Study of Regorafenib as a 3rd-line or Beyond Treatment fo... | NCT01271712 | Trialant
NCT01271712
Sponsor
Bayer
Status
Completed
Last Update Posted
Jan 29, 2021Actual
Enrollment
199Actual
Phase
Phase 3
Conditions
Gastrointestinal Stromal Tumors
Interventions
Regorafenib (Stivarga, BAY73-4506)
Placebo
Best supportive care
Countries
United States
Austria
Belgium
Canada
China
Finland
France
Germany
Israel
Italy
Japan
Netherlands
Poland
Singapore
South Korea
Spain
United Kingdom
Protocol Section
Identification Module
NCT ID
NCT01271712
Obsolete or Duplicate NCT IDs
Not provided
Organization Study
14874
Secondary IDs
ID
Type
Description
Link
2009-017957-37
EudraCT Number
Brief Title
Study of Regorafenib as a 3rd-line or Beyond Treatment for Gastrointestinal Stromal Tumors (GIST)
Official Title
A Randomized, Double-blind, Placebo-controlled Phase III Study of Regorafenib Plus Best Supportive Care Versus Placebo Plus Best Supportive Care for Subjects With Metastatic and/or Unresectable Gastrointestinal Stromal Tumors (GIST) Whose Disease Has Progressed Despite Prior Treatment With at Least Imatinib and Sunitinib
Acronym
GRID
Organization
BayerINDUSTRY
Status Module
Record Verification Date
Jan 2021
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
Jan 4, 2011Actual
Primary Completion Date
Jan 26, 2012Actual
Completion Date
Apr 15, 2019Actual
First Submitted Date
Dec 17, 2010
First Submission Date that Met QC Criteria
Jan 6, 2011
First Posted Date
Jan 7, 2011Estimated
Results Waived
Not provided
Results First Submitted Date
May 24, 2013
Results First Submitted that Met QC Criteria
Aug 21, 2013
Results First Posted Date
Oct 25, 2013Estimated
Certification/Extension (aka Delayed Results) First Submitted Date
Jan 30, 2013
Certification/Extension First Submitted that Passed QC Review
Jan 30, 2013
Certification/Extension First Posted Date
Feb 1, 2013Estimated
Last Update Submitted Date
Jan 27, 2021
Last Update Posted Date
Jan 29, 2021Actual
Sponsor/Collaborators Module
Responsible Party, by Official Title
Sponsor
Lead Sponsor
BayerINDUSTRY
Collaborators
Not provided
Oversight Module
Has Data Monitoring Committee (DMC)
Yes
Is FDA Regulated Drug
Yes
Is FDA Regulated Device
No
Is Unapproved Device
Not provided
Pediatric Postmarket Surveillance of a Device Product
Not provided
Product Exported from US
Not provided
FDAAA801 Violation
Not provided
Description Module
Brief Summary
A randomized, double-blind, placebo-controlled phase III study of regorafenib plus best supportive care versus placebo plus best supportive care for subjects with metastatic and/or unresectable gastrointestinal stromal tumors (GIST) whose disease has progressed despite prior treatment with at least imatinib and sunitinib.
The study is composed of 3 periods: A Screening Period, a Treatment Period, and a Survival Follow up Period.
Subjects randomized to be treated with regorafenib will receive 160 mg po od for 3 weeks of every 4 week (28 day) cycle (ie, 3 weeks on/1 week off). In addition subjects will receive best supportive care which excludes any disease specific anti cancer therapy such as any kinase inhibitor, chemotherapy, radiation therapy, or surgery.
Tumor assessment will be every 4 weeks for the first 3 months, every 6 weeks for the next 3 months (through month 6), and every 8 weeks until the end of treatment, or more frequently if clinically indicated. Tumor assessments include CT or MRI and will be performed until tumor progression is seen in a central radiology review.
Subjects receiving placebo who experience disease progression may be offered active treatment.
Subjects who experience progression during regorafenib treatment may continue open label treatment.
All subjects will enter the Survival Follow-up Period upon discontinuation of randomized study treatment.
Detailed Description
Not provided
Conditions Module
Conditions
Gastrointestinal Stromal Tumors
Keywords
Gastrointestinal stromal cancer
GIST
multikinase inhibitor
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
199Actual
Arms/Interventions Module
Arm Groups
Label
Type
Description
Intervention Names
Regorafenib (Stivarga, BAY73-4506)
Experimental
Participants received Regorafenib (Stivarga) 160 mg (4 x 40 mg tablets) per os once daily, 3 weeks on therapy followed by 1 week off therapy to comprise a cycle of 4 weeks
Drug: Regorafenib (Stivarga, BAY73-4506)
Drug: Best supportive care
Placebo
Placebo Comparator
Participants received matching Placebo tablets per os once daily, 3 weeks on therapy followed by 1 week off therapy to comprise a cycle of 4 weeks
Drug: Placebo
Drug: Best supportive care
Interventions
Name
Type
Description
Arm Group Labels
Other Names
Regorafenib (Stivarga, BAY73-4506)
Drug
160 mg po once daily (od), 3 weeks on/1 week off. Route of administration: oral
Regorafenib (Stivarga, BAY73-4506)
Outcomes Module
Primary Outcomes
Measure
Description
Time Frame
Progression-free Survival
Progression-free Survival (PFS) was defined as the time from date of randomization to radiological disease progression or death due to any cause, whichever occurs first. PFS was based on central radiological assessment using modified RECIST (Response Evaluation Criteria in Solid Tumors) v.1.1. Progression is defined as at least a 20% increase in the sum of diameters of target lesions taking as reference the smallest sum on study; or unequivocal progression of existing non-target lesions; or appearance of new lesions. Subjects without progression or death at the time of analysis were censored at their last date of tumor evaluation. Results are based on central evaluation.
From randomization of the first subject until approximately 144 progression-free survival events had occurred (study duration approximately one year)
Secondary Outcomes
Measure
Description
Time Frame
Overall Survival
Overall Survival (OS) was defined as the time from date of randomization to death due to any cause. Subjects still alive at the time of analysis were censored at their date of last contact. Median OS was not observed at the time of PFS analysis and first analysis of OS, therefore only the proportion of death events was reported in the results posting system. This approach was maintained for the subsequent updates in the results posting system.
Other Outcomes
Not provided
Eligibility Module
Eligibility Criteria
Inclusion Criteria:
Male or female subjects 18 years of age.
Subjects with histologically confirmed metastatic and/or unresectable GIST.
At least imatinib and sunitinib as prior treatment regimens, with objective disease progression or intolerance to imatinib, as well as disease progression while on sunitinib therapy. Additionally, disease progression or intolerance to other systemic therapies, as well as investigational new agents, is allowed, except prior treatment with any other vascular endothelial growth factor receptor (VEGFR) inhibitor.
Subjects must have at least one measurable lesion according to Response Evaluation Criteria in Solid Tumors (RECIST), version 1.1. A lesion in a previously irradiated area is eligible to be considered as measurable disease as long as there is objective evidence of progression of the lesion prior to study enrollment.
Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1.
Adequate bone marrow, liver, and renal function as assessed by laboratory parameters.
Recovery to NCI-CTCAE v4.0 Grade 0 or 1 level or recovery to baseline preceding the prior treatment from any previous drug/procedure-related toxicity (except alopecia and anemia).
Exclusion Criteria:
Major surgical procedure, open biopsy, or significant traumatic injury within 28 days before start of study medication.
Congestive heart failure New York Heart Association (NYHA) class 2.
Unstable angina (angina symptoms at rest, new-onset angina, ie, within the last 3 months) or myocardial infarction (MI) within the past 6 months before start of study medication.
Uncontrolled hypertension (systolic blood pressure 140 mmHg or diastolic pressure 90 mmHg despite optimal medical management).
Arterial thrombotic or embolic events such as cerebrovascular accident (including transient ischemic attacks), or pulmonary embolism within the 6 months before start of study drug or venous thrombotic events such as deep vein thrombosis within the 3 months before start of study drug.
Ongoing infection grade 2 National Cancer Institute-Common Terminology Criteria for Adverse Events (NCI CTCAE) version 4.0.
Symptomatic metastatic brain or meningeal tumors.
Subjects with evidence or history of bleeding diathesis. Any hemorrhage or bleeding event NCI-CTCAE version 4.0 grade 3 or higher within 4 weeks prior to the start of study drug.
Non-healing wound, ulcer, or bone fracture.
Persistent proteinuria of NCI-CTCAE version 4.0 grade 3 or higher (3.5 g/24 hrs, measured by urine protein:creatinine ratio on a random urine sample).
Demetri GD, Reichardt P, Kang YK, Blay JY, Rutkowski P, Gelderblom H, Hohenberger P, Leahy M, von Mehren M, Joensuu H, Badalamenti G, Blackstein M, Le Cesne A, Schoffski P, Maki RG, Bauer S, Nguyen BB, Xu J, Nishida T, Chung J, Kappeler C, Kuss I, Laurent D, Casali PG; GRID study investigators. Efficacy and safety of regorafenib for advanced gastrointestinal stromal tumours after failure of imatinib and sunitinib (GRID): an international, multicentre, randomised, placebo-controlled, phase 3 trial. Lancet. 2013 Jan 26;381(9863):295-302. doi: 10.1016/S0140-6736(12)61857-1. Epub 2012 Nov 22.
Participants were randomized in a 2:1 ratio to receive either regorafenib (133 patients) or placebo (66 patients). Randomization was stratified according 3rd vs. 4th line of therapy (at least 50% of patients were to be 3rd line), and geographical region (Asia vs.rest of world).
Recruitment Details
A total of 240 participants with metastatic and/or unresectable GIST whose disease had progressed despite prior treatments with at least imatinib and sunitinib were screened; 199 were randomized. Patients must have shown objective disease progression or intolerance to imatinib, as well as disease progression while on sunitinib treatment.
Type of Units Analyzed
Not provided
Arm/Group Information
ID
Title
Description
FG000
Regorafenib (Stivarga, BAY73-4506)
Participants received Regorafenib (Stivarga) 160 mg (4 x 40 mg tablets) per os once daily, 3 weeks on therapy followed by 1 week off therapy to comprise a cycle of 4 weeks
FG001
Placebo First, Then Option of Open Label Regorafenib Treatment
once daily (od), 3 weeks on/1 week off. Route of administration: oral
Placebo
Best supportive care
Drug
Best supportive care includes any method to preserve the comfort and dignity of the patients, and excludes any disease-specific anti-neoplastic therapy such as any kinase inhibitor, chemotherapy, radiation therapy, or surgical intervention.
Placebo
Regorafenib (Stivarga, BAY73-4506)
From randomization of the first subject until date of database cutoff (08 Jun 2015)
Time to Progression (TTP)
Time to progression (TTP) was defined as the time from date of randomization to disease progression (based on central radiological assessment using modified RECIST [Response Evaluation Criteria in Solid Tumors] v.1.1). Progression is defined as at least a 20% increase in the sum of diameters of target lesions taking as reference the smallest sum on study; or unequivocal progression of existing non-target lesions; or appearance of new lesions. Subjects without progression at the time of analysis were censored at their last date of tumor evaluation. Results are based on central evaluation.
From randomization of the first subject until until date of database cutoff (26 Jan 2012); study duration approximately 1 year
Tumor Response
Tumor Response of a subject was defined as the best tumor response (Complete Response [CR: disappearance of all clinical and radiological evidence of tumor (both target and non-target).], Partial Response [PR: at least a 30% decrease in the sum of diameters of target lesions taking as reference the baseline sum, no unequivocal progression of existing non-target lesions, and no appearance of new lesions.], Stable Disease [SD: steady state of disease. Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, no unequivocal progression of existing non-target lesions, and no appearance of new lesions.], or Progressive Disease [PD: at least a 20% increase in the sum of diameters of target lesions taking as reference the smallest sum on study or unequivocal progression of existing non-target lesions, or appearance of new lesions.]) observed during the trial period and assessed according to RECIST v1.1 criteria. Results are based on central evaluation.
From randomization of the first subject until date of database cutoff (26 Jan 2012); study duration approximately 1 year
Objective Response Rate
Objective response rate was defined as the percentage of subjects whose best response was Complete Response (CR: disappearance of all clinical and radiological evidence of tumor (both target and non-target).) or Partial Response (PR: at least a 30% decrease in the sum of diameters of target lesions taking as reference the baseline sum, no unequivocal progression of existing non-target lesions, and no appearance of new lesions.) according to Response Evaluation Criteria in Solid Tumors (RECIST v1.1). Results are based on central evaluation.
From randomization of the first subject until date of database cutoff (26 Jan 2012); study duration approximately 1 year.
Disease Control Rate (DCR)
Disease Control Rate (DCR) was defined as the percentage of subjects whose best response was Complete Response (CR: disappearance of all clinical and radiological evidence of tumor (both target and non-target).), Partial Response (PR: at least a 30% decrease in the sum of diameters of target lesions taking as reference the baseline sum, no unequivocal progression of existing non-target lesions, and no appearance of new lesions.), or Stable Disease (SD: steady state of disease. Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, no unequivocal progression of existing non-target lesions, and no appearance of new lesions.) according to RECIST v1.1 criteria. SD had to be maintained for at least 12 weeks from the first demonstration of that rating. Results are based on central evaluation.
From randomization of the first subject until date of database cutoff (26 Jan 2012); study duration approximately 1 year
Duration of Response (DOR)
Duration of Response was defined as the time from date of first response (Complete Response [CR: disappearance of all clinical and radiological evidence of tumor (both target and non-target).] or Partial Response [PR: at least a 30% decrease in the sum of diameters of target lesions taking as reference the baseline sum, no unequivocal progression of existing non-target lesions, and no appearance of new lesions.]) to the date when Progressive Disease (PD: at least a 20% increase in the sum of diameters of target lesions taking as reference the smallest sum on study or unequivocal progression of existing non-target lesions, or appearance of new lesions.) is first documented, or to the date of death, whichever occurs first, according to RECIST v1.1. Subjects still having CR or PR and have not died at the time of analysis were censored at their last date of tumor evaluation. Duration of response defined for responders only, i.e CR or PR. Results are based on central evaluation.
From randomization of the first subject until date of database cutoff (26 Jan 2012); study duration approximately 1 year
Evanston
Illinois
60201
United States
Skokie
Illinois
60076
United States
Boston
Massachusetts
02115
United States
Minneapolis
Minnesota
55455
United States
New York
New York
10065
United States
Portland
Oregon
97239-2964
United States
Philadelphia
Pennsylvania
19111-2497
United States
Seattle
Washington
98109
United States
Graz
Styria
8036
Austria
Innsbruck
6020
Austria
Vienna
1090
Austria
Leuven
3000
Belgium
Edmonton
Alberta
T6G 1Z2
Canada
London
Ontario
N6A 4L6
Canada
Toronto
Ontario
M5G 1X5
Canada
Guangzhou
Guangdong
510060
China
Nanjing
Jiangsu
210002
China
Beijing
100071
China
Shanghai
200030
China
Helsinki
00290
Finland
Bordeaux
33076
France
Lille
59020
France
Lyon
69373
France
Villejuif
94805
France
Mannheim
Baden-Wurttemberg
68167
Germany
Tübingen
Baden-Wurttemberg
72076
Germany
Bad Saarow
Brandenburg
15526
Germany
Hanover
Lower Saxony
30625
Germany
Cologne
North Rhine-Westphalia
50924
Germany
Düsseldorf
North Rhine-Westphalia
40479
Germany
Essen
North Rhine-Westphalia
45122
Germany
Tel Aviv
64239
Israel
Bologna
Emilia-Romagna
40138
Italy
Milan
Lombardy
20133
Italy
Turin
Piedmont
10060
Italy
Palermo
Sicily
90127
Italy
Nagoya
Aichi-ken
466-8650
Japan
Kashiwa
Chiba
277-8577
Japan
Sapporo
Hokkaido
060-8648
Japan
Chuo-ku
Tokyo
104-0045
Japan
Niigata
951-8520
Japan
Osaka
543-0035
Japan
Leiden
2333 ZA
Netherlands
Nijmegen
6525 GA
Netherlands
Warsaw
02-781
Poland
Singapore
169610
Singapore
Goyang-si
Gyeonggido
410-769
South Korea
Busan
49201
South Korea
Seoul
03080
South Korea
Seoul
06351
South Korea
Seoul
138-736
South Korea
L'Hospitalet de Llobregat
Barcelona
08907
Spain
Barcelona
08035
Spain
Leicester
Leicestershire
LE1 5WW
United Kingdom
London
SW3 6JJ
United Kingdom
Manchester
M20 4BX
United Kingdom
Result
Poole CD, Connolly MP, Chang J, Currie CJ. Health utility of patients with advanced gastrointestinal stromal tumors (GIST) after failure of imatinib and sunitinib: findings from GRID, a randomized, double-blind, placebo-controlled phase III study of regorafenib versus placebo. Gastric Cancer. 2015 Jul;18(3):627-34. doi: 10.1007/s10120-014-0391-x. Epub 2014 Jun 24.
Komatsu Y, Doi T, Sawaki A, Kanda T, Yamada Y, Kuss I, Demetri GD, Nishida T. Regorafenib for advanced gastrointestinal stromal tumors following imatinib and sunitinib treatment: a subgroup analysis evaluating Japanese patients in the phase III GRID trial. Int J Clin Oncol. 2015 Oct;20(5):905-12. doi: 10.1007/s10147-015-0790-y. Epub 2015 Feb 6.
Mross K, Frost A, Steinbild S, Hedbom S, Buchert M, Fasol U, Unger C, Kratzschmar J, Heinig R, Boix O, Christensen O. A phase I dose-escalation study of regorafenib (BAY 73-4506), an inhibitor of oncogenic, angiogenic, and stromal kinases, in patients with advanced solid tumors. Clin Cancer Res. 2012 May 1;18(9):2658-67. doi: 10.1158/1078-0432.CCR-11-1900. Epub 2012 Mar 15.
Double blind phase: participants received matching Placebo tablets per os once daily, 3 weeks on therapy followed by 1 week off therapy to comprise a cycle of 4 weeks. Open Label phase: participants on placebo who switched to Regorafenib, received Regorafenib 160 mg (4 x 40 mg tablets) per os once daily, 3 weeks on therapy followed by 1 week off therapy to comprise a cycle of 4 weeks.
FG000133 subjects
FG00166 subjects
Participants Received Treatment
FG000132 subjects
FG00166 subjects
COMPLETED
FG00091 subjects91 participants started open-label treatment with regorafenib
FG00158 subjects58 participants started open-label treatment with regorafenib
NOT COMPLETED
FG00042 subjects
FG0018 subjects
Type
Comment
Reasons
Death
FG0002 subjects
FG0010 subjects
Lack of Efficacy
FG0001 subjects
FG0010 subjects
Adverse Event
FG0009 subjects
FG0014 subjects
Progressive disease
FG00023 subjects
FG0013 subjects
Withdrawal by Subject
FG0004 subjects
FG0011 subjects
Non compliance with study drug
FG0002 subjects
FG0010 subjects
receive no study drug
FG0001 subjects
FG0010 subjects
Open Label Treatment
Type
Comment
Milestone Data
STARTED
FG00091 subjects
FG00158 subjects
COMPLETED
FG0000 subjects
FG0010 subjects
NOT COMPLETED
FG00091 subjects
FG00158 subjects
Type
Comment
Reasons
Death
FG0006 subjects
FG0015 subjects
Withdrawal by Subject
FG0006 subjects
FG001
Safety Follow-up
Type
Comment
Milestone Data
STARTED
FG000118 subjectsAll participants who discontinued study drug entered 30-day Safety Follow-up
FG00152 subjectsAll participants who discontinued study drug entered 30-day Safety Follow-up
COMPLETED
FG00097 subjects
FG00137 subjects
NOT COMPLETED
FG00021 subjects
FG00115 subjects
Type
Comment
Reasons
Death
FG00011 subjects
FG0017 subjects
Withdrawal by Subject
FG0004 subjects
FG001
Survival Follow-up
Type
Comment
Milestone Data
STARTED
FG000100 subjectsAll participants entered Survival Follow-up immediately after safety follow-up
FG00139 subjectsAll participants entered Survival Follow-up immediately after safety follow-up
COMPLETED
FG00085 subjects85 participants died and completed survival follow-up.
FG00133 subjects33 participants died and completed survival follow-up.
NOT COMPLETED
FG00015 subjects
FG0016 subjects
Type
Comment
Reasons
Not analyzed after cutoff 08Jun2015
FG00015 subjects
FG0016 subjects
Type of Units Analyzed
Not provided
Arm/Group Information
ID
Title
Description
BG000
Regorafenib (Stivarga, BAY73-4506)
Participants received Regorafenib (Stivarga) 160 mg (4 x 40 mg tablets) per os once daily, 3 weeks on therapy followed by 1 week off therapy to comprise a cycle of 4 weeks
BG001
Placebo
Participants received matching Placebo tablets per os once daily, 3 weeks on therapy followed by 1 week off therapy to comprise a cycle of 4 weeks
BG002
Total
Total of all reporting groups
Denominators
Units
Counts
Participants
BG000133
BG00166
BG002199
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
BG00058.2± 12.5
BG00158.1± 13.9
BG00258.2± 12.9
Sex: Female, Male
Count of Participants
Participants
Title
Denominators
Categories
Title
Measurements
Female
BG00048
BG00124
BG002
ECOG Performance Status (PS)]
ECOG = Eastern cooperative oncology group PS levels are 0 (Fully active, able to carry on all pre-disease performance), 1 (ambulatory and able to carry out work of a light or sedentary), 2 (Ambulatory and capable of all selfcare but unable to carry out any work activities), 3 (Capable of only limited selfcare, confined to bed or chair more than 50% of awake time), 4 (Completely disabled. Cannot carry on any selfcare. Totally confined to bed or chair) and 5 (death).
Count of Participants
Participants
Title
Denominators
Categories
Title
Measurements
PS 0
BG00073
BG001
Prior anti-cancer drug group
3rd line: 3rd in sequence of multiple therapies: imatinib (1st); sunitinib (2nd). 4th line and beyond: 4th in sequence of multiple therapies: imatinib (1st); sunitinib (2nd); other (3rd).
Count of Participants
Participants
Title
Denominators
Categories
Title
Measurements
3rd line
BG00074
BG001
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
Progression-free Survival (PFS) was defined as the time from date of randomization to radiological disease progression or death due to any cause, whichever occurs first. PFS was based on central radiological assessment using modified RECIST (Response Evaluation Criteria in Solid Tumors) v.1.1. Progression is defined as at least a 20% increase in the sum of diameters of target lesions taking as reference the smallest sum on study; or unequivocal progression of existing non-target lesions; or appearance of new lesions. Subjects without progression or death at the time of analysis were censored at their last date of tumor evaluation. Results are based on central evaluation.
Full Analysis Set (FAS) - defined as all randomized participants.
Posted
Median
95% Confidence Interval
Days
From randomization of the first subject until approximately 144 progression-free survival events had occurred (study duration approximately one year)
ID
Title
Description
OG000
Regorafenib (Stivarga, BAY73-4506)
Participants received Regorafenib (Stivarga) 160 mg (4 x 40 mg tablets) per os once daily, 3 weeks on therapy followed by 1 week off therapy to comprise a cycle of 4 weeks
OG001
Placebo
Participants received matching Placebo tablets per os once daily, 3 weeks on therapy followed by 1 week off therapy to comprise a cycle of 4 weeks
Units
Counts
Participants
OG000133
OG00166
Title
Denominators
Categories
Title
Measurements
OG000147(122 to 173)
OG00128(28 to 32)
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
The two treatment groups were compared using a stratified log rank test with a one-sided alpha of 0.01 stratified by (3rd vs 4th-line; and geographical region). The null hypothesis that both treatment arms have the same PFS distribution was tested against the alternative hypothesis that the distribution of PFS in the regorafenib arm is different from the control arm according to a proportional hazards relation between the treatment arms.
Log Rank
stratified
<0.000001
Superiority or Other (legacy)
Secondary
Overall Survival
Overall Survival (OS) was defined as the time from date of randomization to death due to any cause. Subjects still alive at the time of analysis were censored at their date of last contact. Median OS was not observed at the time of PFS analysis and first analysis of OS, therefore only the proportion of death events was reported in the results posting system. This approach was maintained for the subsequent updates in the results posting system.
Full Analysis Set (FAS). 58 (87.9%) patients in placebo group and 91 (68.4%) patients in regorafenib had started open-label treatment with regorafenib before time of final database cutoff 08 Jun 2015
Posted
Number
Percentage of patients with death
From randomization of the first subject until date of database cutoff (08 Jun 2015)
ID
Title
Description
OG000
Regorafenib (Stivarga, BAY73-4506)
Participants received Regorafenib (Stivarga) 160 mg (4 x 40 mg tablets) per os once daily, 3 weeks on therapy followed by 1 week off therapy to comprise a cycle of 4 weeks
OG001
Placebo
Participants received matching Placebo tablets per os once daily, 3 weeks on therapy followed by 1 week off therapy to comprise a cycle of 4 weeks
Units
Secondary
Time to Progression (TTP)
Time to progression (TTP) was defined as the time from date of randomization to disease progression (based on central radiological assessment using modified RECIST [Response Evaluation Criteria in Solid Tumors] v.1.1). Progression is defined as at least a 20% increase in the sum of diameters of target lesions taking as reference the smallest sum on study; or unequivocal progression of existing non-target lesions; or appearance of new lesions. Subjects without progression at the time of analysis were censored at their last date of tumor evaluation. Results are based on central evaluation.
Full Analysis Set (FAS)
Posted
Median
95% Confidence Interval
Days
From randomization of the first subject until until date of database cutoff (26 Jan 2012); study duration approximately 1 year
ID
Title
Description
OG000
Regorafenib (Stivarga, BAY73-4506)
Participants received Regorafenib (Stivarga) 160 mg (4 x 40 mg tablets) per os once daily, 3 weeks on therapy followed by 1 week off therapy to comprise a cycle of 4 weeks
OG001
Placebo
Participants received matching Placebo tablets per os once daily, 3 weeks on therapy followed by 1 week off therapy to comprise a cycle of 4 weeks
Secondary
Tumor Response
Tumor Response of a subject was defined as the best tumor response (Complete Response [CR: disappearance of all clinical and radiological evidence of tumor (both target and non-target).], Partial Response [PR: at least a 30% decrease in the sum of diameters of target lesions taking as reference the baseline sum, no unequivocal progression of existing non-target lesions, and no appearance of new lesions.], Stable Disease [SD: steady state of disease. Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, no unequivocal progression of existing non-target lesions, and no appearance of new lesions.], or Progressive Disease [PD: at least a 20% increase in the sum of diameters of target lesions taking as reference the smallest sum on study or unequivocal progression of existing non-target lesions, or appearance of new lesions.]) observed during the trial period and assessed according to RECIST v1.1 criteria. Results are based on central evaluation.
Full Analysis Set (FAS)
Posted
Number
95% Confidence Interval
Percentage of Participants
From randomization of the first subject until date of database cutoff (26 Jan 2012); study duration approximately 1 year
ID
Title
Description
OG000
Regorafenib (Stivarga, BAY73-4506)
Participants received Regorafenib (Stivarga) 160 mg (4 x 40 mg tablets) per os once daily, 3 weeks on therapy followed by 1 week off therapy to comprise a cycle of 4 weeks
OG001
Placebo
Secondary
Objective Response Rate
Objective response rate was defined as the percentage of subjects whose best response was Complete Response (CR: disappearance of all clinical and radiological evidence of tumor (both target and non-target).) or Partial Response (PR: at least a 30% decrease in the sum of diameters of target lesions taking as reference the baseline sum, no unequivocal progression of existing non-target lesions, and no appearance of new lesions.) according to Response Evaluation Criteria in Solid Tumors (RECIST v1.1). Results are based on central evaluation.
Full Analysis Set (FAS)
Posted
Number
95% Confidence Interval
Percentage of Participants
From randomization of the first subject until date of database cutoff (26 Jan 2012); study duration approximately 1 year.
ID
Title
Description
OG000
Regorafenib (Stivarga, BAY73-4506)
Participants received Regorafenib (Stivarga) 160 mg (4 x 40 mg tablets) per os once daily, 3 weeks on therapy followed by 1 week off therapy to comprise a cycle of 4 weeks
OG001
Placebo
Participants received matching Placebo tablets per os once daily, 3 weeks on therapy followed by 1 week off therapy to comprise a cycle of 4 weeks
Units
Secondary
Disease Control Rate (DCR)
Disease Control Rate (DCR) was defined as the percentage of subjects whose best response was Complete Response (CR: disappearance of all clinical and radiological evidence of tumor (both target and non-target).), Partial Response (PR: at least a 30% decrease in the sum of diameters of target lesions taking as reference the baseline sum, no unequivocal progression of existing non-target lesions, and no appearance of new lesions.), or Stable Disease (SD: steady state of disease. Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, no unequivocal progression of existing non-target lesions, and no appearance of new lesions.) according to RECIST v1.1 criteria. SD had to be maintained for at least 12 weeks from the first demonstration of that rating. Results are based on central evaluation.
Full Analysis Set (FAS)
Posted
Number
95% Confidence Interval
Percentage of Participants
From randomization of the first subject until date of database cutoff (26 Jan 2012); study duration approximately 1 year
ID
Title
Description
OG000
Regorafenib (Stivarga, BAY73-4506)
Participants received Regorafenib (Stivarga) 160 mg (4 x 40 mg tablets) per os once daily, 3 weeks on therapy followed by 1 week off therapy to comprise a cycle of 4 weeks
OG001
Placebo
Participants received matching Placebo tablets per os once daily, 3 weeks on therapy followed by 1 week off therapy to comprise a cycle of 4 weeks
Secondary
Duration of Response (DOR)
Duration of Response was defined as the time from date of first response (Complete Response [CR: disappearance of all clinical and radiological evidence of tumor (both target and non-target).] or Partial Response [PR: at least a 30% decrease in the sum of diameters of target lesions taking as reference the baseline sum, no unequivocal progression of existing non-target lesions, and no appearance of new lesions.]) to the date when Progressive Disease (PD: at least a 20% increase in the sum of diameters of target lesions taking as reference the smallest sum on study or unequivocal progression of existing non-target lesions, or appearance of new lesions.) is first documented, or to the date of death, whichever occurs first, according to RECIST v1.1. Subjects still having CR or PR and have not died at the time of analysis were censored at their last date of tumor evaluation. Duration of response defined for responders only, i.e CR or PR. Results are based on central evaluation.
Full Analysis Set with response participants
Posted
Median
95% Confidence Interval
Days
From randomization of the first subject until date of database cutoff (26 Jan 2012); study duration approximately 1 year
ID
Title
Description
OG000
Regorafenib (Stivarga, BAY73-4506)
Participants received Regorafenib (Stivarga) 160 mg (4 x 40 mg tablets) per os once daily, 3 weeks on therapy followed by 1 week off therapy to comprise a cycle of 4 weeks
OG001
Placebo
Time Frame
From first administration of treatment till 30 days after last dose of treatment.
Description
At primary completion (cutoff 26JAN2012) blinded patients who received either regorafenib or placebo were reported in "Regorafenib (DoubleBlindOnly)" and "Placebo (DoubleBlindOnly)" respectively; patients who received regorafenib after unblinding were reported in "Placebo, OpenLabelOnly(Switch to Regorafenib)". This safety update (cutoff 15APR2019) was reported in "Treated with Regorafenib at any time" and "Treated with Regorafenib for>1 year".
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
Regorafenib (Double Blind Only)
Participants received Regorafenib (Stivarga) 160 mg (4 x 40 mg tablets) per os once daily, 3 weeks on therapy followed by 1 week off therapy to comprise a cycle of 4 weeks
40
41
23
41
40
41
EG001
Placebo (Double Blind Only)
Participants received matching Placebo tablets per os once daily, 3 weeks on therapy followed by 1 week off therapy to comprise a cycle of 4 weeks
7
8
8
8
7
8
EG002
Placebo, Open Label Only (Switch to Regorafenib)
Participants switched to Open-label Regorafenib treatment from Placebo. Participants received Regorafenib (Stivarga) 160 mg (4 x 40 mg tablets) per os once daily, 3 weeks
47
58
31
58
58
58
EG003
Treated With Regorafenib at Any Time
Treated with Regorafenib at any time: At any time, participants received Regorafenib (Stivarga) 160 mg (4 x 40 mg tablets) per os once daily, 3 weeks on therapy followed by 1 week off therapy to comprise a cycle of 4 weeks
155
190
103
190
189
190
EG004
Treated With Regorafenib for > 1 Year
Treated with Regorafenib for > 1 year: For more than a year, participants received Regorafenib (Stivarga) 160 mg (4 x 40 mg tablets) per os once daily, 3 weeks on therapy followed by 1 week off therapy to comprise a cycle of 4 weeks
48
75
39
75
75
75
Serious Adverse Events
Term
Organ System
Source Vocabulary
Assessment Type
Notes
Statistical Information
Vertigo
Ear and labyrinth disorders
MedDRA (22.0)
Non-systematic Assessment
EG0000 events0 affected41 at risk
EG0010 events0 affected8 at risk
EG0020 events0 affected58 at risk
EG0031 events1 affected190 at risk
EG0040 events0 affected75 at risk
Anemia
Blood and lymphatic system disorders
MedDRA (22.0)
Non-systematic Assessment
EG0000 events0 affected41 at risk
EG0010 events0 affected8 at risk
EG0022 events1 affected58 at risk
EG003
Congenital, familial and genetic disorders - Other
Congenital, familial and genetic disorders
MedDRA (22.0)
Non-systematic Assessment
EG0000 events0 affected41 at risk
EG0010 events0 affected8 at risk
EG0020 events0 affected58 at risk
EG003
Acute coronary syndrome
Cardiac disorders
MedDRA (22.0)
Non-systematic Assessment
EG0000 events0 affected41 at risk
EG0010 events0 affected8 at risk
EG0020 events0 affected58 at risk
EG003
Atrial fibrillation
Cardiac disorders
MedDRA (22.0)
Non-systematic Assessment
EG0000 events0 affected41 at risk
EG0010 events0 affected8 at risk
EG0021 events1 affected58 at risk
EG003
Cardiac arrest
Cardiac disorders
MedDRA (22.0)
Non-systematic Assessment
EG0001 events1 affected41 at risk
EG0010 events0 affected8 at risk
EG0020 events0 affected58 at risk
EG003
Chest pain - cardiac
Cardiac disorders
MedDRA (22.0)
Non-systematic Assessment
EG0000 events0 affected41 at risk
EG0010 events0 affected8 at risk
EG0020 events0 affected58 at risk
EG003
Conduction disorder
Cardiac disorders
MedDRA (22.0)
Non-systematic Assessment
EG0000 events0 affected41 at risk
EG0010 events0 affected8 at risk
EG0020 events0 affected58 at risk
EG003
Heart failure
Cardiac disorders
MedDRA (22.0)
Non-systematic Assessment
EG0000 events0 affected41 at risk
EG0010 events0 affected8 at risk
EG0020 events0 affected58 at risk
EG003
Cardiac disorders - Other
Cardiac disorders
MedDRA (22.0)
Non-systematic Assessment
EG0000 events0 affected41 at risk
EG0010 events0 affected8 at risk
EG0020 events0 affected58 at risk
EG003
Abdominal pain
Gastrointestinal disorders
MedDRA (22.0)
Non-systematic Assessment
EG0005 events5 affected41 at risk
EG0010 events0 affected8 at risk
EG0022 events2 affected58 at risk
EG003
Anal fistula
Gastrointestinal disorders
MedDRA (22.0)
Non-systematic Assessment
EG0000 events0 affected41 at risk
EG0010 events0 affected8 at risk
EG0020 events0 affected58 at risk
EG003
Ascites
Gastrointestinal disorders
MedDRA (22.0)
Non-systematic Assessment
EG0004 events3 affected41 at risk
EG0010 events0 affected8 at risk
EG0020 events0 affected58 at risk
EG003
Colonic fistula
Gastrointestinal disorders
MedDRA (22.0)
Non-systematic Assessment
EG0001 events1 affected41 at risk
EG0010 events0 affected8 at risk
EG0020 events0 affected58 at risk
EG003
Colonic obstruction
Gastrointestinal disorders
MedDRA (22.0)
Non-systematic Assessment
EG0000 events0 affected41 at risk
EG0010 events0 affected8 at risk
EG0022 events1 affected58 at risk
EG003
Colonic perforation
Gastrointestinal disorders
MedDRA (22.0)
Non-systematic Assessment
EG0000 events0 affected41 at risk
EG0010 events0 affected8 at risk
EG0022 events1 affected58 at risk
EG003
Constipation
Gastrointestinal disorders
MedDRA (22.0)
Non-systematic Assessment
EG0000 events0 affected41 at risk
EG0010 events0 affected8 at risk
EG0021 events1 affected58 at risk
EG003
Diarrhea
Gastrointestinal disorders
MedDRA (22.0)
Non-systematic Assessment
EG0001 events1 affected41 at risk
EG0010 events0 affected8 at risk
EG0020 events0 affected58 at risk
EG003
Gastric hemorrhage
Gastrointestinal disorders
MedDRA (22.0)
Non-systematic Assessment
EG0001 events1 affected41 at risk
EG0010 events0 affected8 at risk
EG0021 events1 affected58 at risk
EG003
Intra-abdominal hemorrhage
Gastrointestinal disorders
MedDRA (22.0)
Non-systematic Assessment
EG0001 events1 affected41 at risk
EG0010 events0 affected8 at risk
EG0020 events0 affected58 at risk
EG003
Ileus
Gastrointestinal disorders
MedDRA (22.0)
Non-systematic Assessment
EG0001 events1 affected41 at risk
EG0010 events0 affected8 at risk
EG0021 events1 affected58 at risk
EG003
Lower gastrointestinal hemorrhage
Gastrointestinal disorders
MedDRA (22.0)
Non-systematic Assessment
EG0001 events1 affected41 at risk
EG0010 events0 affected8 at risk
EG0020 events0 affected58 at risk
EG003
Nausea
Gastrointestinal disorders
MedDRA (22.0)
Non-systematic Assessment
EG0000 events0 affected41 at risk
EG0011 events1 affected8 at risk
EG0021 events1 affected58 at risk
EG003
Obstruction gastric
Gastrointestinal disorders
MedDRA (22.0)
Non-systematic Assessment
EG0000 events0 affected41 at risk
EG0010 events0 affected8 at risk
EG0020 events0 affected58 at risk
EG003
Gastrointestinal disorders - Other
Gastrointestinal disorders
MedDRA (22.0)
Non-systematic Assessment
EG0001 events1 affected41 at risk
EG0010 events0 affected8 at risk
EG0020 events0 affected58 at risk
EG003
Peritoneal necrosis
Gastrointestinal disorders
MedDRA (22.0)
Non-systematic Assessment
EG0001 events1 affected41 at risk
EG0010 events0 affected8 at risk
EG0020 events0 affected58 at risk
EG003
Retroperitoneal hemorrhage
Gastrointestinal disorders
MedDRA (22.0)
Non-systematic Assessment
EG0000 events0 affected41 at risk
EG0010 events0 affected8 at risk
EG0020 events0 affected58 at risk
EG003
Small intestinal obstruction
Gastrointestinal disorders
MedDRA (22.0)
Non-systematic Assessment
EG0000 events0 affected41 at risk
EG0010 events0 affected8 at risk
EG0020 events0 affected58 at risk
EG003
Upper gastrointestinal hemorrhage
Gastrointestinal disorders
MedDRA (22.0)
Non-systematic Assessment
EG0000 events0 affected41 at risk
EG0010 events0 affected8 at risk
EG0020 events0 affected58 at risk
EG003
Vomiting
Gastrointestinal disorders
MedDRA (22.0)
Non-systematic Assessment
EG0000 events0 affected41 at risk
EG0010 events0 affected8 at risk
EG0021 events1 affected58 at risk
EG003
Death NOS
General disorders
MedDRA (22.0)
Non-systematic Assessment
EG0001 events1 affected41 at risk
EG0012 events2 affected8 at risk
EG0021 events1 affected58 at risk
EG003
Edema limbs
General disorders
MedDRA (22.0)
Non-systematic Assessment
EG0000 events0 affected41 at risk
EG0010 events0 affected8 at risk
EG0022 events1 affected58 at risk
EG003
Fatigue
General disorders
MedDRA (22.0)
Non-systematic Assessment
EG0004 events2 affected41 at risk
EG0012 events1 affected8 at risk
EG0022 events2 affected58 at risk
EG003
Fever
General disorders
MedDRA (22.0)
Non-systematic Assessment
EG0001 events1 affected41 at risk
EG0010 events0 affected8 at risk
EG0022 events2 affected58 at risk
EG003
Malaise
General disorders
MedDRA (22.0)
Non-systematic Assessment
EG0001 events1 affected41 at risk
EG0010 events0 affected8 at risk
EG0020 events0 affected58 at risk
EG003
Multi-organ failure
General disorders
MedDRA (22.0)
Non-systematic Assessment
EG0000 events0 affected41 at risk
EG0010 events0 affected8 at risk
EG0021 events1 affected58 at risk
EG003
Non-cardiac chest pain
General disorders
MedDRA (22.0)
Non-systematic Assessment
EG0000 events0 affected41 at risk
EG0011 events1 affected8 at risk
EG0020 events0 affected58 at risk
EG003
General disorders and administration site conditions - Other
General disorders
MedDRA (22.0)
Non-systematic Assessment
EG0001 events1 affected41 at risk
EG0011 events1 affected8 at risk
EG0023 events2 affected58 at risk
EG003
Pain
General disorders
MedDRA (22.0)
Non-systematic Assessment
EG0001 events1 affected41 at risk
EG0010 events0 affected8 at risk
EG0023 events2 affected58 at risk
EG003
Bile duct stenosis
Hepatobiliary disorders
MedDRA (22.0)
Non-systematic Assessment
EG0000 events0 affected41 at risk
EG0010 events0 affected8 at risk
EG0021 events1 affected58 at risk
EG003
Cholecystitis
Hepatobiliary disorders
MedDRA (22.0)
Non-systematic Assessment
EG0000 events0 affected41 at risk
EG0010 events0 affected8 at risk
EG0020 events0 affected58 at risk
EG003
Hepatic failure
Hepatobiliary disorders
MedDRA (22.0)
Non-systematic Assessment
EG0002 events1 affected41 at risk
EG0010 events0 affected8 at risk
EG0021 events1 affected58 at risk
EG003
Hepatic hemorrhage
Hepatobiliary disorders
MedDRA (22.0)
Non-systematic Assessment
EG0000 events0 affected41 at risk
EG0010 events0 affected8 at risk
EG0020 events0 affected58 at risk
EG003
Hepatobiliary disorders - Other
Hepatobiliary disorders
MedDRA (22.0)
Non-systematic Assessment
EG0000 events0 affected41 at risk
EG0011 events1 affected8 at risk
EG0021 events1 affected58 at risk
EG003
Portal vein thrombosis
Hepatobiliary disorders
MedDRA (22.0)
Non-systematic Assessment
EG0000 events0 affected41 at risk
EG0010 events0 affected8 at risk
EG0021 events1 affected58 at risk
EG003
Alanine aminotransferase increased
Investigations
MedDRA (22.0)
Non-systematic Assessment
EG0000 events0 affected41 at risk
EG0010 events0 affected8 at risk
EG0022 events1 affected58 at risk
EG003
Aspartate aminotransferase increased
Investigations
MedDRA (22.0)
Non-systematic Assessment
EG0000 events0 affected41 at risk
EG0010 events0 affected8 at risk
EG0021 events1 affected58 at risk
EG003
Blood bilirubin increased
Investigations
MedDRA (22.0)
Non-systematic Assessment
EG0000 events0 affected41 at risk
EG0010 events0 affected8 at risk
EG0022 events2 affected58 at risk
EG003
Creatinine increased
Investigations
MedDRA (22.0)
Non-systematic Assessment
EG0002 events1 affected41 at risk
EG0010 events0 affected8 at risk
EG0020 events0 affected58 at risk
EG003
INR increased
Investigations
MedDRA (22.0)
Non-systematic Assessment
EG0000 events0 affected41 at risk
EG0010 events0 affected8 at risk
EG0020 events0 affected58 at risk
EG003
Neutrophil count decreased
Investigations
MedDRA (22.0)
Non-systematic Assessment
EG0000 events0 affected41 at risk
EG0010 events0 affected8 at risk
EG0021 events1 affected58 at risk
EG003
Investigations - Other
Investigations
MedDRA (22.0)
Non-systematic Assessment
EG0001 events1 affected41 at risk
EG0010 events0 affected8 at risk
EG0020 events0 affected58 at risk
EG003
Platelet count decreased
Investigations
MedDRA (22.0)
Non-systematic Assessment
EG0000 events0 affected41 at risk
EG0010 events0 affected8 at risk
EG0022 events1 affected58 at risk
EG003
Abdominal infection
Infections and infestations
MedDRA (22.0)
Non-systematic Assessment
EG0001 events1 affected41 at risk
EG0010 events0 affected8 at risk
EG0020 events0 affected58 at risk
EG003
Appendicitis
Infections and infestations
MedDRA (22.0)
Non-systematic Assessment
EG0000 events0 affected41 at risk
EG0010 events0 affected8 at risk
EG0020 events0 affected58 at risk
EG003
Bronchial infection
Infections and infestations
MedDRA (22.0)
Non-systematic Assessment
EG0000 events0 affected41 at risk
EG0010 events0 affected8 at risk
EG0020 events0 affected58 at risk
EG003
Catheter related infection
Infections and infestations
MedDRA (22.0)
Non-systematic Assessment
EG0000 events0 affected41 at risk
EG0010 events0 affected8 at risk
EG0022 events1 affected58 at risk
EG003
Enterocolitis infectious
Infections and infestations
MedDRA (22.0)
Non-systematic Assessment
EG0000 events0 affected41 at risk
EG0010 events0 affected8 at risk
EG0023 events2 affected58 at risk
EG003
Lung infection
Infections and infestations
MedDRA (22.0)
Non-systematic Assessment
EG0000 events0 affected41 at risk
EG0010 events0 affected8 at risk
EG0021 events1 affected58 at risk
EG003
Infections and infestations - Other
Infections and infestations
MedDRA (22.0)
Non-systematic Assessment
EG0001 events1 affected41 at risk
EG0010 events0 affected8 at risk
EG0024 events4 affected58 at risk
EG003
Sepsis
Infections and infestations
MedDRA (22.0)
Non-systematic Assessment
EG0000 events0 affected41 at risk
EG0010 events0 affected8 at risk
EG0022 events2 affected58 at risk
EG003
Upper respiratory infection
Infections and infestations
MedDRA (22.0)
Non-systematic Assessment
EG0000 events0 affected41 at risk
EG0010 events0 affected8 at risk
EG0020 events0 affected58 at risk
EG003
Urinary tract infection
Infections and infestations
MedDRA (22.0)
Non-systematic Assessment
EG0000 events0 affected41 at risk
EG0010 events0 affected8 at risk
EG0020 events0 affected58 at risk
EG003
Wound infection
Infections and infestations
MedDRA (22.0)
Non-systematic Assessment
EG0001 events1 affected41 at risk
EG0010 events0 affected8 at risk
EG0020 events0 affected58 at risk
EG003
Fracture
Injury, poisoning and procedural complications
MedDRA (22.0)
Non-systematic Assessment
EG0000 events0 affected41 at risk
EG0010 events0 affected8 at risk
EG0022 events1 affected58 at risk
EG003
Hip fracture
Injury, poisoning and procedural complications
MedDRA (22.0)
Non-systematic Assessment
EG0000 events0 affected41 at risk
EG0010 events0 affected8 at risk
EG0021 events1 affected58 at risk
EG003
Acidosis
Metabolism and nutrition disorders
MedDRA (22.0)
Non-systematic Assessment
EG0001 events1 affected41 at risk
EG0010 events0 affected8 at risk
EG0020 events0 affected58 at risk
EG003
Anorexia
Metabolism and nutrition disorders
MedDRA (22.0)
Non-systematic Assessment
EG0001 events1 affected41 at risk
EG0010 events0 affected8 at risk
EG0020 events0 affected58 at risk
EG003
Dehydration
Metabolism and nutrition disorders
MedDRA (22.0)
Non-systematic Assessment
EG0000 events0 affected41 at risk
EG0011 events1 affected8 at risk
EG0020 events0 affected58 at risk
EG003
Hyperglycemia
Metabolism and nutrition disorders
MedDRA (22.0)
Non-systematic Assessment
EG0000 events0 affected41 at risk
EG0011 events1 affected8 at risk
EG0020 events0 affected58 at risk
EG003
Hyperkalemia
Metabolism and nutrition disorders
MedDRA (22.0)
Non-systematic Assessment
EG0003 events1 affected41 at risk
EG0010 events0 affected8 at risk
EG0020 events0 affected58 at risk
EG003
Back pain
Musculoskeletal and connective tissue disorders
MedDRA (22.0)
Non-systematic Assessment
EG0000 events0 affected41 at risk
EG0010 events0 affected8 at risk
EG0022 events2 affected58 at risk
EG003
Generalized muscle weakness
Musculoskeletal and connective tissue disorders
MedDRA (22.0)
Non-systematic Assessment
EG0000 events0 affected41 at risk
EG0010 events0 affected8 at risk
EG0020 events0 affected58 at risk
EG003
Musculoskeletal and connective tissue disorder - Other
Musculoskeletal and connective tissue disorders
MedDRA (22.0)
Non-systematic Assessment
EG0000 events0 affected41 at risk
EG0010 events0 affected8 at risk
EG0021 events1 affected58 at risk
EG003
Muscle weakness right-sided
Musculoskeletal and connective tissue disorders
MedDRA (22.0)
Non-systematic Assessment
EG0001 events1 affected41 at risk
EG0010 events0 affected8 at risk
EG0020 events0 affected58 at risk
EG003
Amnesia
Nervous system disorders
MedDRA (22.0)
Non-systematic Assessment
EG0000 events0 affected41 at risk
EG0010 events0 affected8 at risk
EG0020 events0 affected58 at risk
EG003
Hypoglossal nerve disorder
Nervous system disorders
MedDRA (22.0)
Non-systematic Assessment
EG0001 events1 affected41 at risk
EG0010 events0 affected8 at risk
EG0020 events0 affected58 at risk
EG003
Intracranial hemorrhage
Nervous system disorders
MedDRA (22.0)
Non-systematic Assessment
EG0000 events0 affected41 at risk
EG0010 events0 affected8 at risk
EG0020 events0 affected58 at risk
EG003
Nervous system disorders - Other
Nervous system disorders
MedDRA (22.0)
Non-systematic Assessment
EG0000 events0 affected41 at risk
EG0010 events0 affected8 at risk
EG0022 events2 affected58 at risk
EG003
Paresthesia
Nervous system disorders
MedDRA (22.0)
Non-systematic Assessment
EG0001 events1 affected41 at risk
EG0010 events0 affected8 at risk
EG0020 events0 affected58 at risk
EG003
Reversible posterior leukoencephalopathy syndrome
Nervous system disorders
MedDRA (22.0)
Non-systematic Assessment
EG0001 events1 affected41 at risk
EG0010 events0 affected8 at risk
EG0020 events0 affected58 at risk
EG003
Somnolence
Nervous system disorders
MedDRA (22.0)
Non-systematic Assessment
EG0001 events1 affected41 at risk
EG0010 events0 affected8 at risk
EG0020 events0 affected58 at risk
EG003
Stroke
Nervous system disorders
MedDRA (22.0)
Non-systematic Assessment
EG0000 events0 affected41 at risk
EG0010 events0 affected8 at risk
EG0021 events1 affected58 at risk
EG003
Transient ischemic attacks
Nervous system disorders
MedDRA (22.0)
Non-systematic Assessment
EG0000 events0 affected41 at risk
EG0010 events0 affected8 at risk
EG0020 events0 affected58 at risk
EG003
Neoplasms benign, malignant and unspecified (incl cysts and polyps) - Other
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
MedDRA (22.0)
Non-systematic Assessment
EG0001 events1 affected41 at risk
EG0010 events0 affected8 at risk
EG0023 events3 affected58 at risk
EG003
Tumor pain
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
MedDRA (22.0)
Non-systematic Assessment
EG0000 events0 affected41 at risk
EG0010 events0 affected8 at risk
EG0024 events2 affected58 at risk
EG003
Eye disorders - Other
Eye disorders
MedDRA (22.0)
Non-systematic Assessment
EG0000 events0 affected41 at risk
EG0010 events0 affected8 at risk
EG0021 events1 affected58 at risk
EG003
Confusion
Psychiatric disorders
MedDRA (22.0)
Non-systematic Assessment
EG0000 events0 affected41 at risk
EG0010 events0 affected8 at risk
EG0021 events1 affected58 at risk
EG003
Mania
Psychiatric disorders
MedDRA (22.0)
Non-systematic Assessment
EG0000 events0 affected41 at risk
EG0014 events1 affected8 at risk
EG0020 events0 affected58 at risk
EG003
Psychiatric disorders - Other
Psychiatric disorders
MedDRA (22.0)
Non-systematic Assessment
EG0001 events1 affected41 at risk
EG0010 events0 affected8 at risk
EG0020 events0 affected58 at risk
EG003
Adult respiratory distress syndrome
Respiratory, thoracic and mediastinal disorders
MedDRA (22.0)
Non-systematic Assessment
EG0000 events0 affected41 at risk
EG0010 events0 affected8 at risk
EG0020 events0 affected58 at risk
EG003
Dyspnea
Respiratory, thoracic and mediastinal disorders
MedDRA (22.0)
Non-systematic Assessment
EG0001 events1 affected41 at risk
EG0010 events0 affected8 at risk
EG0020 events0 affected58 at risk
EG003
Pleural effusion
Respiratory, thoracic and mediastinal disorders
MedDRA (22.0)
Non-systematic Assessment
EG0000 events0 affected41 at risk
EG0010 events0 affected8 at risk
EG0020 events0 affected58 at risk
EG003
Pneumonitis
Respiratory, thoracic and mediastinal disorders
MedDRA (22.0)
Non-systematic Assessment
EG0001 events1 affected41 at risk
EG0010 events0 affected8 at risk
EG0020 events0 affected58 at risk
EG003
Respiratory failure
Respiratory, thoracic and mediastinal disorders
MedDRA (22.0)
Non-systematic Assessment
EG0000 events0 affected41 at risk
EG0010 events0 affected8 at risk
EG0020 events0 affected58 at risk
EG003
Acute kidney injury
Renal and urinary disorders
MedDRA (22.0)
Non-systematic Assessment
EG0002 events2 affected41 at risk
EG0010 events0 affected8 at risk
EG0022 events1 affected58 at risk
EG003
Renal and urinary disorders - Other
Renal and urinary disorders
MedDRA (22.0)
Non-systematic Assessment
EG0000 events0 affected41 at risk
EG0010 events0 affected8 at risk
EG0020 events0 affected58 at risk
EG003
Renal colic
Renal and urinary disorders
MedDRA (22.0)
Non-systematic Assessment
EG0000 events0 affected41 at risk
EG0010 events0 affected8 at risk
EG0020 events0 affected58 at risk
EG003
Urinary retention
Renal and urinary disorders
MedDRA (22.0)
Non-systematic Assessment
EG0001 events1 affected41 at risk
EG0010 events0 affected8 at risk
EG0020 events0 affected58 at risk
EG003
Rash maculo-papular
Skin and subcutaneous tissue disorders
MedDRA (22.0)
Non-systematic Assessment
EG0000 events0 affected41 at risk
EG0010 events0 affected8 at risk
EG0021 events1 affected58 at risk
EG003
Surgical and medical procedures - Other
Surgical and medical procedures
MedDRA (22.0)
Non-systematic Assessment
EG0000 events0 affected41 at risk
EG0010 events0 affected8 at risk
EG0021 events1 affected58 at risk
EG003
Hypertension
Vascular disorders
MedDRA (22.0)
Non-systematic Assessment
EG0001 events1 affected41 at risk
EG0010 events0 affected8 at risk
EG0020 events0 affected58 at risk
EG003
Vascular disorders - Other
Vascular disorders
MedDRA (22.0)
Non-systematic Assessment
EG0000 events0 affected41 at risk
EG0010 events0 affected8 at risk
EG0020 events0 affected58 at risk
EG003
Peripheral ischemia
Vascular disorders
MedDRA (22.0)
Non-systematic Assessment
EG0000 events0 affected41 at risk
EG0010 events0 affected8 at risk
EG0020 events0 affected58 at risk
EG003
Thromboembolic event
Vascular disorders
MedDRA (22.0)
Non-systematic Assessment
EG0001 events1 affected41 at risk
EG0010 events0 affected8 at risk
EG0022 events1 affected58 at risk
EG003
Other Adverse Events
Term
Organ System
Source Vocabulary
Assessment Type
Notes
Statistical Information
Hearing impaired
Ear and labyrinth disorders
MedDRA (22.0)
Non-systematic Assessment
EG0001 events1 affected41 at risk
EG0010 events0 affected8 at risk
EG0021 events1 affected58 at risk
EG0037 events7 affected190 at risk
EG0045 events5 affected75 at risk
Ear and labyrinth disorders - Other
Ear and labyrinth disorders
MedDRA (22.0)
Non-systematic Assessment
EG0000 events0 affected41 at risk
EG0010 events0 affected8 at risk
EG0024 events4 affected58 at risk
EG003
Anemia
Blood and lymphatic system disorders
MedDRA (22.0)
Non-systematic Assessment
EG0007 events4 affected41 at risk
EG0010 events0 affected8 at risk
EG00225 events11 affected58 at risk
EG003
Blood and lymphatic system disorders - Other
Blood and lymphatic system disorders
MedDRA (22.0)
Non-systematic Assessment
EG0000 events0 affected41 at risk
EG0010 events0 affected8 at risk
EG0029 events2 affected58 at risk
EG003
Hypothyroidism
Endocrine disorders
MedDRA (22.0)
Non-systematic Assessment
EG0004 events4 affected41 at risk
EG0010 events0 affected8 at risk
EG0026 events6 affected58 at risk
EG003
Abdominal pain
Gastrointestinal disorders
MedDRA (22.0)
Non-systematic Assessment
EG00018 events14 affected41 at risk
EG0010 events0 affected8 at risk
EG00223 events16 affected58 at risk
EG003
Ascites
Gastrointestinal disorders
MedDRA (22.0)
Non-systematic Assessment
EG0002 events2 affected41 at risk
EG0011 events1 affected8 at risk
EG0022 events2 affected58 at risk
EG003
Bloating
Gastrointestinal disorders
MedDRA (22.0)
Non-systematic Assessment
EG0000 events0 affected41 at risk
EG0010 events0 affected8 at risk
EG0021 events1 affected58 at risk
EG003
Constipation
Gastrointestinal disorders
MedDRA (22.0)
Non-systematic Assessment
EG00014 events10 affected41 at risk
EG0016 events5 affected8 at risk
EG00230 events16 affected58 at risk
EG003
Diarrhea
Gastrointestinal disorders
MedDRA (22.0)
Non-systematic Assessment
EG00020 events15 affected41 at risk
EG0011 events1 affected8 at risk
EG00267 events24 affected58 at risk
EG003
Dyspepsia
Gastrointestinal disorders
MedDRA (22.0)
Non-systematic Assessment
EG0004 events4 affected41 at risk
EG0012 events1 affected8 at risk
EG0029 events6 affected58 at risk
EG003
Dry mouth
Gastrointestinal disorders
MedDRA (22.0)
Non-systematic Assessment
EG0005 events5 affected41 at risk
EG0010 events0 affected8 at risk
EG0026 events5 affected58 at risk
EG003
Flatulence
Gastrointestinal disorders
MedDRA (22.0)
Non-systematic Assessment
EG0004 events4 affected41 at risk
EG0010 events0 affected8 at risk
EG0023 events3 affected58 at risk
EG003
Mucositis oral
Gastrointestinal disorders
MedDRA (22.0)
Non-systematic Assessment
EG00018 events14 affected41 at risk
EG0013 events2 affected8 at risk
EG00248 events21 affected58 at risk
EG003
Nausea
Gastrointestinal disorders
MedDRA (22.0)
Non-systematic Assessment
EG00012 events9 affected41 at risk
EG0014 events3 affected8 at risk
EG00233 events18 affected58 at risk
EG003
Gastrointestinal disorders - Other
Gastrointestinal disorders
MedDRA (22.0)
Non-systematic Assessment
EG0004 events4 affected41 at risk
EG0010 events0 affected8 at risk
EG0027 events4 affected58 at risk
EG003
Stomach pain
Gastrointestinal disorders
MedDRA (22.0)
Non-systematic Assessment
EG0000 events0 affected41 at risk
EG0010 events0 affected8 at risk
EG0022 events2 affected58 at risk
EG003
Vomiting
Gastrointestinal disorders
MedDRA (22.0)
Non-systematic Assessment
EG00011 events10 affected41 at risk
EG0015 events3 affected8 at risk
EG00224 events12 affected58 at risk
EG003
Chills
General disorders
MedDRA (22.0)
Non-systematic Assessment
EG0001 events1 affected41 at risk
EG0010 events0 affected8 at risk
EG0024 events4 affected58 at risk
EG003
Edema limbs
General disorders
MedDRA (22.0)
Non-systematic Assessment
EG0004 events3 affected41 at risk
EG0013 events3 affected8 at risk
EG00220 events11 affected58 at risk
EG003
Fatigue
General disorders
MedDRA (22.0)
Non-systematic Assessment
EG00032 events18 affected41 at risk
EG0014 events3 affected8 at risk
EG00283 events32 affected58 at risk
EG003
Fever
General disorders
MedDRA (22.0)
Non-systematic Assessment
EG00017 events10 affected41 at risk
EG0011 events1 affected8 at risk
EG00224 events18 affected58 at risk
EG003
Flu like symptoms
General disorders
MedDRA (22.0)
Non-systematic Assessment
EG0001 events1 affected41 at risk
EG0010 events0 affected8 at risk
EG0023 events3 affected58 at risk
EG003
Localized edema
General disorders
MedDRA (22.0)
Non-systematic Assessment
EG0002 events2 affected41 at risk
EG0011 events1 affected8 at risk
EG0025 events3 affected58 at risk
EG003
Non-cardiac chest pain
General disorders
MedDRA (22.0)
Non-systematic Assessment
EG0000 events0 affected41 at risk
EG0010 events0 affected8 at risk
EG0021 events1 affected58 at risk
EG003
General disorders and administration site conditions - Other
General disorders
MedDRA (22.0)
Non-systematic Assessment
EG0001 events1 affected41 at risk
EG0010 events0 affected8 at risk
EG0025 events4 affected58 at risk
EG003
Pain
General disorders
MedDRA (22.0)
Non-systematic Assessment
EG0008 events5 affected41 at risk
EG0011 events1 affected8 at risk
EG00246 events19 affected58 at risk
EG003
Alanine aminotransferase increased
Investigations
MedDRA (22.0)
Non-systematic Assessment
EG0009 events4 affected41 at risk
EG0012 events1 affected8 at risk
EG00215 events6 affected58 at risk
EG003
Alkaline phosphatase increased
Investigations
MedDRA (22.0)
Non-systematic Assessment
EG0001 events1 affected41 at risk
EG0011 events1 affected8 at risk
EG0026 events3 affected58 at risk
EG003
Aspartate aminotransferase increased
Investigations
MedDRA (22.0)
Non-systematic Assessment
EG0009 events4 affected41 at risk
EG0012 events2 affected8 at risk
EG00215 events8 affected58 at risk
EG003
Blood bilirubin increased
Investigations
MedDRA (22.0)
Non-systematic Assessment
EG0006 events4 affected41 at risk
EG0013 events1 affected8 at risk
EG00215 events9 affected58 at risk
EG003
GGT increased
Investigations
MedDRA (22.0)
Non-systematic Assessment
EG0000 events0 affected41 at risk
EG0012 events1 affected8 at risk
EG0022 events2 affected58 at risk
EG003
Lipase increased
Investigations
MedDRA (22.0)
Non-systematic Assessment
EG0001 events1 affected41 at risk
EG0010 events0 affected8 at risk
EG00211 events3 affected58 at risk
EG003
Neutrophil count decreased
Investigations
MedDRA (22.0)
Non-systematic Assessment
EG0000 events0 affected41 at risk
EG0010 events0 affected8 at risk
EG0028 events6 affected58 at risk
EG003
Investigations - Other
Investigations
MedDRA (22.0)
Non-systematic Assessment
EG0000 events0 affected41 at risk
EG0010 events0 affected8 at risk
EG00214 events2 affected58 at risk
EG003
Platelet count decreased
Investigations
MedDRA (22.0)
Non-systematic Assessment
EG0005 events1 affected41 at risk
EG0010 events0 affected8 at risk
EG00225 events6 affected58 at risk
EG003
White blood cell decreased
Investigations
MedDRA (22.0)
Non-systematic Assessment
EG0000 events0 affected41 at risk
EG0010 events0 affected8 at risk
EG0022 events2 affected58 at risk
EG003
Weight gain
Investigations
MedDRA (22.0)
Non-systematic Assessment
EG0000 events0 affected41 at risk
EG0011 events1 affected8 at risk
EG0023 events2 affected58 at risk
EG003
Weight loss
Investigations
MedDRA (22.0)
Non-systematic Assessment
EG0005 events4 affected41 at risk
EG0012 events2 affected8 at risk
EG00220 events11 affected58 at risk
EG003
Allergic reaction
Immune system disorders
MedDRA (22.0)
Non-systematic Assessment
EG0000 events0 affected41 at risk
EG0010 events0 affected8 at risk
EG0021 events1 affected58 at risk
EG003
Bronchial infection
Infections and infestations
MedDRA (22.0)
Non-systematic Assessment
EG0000 events0 affected41 at risk
EG0010 events0 affected8 at risk
EG0024 events4 affected58 at risk
EG003
Infections and infestations - Other
Infections and infestations
MedDRA (22.0)
Non-systematic Assessment
EG0003 events2 affected41 at risk
EG0010 events0 affected8 at risk
EG0027 events5 affected58 at risk
EG003
Rash pustular
Infections and infestations
MedDRA (22.0)
Non-systematic Assessment
EG0002 events2 affected41 at risk
EG0010 events0 affected8 at risk
EG00217 events2 affected58 at risk
EG003
Sinusitis
Infections and infestations
MedDRA (22.0)
Non-systematic Assessment
EG0001 events1 affected41 at risk
EG0010 events0 affected8 at risk
EG0021 events1 affected58 at risk
EG003
Skin infection
Infections and infestations
MedDRA (22.0)
Non-systematic Assessment
EG0000 events0 affected41 at risk
EG0010 events0 affected8 at risk
EG0024 events3 affected58 at risk
EG003
Tooth infection
Infections and infestations
MedDRA (22.0)
Non-systematic Assessment
EG0000 events0 affected41 at risk
EG0010 events0 affected8 at risk
EG0021 events1 affected58 at risk
EG003
Upper respiratory infection
Infections and infestations
MedDRA (22.0)
Non-systematic Assessment
EG0000 events0 affected41 at risk
EG0010 events0 affected8 at risk
EG00212 events9 affected58 at risk
EG003
Urinary tract infection
Infections and infestations
MedDRA (22.0)
Non-systematic Assessment
EG0003 events2 affected41 at risk
EG0010 events0 affected8 at risk
EG0024 events2 affected58 at risk
EG003
Anorexia
Metabolism and nutrition disorders
MedDRA (22.0)
Non-systematic Assessment
EG00021 events15 affected41 at risk
EG0015 events3 affected8 at risk
EG00242 events20 affected58 at risk
EG003
Dehydration
Metabolism and nutrition disorders
MedDRA (22.0)
Non-systematic Assessment
EG0000 events0 affected41 at risk
EG0011 events1 affected8 at risk
EG0025 events5 affected58 at risk
EG003
Hypoalbuminemia
Metabolism and nutrition disorders
MedDRA (22.0)
Non-systematic Assessment
EG0002 events2 affected41 at risk
EG0010 events0 affected8 at risk
EG0023 events3 affected58 at risk
EG003
Hypocalcemia
Metabolism and nutrition disorders
MedDRA (22.0)
Non-systematic Assessment
EG0002 events1 affected41 at risk
EG0010 events0 affected8 at risk
EG0028 events3 affected58 at risk
EG003
Hypokalemia
Metabolism and nutrition disorders
MedDRA (22.0)
Non-systematic Assessment
EG0000 events0 affected41 at risk
EG0010 events0 affected8 at risk
EG00218 events12 affected58 at risk
EG003
Hyponatremia
Metabolism and nutrition disorders
MedDRA (22.0)
Non-systematic Assessment
EG0000 events0 affected41 at risk
EG0012 events2 affected8 at risk
EG0024 events3 affected58 at risk
EG003
Hypophosphatemia
Metabolism and nutrition disorders
MedDRA (22.0)
Non-systematic Assessment
EG0001 events1 affected41 at risk
EG0010 events0 affected8 at risk
EG0021 events1 affected58 at risk
EG003
Hypercalcemia
Metabolism and nutrition disorders
MedDRA (22.0)
Non-systematic Assessment
EG0000 events0 affected41 at risk
EG0011 events1 affected8 at risk
EG0023 events3 affected58 at risk
EG003
Hyperglycemia
Metabolism and nutrition disorders
MedDRA (22.0)
Non-systematic Assessment
EG0003 events1 affected41 at risk
EG0010 events0 affected8 at risk
EG0025 events5 affected58 at risk
EG003
Hyperuricemia
Metabolism and nutrition disorders
MedDRA (22.0)
Non-systematic Assessment
EG0001 events1 affected41 at risk
EG0011 events1 affected8 at risk
EG0022 events2 affected58 at risk
EG003
Arthralgia
Musculoskeletal and connective tissue disorders
MedDRA (22.0)
Non-systematic Assessment
EG0001 events1 affected41 at risk
EG0010 events0 affected8 at risk
EG0027 events4 affected58 at risk
EG003
Back pain
Musculoskeletal and connective tissue disorders
MedDRA (22.0)
Non-systematic Assessment
EG0002 events2 affected41 at risk
EG0011 events1 affected8 at risk
EG0026 events4 affected58 at risk
EG003
Bone pain
Musculoskeletal and connective tissue disorders
MedDRA (22.0)
Non-systematic Assessment
EG0000 events0 affected41 at risk
EG0010 events0 affected8 at risk
EG0023 events1 affected58 at risk
EG003
Flank pain
Musculoskeletal and connective tissue disorders
MedDRA (22.0)
Non-systematic Assessment
EG0000 events0 affected41 at risk
EG0010 events0 affected8 at risk
EG0021 events1 affected58 at risk
EG003
Generalized muscle weakness
Musculoskeletal and connective tissue disorders
MedDRA (22.0)
Non-systematic Assessment
EG0001 events1 affected41 at risk
EG0011 events1 affected8 at risk
EG0027 events4 affected58 at risk
EG003
Myalgia
Musculoskeletal and connective tissue disorders
MedDRA (22.0)
Non-systematic Assessment
EG0005 events5 affected41 at risk
EG0013 events3 affected8 at risk
EG00217 events10 affected58 at risk
EG003
Neck pain
Musculoskeletal and connective tissue disorders
MedDRA (22.0)
Non-systematic Assessment
EG0000 events0 affected41 at risk
EG0011 events1 affected8 at risk
EG0020 events0 affected58 at risk
EG003
Musculoskeletal and connective tissue disorder - Other
Musculoskeletal and connective tissue disorders
MedDRA (22.0)
Non-systematic Assessment
EG0001 events1 affected41 at risk
EG0010 events0 affected8 at risk
EG0025 events4 affected58 at risk
EG003
Pain in extremity
Musculoskeletal and connective tissue disorders
MedDRA (22.0)
Non-systematic Assessment
EG0005 events5 affected41 at risk
EG0012 events1 affected8 at risk
EG00215 events7 affected58 at risk
EG003
Dizziness
Nervous system disorders
MedDRA (22.0)
Non-systematic Assessment
EG0000 events0 affected41 at risk
EG0011 events1 affected8 at risk
EG0021 events1 affected58 at risk
EG003
Dysgeusia
Nervous system disorders
MedDRA (22.0)
Non-systematic Assessment
EG0002 events2 affected41 at risk
EG0010 events0 affected8 at risk
EG0024 events4 affected58 at risk
EG003
Headache
Nervous system disorders
MedDRA (22.0)
Non-systematic Assessment
EG0004 events4 affected41 at risk
EG0010 events0 affected8 at risk
EG00221 events11 affected58 at risk
EG003
Paresthesia
Nervous system disorders
MedDRA (22.0)
Non-systematic Assessment
EG0000 events0 affected41 at risk
EG0010 events0 affected8 at risk
EG0025 events3 affected58 at risk
EG003
Peripheral sensory neuropathy
Nervous system disorders
MedDRA (22.0)
Non-systematic Assessment
EG0007 events5 affected41 at risk
EG0010 events0 affected8 at risk
EG0028 events4 affected58 at risk
EG003
Somnolence
Nervous system disorders
MedDRA (22.0)
Non-systematic Assessment
EG0000 events0 affected41 at risk
EG0011 events1 affected8 at risk
EG0020 events0 affected58 at risk
EG003
Tumor pain
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
MedDRA (22.0)
Non-systematic Assessment
EG0002 events1 affected41 at risk
EG0011 events1 affected8 at risk
EG0024 events3 affected58 at risk
EG003
Blurred vision
Eye disorders
MedDRA (22.0)
Non-systematic Assessment
EG0000 events0 affected41 at risk
EG0010 events0 affected8 at risk
EG0022 events2 affected58 at risk
EG003
Eye disorders - Other
Eye disorders
MedDRA (22.0)
Non-systematic Assessment
EG0000 events0 affected41 at risk
EG0010 events0 affected8 at risk
EG0021 events1 affected58 at risk
EG003
Anxiety
Psychiatric disorders
MedDRA (22.0)
Non-systematic Assessment
EG0004 events4 affected41 at risk
EG0010 events0 affected8 at risk
EG0024 events3 affected58 at risk
EG003
Confusion
Psychiatric disorders
MedDRA (22.0)
Non-systematic Assessment
EG0000 events0 affected41 at risk
EG0011 events1 affected8 at risk
EG0021 events1 affected58 at risk
EG003
Depression
Psychiatric disorders
MedDRA (22.0)
Non-systematic Assessment
EG0002 events2 affected41 at risk
EG0010 events0 affected8 at risk
EG0022 events2 affected58 at risk
EG003
Insomnia
Psychiatric disorders
MedDRA (22.0)
Non-systematic Assessment
EG0003 events3 affected41 at risk
EG0011 events1 affected8 at risk
EG0024 events3 affected58 at risk
EG003
Cough
Respiratory, thoracic and mediastinal disorders
MedDRA (22.0)
Non-systematic Assessment
EG0001 events1 affected41 at risk
EG0011 events1 affected8 at risk
EG00218 events11 affected58 at risk
EG003
Dyspnea
Respiratory, thoracic and mediastinal disorders
MedDRA (22.0)
Non-systematic Assessment
EG0006 events4 affected41 at risk
EG0010 events0 affected8 at risk
EG0029 events7 affected58 at risk
EG003
Epistaxis
Respiratory, thoracic and mediastinal disorders
MedDRA (22.0)
Non-systematic Assessment
EG0000 events0 affected41 at risk
EG0010 events0 affected8 at risk
EG0026 events4 affected58 at risk
EG003
Hiccups
Respiratory, thoracic and mediastinal disorders
MedDRA (22.0)
Non-systematic Assessment
EG0000 events0 affected41 at risk
EG0011 events1 affected8 at risk
EG0020 events0 affected58 at risk
EG003
Hoarseness
Respiratory, thoracic and mediastinal disorders
MedDRA (22.0)
Non-systematic Assessment
EG0008 events8 affected41 at risk
EG0010 events0 affected8 at risk
EG00211 events9 affected58 at risk
EG003
Pneumonitis
Respiratory, thoracic and mediastinal disorders
MedDRA (22.0)
Non-systematic Assessment
EG0000 events0 affected41 at risk
EG0010 events0 affected8 at risk
EG0023 events3 affected58 at risk
EG003
Voice alteration
Respiratory, thoracic and mediastinal disorders
MedDRA (22.0)
Non-systematic Assessment
EG0002 events2 affected41 at risk
EG0011 events1 affected8 at risk
EG00212 events11 affected58 at risk
EG003
Hematuria
Renal and urinary disorders
MedDRA (22.0)
Non-systematic Assessment
EG0001 events1 affected41 at risk
EG0010 events0 affected8 at risk
EG0023 events3 affected58 at risk
EG003
Renal and urinary disorders - Other
Renal and urinary disorders
MedDRA (22.0)
Non-systematic Assessment
EG0003 events3 affected41 at risk
EG0010 events0 affected8 at risk
EG0020 events0 affected58 at risk
EG003
Proteinuria
Renal and urinary disorders
MedDRA (22.0)
Non-systematic Assessment
EG0000 events0 affected41 at risk
EG0010 events0 affected8 at risk
EG00211 events6 affected58 at risk
EG003
Urinary frequency
Renal and urinary disorders
MedDRA (22.0)
Non-systematic Assessment
EG0000 events0 affected41 at risk
EG0010 events0 affected8 at risk
EG0022 events2 affected58 at risk
EG003
Alopecia
Skin and subcutaneous tissue disorders
MedDRA (22.0)
Non-systematic Assessment
EG0009 events7 affected41 at risk
EG0010 events0 affected8 at risk
EG00226 events21 affected58 at risk
EG003
Dry skin
Skin and subcutaneous tissue disorders
MedDRA (22.0)
Non-systematic Assessment
EG0003 events2 affected41 at risk
EG0010 events0 affected8 at risk
EG0023 events2 affected58 at risk
EG003
Erythema multiforme
Skin and subcutaneous tissue disorders
MedDRA (22.0)
Non-systematic Assessment
EG0001 events1 affected41 at risk
EG0010 events0 affected8 at risk
EG0023 events1 affected58 at risk
EG003
Erythroderma
Skin and subcutaneous tissue disorders
MedDRA (22.0)
Non-systematic Assessment
EG0000 events0 affected41 at risk
EG0010 events0 affected8 at risk
EG0025 events4 affected58 at risk
EG003
Hyperhidrosis
Skin and subcutaneous tissue disorders
MedDRA (22.0)
Non-systematic Assessment
EG0000 events0 affected41 at risk
EG0012 events1 affected8 at risk
EG0022 events2 affected58 at risk
EG003
Skin and subcutaneous tissue disorders - Other
Skin and subcutaneous tissue disorders
MedDRA (22.0)
Non-systematic Assessment
EG0003 events3 affected41 at risk
EG0010 events0 affected8 at risk
EG00210 events7 affected58 at risk
EG003
Pain of skin
Skin and subcutaneous tissue disorders
MedDRA (22.0)
Non-systematic Assessment
EG0000 events0 affected41 at risk
EG0010 events0 affected8 at risk
EG0021 events1 affected58 at risk
EG003
Palmar-plantar erythrodysesthesia syndrome
Skin and subcutaneous tissue disorders
MedDRA (22.0)
Non-systematic Assessment
EG00037 events17 affected41 at risk
EG0011 events1 affected8 at risk
EG002151 events39 affected58 at risk
EG003
Pruritus
Skin and subcutaneous tissue disorders
MedDRA (22.0)
Non-systematic Assessment
EG0004 events4 affected41 at risk
EG0012 events1 affected8 at risk
EG0028 events7 affected58 at risk
EG003
Rash acneiform
Skin and subcutaneous tissue disorders
MedDRA (22.0)
Non-systematic Assessment
EG0002 events2 affected41 at risk
EG0010 events0 affected8 at risk
EG0023 events3 affected58 at risk
EG003
Rash maculo-papular
Skin and subcutaneous tissue disorders
MedDRA (22.0)
Non-systematic Assessment
EG0007 events6 affected41 at risk
EG0010 events0 affected8 at risk
EG00210 events8 affected58 at risk
EG003
Hypotension
Vascular disorders
MedDRA (22.0)
Non-systematic Assessment
EG0001 events1 affected41 at risk
EG0010 events0 affected8 at risk
EG0021 events1 affected58 at risk
EG003
Hypertension
Vascular disorders
MedDRA (22.0)
Non-systematic Assessment
EG00032 events18 affected41 at risk
EG0013 events3 affected8 at risk
EG00297 events37 affected58 at risk
EG003
Thromboembolic event
Vascular disorders
MedDRA (22.0)
Non-systematic Assessment
EG0000 events0 affected41 at risk
EG0012 events2 affected8 at risk
EG0021 events1 affected58 at risk
EG003
Overall survival results are confounded by the fact that 85% of the participants initially randomized to placebo switched to open-label regorafenib.
Certain Agreements
Are all PI(s) employees of the sponsor?
No
Restriction Type
GT60
Results Disclosure Restriction on PI(s)?
Yes
Other Details
Not provided
Point of Contact
Title
Organization
Phone
Extension
Email
Therapeutic Area Head
BAYER
clinical-trials-contact@bayer.com
ID
Term
D046152
Gastrointestinal Stromal Tumors
Ancestor Terms
ID
Term
D009372
Neoplasms, Connective Tissue
D018204
Neoplasms, Connective and Soft Tissue
D009370
Neoplasms by Histologic Type
D009369
Neoplasms
D005770
Gastrointestinal Neoplasms
D004067
Digestive System Neoplasms
D004066
Digestive System Diseases
D005767
Gastrointestinal Diseases
Browse Leaves
Not provided
Browse Branches
Not provided
ID
Term
C559147
regorafenib
Ancestor Terms
Not provided
Browse Leaves
Not provided
Browse Branches
Not provided
11 subjects
Physician Decision
FG0002 subjects
FG0010 subjects
Adverse Event
FG00014 subjects
FG0018 subjects
Progressive disease
FG00059 subjects
FG00132 subjects
transferred to rollover study
FG0001 subjects
FG0010 subjects
Non-compliance with study drug
FG0001 subjects
FG0010 subjects
Protocol Violation
FG0000 subjects
FG0011 subjects
Switching to other therapy
FG0002 subjects
FG0011 subjects
2 subjects
Protocol Violation
FG0001 subjects
FG0011 subjects
Not analyzed after cutoff 08Jun2015
FG0003 subjects
FG0014 subjects
No follow-up
FG0001 subjects
FG0011 subjects
Progressive disease
FG0001 subjects
FG0010 subjects
72
Male
BG00085
BG00142
BG002127
37
BG002110
PS 1
BG00060
BG00129
BG00289
PS 2
BG0000
BG0010
BG0020
Missing
BG0000
BG0010
BG0020
39
BG002113
4th line and beyond
BG00059
BG00127
BG00286
OG000
OG001
Hazard ratio and its 95% CI (Confidence Interval) was based on stratified Cox Regression Model
Regression, Cox
stratified
Hazard Ratio (HR)
0.268
2-Sided
95
0.185
0.388
regorafenib over placebo
Superiority or Other (legacy)
Counts
Participants
OG000133
OG00166
Title
Denominators
Categories
Title
Measurements
OG00082.0
OG00180.3
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
Log Rank
stratified
0.285777
Superiority or Other (legacy)
OG000
OG001
Hazard ratio and its 95% CI was based on stratified Cox Regression Model
Regression, Cox
stratified
Hazard Ratio (HR)
0.909
2-Sided
95
0.653
1.265
regorafenib over control. 58 (87.9%) patients in placebo group and 91 (68.4%) patients in regorafenib had started open-label treatment with regorafenib before time of final database cutoff 08 Jun 2015.
Superiority or Other (legacy)
Units
Counts
Participants
OG000133
OG00166
Title
Denominators
Categories
Title
Measurements
OG000165(125 to 174)
OG00128(28 to 34)
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
Log Rank
stratified
<0.000001
Superiority or Other (legacy)
OG000
OG001
Regression, Cox
stratified
Hazard Ratio (HR)
0.248
2-Sided
95
0.170
0.364
Superiority or Other (legacy)
Participants received matching Placebo tablets per os once daily, 3 weeks on therapy followed by 1 week off therapy to comprise a cycle of 4 weeks
Units
Counts
Participants
OG000133
OG00166
Title
Denominators
Categories
Complete Response (CR)
Title
Measurements
OG0000(0 to 0)
OG0010(0 to 0)
Partial Response (PR)
Title
Measurements
OG0004.5(1.7 to 9.6)
OG0011.5(0 to 8.2)
Stable Disease (SD)
Title
Measurements
OG00071.4(63.0 to 78.9)
OG00133.3(22.2 to 46.0)
Progressive Disease (PD)
Title
Measurements
OG00021.1(14.5 to 29.0)
OG00163.6(50.9 to 75.1)
Not Assessable
Title
Measurements
OG0003.0(0.8 to 7.5)
OG0011.5(0 to 8.2)
Counts
Participants
OG000133
OG00166
Title
Denominators
Categories
Title
Measurements
OG0004.5(1.7 to 9.6)
OG0011.5(0.0 to 8.2)
Units
Counts
Participants
OG000133
OG00166
Title
Denominators
Categories
Title
Measurements
OG00052.6(43.8 to 61.3)
OG0019.1(3.4 to 18.7)
Participants received matching Placebo tablets per os once daily, 3 weeks on therapy followed by 1 week off therapy to comprise a cycle of 4 weeks
Units
Counts
Participants
OG0006
OG0011
Title
Denominators
Categories
Title
Measurements
OG00099(42 to NA)A complete confidence interval (CI) cannot be calculated because there are too few patients in the data set.
OG00130(NA to NA)CI cannot be calculated because there is only 1 patient in the data set.