRA (9.0)
Systematic Assessment
EG0000 affected316 at risk
EG0010 affected313 at risk
EG0020 affected339 at risk
EG003
Melaena
Gastrointestinal disorders
MedDRA (9.0)
Systematic Assessment
EG0000 affected316 at risk
EG0011 affected313 at risk
EG0021 affected339 at risk
EG003
Abdominal adhesions
Gastrointestinal disorders
MedDRA (9.0)
Systematic Assessment
EG0000 affected316 at risk
EG0011 affected313 at risk
EG0020 affected339 at risk
EG003
Abdominal distension
Gastrointestinal disorders
MedDRA (9.0)
Systematic Assessment
EG0001 affected316 at risk
EG0010 affected313 at risk
EG0020 affected339 at risk
EG003
Caecitis
Gastrointestinal disorders
MedDRA (9.0)
Systematic Assessment
EG0000 affected316 at risk
EG0012 affected313 at risk
EG0020 affected339 at risk
EG003
Enterocolitis
Gastrointestinal disorders
MedDRA (9.0)
Systematic Assessment
EG0001 affected316 at risk
EG0010 affected313 at risk
EG0020 affected339 at risk
EG003
Enterovesical fistula
Gastrointestinal disorders
MedDRA (9.0)
Systematic Assessment
EG0001 affected316 at risk
EG0010 affected313 at risk
EG0020 affected339 at risk
EG003
Gastritis
Gastrointestinal disorders
MedDRA (9.0)
Systematic Assessment
EG0001 affected316 at risk
EG0011 affected313 at risk
EG0020 affected339 at risk
EG003
Gastrointestinal disorder
Gastrointestinal disorders
MedDRA (9.0)
Systematic Assessment
EG0000 affected316 at risk
EG0010 affected313 at risk
EG0020 affected339 at risk
EG003
Gastrointestinal hypomotility
Gastrointestinal disorders
MedDRA (9.0)
Systematic Assessment
EG0000 affected316 at risk
EG0010 affected313 at risk
EG0021 affected339 at risk
EG003
Gastrointestinal obstruction
Gastrointestinal disorders
MedDRA (9.0)
Systematic Assessment
EG0001 affected316 at risk
EG0010 affected313 at risk
EG0020 affected339 at risk
EG003
Gastrooesophageal reflux disease
Gastrointestinal disorders
MedDRA (9.0)
Systematic Assessment
EG0001 affected316 at risk
EG0011 affected313 at risk
EG0020 affected339 at risk
EG003
Ileus paralytic
Gastrointestinal disorders
MedDRA (9.0)
Systematic Assessment
EG0001 affected316 at risk
EG0011 affected313 at risk
EG0020 affected339 at risk
EG003
Intestinal haemorrhage
Gastrointestinal disorders
MedDRA (9.0)
Systematic Assessment
EG0000 affected316 at risk
EG0011 affected313 at risk
EG0020 affected339 at risk
EG003
Pericoronitis
Gastrointestinal disorders
MedDRA (9.0)
Systematic Assessment
EG0000 affected316 at risk
EG0010 affected313 at risk
EG0020 affected339 at risk
EG003
Peritonitis
Gastrointestinal disorders
MedDRA (9.0)
Systematic Assessment
EG0000 affected316 at risk
EG0010 affected313 at risk
EG0020 affected339 at risk
EG003
Abdominal pain lower
Gastrointestinal disorders
MedDRA (9.0)
Systematic Assessment
EG0000 affected316 at risk
EG0010 affected313 at risk
EG0020 affected339 at risk
EG003
Anal fissure
Gastrointestinal disorders
MedDRA (9.0)
Systematic Assessment
EG0000 affected316 at risk
EG0011 affected313 at risk
EG0020 affected339 at risk
EG003
Anal stenosis
Gastrointestinal disorders
MedDRA (9.0)
Systematic Assessment
EG0000 affected316 at risk
EG0010 affected313 at risk
EG0021 affected339 at risk
EG003
Colonic obstruction
Gastrointestinal disorders
MedDRA (9.0)
Systematic Assessment
EG0000 affected316 at risk
EG0010 affected313 at risk
EG0020 affected339 at risk
EG003
Crohn's disease
Gastrointestinal disorders
MedDRA (9.0)
Systematic Assessment
EG0000 affected316 at risk
EG0010 affected313 at risk
EG0020 affected339 at risk
EG003
Duodenal ulcer
Gastrointestinal disorders
MedDRA (9.0)
Systematic Assessment
EG0000 affected316 at risk
EG0010 affected313 at risk
EG0021 affected339 at risk
EG003
Dyspepsia
Gastrointestinal disorders
MedDRA (9.0)
Systematic Assessment
EG0000 affected316 at risk
EG0010 affected313 at risk
EG0021 affected339 at risk
EG003
Enterocolonic fistula
Gastrointestinal disorders
MedDRA (9.0)
Systematic Assessment
EG0000 affected316 at risk
EG0010 affected313 at risk
EG0020 affected339 at risk
EG003
Faecaloma
Gastrointestinal disorders
MedDRA (9.0)
Systematic Assessment
EG0000 affected316 at risk
EG0010 affected313 at risk
EG0020 affected339 at risk
EG003
Gastrointestinal necrosis
Gastrointestinal disorders
MedDRA (9.0)
Systematic Assessment
EG0001 affected316 at risk
EG0010 affected313 at risk
EG0020 affected339 at risk
EG003
Gastrointestinal perforation
Gastrointestinal disorders
MedDRA (9.0)
Systematic Assessment
EG0000 affected316 at risk
EG0010 affected313 at risk
EG0020 affected339 at risk
EG003
Haematochezia
Gastrointestinal disorders
MedDRA (9.0)
Systematic Assessment
EG0000 affected316 at risk
EG0010 affected313 at risk
EG0020 affected339 at risk
EG003
Inguinal hernia
Gastrointestinal disorders
MedDRA (9.0)
Systematic Assessment
EG0000 affected316 at risk
EG0010 affected313 at risk
EG0020 affected339 at risk
EG003
Intestinal ischemia
Gastrointestinal disorders
MedDRA (9.0)
Systematic Assessment
EG0000 affected316 at risk
EG0010 affected313 at risk
EG0020 affected339 at risk
EG003
Lower gastrointestinal haemorrhage
Gastrointestinal disorders
MedDRA (9.0)
Systematic Assessment
EG0000 affected316 at risk
EG0010 affected313 at risk
EG0020 affected339 at risk
EG003
Oesophagitis
Gastrointestinal disorders
MedDRA (9.0)
Systematic Assessment
EG0000 affected316 at risk
EG0010 affected313 at risk
EG0020 affected339 at risk
EG003
Proctalgia
Gastrointestinal disorders
MedDRA (9.0)
Systematic Assessment
EG0000 affected316 at risk
EG0010 affected313 at risk
EG0020 affected339 at risk
EG003
Rectal perforation
Gastrointestinal disorders
MedDRA (9.0)
Systematic Assessment
EG0000 affected316 at risk
EG0010 affected313 at risk
EG0021 affected339 at risk
EG003
Subileus
Gastrointestinal disorders
MedDRA (9.0)
Systematic Assessment
EG0000 affected316 at risk
EG0010 affected313 at risk
EG0020 affected339 at risk
EG003
Toxic dilatation of intestine
Gastrointestinal disorders
MedDRA (9.0)
Systematic Assessment
EG0001 affected316 at risk
EG0010 affected313 at risk
EG0020 affected339 at risk
EG003
Upper gastrointestinal haemorrhage
Gastrointestinal disorders
MedDRA (9.0)
Systematic Assessment
EG0000 affected316 at risk
EG0010 affected313 at risk
EG0020 affected339 at risk
EG003
Central line infection
Infections and infestations
MedDRA (9.0)
Systematic Assessment
EG0001 affected316 at risk
EG0014 affected313 at risk
EG0021 affected339 at risk
EG003
Pneumonia
Infections and infestations
MedDRA (9.0)
Systematic Assessment
EG0002 affected316 at risk
EG0015 affected313 at risk
EG0024 affected339 at risk
EG003
Infection
Infections and infestations
MedDRA (9.0)
Systematic Assessment
EG0000 affected316 at risk
EG0011 affected313 at risk
EG0021 affected339 at risk
EG003
Sepsis
Infections and infestations
MedDRA (9.0)
Systematic Assessment
EG0004 affected316 at risk
EG0014 affected313 at risk
EG0021 affected339 at risk
EG003
Urinary tract infection
Infections and infestations
MedDRA (9.0)
Systematic Assessment
EG0001 affected316 at risk
EG0011 affected313 at risk
EG0023 affected339 at risk
EG003
Septic shock
Infections and infestations
MedDRA (9.0)
Systematic Assessment
EG0001 affected316 at risk
EG0012 affected313 at risk
EG0021 affected339 at risk
EG003
Cellulitis
Infections and infestations
MedDRA (9.0)
Systematic Assessment
EG0002 affected316 at risk
EG0011 affected313 at risk
EG0022 affected339 at risk
EG003
Catheter site infection
Infections and infestations
MedDRA (9.0)
Systematic Assessment
EG0000 affected316 at risk
EG0012 affected313 at risk
EG0020 affected339 at risk
EG003
Lower respiratory tract infection
Infections and infestations
MedDRA (9.0)
Systematic Assessment
EG0001 affected316 at risk
EG0011 affected313 at risk
EG0021 affected339 at risk
EG003
Neutropenic sepsis
Infections and infestations
MedDRA (9.0)
Systematic Assessment
EG0000 affected316 at risk
EG0012 affected313 at risk
EG0020 affected339 at risk
EG003
Diverticulitis
Infections and infestations
MedDRA (9.0)
Systematic Assessment
EG0000 affected316 at risk
EG0010 affected313 at risk
EG0020 affected339 at risk
EG003
Abdominal abscess
Infections and infestations
MedDRA (9.0)
Systematic Assessment
EG0000 affected316 at risk
EG0010 affected313 at risk
EG0020 affected339 at risk
EG003
Bacteraemia
Infections and infestations
MedDRA (9.0)
Systematic Assessment
EG0000 affected316 at risk
EG0010 affected313 at risk
EG0021 affected339 at risk
EG003
Respiratory tract infection
Infections and infestations
MedDRA (9.0)
Systematic Assessment
EG0001 affected316 at risk
EG0010 affected313 at risk
EG0020 affected339 at risk
EG003
Bacterial sepsis
Infections and infestations
MedDRA (9.0)
Systematic Assessment
EG0000 affected316 at risk
EG0011 affected313 at risk
EG0020 affected339 at risk
EG003
Clostridium difficile colitis
Infections and infestations
MedDRA (9.0)
Systematic Assessment
EG0001 affected316 at risk
EG0010 affected313 at risk
EG0021 affected339 at risk
EG003
Postoperative wound infection
Infections and infestations
MedDRA (9.0)
Systematic Assessment
EG0000 affected316 at risk
EG0010 affected313 at risk
EG0020 affected339 at risk
EG003
Abdominal infection
Infections and infestations
MedDRA (9.0)
Systematic Assessment
EG0000 affected316 at risk
EG0010 affected313 at risk
EG0020 affected339 at risk
EG003
Abdominal wall infection
Infections and infestations
MedDRA (9.0)
Systematic Assessment
EG0000 affected316 at risk
EG0010 affected313 at risk
EG0020 affected339 at risk
EG003
Abscess
Infections and infestations
MedDRA (9.0)
Systematic Assessment
EG0000 affected316 at risk
EG0010 affected313 at risk
EG0020 affected339 at risk
EG003
Diarrhoea infectious
Infections and infestations
MedDRA (9.0)
Systematic Assessment
EG0000 affected316 at risk
EG0011 affected313 at risk
EG0020 affected339 at risk
EG003
Gastroenteritis
Infections and infestations
MedDRA (9.0)
Systematic Assessment
EG0001 affected316 at risk
EG0010 affected313 at risk
EG0021 affected339 at risk
EG003
Gastrointestinal infection
Infections and infestations
MedDRA (9.0)
Systematic Assessment
EG0000 affected316 at risk
EG0010 affected313 at risk
EG0020 affected339 at risk
EG003
Hepatitis B
Infections and infestations
MedDRA (9.0)
Systematic Assessment
EG0000 affected316 at risk
EG0010 affected313 at risk
EG0020 affected339 at risk
EG003
Pneumonia pneumococcal
Infections and infestations
MedDRA (9.0)
Systematic Assessment
EG0000 affected316 at risk
EG0010 affected313 at risk
EG0020 affected339 at risk
EG003
Pyelonephritis
Infections and infestations
MedDRA (9.0)
Systematic Assessment
EG0001 affected316 at risk
EG0010 affected313 at risk
EG0020 affected339 at risk
EG003
Urosepsis
Infections and infestations
MedDRA (9.0)
Systematic Assessment
EG0001 affected316 at risk
EG0010 affected313 at risk
EG0020 affected339 at risk
EG003
Viral pharyngitis
Infections and infestations
MedDRA (9.0)
Systematic Assessment
EG0000 affected316 at risk
EG0010 affected313 at risk
EG0020 affected339 at risk
EG003
Abdominal wall abscess
Infections and infestations
MedDRA (9.0)
Systematic Assessment
EG0000 affected316 at risk
EG0011 affected313 at risk
EG0020 affected339 at risk
EG003
Acinetobacter bacteraemia
Infections and infestations
MedDRA (9.0)
Systematic Assessment
EG0000 affected316 at risk
EG0010 affected313 at risk
EG0020 affected339 at risk
EG003
Anal fistula infection
Infections and infestations
MedDRA (9.0)
Systematic Assessment
EG0000 affected316 at risk
EG0011 affected313 at risk
EG0020 affected339 at risk
EG003
Bacterial infection
Infections and infestations
MedDRA (9.0)
Systematic Assessment
EG0000 affected316 at risk
EG0010 affected313 at risk
EG0020 affected339 at risk
EG003
Bronchitis
Infections and infestations
MedDRA (9.0)
Systematic Assessment
EG0000 affected316 at risk
EG0011 affected313 at risk
EG0020 affected339 at risk
EG003
Bronchopneumonia
Infections and infestations
MedDRA (9.0)
Systematic Assessment
EG0000 affected316 at risk
EG0010 affected313 at risk
EG0021 affected339 at risk
EG003
Catheter related infection
Infections and infestations
MedDRA (9.0)
Systematic Assessment
EG0000 affected316 at risk
EG0011 affected313 at risk
EG0020 affected339 at risk
EG003
Catheter sepsis
Infections and infestations
MedDRA (9.0)
Systematic Assessment
EG0000 affected316 at risk
EG0011 affected313 at risk
EG0020 affected339 at risk
EG003
Fungaemia
Infections and infestations
MedDRA (9.0)
Systematic Assessment
EG0000 affected316 at risk
EG0010 affected313 at risk
EG0020 affected339 at risk
EG003
Neutropenic infection
Infections and infestations
MedDRA (9.0)
Systematic Assessment
EG0000 affected316 at risk
EG0010 affected313 at risk
EG0020 affected339 at risk
EG003
Peritoneal infection
Infections and infestations
MedDRA (9.0)
Systematic Assessment
EG0000 affected316 at risk
EG0011 affected313 at risk
EG0020 affected339 at risk
EG003
Pseudomonas infection
Infections and infestations
MedDRA (9.0)
Systematic Assessment
EG0000 affected316 at risk
EG0010 affected313 at risk
EG0021 affected339 at risk
EG003
Pyonephrosis
Infections and infestations
MedDRA (9.0)
Systematic Assessment
EG0000 affected316 at risk
EG0010 affected313 at risk
EG0020 affected339 at risk
EG003
Rectal abscess
Infections and infestations
MedDRA (9.0)
Systematic Assessment
EG0000 affected316 at risk
EG0011 affected313 at risk
EG0020 affected339 at risk
EG003
Staphylococcal infection
Infections and infestations
MedDRA (9.0)
Systematic Assessment
EG0001 affected316 at risk
EG0010 affected313 at risk
EG0020 affected339 at risk
EG003
Staphylococcal sepsis
Infections and infestations
MedDRA (9.0)
Systematic Assessment
EG0000 affected316 at risk
EG0010 affected313 at risk
EG0020 affected339 at risk
EG003
Upper respiratory tract infection
Infections and infestations
MedDRA (9.0)
Systematic Assessment
EG0000 affected316 at risk
EG0011 affected313 at risk
EG0020 affected339 at risk
EG003
Pyrexia
General disorders
MedDRA (9.0)
Systematic Assessment
EG00016 affected316 at risk
EG00116 affected313 at risk
EG0026 affected339 at risk
EG003
Asthenia
General disorders
MedDRA (9.0)
Systematic Assessment
EG0001 affected316 at risk
EG0011 affected313 at risk
EG0022 affected339 at risk
EG003
Chest pain
General disorders
MedDRA (9.0)
Systematic Assessment
EG0002 affected316 at risk
EG0011 affected313 at risk
EG0021 affected339 at risk
EG003
Catheter related complication
General disorders
MedDRA (9.0)
Systematic Assessment
EG0001 affected316 at risk
EG0012 affected313 at risk
EG0021 affected339 at risk
EG003
Fatigue
General disorders
MedDRA (9.0)
Systematic Assessment
EG0000 affected316 at risk
EG0011 affected313 at risk
EG0020 affected339 at risk
EG003
General physical health deterioration
General disorders
MedDRA (9.0)
Systematic Assessment
EG0002 affected316 at risk
EG0010 affected313 at risk
EG0021 affected339 at risk
EG003
Oedema peripheral
General disorders
MedDRA (9.0)
Systematic Assessment
EG0000 affected316 at risk
EG0012 affected313 at risk
EG0020 affected339 at risk
EG003
Multi-organ failure
General disorders
MedDRA (9.0)
Systematic Assessment
EG0000 affected316 at risk
EG0011 affected313 at risk
EG0020 affected339 at risk
EG003
Performance status decreased
General disorders
MedDRA (9.0)
Systematic Assessment
EG0000 affected316 at risk
EG0010 affected313 at risk
EG0021 affected339 at risk
EG003
Extravasation
General disorders
MedDRA (9.0)
Systematic Assessment
EG0000 affected316 at risk
EG0010 affected313 at risk
EG0020 affected339 at risk
EG003
Non-cardiac chest pain
General disorders
MedDRA (9.0)
Systematic Assessment
EG0001 affected316 at risk
EG0010 affected313 at risk
EG0021 affected339 at risk
EG003
Pain
General disorders
MedDRA (9.0)
Systematic Assessment
EG0000 affected316 at risk
EG0010 affected313 at risk
EG0021 affected339 at risk
EG003
Infusion related reaction
General disorders
MedDRA (9.0)
Systematic Assessment
EG0000 affected316 at risk
EG0010 affected313 at risk
EG0020 affected339 at risk
EG003
Sudden death
General disorders
MedDRA (9.0)
Systematic Assessment
EG0000 affected316 at risk
EG0010 affected313 at risk
EG0020 affected339 at risk
EG003
Wound necrosis
General disorders
MedDRA (9.0)
Systematic Assessment
EG0000 affected316 at risk
EG0010 affected313 at risk
EG0020 affected339 at risk
EG003
Chills
General disorders
MedDRA (9.0)
Systematic Assessment
EG0001 affected316 at risk
EG0010 affected313 at risk
EG0020 affected339 at risk
EG003
Impaired healing
General disorders
MedDRA (9.0)
Systematic Assessment
EG0000 affected316 at risk
EG0010 affected313 at risk
EG0020 affected339 at risk
EG003
Oedema
General disorders
MedDRA (9.0)
Systematic Assessment
EG0000 affected316 at risk
EG0010 affected313 at risk
EG0020 affected339 at risk
EG003
Febrile neutropenia
Blood and lymphatic system disorders
MedDRA (9.0)
Systematic Assessment
EG0003 affected316 at risk
EG00114 affected313 at risk
EG0021 affected339 at risk
EG003
Neutropenia
Blood and lymphatic system disorders
MedDRA (9.0)
Systematic Assessment
EG0002 affected316 at risk
EG0019 affected313 at risk
EG0021 affected339 at risk
EG003
Thrombocytopenia
Blood and lymphatic system disorders
MedDRA (9.0)
Systematic Assessment
EG0000 affected316 at risk
EG0012 affected313 at risk
EG0022 affected339 at risk
EG003
Anaemia
Blood and lymphatic system disorders
MedDRA (9.0)
Systematic Assessment
EG0001 affected316 at risk
EG0012 affected313 at risk
EG0021 affected339 at risk
EG003
Blood disorder
Blood and lymphatic system disorders
MedDRA (9.0)
Systematic Assessment
EG0000 affected316 at risk
EG0010 affected313 at risk
EG0020 affected339 at risk
EG003
Coagulopathy
Blood and lymphatic system disorders
MedDRA (9.0)
Systematic Assessment
EG0001 affected316 at risk
EG0011 affected313 at risk
EG0020 affected339 at risk
EG003
Leukopenia
Blood and lymphatic system disorders
MedDRA (9.0)
Systematic Assessment
EG0000 affected316 at risk
EG0010 affected313 at risk
EG0021 affected339 at risk
EG003
Agranulocytosis
Blood and lymphatic system disorders
MedDRA (9.0)
Systematic Assessment
EG0000 affected316 at risk
EG0010 affected313 at risk
EG0020 affected339 at risk
EG003
Haemolytic anaemia
Blood and lymphatic system disorders
MedDRA (9.0)
Systematic Assessment
EG0000 affected316 at risk
EG0010 affected313 at risk
EG0020 affected339 at risk
EG003
Pancytopenia
Blood and lymphatic system disorders
MedDRA (9.0)
Systematic Assessment
EG0000 affected316 at risk
EG0010 affected313 at risk
EG0020 affected339 at risk
EG003
Thrombotic thrombocytopenic purpura
Blood and lymphatic system disorders
MedDRA (9.0)
Systematic Assessment
EG0000 affected316 at risk
EG0010 affected313 at risk
EG0020 affected339 at risk
EG003
Pulmonary embolism
Respiratory, thoracic and mediastinal disorders
MedDRA (9.0)
Systematic Assessment
EG0009 affected316 at risk
EG0013 affected313 at risk
EG0023 affected339 at risk
EG003
Dyspnoea
Respiratory, thoracic and mediastinal disorders
MedDRA (9.0)
Systematic Assessment
EG0001 affected316 at risk
EG0011 affected313 at risk
EG0022 affected339 at risk
EG003
Pneumothorax
Respiratory, thoracic and mediastinal disorders
MedDRA (9.0)
Systematic Assessment
EG0000 affected316 at risk
EG0012 affected313 at risk
EG0020 affected339 at risk
EG003
Dysaesthesia pharynx
Respiratory, thoracic and mediastinal disorders
MedDRA (9.0)
Systematic Assessment
EG0000 affected316 at risk
EG0010 affected313 at risk
EG0024 affected339 at risk
EG003
Respiratory failure
Respiratory, thoracic and mediastinal disorders
MedDRA (9.0)
Systematic Assessment
EG0001 affected316 at risk
EG0011 affected313 at risk
EG0020 affected339 at risk
EG003
Acute respiratory distress syndrome
Respiratory, thoracic and mediastinal disorders
MedDRA (9.0)
Systematic Assessment
EG0000 affected316 at risk
EG0011 affected313 at risk
EG0021 affected339 at risk
EG003
Alveolitis fibrosing
Respiratory, thoracic and mediastinal disorders
MedDRA (9.0)
Systematic Assessment
EG0000 affected316 at risk
EG0010 affected313 at risk
EG0020 affected339 at risk
EG003
Bronchospasm
Respiratory, thoracic and mediastinal disorders
MedDRA (9.0)
Systematic Assessment
EG0001 affected316 at risk
EG0010 affected313 at risk
EG0020 affected339 at risk
EG003
Pneumonia aspiration
Respiratory, thoracic and mediastinal disorders
MedDRA (9.0)
Systematic Assessment
EG0000 affected316 at risk
EG0010 affected313 at risk
EG0021 affected339 at risk
EG003
Atelectasis
Respiratory, thoracic and mediastinal disorders
MedDRA (9.0)
Systematic Assessment
EG0000 affected316 at risk
EG0010 affected313 at risk
EG0020 affected339 at risk
EG003
Chronic obstructive pulmonary disease
Respiratory, thoracic and mediastinal disorders
MedDRA (9.0)
Systematic Assessment
EG0000 affected316 at risk
EG0011 affected313 at risk
EG0020 affected339 at risk
EG003
Dyspnoea exertional
Respiratory, thoracic and mediastinal disorders
MedDRA (9.0)
Systematic Assessment
EG0000 affected316 at risk
EG0011 affected313 at risk
EG0020 affected339 at risk
EG003
Epistaxis
Respiratory, thoracic and mediastinal disorders
MedDRA (9.0)
Systematic Assessment
EG0000 affected316 at risk
EG0010 affected313 at risk
EG0020 affected339 at risk
EG003
Lung disorder
Respiratory, thoracic and mediastinal disorders
MedDRA (9.0)
Systematic Assessment
EG0000 affected316 at risk
EG0010 affected313 at risk
EG0021 affected339 at risk
EG003
Pleural effusion
Respiratory, thoracic and mediastinal disorders
MedDRA (9.0)
Systematic Assessment
EG0000 affected316 at risk
EG0010 affected313 at risk
EG0021 affected339 at risk
EG003
Acute respiratory failure
Respiratory, thoracic and mediastinal disorders
MedDRA (9.0)
Systematic Assessment
EG0000 affected316 at risk
EG0010 affected313 at risk
EG0020 affected339 at risk
EG003
Haemoptysis
Respiratory, thoracic and mediastinal disorders
MedDRA (9.0)
Systematic Assessment
EG0000 affected316 at risk
EG0011 affected313 at risk
EG0020 affected339 at risk
EG003
Hypoxia
Respiratory, thoracic and mediastinal disorders
MedDRA (9.0)
Systematic Assessment
EG0000 affected316 at risk
EG0010 affected313 at risk
EG0020 affected339 at risk
EG003
Interstitial lung disease
Respiratory, thoracic and mediastinal disorders
MedDRA (9.0)
Systematic Assessment
EG0001 affected316 at risk
EG0010 affected313 at risk
EG0020 affected339 at risk
EG003
Laryngospasm
Respiratory, thoracic and mediastinal disorders
MedDRA (9.0)
Systematic Assessment
EG0000 affected316 at risk
EG0010 affected313 at risk
EG0021 affected339 at risk
EG003
Pulmonary fibrosis
Respiratory, thoracic and mediastinal disorders
MedDRA (9.0)
Systematic Assessment
EG0001 affected316 at risk
EG0010 affected313 at risk
EG0020 affected339 at risk
EG003
Dehydration
Metabolism and nutrition disorders
MedDRA (9.0)
Systematic Assessment
EG0004 affected316 at risk
EG0019 affected313 at risk
EG00210 affected339 at risk
EG003
Hypokalaemia'
Metabolism and nutrition disorders
MedDRA (9.0)
Systematic Assessment
EG0002 affected316 at risk
EG0010 affected313 at risk
EG0021 affected339 at risk
EG003
Hyperglycaemia
Metabolism and nutrition disorders
MedDRA (9.0)
Systematic Assessment
EG0001 affected316 at risk
EG0010 affected313 at risk
EG0022 affected339 at risk
EG003
Anorexia
Metabolism and nutrition disorders
MedDRA (9.0)
Systematic Assessment
EG0000 affected316 at risk
EG0010 affected313 at risk
EG0021 affected339 at risk
EG003
Hypernatraemia
Metabolism and nutrition disorders
MedDRA (9.0)
Systematic Assessment
EG0000 affected316 at risk
EG0011 affected313 at risk
EG0020 affected339 at risk
EG003
Hyponatraemia
Metabolism and nutrition disorders
MedDRA (9.0)
Systematic Assessment
EG0001 affected316 at risk
EG0010 affected313 at risk
EG0021 affected339 at risk
EG003
Hypocalcaemia
Metabolism and nutrition disorders
MedDRA (9.0)
Systematic Assessment
EG0000 affected316 at risk
EG0010 affected313 at risk
EG0020 affected339 at risk
EG003
Hypoalbuminaemia
Metabolism and nutrition disorders
MedDRA (9.0)
Systematic Assessment
EG0001 affected316 at risk
EG0010 affected313 at risk
EG0020 affected339 at risk
EG003
Hypomagnesaemia
Metabolism and nutrition disorders
MedDRA (9.0)
Systematic Assessment
EG0001 affected316 at risk
EG0010 affected313 at risk
EG0020 affected339 at risk
EG003
Malnutrition
Metabolism and nutrition disorders
MedDRA (9.0)
Systematic Assessment
EG0000 affected316 at risk
EG0011 affected313 at risk
EG0020 affected339 at risk
EG003
Cachexia
Metabolism and nutrition disorders
MedDRA (9.0)
Systematic Assessment
EG0000 affected316 at risk
EG0010 affected313 at risk
EG0020 affected339 at risk
EG003
Diabetic ketoacidosis
Metabolism and nutrition disorders
MedDRA (9.0)
Systematic Assessment
EG0000 affected316 at risk
EG0011 affected313 at risk
EG0020 affected339 at risk
EG003
Hypercalcaemia
Metabolism and nutrition disorders
MedDRA (9.0)
Systematic Assessment
EG0000 affected316 at risk
EG0010 affected313 at risk
EG0021 affected339 at risk
EG003
Hypovolaemia
Metabolism and nutrition disorders
MedDRA (9.0)
Systematic Assessment
EG0000 affected316 at risk
EG0011 affected313 at risk
EG0020 affected339 at risk
EG003
Deep vein thrombosis
Vascular disorders
MedDRA (9.0)
Systematic Assessment
EG0006 affected316 at risk
EG0016 affected313 at risk
EG0021 affected339 at risk
EG003
Thrombosis
Vascular disorders
MedDRA (9.0)
Systematic Assessment
EG0002 affected316 at risk
EG0010 affected313 at risk
EG0021 affected339 at risk
EG003
Hypertension
Vascular disorders
MedDRA (9.0)
Systematic Assessment
EG0000 affected316 at risk
EG0010 affected313 at risk
EG0020 affected339 at risk
EG003
Jugular vein thrombosis
Vascular disorders
MedDRA (9.0)
Systematic Assessment
EG0000 affected316 at risk
EG0010 affected313 at risk
EG0020 affected339 at risk
EG003
Hypotension
Vascular disorders
MedDRA (9.0)
Systematic Assessment
EG0000 affected316 at risk
EG0010 affected313 at risk
EG0021 affected339 at risk
EG003
Thrombophlebitis
Vascular disorders
MedDRA (9.0)
Systematic Assessment
EG0000 affected316 at risk
EG0010 affected313 at risk
EG0020 affected339 at risk
EG003
Embolism
Vascular disorders
MedDRA (9.0)
Systematic Assessment
EG0000 affected316 at risk
EG0010 affected313 at risk
EG0020 affected339 at risk
EG003
Peripheral ischaemia
Vascular disorders
MedDRA (9.0)
Systematic Assessment
EG0000 affected316 at risk
EG0010 affected313 at risk
EG0020 affected339 at risk
EG003
Hypertensive crisis
Vascular disorders
MedDRA (9.0)
Systematic Assessment
EG0000 affected316 at risk
EG0010 affected313 at risk
EG0020 affected339 at risk
EG003
Pelvic venous thrombosis
Vascular disorders
MedDRA (9.0)
Systematic Assessment
EG0001 affected316 at risk
EG0010 affected313 at risk
EG0020 affected339 at risk
EG003
Venous thrombosis limb
Vascular disorders
MedDRA (9.0)
Systematic Assessment
EG0000 affected316 at risk
EG0010 affected313 at risk
EG0020 affected339 at risk
EG003
Circulatory collapse
Vascular disorders
MedDRA (9.0)
Systematic Assessment
EG0000 affected316 at risk
EG0010 affected313 at risk
EG0020 affected339 at risk
EG003
Embolism venous
Vascular disorders
MedDRA (9.0)
Systematic Assessment
EG0000 affected316 at risk
EG0010 affected313 at risk
EG0020 affected339 at risk
EG003
Haematoma
Vascular disorders
MedDRA (9.0)
Systematic Assessment
EG0000 affected316 at risk
EG0010 affected313 at risk
EG0020 affected339 at risk
EG003
Haemorrhage
Vascular disorders
MedDRA (9.0)
Systematic Assessment
EG0000 affected316 at risk
EG0010 affected313 at risk
EG0020 affected339 at risk
EG003
Hypovolaemic shock
Vascular disorders
MedDRA (9.0)
Systematic Assessment
EG0001 affected316 at risk
EG0010 affected313 at risk
EG0020 affected339 at risk
EG003
Poor venous access
Vascular disorders
MedDRA (9.0)
Systematic Assessment
EG0000 affected316 at risk
EG0010 affected313 at risk
EG0020 affected339 at risk
EG003
Shock
Vascular disorders
MedDRA (9.0)
Systematic Assessment
EG0000 affected316 at risk
EG0010 affected313 at risk
EG0020 affected339 at risk
EG003
Shock haemorrhagic
Vascular disorders
MedDRA (9.0)
Systematic Assessment
EG0000 affected316 at risk
EG0010 affected313 at risk
EG0020 affected339 at risk
EG003
Subclavian vein thrombosis
Vascular disorders
MedDRA (9.0)
Systematic Assessment
EG0000 affected316 at risk
EG0010 affected313 at risk
EG0020 affected339 at risk
EG003
Venous thrombosis
Vascular disorders
MedDRA (9.0)
Systematic Assessment
EG0000 affected316 at risk
EG0010 affected313 at risk
EG0020 affected339 at risk
EG003
Atrial fibrillation
Cardiac disorders
MedDRA (9.0)
Systematic Assessment
EG0000 affected316 at risk
EG0011 affected313 at risk
EG0020 affected339 at risk
EG003
Myocardial infarction
Cardiac disorders
MedDRA (9.0)
Systematic Assessment
EG0000 affected316 at risk
EG0013 affected313 at risk
EG0020 affected339 at risk
EG003
Pericardial effusion
Cardiac disorders
MedDRA (9.0)
Systematic Assessment
EG0002 affected316 at risk
EG0010 affected313 at risk
EG0020 affected339 at risk
EG003
Cardiac arrest
Cardiac disorders
MedDRA (9.0)
Systematic Assessment
EG0000 affected316 at risk
EG0011 affected313 at risk
EG0020 affected339 at risk
EG003
Angina pectoris
Cardiac disorders
MedDRA (9.0)
Systematic Assessment
EG0001 affected316 at risk
EG0011 affected313 at risk
EG0020 affected339 at risk
EG003
Cardiomyopathy
Cardiac disorders
MedDRA (9.0)
Systematic Assessment
EG0000 affected316 at risk
EG0011 affected313 at risk
EG0020 affected339 at risk
EG003
Myocardial ischaemia
Cardiac disorders
MedDRA (9.0)
Systematic Assessment
EG0000 affected316 at risk
EG0010 affected313 at risk
EG0020 affected339 at risk
EG003
Arrhythmia
Cardiac disorders
MedDRA (9.0)
Systematic Assessment
EG0000 affected316 at risk
EG0010 affected313 at risk
EG0020 affected339 at risk
EG003
Acute left ventricular failure
Cardiac disorders
MedDRA (9.0)
Systematic Assessment
EG0000 affected316 at risk
EG0010 affected313 at risk
EG0020 affected339 at risk
EG003
Acute myocardial infarction
Cardiac disorders
MedDRA (9.0)
Systematic Assessment
EG0001 affected316 at risk
EG0010 affected313 at risk
EG0020 affected339 at risk
EG003
Atrial thrombosis
Cardiac disorders
MedDRA (9.0)
Systematic Assessment
EG0000 affected316 at risk
EG0010 affected313 at risk
EG0021 affected339 at risk
EG003
Bradycardia
Cardiac disorders
MedDRA (9.0)
Systematic Assessment
EG0000 affected316 at risk
EG0011 affected313 at risk
EG0020 affected339 at risk
EG003
Cardiac failure congestive
Cardiac disorders
MedDRA (9.0)
Systematic Assessment
EG0000 affected316 at risk
EG0010 affected313 at risk
EG0020 affected339 at risk
EG003
Cardio-respiratory arrest
Cardiac disorders
MedDRA (9.0)
Systematic Assessment
EG0000 affected316 at risk
EG0010 affected313 at risk
EG0020 affected339 at risk
EG003
Cardiogenic shock
Cardiac disorders
MedDRA (9.0)
Systematic Assessment
EG0000 affected316 at risk
EG0010 affected313 at risk
EG0020 affected339 at risk
EG003
Cardiopulmonary failure
Cardiac disorders
MedDRA (9.0)
Systematic Assessment
EG0000 affected316 at risk
EG0010 affected313 at risk
EG0020 affected339 at risk
EG003
Sick sinus syndrome
Cardiac disorders
MedDRA (9.0)
Systematic Assessment
EG0000 affected316 at risk
EG0010 affected313 at risk
EG0020 affected339 at risk
EG003
Supraventricular tachycardia
Cardiac disorders
MedDRA (9.0)
Systematic Assessment
EG0000 affected316 at risk
EG0010 affected313 at risk
EG0020 affected339 at risk
EG003
Ventricular fibrillation
Cardiac disorders
MedDRA (9.0)
Systematic Assessment
EG0000 affected316 at risk
EG0011 affected313 at risk
EG0020 affected339 at risk
EG003
Dizziness
Nervous system disorders
MedDRA (9.0)
Systematic Assessment
EG0002 affected316 at risk
EG0010 affected313 at risk
EG0020 affected339 at risk
EG003
Neuropathy peripheral
Nervous system disorders
MedDRA (9.0)
Systematic Assessment
EG0000 affected316 at risk
EG0011 affected313 at risk
EG0020 affected339 at risk
EG003
Convulsion
Nervous system disorders
MedDRA (9.0)
Systematic Assessment
EG0001 affected316 at risk
EG0011 affected313 at risk
EG0020 affected339 at risk
EG003
Syncope
Nervous system disorders
MedDRA (9.0)
Systematic Assessment
EG0000 affected316 at risk
EG0010 affected313 at risk
EG0020 affected339 at risk
EG003
Cerebrovascular accident
Nervous system disorders
MedDRA (9.0)
Systematic Assessment
EG0000 affected316 at risk
EG0010 affected313 at risk
EG0020 affected339 at risk
EG003
Headache
Nervous system disorders
MedDRA (9.0)
Systematic Assessment
EG0001 affected316 at risk
EG0010 affected313 at risk
EG0020 affected339 at risk
EG003
Transient ischaemic attack
Nervous system disorders
MedDRA (9.0)
Systematic Assessment
EG0000 affected316 at risk
EG0010 affected313 at risk
EG0021 affected339 at risk
EG003
Cerebral infarction
Nervous system disorders
MedDRA (9.0)
Systematic Assessment
EG0000 affected316 at risk
EG0010 affected313 at risk
EG0020 affected339 at risk
EG003
Coordination abnormal
Nervous system disorders
MedDRA (9.0)
Systematic Assessment
EG0001 affected316 at risk
EG0010 affected313 at risk
EG0020 affected339 at risk
EG003
Dementia
Nervous system disorders
MedDRA (9.0)
Systematic Assessment
EG0000 affected316 at risk
EG0010 affected313 at risk
EG0020 affected339 at risk
EG003
Loss of consciousness
Nervous system disorders
MedDRA (9.0)
Systematic Assessment
EG0000 affected316 at risk
EG0010 affected313 at risk
EG0021 affected339 at risk
EG003
Neuralgia
Nervous system disorders
MedDRA (9.0)
Systematic Assessment
EG0000 affected316 at risk
EG0010 affected313 at risk
EG0020 affected339 at risk
EG003
Spinal cord compression
Nervous system disorders
MedDRA (9.0)
Systematic Assessment
EG0001 affected316 at risk
EG0010 affected313 at risk
EG0021 affected339 at risk
EG003
Cerebral haemorrhage
Nervous system disorders
MedDRA (9.0)
Systematic Assessment
EG0001 affected316 at risk
EG0010 affected313 at risk
EG0020 affected339 at risk
EG003
Cerebral ischaemia
Nervous system disorders
MedDRA (9.0)
Systematic Assessment
EG0000 affected316 at risk
EG0010 affected313 at risk
EG0020 affected339 at risk
EG003
Depressed level of consciousness
Nervous system disorders
MedDRA (9.0)
Systematic Assessment
EG0000 affected316 at risk
EG0010 affected313 at risk
EG0020 affected339 at risk
EG003
Encephalophathy
Nervous system disorders
MedDRA (9.0)
Systematic Assessment
EG0000 affected316 at risk
EG0010 affected313 at risk
EG0021 affected339 at risk
EG003
Hepatic encephalopathy
Nervous system disorders
MedDRA (9.0)
Systematic Assessment
EG0001 affected316 at risk
EG0010 affected313 at risk
EG0020 affected339 at risk
EG003
Hypoaesthesia
Nervous system disorders
MedDRA (9.0)
Systematic Assessment
EG0000 affected316 at risk
EG0010 affected313 at risk
EG0021 affected339 at risk
EG003
Paraesthesia
Nervous system disorders
MedDRA (9.0)
Systematic Assessment
EG0000 affected316 at risk
EG0010 affected313 at risk
EG0020 affected339 at risk
EG003
Post procedural haemorrhage
Injury, poisoning and procedural complications
MedDRA (9.0)
Systematic Assessment
EG0001 affected316 at risk
EG0010 affected313 at risk
EG0021 affected339 at risk
EG003
Gastrointestinal stoma complication
Injury, poisoning and procedural complications
MedDRA (9.0)
Systematic Assessment
EG0000 affected316 at risk
EG0011 affected313 at risk
EG0020 affected339 at risk
EG003
Lumbar vertebral fracture
Injury, poisoning and procedural complications
MedDRA (9.0)
Systematic Assessment
EG0000 affected316 at risk
EG0010 affected313 at risk
EG0021 affected339 at risk
EG003
Stent occlussion
Injury, poisoning and procedural complications
MedDRA (9.0)
Systematic Assessment
EG0001 affected316 at risk
EG0010 affected313 at risk
EG0021 affected339 at risk
EG003
Fall
Injury, poisoning and procedural complications
MedDRA (9.0)
Systematic Assessment
EG0000 affected316 at risk
EG0010 affected313 at risk
EG0020 affected339 at risk
EG003
Femur fracture
Injury, poisoning and procedural complications
MedDRA (9.0)
Systematic Assessment
EG0000 affected316 at risk
EG0010 affected313 at risk
EG0020 affected339 at risk
EG003
Head injury
Injury, poisoning and procedural complications
MedDRA (9.0)
Systematic Assessment
EG0001 affected316 at risk
EG0011 affected313 at risk
EG0020 affected339 at risk
EG003
Radius fracture
Injury, poisoning and procedural complications
MedDRA (9.0)
Systematic Assessment
EG0000 affected316 at risk
EG0010 affected313 at risk
EG0020 affected339 at risk
EG003
Device migration
Injury, poisoning and procedural complications
MedDRA (9.0)
Systematic Assessment
EG0000 affected316 at risk
EG0011 affected313 at risk
EG0020 affected339 at risk
EG003
Failure to anastomose
Injury, poisoning and procedural complications
MedDRA (9.0)
Systematic Assessment
EG0000 affected316 at risk
EG0010 affected313 at risk
EG0020 affected339 at risk
EG003
Femoral neck fracture
Injury, poisoning and procedural complications
MedDRA (9.0)
Systematic Assessment
EG0001 affected316 at risk
EG0010 affected313 at risk
EG0020 affected339 at risk
EG003
Hip fracture
Injury, poisoning and procedural complications
MedDRA (9.0)
Systematic Assessment
EG0000 affected316 at risk
EG0011 affected313 at risk
EG0020 affected339 at risk
EG003
Overdose
Injury, poisoning and procedural complications
MedDRA (9.0)
Systematic Assessment
EG0000 affected316 at risk
EG0010 affected313 at risk
EG0021 affected339 at risk
EG003
Skull fracture
Injury, poisoning and procedural complications
MedDRA (9.0)
Systematic Assessment
EG0000 affected316 at risk
EG0010 affected313 at risk
EG0020 affected339 at risk
EG003
Tendon rupture
Injury, poisoning and procedural complications
MedDRA (9.0)
Systematic Assessment
EG0000 affected316 at risk
EG0011 affected313 at risk
EG0020 affected339 at risk
EG003
Thoracic vertebral fracture
Injury, poisoning and procedural complications
MedDRA (9.0)
Systematic Assessment
EG0000 affected316 at risk
EG0010 affected313 at risk
EG0020 affected339 at risk
EG003
Ulna fracture
Injury, poisoning and procedural complications
MedDRA (9.0)
Systematic Assessment
EG0000 affected316 at risk
EG0010 affected313 at risk
EG0021 affected339 at risk
EG003
Vascular graft occlussion
Injury, poisoning and procedural complications
MedDRA (9.0)
Systematic Assessment
EG0000 affected316 at risk
EG0010 affected313 at risk
EG0021 affected339 at risk
EG003
Renal failure acute
Renal and urinary disorders
MedDRA (9.0)
Systematic Assessment
EG0001 affected316 at risk
EG0010 affected313 at risk
EG0023 affected339 at risk
EG003
Renal failure
Renal and urinary disorders
MedDRA (9.0)
Systematic Assessment
EG0001 affected316 at risk
EG0010 affected313 at risk
EG0021 affected339 at risk
EG003
Haematuria
Renal and urinary disorders
MedDRA (9.0)
Systematic Assessment
EG0003 affected316 at risk
EG0011 affected313 at risk
EG0020 affected339 at risk
EG003
Hydronephrosis
Renal and urinary disorders
MedDRA (9.0)
Systematic Assessment
EG0000 affected316 at risk
EG0010 affected313 at risk
EG0020 affected339 at risk
EG003
Renal colic
Renal and urinary disorders
MedDRA (9.0)
Systematic Assessment
EG0000 affected316 at risk
EG0011 affected313 at risk
EG0020 affected339 at risk
EG003
Urinary bladder haemmorhage
Renal and urinary disorders
MedDRA (9.0)
Systematic Assessment
EG0000 affected316 at risk
EG0010 affected313 at risk
EG0021 affected339 at risk
EG003
Urinary retention
Renal and urinary disorders
MedDRA (9.0)
Systematic Assessment
EG0000 affected316 at risk
EG0010 affected313 at risk
EG0020 affected339 at risk
EG003
Obstructive uropathy
Renal and urinary disorders
MedDRA (9.0)
Systematic Assessment
EG0000 affected316 at risk
EG0011 affected313 at risk
EG0020 affected339 at risk
EG003
Renal impairment
Renal and urinary disorders
MedDRA (9.0)
Systematic Assessment
EG0001 affected316 at risk
EG0010 affected313 at risk
EG0020 affected339 at risk
EG003
Renal tubular disorder
Renal and urinary disorders
MedDRA (9.0)
Systematic Assessment
EG0000 affected316 at risk
EG0010 affected313 at risk
EG0020 affected339 at risk
EG003
Renal tubular necrosis
Renal and urinary disorders
MedDRA (9.0)
Systematic Assessment
EG0000 affected316 at risk
EG0010 affected313 at risk
EG0020 affected339 at risk
EG003
Ureteric obstruction
Renal and urinary disorders
MedDRA (9.0)
Systematic Assessment
EG0000 affected316 at risk
EG0011 affected313 at risk
EG0020 affected339 at risk
EG003
Hepatic failure
Hepatobiliary disorders
MedDRA (9.0)
Systematic Assessment
EG0001 affected316 at risk
EG0010 affected313 at risk
EG0020 affected339 at risk
EG003
Bile duct obstruction
Hepatobiliary disorders
MedDRA (9.0)
Systematic Assessment
EG0001 affected316 at risk
EG0011 affected313 at risk
EG0020 affected339 at risk
EG003
Hyperbilirubinaemia
Hepatobiliary disorders
MedDRA (9.0)
Systematic Assessment
EG0000 affected316 at risk
EG0010 affected313 at risk
EG0020 affected339 at risk
EG003
Portal vein thrombosis
Hepatobiliary disorders
MedDRA (9.0)
Systematic Assessment
EG0000 affected316 at risk
EG0010 affected313 at risk
EG0021 affected339 at risk
EG003
Cholangitis
Hepatobiliary disorders
MedDRA (9.0)
Systematic Assessment
EG0000 affected316 at risk
EG0010 affected313 at risk
EG0020 affected339 at risk
EG003
Cholecystitis
Hepatobiliary disorders
MedDRA (9.0)
Systematic Assessment
EG0000 affected316 at risk
EG0011 affected313 at risk
EG0020 affected339 at risk
EG003
Hepatic function abnormal
Hepatobiliary disorders
MedDRA (9.0)
Systematic Assessment
EG0000 affected316 at risk
EG0010 affected313 at risk
EG0020 affected339 at risk
EG003
Hepatitis
Hepatobiliary disorders
MedDRA (9.0)
Systematic Assessment
EG0000 affected316 at risk
EG0010 affected313 at risk
EG0021 affected339 at risk
EG003
Hepatitis Cholestatic
Hepatobiliary disorders
MedDRA (9.0)
Systematic Assessment
EG0001 affected316 at risk
EG0010 affected313 at risk
EG0020 affected339 at risk
EG003
Pain in extremity
Musculoskeletal and connective tissue disorders
MedDRA (9.0)
Systematic Assessment
EG0002 affected316 at risk
EG0012 affected313 at risk
EG0020 affected339 at risk
EG003
Musculoskeletal chest pain
Musculoskeletal and connective tissue disorders
MedDRA (9.0)
Systematic Assessment
EG0000 affected316 at risk
EG0010 affected313 at risk
EG0020 affected339 at risk
EG003
Muscular weakness
Musculoskeletal and connective tissue disorders
MedDRA (9.0)
Systematic Assessment
EG0000 affected316 at risk
EG0010 affected313 at risk
EG0020 affected339 at risk
EG003
Muscle contracture
Musculoskeletal and connective tissue disorders
MedDRA (9.0)
Systematic Assessment
EG0000 affected316 at risk
EG0010 affected313 at risk
EG0021 affected339 at risk
EG003
Myalgia
Musculoskeletal and connective tissue disorders
MedDRA (9.0)
Systematic Assessment
EG0000 affected316 at risk
EG0010 affected313 at risk
EG0020 affected339 at risk
EG003
Neck pain
Musculoskeletal and connective tissue disorders
MedDRA (9.0)
Systematic Assessment
EG0000 affected316 at risk
EG0010 affected313 at risk
EG0020 affected339 at risk
EG003
Shoulder pain
Musculoskeletal and connective tissue disorders
MedDRA (9.0)
Systematic Assessment
EG0000 affected316 at risk
EG0011 affected313 at risk
EG0020 affected339 at risk
EG003
Arthralgia
Musculoskeletal and connective tissue disorders
MedDRA (9.0)
Systematic Assessment
EG0001 affected316 at risk
EG0010 affected313 at risk
EG0020 affected339 at risk
EG003
Flank pain
Musculoskeletal and connective tissue disorders
MedDRA (9.0)
Systematic Assessment
EG0001 affected316 at risk
EG0010 affected313 at risk
EG0020 affected339 at risk
EG003
Hypersensitivity
Immune system disorders
MedDRA (9.0)
Systematic Assessment
EG0000 affected316 at risk
EG0010 affected313 at risk
EG0022 affected339 at risk
EG003
Drug hypersensitivity
Immune system disorders
MedDRA (9.0)
Systematic Assessment
EG0000 affected316 at risk
EG0010 affected313 at risk
EG0022 affected339 at risk
EG003
Anaphylactic reaction
Immune system disorders
MedDRA (9.0)
Systematic Assessment
EG0000 affected316 at risk
EG0010 affected313 at risk
EG0021 affected339 at risk
EG003
Anaphylactic shock
Immune system disorders
MedDRA (9.0)
Systematic Assessment
EG0000 affected316 at risk
EG0011 affected313 at risk
EG0020 affected339 at risk
EG003
Cancer pain
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
MedDRA (9.0)
Systematic Assessment
EG0000 affected316 at risk
EG0010 affected313 at risk
EG0022 affected339 at risk
EG003
Tumor haemorrhage
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
MedDRA (9.0)
Systematic Assessment
EG0000 affected316 at risk
EG0010 affected313 at risk
EG0020 affected339 at risk
EG003
Colon neoplasm
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
MedDRA (9.0)
Systematic Assessment
EG0000 affected316 at risk
EG0010 affected313 at risk
EG0020 affected339 at risk
EG003
Breast cancer
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
MedDRA (9.0)
Systematic Assessment
EG0000 affected316 at risk
EG0011 affected313 at risk
EG0020 affected339 at risk
EG003
Gastric neoplasm
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
MedDRA (9.0)
Systematic Assessment
EG0000 affected316 at risk
EG0010 affected313 at risk
EG0020 affected339 at risk
EG003
Malignant pleural effusion
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
MedDRA (9.0)
Systematic Assessment
EG0000 affected316 at risk
EG0010 affected313 at risk
EG0021 affected339 at risk
EG003
Metastases to ovary
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
MedDRA (9.0)
Systematic Assessment
EG0000 affected316 at risk
EG0010 affected313 at risk
EG0021 affected339 at risk
EG003
Neoplasm
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
MedDRA (9.0)
Systematic Assessment
EG0000 affected316 at risk
EG0010 affected313 at risk
EG0020 affected339 at risk
EG003
Tumour associated fever
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
MedDRA (9.0)
Systematic Assessment
EG0000 affected316 at risk
EG0010 affected313 at risk
EG0021 affected339 at risk
EG003
Blood creatinine increased
Investigations
MedDRA (9.0)
Systematic Assessment
EG0000 affected316 at risk
EG0011 affected313 at risk
EG0020 affected339 at risk
EG003
Transaminases increased
Investigations
MedDRA (9.0)
Systematic Assessment
EG0000 affected316 at risk
EG0010 affected313 at risk
EG0020 affected339 at risk
EG003
International normalized ratio increased
Investigations
MedDRA (9.0)
Systematic Assessment
EG0000 affected316 at risk
EG0010 affected313 at risk
EG0020 affected339 at risk
EG003
Blood bilirubin abnormal
Investigations
MedDRA (9.0)
Systematic Assessment
EG0000 affected316 at risk
EG0010 affected313 at risk
EG0020 affected339 at risk
EG003
Endoscopic retrograde cholangiopancreatography
Investigations
MedDRA (9.0)
Systematic Assessment
EG0000 affected316 at risk
EG0011 affected313 at risk
EG0020 affected339 at risk
EG003
Palmar-plantar erythrodysaesthesia syndrome
Skin and subcutaneous tissue disorders
MedDRA (9.0)
Systematic Assessment
EG0000 affected316 at risk
EG0010 affected313 at risk
EG0021 affected339 at risk
EG003
Rash maculo-papular
Skin and subcutaneous tissue disorders
MedDRA (9.0)
Systematic Assessment
EG0000 affected316 at risk
EG0010 affected313 at risk
EG0020 affected339 at risk
EG003
Angioneurotic oedema
Skin and subcutaneous tissue disorders
MedDRA (9.0)
Systematic Assessment
EG0000 affected316 at risk
EG0010 affected313 at risk
EG0020 affected339 at risk
EG003
Skin toxicity
Skin and subcutaneous tissue disorders
MedDRA (9.0)
Systematic Assessment
EG0000 affected316 at risk
EG0010 affected313 at risk
EG0020 affected339 at risk
EG003
Skin ulcer
Skin and subcutaneous tissue disorders
MedDRA (9.0)
Systematic Assessment
EG0000 affected316 at risk
EG0010 affected313 at risk
EG0020 affected339 at risk
EG003
Urticaria
Skin and subcutaneous tissue disorders
MedDRA (9.0)
Systematic Assessment
EG0000 affected316 at risk
EG0010 affected313 at risk
EG0020 affected339 at risk
EG003
Vascular purpura
Skin and subcutaneous tissue disorders
MedDRA (9.0)
Systematic Assessment
EG0000 affected316 at risk
EG0010 affected313 at risk
EG0020 affected339 at risk
EG003
Confusional state
Psychiatric disorders
MedDRA (9.0)
Systematic Assessment
EG0001 affected316 at risk
EG0011 affected313 at risk
EG0021 affected339 at risk
EG003
Anxiety
Psychiatric disorders
MedDRA (9.0)
Systematic Assessment
EG0000 affected316 at risk
EG0011 affected313 at risk
EG0020 affected339 at risk
EG003
Depression
Psychiatric disorders
MedDRA (9.0)
Systematic Assessment
EG0000 affected316 at risk
EG0010 affected313 at risk
EG0020 affected339 at risk
EG003
Vertigo
Ear and labyrinth disorders
MedDRA (9.0)
Systematic Assessment
EG0000 affected316 at risk
EG0011 affected313 at risk
EG0020 affected339 at risk
EG003
Retinal vascular thrombosis
Eye disorders
MedDRA (9.0)
Systematic Assessment
EG0000 affected316 at risk
EG0010 affected313 at risk
EG0021 affected339 at risk
EG003
Amaurosis
Eye disorders
MedDRA (9.0)
Systematic Assessment
EG0000 affected316 at risk
EG0010 affected313 at risk
EG0021 affected339 at risk
EG003
Catheter placement
Surgical and medical procedures
MedDRA (9.0)
Systematic Assessment
EG0000 affected316 at risk
EG0010 affected313 at risk
EG0020 affected339 at risk
EG003
Colostomy closure
Surgical and medical procedures
MedDRA (9.0)
Systematic Assessment
EG0000 affected316 at risk
EG0010 affected313 at risk
EG0021 affected339 at risk
EG003
Ileostomy closure
Surgical and medical procedures
MedDRA (9.0)
Systematic Assessment
EG0000 affected316 at risk
EG0010 affected313 at risk
EG0021 affected339 at risk
EG003
Vaginal fistula
Reproductive system and breast disorders
MedDRA (9.0)
Systematic Assessment
EG0000 affected316 at risk
EG0011 affected313 at risk
EG0020 affected339 at risk
EG003
Vaginal haemorrhage
Reproductive system and breast disorders
MedDRA (9.0)
Systematic Assessment
EG0001 affected316 at risk
EG0010 affected313 at risk
EG0020 affected339 at risk
EG003
Other Adverse Events
Term
Organ System
Source Vocabulary
Assessment Type
Notes
Statistical Information
Diarrhoea
Gastrointestinal disorders
MedDRA (9.0)
Systematic Assessment
EG000207 affected316 at risk
EG001186 affected313 at risk
EG002208 affected339 at risk
EG003197 affected336 at risk
EG004210 affected353 at risk
EG005218 affected341 at risk
Nausea
Gastrointestinal disorders
MedDRA (9.0)
Systematic Assessment
EG000194 affected316 at risk
EG001208 affected313 at risk
EG002209 affected339 at risk
EG003
Vomiting
Gastrointestinal disorders
MedDRA (9.0)
Systematic Assessment
EG000136 affected316 at risk
EG001123 affected313 at risk
EG002134 affected339 at risk
EG003
Stomatitis All
Gastrointestinal disorders
MedDRA (9.0)
Systematic Assessment
EG00063 affected316 at risk
EG001111 affected313 at risk
EG00276 affected339 at risk
EG003
Constipation
Gastrointestinal disorders
MedDRA (9.0)
Systematic Assessment
EG00073 affected316 at risk
EG00178 affected313 at risk
EG00277 affected339 at risk
EG003
Abdominal pain
Gastrointestinal disorders
MedDRA (9.0)
Systematic Assessment
EG00081 affected316 at risk
EG00176 affected313 at risk
EG00286 affected339 at risk
EG003
Dyspepsia
Gastrointestinal disorders
MedDRA (9.0)
Systematic Assessment
EG00030 affected316 at risk
EG00153 affected313 at risk
EG00241 affected339 at risk
EG003
Abdominal pain upper
Gastrointestinal disorders
MedDRA (9.0)
Systematic Assessment
EG00025 affected316 at risk
EG00127 affected313 at risk
EG00228 affected339 at risk
EG003
Dry mouth
Gastrointestinal disorders
MedDRA (9.0)
Systematic Assessment
EG00010 affected316 at risk
EG00116 affected313 at risk
EG00211 affected339 at risk
EG003
Paraesthesia
Nervous system disorders
MedDRA (9.0)
Systematic Assessment
EG000116 affected316 at risk
EG001117 affected313 at risk
EG002126 affected339 at risk
EG003
Peripheral Sensory Neuropathy
Nervous system disorders
MedDRA (9.0)
Systematic Assessment
EG00048 affected316 at risk
EG00131 affected313 at risk
EG00260 affected339 at risk
EG003
Neuropathy Peripheral
Nervous system disorders
MedDRA (9.0)
Systematic Assessment
EG00064 affected316 at risk
EG00170 affected313 at risk
EG00264 affected339 at risk
EG003
Dysaesthesia
Nervous system disorders
MedDRA (9.0)
Systematic Assessment
EG00037 affected316 at risk
EG00138 affected313 at risk
EG00243 affected339 at risk
EG003
Neuropathy
Nervous system disorders
MedDRA (9.0)
Systematic Assessment
EG00042 affected316 at risk
EG00133 affected313 at risk
EG00251 affected339 at risk
EG003
Lethargy
Nervous system disorders
MedDRA (9.0)
Systematic Assessment
EG00034 affected316 at risk
EG00146 affected313 at risk
EG00230 affected339 at risk
EG003
Headache
Nervous system disorders
MedDRA (9.0)
Systematic Assessment
EG00041 affected316 at risk
EG00134 affected313 at risk
EG00236 affected339 at risk
EG003
Dysgeusia
Nervous system disorders
MedDRA (9.0)
Systematic Assessment
EG00046 affected316 at risk
EG00148 affected313 at risk
EG00239 affected339 at risk
EG003
Hypoaesthesia
Nervous system disorders
MedDRA (9.0)
Systematic Assessment
EG00032 affected316 at risk
EG00129 affected313 at risk
EG00220 affected339 at risk
EG003
Dizziness
Nervous system disorders
MedDRA (9.0)
Systematic Assessment
EG00045 affected316 at risk
EG00142 affected313 at risk
EG00240 affected339 at risk
EG003
Neurotoxicity
Nervous system disorders
MedDRA (9.0)
Systematic Assessment
EG00019 affected316 at risk
EG00112 affected313 at risk
EG0029 affected339 at risk
EG003
Fatigue
General disorders
MedDRA (9.0)
Systematic Assessment
EG000132 affected316 at risk
EG001152 affected313 at risk
EG002118 affected339 at risk
EG003
Asthenia
General disorders
MedDRA (9.0)
Systematic Assessment
EG00043 affected316 at risk
EG00141 affected313 at risk
EG00281 affected339 at risk
EG003
Pyrexia
General disorders
MedDRA (9.0)
Systematic Assessment
EG00043 affected316 at risk
EG00176 affected313 at risk
EG00266 affected339 at risk
EG003
Temperature Intolerance
General disorders
MedDRA (9.0)
Systematic Assessment
EG00021 affected316 at risk
EG00129 affected313 at risk
EG00231 affected339 at risk
EG003
Oedema Peripheral
General disorders
MedDRA (9.0)
Systematic Assessment
EG00028 affected316 at risk
EG00136 affected313 at risk
EG00223 affected339 at risk
EG003
Chills
General disorders
MedDRA (9.0)
Systematic Assessment
EG00010 affected316 at risk
EG00118 affected313 at risk
EG00216 affected339 at risk
EG003
Chest pain
General disorders
MedDRA (9.0)
Systematic Assessment
EG00010 affected316 at risk
EG00114 affected313 at risk
EG00214 affected339 at risk
EG003
Neutropenia
Blood and lymphatic system disorders
MedDRA (9.0)
Systematic Assessment
EG00088 affected316 at risk
EG001172 affected313 at risk
EG00290 affected339 at risk
EG003
Thrombocytopenia
Blood and lymphatic system disorders
MedDRA (9.0)
Systematic Assessment
EG00085 affected316 at risk
EG00170 affected313 at risk
EG00261 affected339 at risk
EG003
Anaemia
Blood and lymphatic system disorders
MedDRA (9.0)
Systematic Assessment
EG00050 affected316 at risk
EG00137 affected313 at risk
EG00241 affected339 at risk
EG003
Leukopenia
Blood and lymphatic system disorders
MedDRA (9.0)
Systematic Assessment
EG00010 affected316 at risk
EG00124 affected313 at risk
EG0027 affected339 at risk
EG003
Palmar-Plantar Erythrodysaesthesia Syndrome
Skin and subcutaneous tissue disorders
MedDRA (9.0)
Systematic Assessment
EG00095 affected316 at risk
EG00130 affected313 at risk
EG002103 affected339 at risk
EG003
Alopecia
Skin and subcutaneous tissue disorders
MedDRA (9.0)
Systematic Assessment
EG00019 affected316 at risk
EG00152 affected313 at risk
EG00218 affected339 at risk
EG003
Rash
Skin and subcutaneous tissue disorders
MedDRA (9.0)
Systematic Assessment
EG00014 affected316 at risk
EG00132 affected313 at risk
EG00231 affected339 at risk
EG003
Pruritus
Skin and subcutaneous tissue disorders
MedDRA (9.0)
Systematic Assessment
EG00011 affected316 at risk
EG00120 affected313 at risk
EG0029 affected339 at risk
EG003
Dry skin
Skin and subcutaneous tissue disorders
MedDRA (9.0)
Systematic Assessment
EG00015 affected316 at risk
EG00117 affected313 at risk
EG00221 affected339 at risk
EG003
Erythema
Skin and subcutaneous tissue disorders
MedDRA (9.0)
Systematic Assessment
EG00011 affected316 at risk
EG00118 affected313 at risk
EG00213 affected339 at risk
EG003
Epistaxis
Respiratory, thoracic and mediastinal disorders
MedDRA (9.0)
Systematic Assessment
EG00022 affected316 at risk
EG00141 affected313 at risk
EG00224 affected339 at risk
EG003
Dysaesthesia pharynx
Respiratory, thoracic and mediastinal disorders
MedDRA (9.0)
Systematic Assessment
EG00041 affected316 at risk
EG00121 affected313 at risk
EG00245 affected339 at risk
EG003
Cough
Respiratory, thoracic and mediastinal disorders
MedDRA (9.0)
Systematic Assessment
EG00036 affected316 at risk
EG00140 affected313 at risk
EG00232 affected339 at risk
EG003
Dyspnoea
Respiratory, thoracic and mediastinal disorders
MedDRA (9.0)
Systematic Assessment
EG00037 affected316 at risk
EG00120 affected313 at risk
EG00234 affected339 at risk
EG003
Hiccups
Respiratory, thoracic and mediastinal disorders
MedDRA (9.0)
Systematic Assessment
EG00014 affected316 at risk
EG00121 affected313 at risk
EG00217 affected339 at risk
EG003
Pharyngolaryngeal pain
Respiratory, thoracic and mediastinal disorders
MedDRA (9.0)
Systematic Assessment
EG00017 affected316 at risk
EG00116 affected313 at risk
EG00212 affected339 at risk
EG003
Rhinorrhoea
Respiratory, thoracic and mediastinal disorders
MedDRA (9.0)
Systematic Assessment
EG0009 affected316 at risk
EG00116 affected313 at risk
EG00210 affected339 at risk
EG003
Dysphonia
Respiratory, thoracic and mediastinal disorders
MedDRA (9.0)
Systematic Assessment
EG0005 affected316 at risk
EG0013 affected313 at risk
EG0026 affected339 at risk
EG003
Anorexia
Metabolism and nutrition disorders
MedDRA (9.0)
Systematic Assessment
EG00095 affected316 at risk
EG00193 affected313 at risk
EG00284 affected339 at risk
EG003
Hypokalaemia
Metabolism and nutrition disorders
MedDRA (9.0)
Systematic Assessment
EG00035 affected316 at risk
EG00132 affected313 at risk
EG00231 affected339 at risk
EG003
Decreased appetite
Metabolism and nutrition disorders
MedDRA (9.0)
Systematic Assessment
EG00016 affected316 at risk
EG00115 affected313 at risk
EG00214 affected339 at risk
EG003
Dehydration
Metabolism and nutrition disorders
MedDRA (9.0)
Systematic Assessment
EG00028 affected316 at risk
EG00116 affected313 at risk
EG00217 affected339 at risk
EG003
Pain in extremity
Musculoskeletal and connective tissue disorders
MedDRA (9.0)
Systematic Assessment
EG00043 affected316 at risk
EG00120 affected313 at risk
EG00235 affected339 at risk
EG003
Pain in jaw
Musculoskeletal and connective tissue disorders
MedDRA (9.0)
Systematic Assessment
EG00023 affected316 at risk
EG00116 affected313 at risk
EG00213 affected339 at risk
EG003
Back pain
Musculoskeletal and connective tissue disorders
MedDRA (9.0)
Systematic Assessment
EG00033 affected316 at risk
EG00127 affected313 at risk
EG00228 affected339 at risk
EG003
Muscle spasms
Musculoskeletal and connective tissue disorders
MedDRA (9.0)
Systematic Assessment
EG00017 affected316 at risk
EG00110 affected313 at risk
EG00216 affected339 at risk
EG003
Arthralgia
Musculoskeletal and connective tissue disorders
MedDRA (9.0)
Systematic Assessment
EG00013 affected316 at risk
EG00116 affected313 at risk
EG00212 affected339 at risk
EG003
Myalgia
Musculoskeletal and connective tissue disorders
MedDRA (9.0)
Systematic Assessment
EG0009 affected316 at risk
EG0019 affected313 at risk
EG00218 affected339 at risk
EG003
Insomnia
Psychiatric disorders
MedDRA (9.0)
Systematic Assessment
EG00033 affected316 at risk
EG00144 affected313 at risk
EG00231 affected339 at risk
EG003
Depression
Psychiatric disorders
MedDRA (9.0)
Systematic Assessment
EG00020 affected316 at risk
EG00113 affected313 at risk
EG00223 affected339 at risk
EG003
Anxiety
Psychiatric disorders
MedDRA (9.0)
Systematic Assessment
EG00014 affected316 at risk
EG00116 affected313 at risk
EG00217 affected339 at risk
EG003
Nasopharyngitis
Infections and infestations
MedDRA (9.0)
Systematic Assessment
EG0009 affected316 at risk
EG00118 affected313 at risk
EG00227 affected339 at risk
EG003
Urinary tract infection
Infections and infestations
MedDRA (9.0)
Systematic Assessment
EG00011 affected316 at risk
EG00117 affected313 at risk
EG00211 affected339 at risk
EG003
Upper respiratory tract infection
Infections and infestations
MedDRA (9.0)
Systematic Assessment
EG00012 affected316 at risk
EG00121 affected313 at risk
EG0027 affected339 at risk
EG003
Hypertension
Vascular disorders
MedDRA (9.0)
Systematic Assessment
EG0003 affected316 at risk
EG00110 affected313 at risk
EG00216 affected339 at risk
EG003
Flushing
Vascular disorders
MedDRA (9.0)
Systematic Assessment
EG0007 affected316 at risk
EG00122 affected313 at risk
EG0024 affected339 at risk
EG003
Weight decreased
Investigations
MedDRA (9.0)
Systematic Assessment
EG00027 affected316 at risk
EG00127 affected313 at risk
EG00235 affected339 at risk
EG003
Proteinuria
Renal and urinary disorders
MedDRA (9.0)
Systematic Assessment
EG0001 affected316 at risk
EG0010 affected313 at risk
EG00210 affected339 at risk
EG003
Dysuria
Renal and urinary disorders
MedDRA (9.0)
Systematic Assessment
EG0006 affected316 at risk
EG0017 affected313 at risk
EG0026 affected339 at risk
EG003
Lacrimation increased
Eye disorders
MedDRA (9.0)
Systematic Assessment
EG0008 affected316 at risk
EG00120 affected313 at risk
EG00217 affected339 at risk
EG003
Hyperbilirubinaemia
Hepatobiliary disorders
MedDRA (9.0)
Systematic Assessment
EG00010 affected316 at risk
EG0014 affected313 at risk
EG00218 affected339 at risk
EG003
Hypersensitivity
Immune system disorders
MedDRA (9.0)
Systematic Assessment
EG0005 affected316 at risk
EG0019 affected313 at risk
EG0025 affected339 at risk
EG003
Certain Agreements
Are all PI(s) employees of the sponsor?
No
Restriction Type
OTHER
Results Disclosure Restriction on PI(s)?
Yes
Other Details
The Study being conducted under this Agreement is part of the Overall Study. Investigator is free to publish in reputable journals or to present at professional conferences the results of the Study, but only after the first publication or presentation that involves the Overall Study. The Sponsor may request that Confidential Information be deleted and/or the publication be postponed in order to protect the Sponsor's intellectual property rights.
Point of Contact
Title
Organization
Phone
Extension
Email
Roche Trial Information Hotline
F. Hoffmann-La Roche AG
+41 61 6878333
global.trial_information@roche.com
ID
Term
D015179
Colorectal Neoplasms
Ancestor Terms
ID
Term
D007414
Intestinal Neoplasms
D005770
Gastrointestinal Neoplasms
D004067
Digestive System Neoplasms
D009371
Neoplasms by Site
D009369
Neoplasms
D004066
Digestive System Diseases
D005767
Gastrointestinal Diseases
D003108
Colonic Diseases
D007410
Intestinal Diseases
D012002
Rectal Diseases
Browse Leaves
Not provided
Browse Branches
Not provided
ID
Term
D000077150
Oxaliplatin
D000069287
Capecitabine
D000068258
Bevacizumab
D002955
Leucovorin
D005472
Fluorouracil
Ancestor Terms
ID
Term
D056831
Coordination Complexes
D009930
Organic Chemicals
D003841
Deoxycytidine
D003562
Cytidine
D011741
Pyrimidine Nucleosides
D011743
Pyrimidines
D006573
Heterocyclic Compounds, 1-Ring
D006571
Heterocyclic Compounds
D014498
Uracil
D011744
Pyrimidinones
D003853
Deoxyribonucleosides
D009705
Nucleosides
D009706
Nucleic Acids, Nucleotides, and Nucleosides
D061067
Antibodies, Monoclonal, Humanized
D000911
Antibodies, Monoclonal
D000906
Antibodies
D007136
Immunoglobulins
D007162
Immunoproteins
D001798
Blood Proteins
D011506
Proteins
D000602
Amino Acids, Peptides, and Proteins
D012712
Serum Globulins
D005916
Globulins
D005575
Formyltetrahydrofolates
D013763
Tetrahydrofolates
D005492
Folic Acid
D011622
Pterins
D011621
Pteridines
D006574
Heterocyclic Compounds, 2-Ring
D000072471
Heterocyclic Compounds, Fused-Ring
D003067
Coenzymes
D045762
Enzymes and Coenzymes
Browse Leaves
Not provided
Browse Branches
Not provided
48 subjects
FG00542 subjects
109 subjects
FG005101 subjects
8 subjects
FG0058 subjects
0 subjects
FG0052 subjects
101 subjects
FG005102 subjects
24 subjects
FG00527 subjects
4 subjects
FG0059 subjects
0 subjects
FG0051 subjects
1 subjects
FG0055 subjects
0 subjects
FG0050 subjects
36 subjects
FG00529 subjects
8 subjects
FG00418 subjects
FG00517 subjects
Adverse Event
FG0002 subjects
FG0013 subjects
FG0021 subjects
FG0030 subjects
FG0045 subjects
FG0051 subjects
Eligible for surgery
FG0002 subjects
FG0010 subjects
FG0020 subjects
FG0030 subjects
FG0040 subjects
FG0050 subjects
Insufficient therapeutic response
FG0001 subjects
FG0014 subjects
FG0025 subjects
FG0036 subjects
FG0047 subjects
FG0059 subjects
Participant refusal/Admin reasons
FG0001 subjects
FG0010 subjects
FG0020 subjects
FG0030 subjects
FG0040 subjects
FG0051 subjects
Participant had complete response
FG0001 subjects
FG0011 subjects
FG0020 subjects
FG0030 subjects
FG0040 subjects
FG0050 subjects
More than 21 days delay between cycles
FG0000 subjects
FG0011 subjects
FG0020 subjects
FG0030 subjects
FG0040 subjects
FG0050 subjects
Investigator decision (enough treatment)
FG0000 subjects
FG0011 subjects
FG0021 subjects
FG0030 subjects
FG0041 subjects
FG0050 subjects
Participant withdrew consent
FG0000 subjects
FG0010 subjects
FG0021 subjects
FG0030 subjects
FG0040 subjects
FG0050 subjects
Participant will start new treatment
FG0000 subjects
FG0010 subjects
FG0021 subjects
FG0030 subjects
FG0040 subjects
FG0050 subjects
Participant wanted break from treatment
FG0000 subjects
FG0010 subjects
FG0020 subjects
FG0031 subjects
FG0040 subjects
FG0050 subjects
Participant completed treatment
FG0000 subjects
FG0010 subjects
FG0020 subjects
FG0031 subjects
FG0040 subjects
FG0050 subjects
Surgery
FG0000 subjects
FG0010 subjects
FG0020 subjects
FG0031 subjects
FG0041 subjects
FG0050 subjects
Death
FG0000 subjects
FG0010 subjects
FG0020 subjects
FG0030 subjects
FG0041 subjects
FG0050 subjects
Participant had progressive disease
FG0000 subjects
FG0010 subjects
FG0020 subjects
FG0030 subjects
FG0041 subjects
FG0050 subjects
Participant/Physician decision to stop
FG0000 subjects
FG0010 subjects
FG0020 subjects
FG0030 subjects
FG0041 subjects
FG0050 subjects
Preplanned 6 cycles after surgery
FG0000 subjects
FG0010 subjects
FG0020 subjects
FG0030 subjects
FG0041 subjects
FG0050 subjects
Investigator decision
FG0000 subjects
FG0010 subjects
FG0020 subjects
FG0030 subjects
FG0040 subjects
FG0051 subjects
186 subjects
FG005171 subjects
92 subjects
FG005101 subjects
112 subjects
FG00492 subjects
FG005101 subjects
58.8
± 10.87
BG00459.7± 11.28
BG00559.7± 10.74
BG00659.7± 11.14
145
BG003165
BG004137
BG005144
BG006827
Male
BG000194
BG001204
BG002205
BG003186
BG004213
BG005205
BG0061207
OG001
XELOX/XELOX+P/XELOX+BV
Participants from the initial 2-arm part and the 2x2 factorial part of the study including the following groups -
Xelox: Capecitabine was administered as an oral twice-daily outpatient intermittent treatment (3-week cycles consisting of 2 weeks of treatment followed by 1 week without treatment) combined with intravenous oxaliplatin (given on day 1).
Xelox+P: Capecitabine was administered as an oral twice-daily outpatient intermittent treatment (3-week cycles consisting of 2 weeks of treatment followed by 1 week without treatment) combined with intravenous oxaliplatin and placebo (P) control for bevacizumab (both given on day 1 every 3 weeks).
Xelox+BV: Capecitabine was administered as an oral twice-daily outpatient intermittent treatment (3-week cycles consisting of 2 weeks of treatment followed by 1 week without treatment) combined with intravenous oxaliplatin and intravenous bevacizumab (both given on day 1 every 3 weeks).
Units
Counts
Participants
OG000937
OG001967
Title
Denominators
Categories
Title
Measurements
OG000304.0(281 to 319)
OG001261.0(246 to 276)
Group IDs
Group Description
Statistical Method
Statistical Comment
P-Value
P-Value Comment
Parameter Type
Parameter Value
Dispersion Type
Dispersion Value
Confidence Interval Sides
Confidence Interval %
CI Lower Limit
CI Upper Limit
CI Lower Limit Comment
CI Upper Limit Comment
Estimate Comment
Tested Non-Inferiority
Non-Inferiority Type
Non-Inferiority Comment
Other Analysis Description
OG000
OG001
Equivalence of treatment arm A ('XELOX') to treatment arm B ('FOLFOX-4') was tested via the following hypotheses - H0: HRA/B >/= 1.23 versus H1: HRA/B < 1.23. HRA/B denotes the hazard of disease progression or death under treatment A ('XELOX') divided by the hazard of disease progression or death under treatment B ('FOLFOX-4').
Hazard Ratio (HR)
1.22
2-Sided
97.5
1.05
1.42
Yes
Non-Inferiority or Equivalence
Non-inferiority was demonstrated if the upper limit of the 2-sided 97.5% confidence interval (CI) for the hazard ratio (HR) was less than the predefined limit of 1.23 (the non-inferiority margin). A stratified Cox model was used. In order to retain an experiment-wise two-sided type I error of 5%, the non-inferiority analysis for PFS used a two-sided significance level of 2.5%.
OG001
FOLFOX-4+BV/XELOX+BV
Participants from the 2x2 factorial part of the study including the following groups -
Folfox-4+BV: Participants who received 2-week cycles of infused leucovorin, bolus injection fluorouracil and continuous infusion fluorouracil (given on days 1 and 2), combined with intravenous oxaliplatin and intravenous bevacizumab (both given on day 1 every 2 weeks).
Xelox+BV: Capecitabine was administered as an oral twice-daily outpatient intermittent treatment (3-week cycles consisting of 2 weeks of treatment followed by 1 week without treatment) combined with intravenous oxaliplatin and intravenous bevacizumab (both given on day 1 every 3 weeks).
Units
Counts
Participants
OG000701
OG001699
Title
Denominators
Categories
Title
Measurements
OG000259.0(244 to 278)
OG001335.0(310 to 363)
Group IDs
Group Description
Statistical Method
Statistical Comment
P-Value
P-Value Comment
Parameter Type
Parameter Value
Dispersion Type
Dispersion Value
Confidence Interval Sides
Confidence Interval %
CI Lower Limit
CI Upper Limit
CI Lower Limit Comment
CI Upper Limit Comment
Estimate Comment
Tested Non-Inferiority
Non-Inferiority Type
Non-Inferiority Comment
Other Analysis Description
OG000
OG001
Testing for superiority was based on the stratified log-rank test and used a two-sided significance level of 2.5%.The hazard ratio (HR) of bevacizumab in combination with chemotherapy versus chemotherapy alone [HR(FOLFOX-4+P/XELOX+P)/(FOLFOX-4+BV/XELOX+BV)] was presented.
Log Rank
<0.0001
Hazard Ratio (HR)
0.70
2-Sided
97.5
0.58
0.83
No
Superiority or Other
OG001
XELOX/XELOX+P/XELOX+BV
Participants from the initial 2-arm part and the 2x2 factorial part of the study including the following groups -
Xelox: Capecitabine was administered as an oral twice-daily outpatient intermittent treatment (3-week cycles consisting of 2 weeks of treatment followed by 1 week without treatment) combined with intravenous oxaliplatin (given on day 1).
Xelox+P: Capecitabine was administered as an oral twice-daily outpatient intermittent treatment (3-week cycles consisting of 2 weeks of treatment followed by 1 week without treatment) combined with intravenous oxaliplatin and placebo (P) control for bevacizumab (both given on day 1 every 3 weeks).
Xelox+BV: Capecitabine was administered as an oral twice-daily outpatient intermittent treatment (3-week cycles consisting of 2 weeks of treatment followed by 1 week without treatment) combined with intravenous oxaliplatin and intravenous bevacizumab (both given on day 1 every 3 weeks).
Units
Counts
Participants
OG000937
OG001967
Title
Denominators
Categories
Title
Measurements
OG000268.0(252 to 290)
OG001234.0(221 to 251)
Group IDs
Group Description
Statistical Method
Statistical Comment
P-Value
P-Value Comment
Parameter Type
Parameter Value
Dispersion Type
Dispersion Value
Confidence Interval Sides
Confidence Interval %
CI Lower Limit
CI Upper Limit
CI Lower Limit Comment
CI Upper Limit Comment
Estimate Comment
Tested Non-Inferiority
Non-Inferiority Type
Non-Inferiority Comment
Other Analysis Description
OG000
OG001
HRs and 97.5% confidence interval were reported for treatment arm A (XELOX/XELOX+P/XELOX+BV) versus treatment arm B (FOLFOX-4/FOLFOX-4+P/FOLFOX-4+BV).
Hazard Ratio (HR)
1.24
2-Sided
97.5
1.07
1.44
Yes
Non-Inferiority or Equivalence
Fewer events were expected in the 'on-treatment analysis', thus leading to reduced power. No formal statistical testing was therefore applied.
OG001
FOLFOX-4+BV/XELOX+BV
Participants from the 2x2 factorial part of the study including the following groups -
Folfox-4+BV: Participants who received 2-week cycles of infused leucovorin, bolus injection fluorouracil and continuous infusion fluorouracil (given on days 1 and 2), combined with intravenous oxaliplatin and intravenous bevacizumab (both given on day 1 every 2 weeks).
Xelox+BV: Capecitabine was administered as an oral twice-daily outpatient intermittent treatment (3-week cycles consisting of 2 weeks of treatment followed by 1 week without treatment) combined with intravenous oxaliplatin and intravenous bevacizumab (both given on day 1 every 3 weeks).
Units
Counts
Participants
OG000701
OG001699
Title
Denominators
Categories
Title
Measurements
OG000241.0(227 to 254)
OG001316.0(294 to 338)
Group IDs
Group Description
Statistical Method
Statistical Comment
P-Value
P-Value Comment
Parameter Type
Parameter Value
Dispersion Type
Dispersion Value
Confidence Interval Sides
Confidence Interval %
CI Lower Limit
CI Upper Limit
CI Lower Limit Comment
CI Upper Limit Comment
Estimate Comment
Tested Non-Inferiority
Non-Inferiority Type
Non-Inferiority Comment
Other Analysis Description
OG000
OG001
Testing for superiority was based on the stratified log-rank test and used a two-sided significance level of 2.5%.The hazard ratio (HR) of bevacizumab in combination with chemotherapy versus chemotherapy alone [HR(FOLFOX-4+P/XELOX+P)/(FOLFOX-4+BV/XELOX+BV)] was presented.
Log Rank
<0.0001
Hazard Ratio (HR)
0.63
2-Sided
97.5
0.52
0.75
No
Superiority or Other
OG001
XELOX/XELOX+P/XELOX+BV
Participants from the initial 2-arm part and the 2x2 factorial part of the study including the following groups -
Xelox: Capecitabine was administered as an oral twice-daily outpatient intermittent treatment (3-week cycles consisting of 2 weeks of treatment followed by 1 week without treatment) combined with intravenous oxaliplatin (given on day 1).
Xelox+P: Capecitabine was administered as an oral twice-daily outpatient intermittent treatment (3-week cycles consisting of 2 weeks of treatment followed by 1 week without treatment) combined with intravenous oxaliplatin and placebo (P) control for bevacizumab (both given on day 1 every 3 weeks).
Xelox+BV: Capecitabine was administered as an oral twice-daily outpatient intermittent treatment (3-week cycles consisting of 2 weeks of treatment followed by 1 week without treatment) combined with intravenous oxaliplatin and intravenous bevacizumab (both given on day 1 every 3 weeks).
Units
Counts
Participants
OG000937
OG001967
Title
Denominators
Categories
Title
Measurements
OG000260.0(247 to 270)
OG001244.0(230 to 255)
Group IDs
Group Description
Statistical Method
Statistical Comment
P-Value
P-Value Comment
Parameter Type
Parameter Value
Dispersion Type
Dispersion Value
Confidence Interval Sides
Confidence Interval %
CI Lower Limit
CI Upper Limit
CI Lower Limit Comment
CI Upper Limit Comment
Estimate Comment
Tested Non-Inferiority
Non-Inferiority Type
Non-Inferiority Comment
Other Analysis Description
OG000
OG001
Equivalence of treatment arm A ('XELOX') to treatment arm B ('FOLFOX-4') was tested via the following hypotheses - H0: HRA/B >/= 1.23 versus H1: HRA/B < 1.23. HRA/B denotes the hazard of disease progression or death under treatment A ('XELOX') divided by the hazard of disease progression or death under treatment B ('FOLFOX-4').
Hazard Ratio (HR)
1.03
2-Sided
97.5
0.92
1.15
Yes
Non-Inferiority or Equivalence
Non-inferiority was demonstrated if the upper limit of the 2-sided 97.5% confidence interval (CI) for the hazard ratio (HR) was less than the predefined limit of 1.23 (the non-inferiority margin). A stratified Cox model was used. In order to retain an experiment-wise two-sided type I error of 5%, the non-inferiority analysis for PFS used a two-sided significance level of 2.5%.
OG001
FOLFOX-4+BV/XELOX+BV
Participants from the 2x2 factorial part of the study including the following groups -
Folfox-4+BV: Participants who received 2-week cycles of infused leucovorin, bolus injection fluorouracil and continuous infusion fluorouracil (given on days 1 and 2), combined with intravenous oxaliplatin and intravenous bevacizumab (both given on day 1 every 2 weeks).
Xelox+BV: Capecitabine was administered as an oral twice-daily outpatient intermittent treatment (3-week cycles consisting of 2 weeks of treatment followed by 1 week without treatment) combined with intravenous oxaliplatin and intravenous bevacizumab (both given on day 1 every 3 weeks).
Units
Counts
Participants
OG000701
OG001699
Title
Denominators
Categories
Title
Measurements
OG000245.0(230 to 258)
OG001287.0(276 to 300)
Group IDs
Group Description
Statistical Method
Statistical Comment
P-Value
P-Value Comment
Parameter Type
Parameter Value
Dispersion Type
Dispersion Value
Confidence Interval Sides
Confidence Interval %
CI Lower Limit
CI Upper Limit
CI Lower Limit Comment
CI Upper Limit Comment
Estimate Comment
Tested Non-Inferiority
Non-Inferiority Type
Non-Inferiority Comment
Other Analysis Description
OG000
OG001
Testing for superiority was based on the stratified log-rank test and used a two-sided significance level of 2.5%.The hazard ratio (HR) of bevacizumab in combination with chemotherapy versus chemotherapy alone [HR(FOLFOX-4+P/XELOX+P)/(FOLFOX-4+BV/XELOX+BV)] was presented.
Log Rank
0.0015
Hazard Ratio (HR)
0.83
2-Sided
97.5
0.72
0.95
No
Superiority or Other
OG001
XELOX/XELOX+P/XELOX+BV
Participants from the initial 2-arm part and the 2x2 factorial part of the study including the following groups -
Xelox: Capecitabine was administered as an oral twice-daily outpatient intermittent treatment (3-week cycles consisting of 2 weeks of treatment followed by 1 week without treatment) combined with intravenous oxaliplatin (given on day 1).
Xelox+P: Capecitabine was administered as an oral twice-daily outpatient intermittent treatment (3-week cycles consisting of 2 weeks of treatment followed by 1 week without treatment) combined with intravenous oxaliplatin and placebo (P) control for bevacizumab (both given on day 1 every 3 weeks).
Xelox+BV: Capecitabine was administered as an oral twice-daily outpatient intermittent treatment (3-week cycles consisting of 2 weeks of treatment followed by 1 week without treatment) combined with intravenous oxaliplatin and intravenous bevacizumab (both given on day 1 every 3 weeks).
Units
Counts
Participants
OG000937
OG001967
Title
Denominators
Categories
Title
Measurements
OG000549.0(528 to 576)
OG001577.0(535 to 615)
Group IDs
Group Description
Statistical Method
Statistical Comment
P-Value
P-Value Comment
Parameter Type
Parameter Value
Dispersion Type
Dispersion Value
Confidence Interval Sides
Confidence Interval %
CI Lower Limit
CI Upper Limit
CI Lower Limit Comment
CI Upper Limit Comment
Estimate Comment
Tested Non-Inferiority
Non-Inferiority Type
Non-Inferiority Comment
Other Analysis Description
OG000
OG001
HRs and 97.5% confidence interval were reported for treatment arm A (XELOX/XELOX+P/XELOX+BV) versus treatment arm B (FOLFOX-4/FOLFOX-4+P/FOLFOX-4+BV).
Hazard Ratio (HR)
0.97
2-Sided
97.5
0.84
1.14
Yes
Non-Inferiority or Equivalence
This study was not powered for testing non-inferiority of XELOX vs FOLFOX-4 with respect to overall survival and no margin could be derived following the effect retention concept. The same margins used for the PFS analysis [Non-inferiority was demonstrated if the upper limit of the 2-sided 97.5% confidence interval (CI) for the hazard ratio (HR) was less than the predefined limit of 1.23 (the non-inferiority margin)] were therefore applied to OS as well.
Units
Counts
Participants
OG000701
OG001699
Title
Denominators
Categories
Title
Measurements
OG000574.0(537 to 592)
OG001551.0(528 to 635)
Group IDs
Group Description
Statistical Method
Statistical Comment
P-Value
P-Value Comment
Parameter Type
Parameter Value
Dispersion Type
Dispersion Value
Confidence Interval Sides
Confidence Interval %
CI Lower Limit
CI Upper Limit
CI Lower Limit Comment
CI Upper Limit Comment
Estimate Comment
Tested Non-Inferiority
Non-Inferiority Type
Non-Inferiority Comment
Other Analysis Description
OG000
OG001
Testing for superiority was based on the stratified log-rank test and used a two-sided significance level of 2.5%.The hazard ratio (HR) of bevacizumab in combination with chemotherapy versus chemotherapy alone [HR(FOLFOX-4+P/XELOX+P)/(FOLFOX-4+BV/XELOX+BV)] was presented together with the 97.5% confidence interval.
Log Rank
0.1921
Hazard Ratio (HR)
0.89
2-Sided
97.5
0.72
1.09
No
Superiority or Other
OG001
FOLFOX-4+BV/XELOX+BV
Participants from the 2x2 factorial part of the study including the following groups -
Folfox-4+BV: Participants who received 2-week cycles of infused leucovorin, bolus injection fluorouracil and continuous infusion fluorouracil (given on days 1 and 2), combined with intravenous oxaliplatin and intravenous bevacizumab (both given on day 1 every 2 weeks).
Xelox+BV: Capecitabine was administered as an oral twice-daily outpatient intermittent treatment (3-week cycles consisting of 2 weeks of treatment followed by 1 week without treatment) combined with intravenous oxaliplatin and intravenous bevacizumab (both given on day 1 every 3 weeks).
Units
Counts
Participants
OG000701
OG001699
Title
Denominators
Categories
Title
Measurements
OG000244.0(230 to 257)
OG001285.0(271 to 297)
Group IDs
Group Description
Statistical Method
Statistical Comment
P-Value
P-Value Comment
Parameter Type
Parameter Value
Dispersion Type
Dispersion Value
Confidence Interval Sides
Confidence Interval %
CI Lower Limit
CI Upper Limit
CI Lower Limit Comment
CI Upper Limit Comment
Estimate Comment
Tested Non-Inferiority
Non-Inferiority Type
Non-Inferiority Comment
Other Analysis Description
OG000
OG001
Testing for superiority was based on the stratified log-rank test and used a two-sided significance level of 2.5%.The hazard ratio (HR) of bevacizumab in combination with chemotherapy versus chemotherapy alone [HR(FOLFOX-4+P/XELOX+P)/(FOLFOX-4+BV/XELOX+BV)] was presented.
Log Rank
0.0023
Hazard Ratio (HR)
0.83
2-Sided
97.5
0.72
0.95
No
Superiority or Other
OG001
XELOX/XELOX+P/XELOX+BV
Participants from the initial 2-arm part and the 2x2 factorial part of the study including the following groups -
Xelox: Capecitabine was administered as an oral twice-daily outpatient intermittent treatment (3-week cycles consisting of 2 weeks of treatment followed by 1 week without treatment) combined with intravenous oxaliplatin (given on day 1).
Xelox+P: Capecitabine was administered as an oral twice-daily outpatient intermittent treatment (3-week cycles consisting of 2 weeks of treatment followed by 1 week without treatment) combined with intravenous oxaliplatin and placebo (P) control for bevacizumab (both given on day 1 every 3 weeks).
Xelox+BV: Capecitabine was administered as an oral twice-daily outpatient intermittent treatment (3-week cycles consisting of 2 weeks of treatment followed by 1 week without treatment) combined with intravenous oxaliplatin and intravenous bevacizumab (both given on day 1 every 3 weeks).
Units
Counts
Participants
OG000937
OG001967
Title
Denominators
Categories
Title
Measurements
OG00049.4
OG00146.4
Group IDs
Group Description
Statistical Method
Statistical Comment
P-Value
P-Value Comment
Parameter Type
Parameter Value
Dispersion Type
Dispersion Value
Confidence Interval Sides
Confidence Interval %
CI Lower Limit
CI Upper Limit
CI Lower Limit Comment
CI Upper Limit Comment
Estimate Comment
Tested Non-Inferiority
Non-Inferiority Type
Non-Inferiority Comment
Other Analysis Description
OG000
OG001
Non-inferiority of XELOX with/without bevacizumab to FOLFOX-4 with/without bevacizumab was tested by the pair of hypotheses - H0: OR(XELOX/XELOX+P/XELOX+BV)/(FOLFOX-4/FOLFOX-4+P/FOLFOX-4+BV) </= 0.66 versus H1: OR(XELOX/XELOX+P/XELOX+BV)/(FOLFOX-4/FOLFOX-4+P/FOLFOX-4+BV) > 0.66, where OR denotes Odds ratio.
Odds Ratio (OR)
0.89
2-Sided
97.5
0.72
1.09
Yes
Non-Inferiority or Equivalence
The analysis was based on the two-sided 97.5% confidence interval for OR(XELOX/XELOX+P/XELOX+BV)/(FOLFOX-4/FOLFOX-4+P/FOLFOX-4+BV). Non-inferiority of XELOX with/without bevacizumab to FOLFOX-4 with/without bevacizumab was concluded if the lower limit of this confidence interval is above 0.66.
OG001
FOLFOX-4+BV/XELOX+BV
Participants from the 2x2 factorial part of the study including the following groups -
Folfox-4+BV: Participants who received 2-week cycles of infused leucovorin, bolus injection fluorouracil and continuous infusion fluorouracil (given on days 1 and 2), combined with intravenous oxaliplatin and intravenous bevacizumab (both given on day 1 every 2 weeks).
Xelox+BV: Capecitabine was administered as an oral twice-daily outpatient intermittent treatment (3-week cycles consisting of 2 weeks of treatment followed by 1 week without treatment) combined with intravenous oxaliplatin and intravenous bevacizumab (both given on day 1 every 3 weeks).
Units
Counts
Participants
OG000701
OG001699
Title
Denominators
Categories
Title
Measurements
OG00049.2
OG00146.5
Group IDs
Group Description
Statistical Method
Statistical Comment
P-Value
P-Value Comment
Parameter Type
Parameter Value
Dispersion Type
Dispersion Value
Confidence Interval Sides
Confidence Interval %
CI Lower Limit
CI Upper Limit
CI Lower Limit Comment
CI Upper Limit Comment
Estimate Comment
Tested Non-Inferiority
Non-Inferiority Type
Non-Inferiority Comment
Other Analysis Description
OG000
OG001
Superiority of adding bevacizumab to chemotherapy was tested as follows - H0: OR(FOLFOX-4+BV/XELOX+BV)/(FOLFOX-4+P/XELOX+P) </= 1.0 versus H1: OR(FOLFOX-4+BV/XELOX+BV)/(FOLFOX-4+P/XELOX+P) > 1.0. The test used a two-sided significance level of 2.5%.
Chi-squared
0.3091
Odds Ratio (OR)
0.90
2-Sided
97.5
0.71
1.14
No
Superiority or Other
OG001
XELOX/XELOX+P/XELOX+BV
Participants from the initial 2-arm part and the 2x2 factorial part of the study including the following groups -
Xelox: Capecitabine was administered as an oral twice-daily outpatient intermittent treatment (3-week cycles consisting of 2 weeks of treatment followed by 1 week without treatment) combined with intravenous oxaliplatin (given on day 1).
Xelox+P: Capecitabine was administered as an oral twice-daily outpatient intermittent treatment (3-week cycles consisting of 2 weeks of treatment followed by 1 week without treatment) combined with intravenous oxaliplatin and placebo (P) control for bevacizumab (both given on day 1 every 3 weeks).
Xelox+BV: Capecitabine was administered as an oral twice-daily outpatient intermittent treatment (3-week cycles consisting of 2 weeks of treatment followed by 1 week without treatment) combined with intravenous oxaliplatin and intravenous bevacizumab (both given on day 1 every 3 weeks).
Units
Counts
Participants
OG000937
OG001967
Title
Denominators
Categories
Title
Measurements
OG00038.6
OG00137.1
Group IDs
Group Description
Statistical Method
Statistical Comment
P-Value
P-Value Comment
Parameter Type
Parameter Value
Dispersion Type
Dispersion Value
Confidence Interval Sides
Confidence Interval %
CI Lower Limit
CI Upper Limit
CI Lower Limit Comment
CI Upper Limit Comment
Estimate Comment
Tested Non-Inferiority
Non-Inferiority Type
Non-Inferiority Comment
Other Analysis Description
OG000
OG001
Non-inferiority of XELOX with/without bevacizumab to FOLFOX-4 with/without bevacizumab was tested by the pair of hypotheses - H0: OR(XELOX/XELOX+P/XELOX+BV)/(FOLFOX-4/FOLFOX-4+P/FOLFOX-4+BV) </= 0.66 versus H1: OR(XELOX/XELOX+P/XELOX+BV)/(FOLFOX-4/FOLFOX-4+P/FOLFOX-4+BV) > 0.66
Odds Ratio (OR)
0.94
2-Sided
97.5
0.76
1.16
Yes
Non-Inferiority or Equivalence
The analysis was based on the two-sided 97.5% confidence interval for OR(XELOX/XELOX+P/XELOX+BV)/(FOLFOX-4/FOLFOX-4+P/FOLFOX-4+BV). Non-inferiority of XELOX with/without bevacizumab to FOLFOX-4 with/without bevacizumab shall be concluded if the lower limit of this confidence interval is above 0.66.
OG001
FOLFOX-4+BV/XELOX+BV
Participants from the 2x2 factorial part of the study including the following groups -
Folfox-4+BV: Participants who received 2-week cycles of infused leucovorin, bolus injection fluorouracil and continuous infusion fluorouracil (given on days 1 and 2), combined with intravenous oxaliplatin and intravenous bevacizumab (both given on day 1 every 2 weeks).
Xelox+BV: Capecitabine was administered as an oral twice-daily outpatient intermittent treatment (3-week cycles consisting of 2 weeks of treatment followed by 1 week without treatment) combined with intravenous oxaliplatin and intravenous bevacizumab (both given on day 1 every 3 weeks).
Units
Counts
Participants
OG000701
OG001699
Title
Denominators
Categories
Title
Measurements
OG00037.5
OG00137.5
Group IDs
Group Description
Statistical Method
Statistical Comment
P-Value
P-Value Comment
Parameter Type
Parameter Value
Dispersion Type
Dispersion Value
Confidence Interval Sides
Confidence Interval %
CI Lower Limit
CI Upper Limit
CI Lower Limit Comment
CI Upper Limit Comment
Estimate Comment
Tested Non-Inferiority
Non-Inferiority Type
Non-Inferiority Comment
Other Analysis Description
OG000
OG001
Superiority of adding bevacizumab to chemotherapy was tested as follows - H0: OR(FOLFOX-4+BV/XELOX+BV)/(FOLFOX 4+P/XELOX+P) </= 1.0 versus H1: OR(FOLFOX-4+BV/XELOX+BV)/(FOLFOX-4+P/XELOX+P) > 1.0. The test used a two-sided significance level of 2.5%
Chi-squared
0.9887
Odds Ratio (OR)
1.00
2-Sided
97.5
0.78
1.28
No
Superiority or Other
OG001
XELOX/XELOX+P/XELOX+BV
Participants from the initial 2-arm part and the 2x2 factorial part of the study including the following groups -
Xelox: Capecitabine was administered as an oral twice-daily outpatient intermittent treatment (3-week cycles consisting of 2 weeks of treatment followed by 1 week without treatment) combined with intravenous oxaliplatin (given on day 1).
Xelox+P: Capecitabine was administered as an oral twice-daily outpatient intermittent treatment (3-week cycles consisting of 2 weeks of treatment followed by 1 week without treatment) combined with intravenous oxaliplatin and placebo (P) control for bevacizumab (both given on day 1 every 3 weeks).
Xelox+BV: Capecitabine was administered as an oral twice-daily outpatient intermittent treatment (3-week cycles consisting of 2 weeks of treatment followed by 1 week without treatment) combined with intravenous oxaliplatin and intravenous bevacizumab (both given on day 1 every 3 weeks).
Units
Counts
Participants
OG000990
OG0011008
Title
Denominators
Categories
General Approach
Title
Measurements
OG000191.0(183 to 202)
OG001179.0(171 to 187)
On-treatment Approach
Title
Measurements
OG000190.0(182 to 200)
OG001176.0(170 to 185)
Group IDs
Group Description
Statistical Method
Statistical Comment
P-Value
P-Value Comment
Parameter Type
Parameter Value
Dispersion Type
Dispersion Value
Confidence Interval Sides
Confidence Interval %
CI Lower Limit
CI Upper Limit
CI Lower Limit Comment
CI Upper Limit Comment
Estimate Comment
Tested Non-Inferiority
Non-Inferiority Type
Non-Inferiority Comment
Other Analysis Description
OG000
OG001
General approach: HRs and 97.5% confidence interval were reported for treatment arm A (XELOX/XELOX+P/XELOX+BV) versus treatment arm B (FOLFOX-4/FOLFOX-4+P/FOLFOX-4+BV)
Hazard Ratio (HR)
1.08
2-Sided
97.5
0.97
1.20
Yes
Non-Inferiority or Equivalence
No formal statistical testing was done.
OG000
OG001
On-treatment Approach: HRs and 97.5% confidence interval were reported for treatment arm A (XELOX/XELOX+P/XELOX+BV) versus treatment arm B (FOLFOX-4/FOLFOX-4+P/FOLFOX-4+BV).
Hazard Ratio (HR)
1.10
2-Sided
97.5
0.98
1.23
Yes
Non-Inferiority or Equivalence
Fewer events were expected in analyses using the on-treatment approach than in the analyses using the general approach, thus leading to reduced power.Therefore, no formal statistical testing was performed.
OG001
FOLFOX-4+BV/XELOX+BV
Participants from the 2x2 factorial part of the study including the following groups -
Folfox-4+BV: Participants who received 2-week cycles of infused leucovorin, bolus injection fluorouracil and continuous infusion fluorouracil (given on days 1 and 2), combined with intravenous oxaliplatin and intravenous bevacizumab (both given on day 1 every 2 weeks).
Xelox+BV: Capecitabine was administered as an oral twice-daily outpatient intermittent treatment (3-week cycles consisting of 2 weeks of treatment followed by 1 week without treatment) combined with intravenous oxaliplatin and intravenous bevacizumab (both given on day 1 every 3 weeks).
Units
Counts
Participants
OG000675
OG001694
Title
Denominators
Categories
General Approach
Title
Measurements
OG000183.0(176 to 198)
OG001209.0(199 to 220)
On-treatment Approach
Title
Measurements
OG000182.0(175 to 196)
OG001208.0(198 to 220)
Group IDs
Group Description
Statistical Method
Statistical Comment
P-Value
P-Value Comment
Parameter Type
Parameter Value
Dispersion Type
Dispersion Value
Confidence Interval Sides
Confidence Interval %
CI Lower Limit
CI Upper Limit
CI Lower Limit Comment
CI Upper Limit Comment
Estimate Comment
Tested Non-Inferiority
Non-Inferiority Type
Non-Inferiority Comment
Other Analysis Description
OG000
OG001
General approach: Testing for superiority was based on the stratified log-rank test and used a two-sided significance level of 2.5%.The hazard ratio (HR) of bevacizumab in combination with chemotherapy versus chemotherapy alone [HR(FOLFOX-4+P/XELOX+P)/(FOLFOX-4+BV/XELOX+BV)] was presented.
Log Rank
0.0030
Hazard Ratio (HR)
0.84
2-Sided
97.5
0.74
0.96
No
Superiority or Other
OG000
OG001
On treatment approach: Testing for superiority was based on the stratified log-rank test and used a two-sided significance level of 2.5%.The hazard ratio (HR) of bevacizumab in combination with chemotherapy versus chemotherapy alone [HR(FOLFOX-4+P/XELOX+P)/(FOLFOX-4+BV/XELOX+BV)] was presented.
Log Rank
0.0004
Hazard Ratio (HR)
0.81
2-Sided
97.5
0.70
0.92
No
Superiority or Other
OG001
XELOX/XELOX+P/XELOX+BV
Participants from the initial 2-arm part and the 2x2 factorial part of the study including the following groups -
Xelox: Capecitabine was administered as an oral twice-daily outpatient intermittent treatment (3-week cycles consisting of 2 weeks of treatment followed by 1 week without treatment) combined with intravenous oxaliplatin (given on day 1).
Xelox+P: Capecitabine was administered as an oral twice-daily outpatient intermittent treatment (3-week cycles consisting of 2 weeks of treatment followed by 1 week without treatment) combined with intravenous oxaliplatin and placebo (P) control for bevacizumab (both given on day 1 every 3 weeks).
Xelox+BV: Capecitabine was administered as an oral twice-daily outpatient intermittent treatment (3-week cycles consisting of 2 weeks of treatment followed by 1 week without treatment) combined with intravenous oxaliplatin and intravenous bevacizumab (both given on day 1 every 3 weeks).
Units
Counts
Participants
OG000937
OG001967
Title
Denominators
Categories
Week 1-6
Title
Measurements
OG00067
OG00193
Week 7-12
Title
Measurements
OG000190
OG001191
Week 13-18
Title
Measurements
OG000155
OG001110
Week 19-24
Title
Measurements
OG00025
OG00138
Week 25-30
Title
Measurements
OG00014
OG00113
Week 31-36
Title
Measurements
OG0007
OG0013
Week 37-42
Title
Measurements
OG0003
OG0011
Week 49-54
Title
Measurements
OG0002
OG0010
Participants from the initial 2-arm part and the 2x2 factorial part of the study including the following groups -
Xelox: Capecitabine was administered as an oral twice-daily outpatient intermittent treatment (3-week cycles consisting of 2 weeks of treatment followed by 1 week without treatment) combined with intravenous oxaliplatin (given on day 1).
Xelox+P: Capecitabine was administered as an oral twice-daily outpatient intermittent treatment (3-week cycles consisting of 2 weeks of treatment followed by 1 week without treatment) combined with intravenous oxaliplatin and placebo (P) control for bevacizumab (both given on day 1 every 3 weeks).
Xelox+BV: Capecitabine was administered as an oral twice-daily outpatient intermittent treatment (3-week cycles consisting of 2 weeks of treatment followed by 1 week without treatment) combined with intravenous oxaliplatin and intravenous bevacizumab (both given on day 1 every 3 weeks).
Units
Counts
Participants
OG000701
OG001699
Title
Denominators
Categories
Week 1-6
Title
Measurements
OG00058
OG00148
Week 7-12
Title
Measurements
OG000146
OG001138
Week 13-18
Title
Measurements
OG000105
OG00187
Week 19-24
Title
Measurements
OG00026
OG00129
Week 25-30
Title
Measurements
OG0007
OG00112
Week 31-36
Title
Measurements
OG0002
OG0018
Week 37-42
Title
Measurements
OG0001
OG0012
Week 49-54
Title
Measurements
OG0000
OG0011
OG001
XELOX/XELOX+P/XELOX+BV
Participants from the initial 2-arm part and the 2x2 factorial part of the study including the following groups -
Xelox: Capecitabine was administered as an oral twice-daily outpatient intermittent treatment (3-week cycles consisting of 2 weeks of treatment followed by 1 week without treatment) combined with intravenous oxaliplatin (given on day 1).
Xelox+P: Capecitabine was administered as an oral twice-daily outpatient intermittent treatment (3-week cycles consisting of 2 weeks of treatment followed by 1 week without treatment) combined with intravenous oxaliplatin and placebo (P) control for bevacizumab (both given on day 1 every 3 weeks).
Xelox+BV: Capecitabine was administered as an oral twice-daily outpatient intermittent treatment (3-week cycles consisting of 2 weeks of treatment followed by 1 week without treatment) combined with intravenous oxaliplatin and intravenous bevacizumab (both given on day 1 every 3 weeks).
Units
Counts
Participants
OG000937
OG001967
Title
Denominators
Categories
Title
Measurements
OG000239.0(225 to 256)
OG001226.0(211 to 246)
Group IDs
Group Description
Statistical Method
Statistical Comment
P-Value
P-Value Comment
Parameter Type
Parameter Value
Dispersion Type
Dispersion Value
Confidence Interval Sides
Confidence Interval %
CI Lower Limit
CI Upper Limit
CI Lower Limit Comment
CI Upper Limit Comment
Estimate Comment
Tested Non-Inferiority
Non-Inferiority Type
Non-Inferiority Comment
Other Analysis Description
OG000
OG001
HRs and 97.5% confidence interval were reported for treatment arm A (XELOX/XELOX+P/XELOX+BV) versus treatment arm B (FOLFOX-4/FOLFOX-4+P/FOLFOX-4+BV)
Hazard Ratio (HR)
1.02
2-Sided
97.5
0.86
1.22
Yes
Non-Inferiority or Equivalence
No formal statistical testing was performed for duration of overall response.
OG001
FOLFOX-4+BV/XELOX+BV
Participants from the 2x2 factorial part of the study including the following groups -
Folfox-4+BV: Participants who received 2-week cycles of infused leucovorin, bolus injection fluorouracil and continuous infusion fluorouracil (given on days 1 and 2), combined with intravenous oxaliplatin and intravenous bevacizumab (both given on day 1 every 2 weeks).
Xelox+BV: Capecitabine was administered as an oral twice-daily outpatient intermittent treatment (3-week cycles consisting of 2 weeks of treatment followed by 1 week without treatment) combined with intravenous oxaliplatin and intravenous bevacizumab (both given on day 1 every 3 weeks).
Units
Counts
Participants
OG000701
OG001699
Title
Denominators
Categories
Title
Measurements
OG000225.0(217 to 240)
OG001257.0(241 to 278)
Group IDs
Group Description
Statistical Method
Statistical Comment
P-Value
P-Value Comment
Parameter Type
Parameter Value
Dispersion Type
Dispersion Value
Confidence Interval Sides
Confidence Interval %
CI Lower Limit
CI Upper Limit
CI Lower Limit Comment
CI Upper Limit Comment
Estimate Comment
Tested Non-Inferiority
Non-Inferiority Type
Non-Inferiority Comment
Other Analysis Description
OG000
OG001
Testing for superiority was based on the stratified log-rank test and used a two-sided significance level of 2.5%.The hazard ratio (HR) of bevacizumab in combination with chemotherapy versus chemotherapy alone [HR(FOLFOX-4+P/XELOX+P)/(FOLFOX-4+BV/XELOX+BV)] was presented.
Log Rank
0.0307
Hazard Ratio (HR)
0.82
2-Sided
97.5
0.66
1.01
No
Superiority or Other
OG001
XELOX/XELOX+P/XELOX+BV
Participants from the initial 2-arm part and the 2x2 factorial part of the study including the following groups -
Xelox: Capecitabine was administered as an oral twice-daily outpatient intermittent treatment (3-week cycles consisting of 2 weeks of treatment followed by 1 week without treatment) combined with intravenous oxaliplatin (given on day 1).
Xelox+P: Capecitabine was administered as an oral twice-daily outpatient intermittent treatment (3-week cycles consisting of 2 weeks of treatment followed by 1 week without treatment) combined with intravenous oxaliplatin and placebo (P) control for bevacizumab (both given on day 1 every 3 weeks).
Xelox+BV: Capecitabine was administered as an oral twice-daily outpatient intermittent treatment (3-week cycles consisting of 2 weeks of treatment followed by 1 week without treatment) combined with intravenous oxaliplatin and intravenous bevacizumab (both given on day 1 every 3 weeks).
Units
Counts
Participants
OG000937
OG001967
Title
Denominators
Categories
Title
Measurements
OG000347.0(196 to 403)
OG001589.0(270 to NA)The estimate is Not Available due to insufficient follow-up time to estimate the missing parameter.
Group IDs
Group Description
Statistical Method
Statistical Comment
P-Value
P-Value Comment
Parameter Type
Parameter Value
Dispersion Type
Dispersion Value
Confidence Interval Sides
Confidence Interval %
CI Lower Limit
CI Upper Limit
CI Lower Limit Comment
CI Upper Limit Comment
Estimate Comment
Tested Non-Inferiority
Non-Inferiority Type
Non-Inferiority Comment
Other Analysis Description
OG000
OG001
HRs and 97.5% confidence interval were reported for treatment arm A (XELOX/XELOX+P/XELOX+BV) versus treatment arm B (FOLFOX-4/FOLFOX-4+P/FOLFOX-4+BV).
Hazard Ratio (HR)
0.35
2-Sided
97.5
0.09
1.39
Yes
Non-Inferiority or Equivalence
No formal statistical testing was done.
Units
Counts
Participants
OG000701
OG001699
Title
Denominators
Categories
Title
Measurements
OG000403.0(228 to NA)The estimate is Not Available due to insufficient follow-up time to estimate the missing parameter.
OG001386.0(133 to 386)
Group IDs
Group Description
Statistical Method
Statistical Comment
P-Value
P-Value Comment
Parameter Type
Parameter Value
Dispersion Type
Dispersion Value
Confidence Interval Sides
Confidence Interval %
CI Lower Limit
CI Upper Limit
CI Lower Limit Comment
CI Upper Limit Comment
Estimate Comment
Tested Non-Inferiority
Non-Inferiority Type
Non-Inferiority Comment
Other Analysis Description
OG000
OG001
Testing for superiority was based on the stratified log-rank test and used a two-sided significance level of 2.5%.The hazard ratio (HR) of bevacizumab in combination with chemotherapy versus chemotherapy alone [HR(FOLFOX-4+P/XELOX+P)/(FOLFOX-4+BV/XELOX+BV)] was presented.