Study of Modified FOLFOX6 Plus or Minus Sorafenib in Stag... | NCT00865709

NCT00865709

ID	Type	Description	Link
2008-005025-11	EudraCT Number

Status Module

Name	Class
Amgen	INDUSTRY

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
Sorafenib (Nexavar, BAY43-9006) + mFOLFOX6	Experimental	Subjects will receive oral Sorafenib 400 mg twice daily (BID) continuously and intravenous (IV) mFOLFOX6 (5-FU 400 mg/m^2 bolus and 2400 mg/m^2 for 46-48 hrs; levo-leucovorin 200 mg/m^2; 85 mg/m^2 oxaliplatin) every 14 days until progressive disease (PD)	Drug: Sorafenib (Nexavar, BAY43-9006) + mFOLFOX6 (5-FU, levo-leucovorin, oxaliplatin)
Matching placebo + mFOLFOX6	Placebo Comparator	Subjects will receive oral matching placebo 2 tablets BID continuously and IV mFOLFOX6 (5-FU 400 mg/m^2 bolus and 2400 mg/m^2 for 46-48 hrs; levo-leucovorin 200 mg/m^2; 85 mg/m^2 oxaliplatin) every 14 days until progressive disease	Drug: Matching placebo + mFOLFOX6 (5-FU, levo-leucovorin, oxaliplatin)

Interventions

Name	Type	Description	Arm Group Labels	Other Names
Sorafenib (Nexavar, BAY43-9006) + mFOLFOX6 (5-FU, levo-leucovorin, oxaliplatin)	Drug	Subjects will receive oral Sorafenib 400 mg twice daily (BID) continuously and intravenous (IV) mFOLFOX6 (5-FU 400 mg/m^2 bolus and 2400 mg/m^2 for 46-48 hrs; levo-leucovorin 200 mg/m^2; 85 mg/m^2 oxaliplatin) every 14 days until progressive disease (PD)

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Progression-Free Survival (PFS)	Progression-free Survival (PFS) was defined as the time from date of randomization to disease progression or death due to any cause, whichever occurred first. Subjects without progression or death at the time of analysis were censored at their last date of tumor evaluation. Disease progression was defined as an increase of at least 20% in the sum of tumor lesions sizes.	From randomization of the first subject until 23 months later, assessed every 8 weeks.

Secondary Outcomes

Measure	Description	Time Frame
Overall Survival (OS)	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 last date of last contact.	From randomization of the first subject until 33 months later.
Time to Progression (TTP)

Eligibility Module

Eligibility Criteria

Inclusion Criteria:

Histological confirmation of adenocarcinoma of the colon or rectum
Tumor tissue sample available for KRAS and BRAF assessment
Measurable metastatic Stage IV disease including at least one measurable lesion that has not previously been radiated
No prior chemotherapy for metastatic CRC
Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 or 1
Life expectancy of at least 12 weeks
Adequate bone marrow, liver, and renal function; adequate clotting parameters

Exclusion Criteria:

Prior treatment with sorafenib
Clinical or radiographic evidence of brain metastasis
Major surgery, surgical biopsy, or significant traumatic injury within 28 days of randomization; evidence or history of bleeding diathesis or coagulopathy
Red blood cell (RBC), white blood cell (WBC), or platelet transfusions and/or growth factor use within 28 days before randomization
Adjuvant therapy for CRC (Stage I, II, or III) completed within 12 months before randomization
Serious, non-healing wound, ulcer, or bone fracture; Grade 3 or 4 hemorrhage within 28 days before randomization
Use of anticoagulation therapy (low dose anticoagulation therapy to mitigate risk of thrombosis due to placement of a semi-permanent central venous port for administration of chemotherapy is allowed. The use of coumadin and related compounds is excluded.)
Uncontrolled hypertension (systolic blood pressure > 150 mmHg or diastolic pressure > 100 mmHg on repeated measurement) despite optimal medical management
Thrombolic, embolic, venous, or arterial events (eg, cerebrovascular accident, including transient ischemic attacks) within 6 months before randomization
Active cardiac disease including:
- Congestive heart failure
- Unstable angina or myocardial infarction within the 6 months before randomization
- Cardiac ventricular arrhythmias requiring antiarrhythmic treatment
Peripheral neuropathy > Grade 1 (CTCAE)
Known HIV infection or chronic hepatitis B or C infection
Any active infection >/= Grade 2 (CTCAE)
Any medical, psychological, or social condition that may interfere with the subject's participation in the study or evaluation of the study results
Use of any investigational drug within 28 days or 5 half-lives of that drug, whichever is longer, before randomization
Subjects with metastatic CRC who are currently candidates for surgery with curative intent

Name	Affiliation	Role
Bayer Study Director	Bayer	Study Director

References Module

Citations

PubMed Identifier	Type	Citation	Retractions
23532888	Result	Tabernero J, Garcia-Carbonero R, Cassidy J, Sobrero A, Van Cutsem E, Kohne CH, Tejpar S, Gladkov O, Davidenko I, Salazar R, Vladimirova L, Cheporov S, Burdaeva O, Rivera F, Samuel L, Bulavina I, Potter V, Chang YL, Lokker NA, O'Dwyer PJ. Sorafenib in combination with oxaliplatin, leucovorin, and fluorouracil (modified FOLFOX6) as first-line treatment of metastatic colorectal cancer: the RESPECT trial. Clin Cancer Res. 2013 May 1;19(9):2541-50. doi: 10.1158/1078-0432.CCR-13-0107. Epub 2013 Mar 26.

Label	URL
Click here and search for Bayer Product information provided by the EMA	View source

Results Section

Participant Flow Module

Arm/Group Information

ID	Title	Description
FG000	Sorafenib (Nexavar, BAY43-9006) + mFOLFOX6	Subjects will receive oral Sorafenib 400 mg twice daily (BID) continuously and intravenous (IV) mFOLFOX6 (5-FU 400 mg/m^2 bolus and 2400 mg/m^2 for 46-48 hrs; levo-leucovorin 200 mg/m^2; 85 mg/m^2 oxaliplatin) every 14 days until progressive disease (PD)
FG001

Baseline Characteristics Module

Outcome Measures Module

Adverse Events Module

More Info Module

Arm/Group Information

ID	Title	Description
BG000	Sorafenib (Nexavar, BAY43-9006) + mFOLFOX6	Subjects will receive oral Sorafenib 400 mg twice daily (BID) continuously and intravenous (IV) mFOLFOX6 (5-FU 400 mg/m^2 bolus and 2400 mg/m^2 for 46-48 hrs; levo-leucovorin 200 mg/m^2; 85 mg/m^2 oxaliplatin) every 14 days until progressive disease (PD)
BG001	Matching Placebo + mFOLFOX6	Subjects will receive oral matching placebo 2 tablets BID continuously and IV mFOLFOX6 (5-FU 400 mg/m^2 bolus and 2400 mg/m^2 for 46-48 hrs; levo-leucovorin 200 mg/m^2; 85 mg/m^2 oxaliplatin) every 14 days until progressive disease
BG002	Total	Total of all reporting groups

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
	BG00059.2± 10.3 BG00160.3± 8.3 BG00259.8± 9.3

Sex: Female, Male

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
Female	BG00055 BG00138 BG002

Region of Enrollment

Number

participants

Title

Denominators

Categories

United States

Title	Measurements
	BG0002 BG0012 BG002

ECOG (Eastern Cooperative Oncology Group) Performance Status

Eastern Cooperative Oncology Group (ECOG) Performance Status is a scale that measures how cancer affects the daily life of a patient on an ordinal scale from grade 0 (best) to grade 5 (worst).

Number

Participants

Title

Denominators

Categories

0=Fully active without restriction

Title	Measurements
	BG00034 BG001

Stage of Disease at study entry (TNM Classification, Stage IV)

The TNM (Tumor, Nodes, Metastasis) classification is a three-dimensional solid tumor classification system. The "T" dimension categorizes the size and degree of tumor spreading on an ordinal scale from T0 (best) to T4 (worst). The "N" dimension categorizes the degree of spreading of the tumor into lymph nodes on an ordinal scale from N0 (best) to N3 (worst). The "M" dimension categorizes whether or not the cancer has metastases beyond the lymph nodes on an ordinal scale from M0 (no metastases) to M1 (metastases). All of the 198 randomized patients were at Stage IV of disease.

Number

Participants

Title

Denominators

Categories

Title	Measurements
	BG00097 BG001

Time since initial diagnosis

Time since initial diagnosis was the mean time from initial diagnosis to randomization into the study.

Mean

Standard Deviation

Months

Title

Denominators

Categories

Title	Measurements
	BG0009.8± 16.2 BG0019.2± 16.9

Liver metastases by Principal Investigator

Number

Participants

Title

Denominators

Categories

Yes

Title	Measurements
	BG00079 BG00181 BG002

Number of metastatic sites by Principal Investigator

Number

Participants

Title

Denominators

Categories

Title	Measurements
	BG00071 BG00171 BG002

KRAS

Kirsten rat sarcoma viral oncogene homolog (KRAS)

Number

Participants

Title

Denominators

Categories

Mutant

Title	Measurements
	BG00033 BG00143 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)

Progression-free Survival (PFS) was defined as the time from date of randomization to disease progression or death due to any cause, whichever occurred first. Subjects without progression or death at the time of analysis were censored at their last date of tumor evaluation. Disease progression was defined as an increase of at least 20% in the sum of tumor lesions sizes.

The test was conducted using the intent-to-treat (ITT) population (all subjects who were randomized).

Posted

Median

95% Confidence Interval

Months

From randomization of the first subject until 23 months later, assessed every 8 weeks.

ID	Title	Description
OG000	Sorafenib (Nexavar, BAY43-9006) + mFOLFOX6	Subjects will receive oral Sorafenib 400 mg twice daily (BID) continuously and intravenous (IV) mFOLFOX6 (5-FU 400 mg/m^2 bolus and 2400 mg/m^2 for 46-48 hrs; levo-leucovorin 200 mg/m^2; 85 mg/m^2 oxaliplatin) every 14 days until progressive disease (PD)
OG001	Matching Placebo + mFOLFOX6	Subjects will receive oral matching placebo 2 tablets BID continuously and IV mFOLFOX6 (5-FU 400 mg/m^2 bolus and 2400 mg/m^2 for 46-48 hrs; levo-leucovorin 200 mg/m^2; 85 mg/m^2 oxaliplatin) every 14 days until progressive disease

Units	Counts
Participants	OG00097 OG001101

Title

Denominators

Categories

Title	Measurements
	OG0009.1(7.6 to 9.7) OG0018.7(7.4 to 9.5)

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	A sample size of 120 PFS events would provide a > 85% power at a target HR = 0.65 between sorafenib and matching placebo, with a 1-sided alpha = 0.10, for testing the null hypothesis H0: HR ≥ 1 versus the alternative hypothesis H1: HR < 1 based on the log-rank test. The test was conducted using the intent-to-treat (ITT) population, defined as all subjects who were randomized to treatment.	Log Rank		0.2309	1-sided p-value from stratified log-rank test, stratified by factors of # metastatic sites and liver metastasis determined by Principal Investigator	Hazard Ratio (HR)	0.884			2-Sided	95	0.635	1.231			The relative risk (sorafenib to placebo) was estimated by the hazard ratio from stratified Cox regression with a 95% confidence interval.

Secondary

Overall Survival (OS)

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 last date of last contact.

Posted

Median

95% Confidence Interval

days

From randomization of the first subject until 33 months later.

ID	Title	Description
OG000	Sorafenib (Nexavar, BAY43-9006) + mFOLFOX6	Subjects will receive oral Sorafenib 400 mg twice daily (BID) continuously and intravenous (IV) mFOLFOX6 (5-FU 400 mg/m^2 bolus and 2400 mg/m^2 for 46-48 hrs; levo-leucovorin 200 mg/m^2; 85 mg/m^2 oxaliplatin) every 14 days until progressive disease (PD)
OG001	Matching Placebo + mFOLFOX6	Subjects will receive oral matching placebo 2 tablets BID continuously and IV mFOLFOX6 (5-FU 400 mg/m^2 bolus and 2400 mg/m^2 for 46-48 hrs; levo-leucovorin 200 mg/m^2; 85 mg/m^2 oxaliplatin) every 14 days until progressive disease

Units	Counts
Participants	OG000

Secondary

Time to Progression (TTP)

Time to progression (TTP) was defined as the time from date of randomization to disease progression. Subjects without progression at the time of analysis were censored at their last date of tumor evaluation. Disease progression was defined as an increase of at least 20% in the sum of tumor lesions sizes.

The test was conducted using the intent-to-treat (ITT) population (all subjects who were randomized).

Posted

Median

95% Confidence Interval

Months

From randomization of the first subject until 23 months later, assessed every 8 weeks.

ID	Title	Description
OG000	Sorafenib (Nexavar, BAY43-9006) + mFOLFOX6	Subjects will receive oral Sorafenib 400 mg twice daily (BID) continuously and intravenous (IV) mFOLFOX6 (5-FU 400 mg/m^2 bolus and 2400 mg/m^2 for 46-48 hrs; levo-leucovorin 200 mg/m^2; 85 mg/m^2 oxaliplatin) every 14 days until progressive disease (PD)
OG001	Matching Placebo + mFOLFOX6	Subjects will receive oral matching placebo 2 tablets BID continuously and IV mFOLFOX6 (5-FU 400 mg/m^2 bolus and 2400 mg/m^2 for 46-48 hrs; levo-leucovorin 200 mg/m^2; 85 mg/m^2 oxaliplatin) every 14 days until progressive disease

Units	Counts

Secondary

Overall Response

Overall response of a subject was defined as the best tumor response (Complete Response (CR) or Partial Response (PR)) observed during trial period assessed according to the Response Evaluation Criteria in Solid Tumors (RECIST) criteria. CR was defined as disappearance of tumor lesions, PR was defined as a decrease of at least 30% in the sum of tumor lesion sizes.

The test was conducted using the intent-to-treat (ITT) population (all subjects who were randomized).

Posted

Number

participants

From randomization of the first subject until 23 months later, assessed every 8 weeks.

ID	Title	Description
OG000	Sorafenib (Nexavar, BAY43-9006) + mFOLFOX6	Subjects will receive oral Sorafenib 400 mg twice daily (BID) continuously and intravenous (IV) mFOLFOX6 (5-FU 400 mg/m^2 bolus and 2400 mg/m^2 for 46-48 hrs; levo-leucovorin 200 mg/m^2; 85 mg/m^2 oxaliplatin) every 14 days until progressive disease (PD)
OG001	Matching Placebo + mFOLFOX6	Subjects will receive oral matching placebo 2 tablets BID continuously and IV mFOLFOX6 (5-FU 400 mg/m^2 bolus and 2400 mg/m^2 for 46-48 hrs; levo-leucovorin 200 mg/m^2; 85 mg/m^2 oxaliplatin) every 14 days until progressive disease

Secondary

Duration of Response

Duration of Response was defined as the time from date of first response (Complete Response (CR) or Partial Response (PR)) to the date when Progressive Disease (PD) was first documented or to the date of death, whichever occurred first according to Response Evaluation Criteria in Solid Tumors (RECIST). Subjects still having CR or PR and alive at the time of analysis were censored at their last date of tumor evaluation. CR was defined as disappearance of tumor lesions, PR as a decrease of at least 30% and PD as an increase of at least 20% in the sum of tumor lesions sizes.

Duration of response was the time from the first documented CR or PR until the first documented PD or death (if before progression). Only responders (CR or PR) were included in the analysis

Posted

Number

95% Confidence Interval

months

From randomization of the first subject until 23 months later, assessed every 8 weeks

ID	Title	Description
OG000	Sorafenib (Nexavar, BAY43-9006) + mFOLFOX6	Subjects will receive oral Sorafenib 400 mg twice daily (BID) continuously and intravenous (IV) mFOLFOX6 (5-FU 400 mg/m^2 bolus and 2400 mg/m^2 for 46-48 hrs; levo-leucovorin 200 mg/m^2; 85 mg/m^2 oxaliplatin) every 14 days until progressive disease (PD)
OG001	Matching Placebo + mFOLFOX6	Subjects will receive oral matching placebo 2 tablets BID continuously and IV mFOLFOX6 (5-FU 400 mg/m^2 bolus and 2400 mg/m^2 for 46-48 hrs; levo-leucovorin 200 mg/m^2; 85 mg/m^2 oxaliplatin) every 14 days until progressive disease

Arm/Groups

ID	Title	Description	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Sorafenib (Nexavar, BAY43-9006) + mFOLFOX6	Subjects will receive oral Sorafenib 400 mg twice daily (BID) continuously and intravenous (IV) mFOLFOX6 (5-FU 400 mg/m^2 bolus and 2400 mg/m^2 for 46-48 hrs; levo-leucovorin 200 mg/m^2; 85 mg/m^2 oxaliplatin) every 14 days until progressive disease (PD)	30	97	96	97
EG001	Matching Placebo + mFOLFOX6	Subjects will receive oral matching placebo 2 tablets BID continuously and IV mFOLFOX6 (5-FU 400 mg/m^2 bolus and 2400 mg/m^2 for 46-48 hrs; levo-leucovorin 200 mg/m^2; 85 mg/m^2 oxaliplatin) every 14 days until progressive disease	27	101	99	101
EG002	Sorafenib (Nexavar, BAY43-9006) + mFOLFOX6 (OS Update)	Subjects will receive oral Sorafenib 400 mg twice daily (BID) continuously and intravenous (IV) mFOLFOX6 (5-FU 400 mg/m^2 bolus and 2400 mg/m^2 for 46-48 hrs; levo-leucovorin 200 mg/m^2; 85 mg/m^2 oxaliplatin) every 14 days until progressive disease (PD)	33	97	96	97
EG003	Matching Placebo + mFOLFOX6 (OS Update)	Subjects will receive oral matching placebo 2 tablets BID continuously and IV mFOLFOX6 (5-FU 400 mg/m^2 bolus and 2400 mg/m^2 for 46-48 hrs; levo-leucovorin 200 mg/m^2; 85 mg/m^2 oxaliplatin) every 14 days until progressive disease	30	101	99	101

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Diarrhoea	Gastrointestinal disorders	MedDRA (13.1)	Non-systematic Assessment	EG0002 affected97 at risk EG0011 affected101 at risk EG0022 affected97 at risk EG0031 affected101 at risk
Intestinal obstruction	Gastrointestinal disorders	MedDRA (13.1)	Non-systematic Assessment	EG0000 affected97 at risk EG0013 affected101 at risk EG0020 affected97 at risk EG003
Vomiting	Gastrointestinal disorders	MedDRA (13.1)	Non-systematic Assessment	EG0001 affected97 at risk EG0012 affected101 at risk EG0021 affected97 at risk EG003
Abdominal pain	Gastrointestinal disorders	MedDRA (13.1)	Non-systematic Assessment	EG0000 affected97 at risk EG0012 affected101 at risk EG0021 affected97 at risk EG003
Large intestine perforation	Gastrointestinal disorders	MedDRA (13.1)	Non-systematic Assessment	EG0001 affected97 at risk EG0011 affected101 at risk EG0021 affected97 at risk EG003
Subileus	Gastrointestinal disorders	MedDRA (13.1)	Non-systematic Assessment	EG0000 affected97 at risk EG0012 affected101 at risk EG0020 affected97 at risk EG003
Colonic obstruction	Gastrointestinal disorders	MedDRA (13.1)	Non-systematic Assessment	EG0000 affected97 at risk EG0011 affected101 at risk EG0020 affected97 at risk EG003
Constipation	Gastrointestinal disorders	MedDRA (13.1)	Non-systematic Assessment	EG0000 affected97 at risk EG0011 affected101 at risk EG0020 affected97 at risk EG003
Duodenal perforation	Gastrointestinal disorders	MedDRA (13.1)	Non-systematic Assessment	EG0001 affected97 at risk EG0010 affected101 at risk EG0021 affected97 at risk EG003
Enteritis	Gastrointestinal disorders	MedDRA (13.1)	Non-systematic Assessment	EG0001 affected97 at risk EG0010 affected101 at risk EG0021 affected97 at risk EG003
Enterovesical fistula	Gastrointestinal disorders	MedDRA (13.1)	Non-systematic Assessment	EG0000 affected97 at risk EG0011 affected101 at risk EG0020 affected97 at risk EG003
Intestinal haemorrhage	Gastrointestinal disorders	MedDRA (13.1)	Non-systematic Assessment	EG0001 affected97 at risk EG0010 affected101 at risk EG0021 affected97 at risk EG003
Device related infection	Infections and infestations	MedDRA (13.1)	Non-systematic Assessment	EG0001 affected97 at risk EG0012 affected101 at risk EG0021 affected97 at risk EG003
Cellulitis	Infections and infestations	MedDRA (13.1)	Non-systematic Assessment	EG0001 affected97 at risk EG0011 affected101 at risk EG0021 affected97 at risk EG003
Abdominal abscess	Infections and infestations	MedDRA (13.1)	Non-systematic Assessment	EG0000 affected97 at risk EG0011 affected101 at risk EG0020 affected97 at risk EG003
Diabetic foot infection	Infections and infestations	MedDRA (13.1)	Non-systematic Assessment	EG0001 affected97 at risk EG0010 affected101 at risk EG0021 affected97 at risk EG003
Gastroenteritis salmonella	Infections and infestations	MedDRA (13.1)	Non-systematic Assessment	EG0000 affected97 at risk EG0011 affected101 at risk EG0020 affected97 at risk EG003
Lobar pneumonia	Infections and infestations	MedDRA (13.1)	Non-systematic Assessment	EG0000 affected97 at risk EG0011 affected101 at risk EG0020 affected97 at risk EG003
Osteomyelitis	Infections and infestations	MedDRA (13.1)	Non-systematic Assessment	EG0001 affected97 at risk EG0010 affected101 at risk EG0021 affected97 at risk EG003
Peritoneal infection	Infections and infestations	MedDRA (13.1)	Non-systematic Assessment	EG0000 affected97 at risk EG0011 affected101 at risk EG0020 affected97 at risk EG003
Proctitis bacterial	Infections and infestations	MedDRA (13.1)	Non-systematic Assessment	EG0001 affected97 at risk EG0010 affected101 at risk EG0021 affected97 at risk EG003
Upper respiratory tract infection	Infections and infestations	MedDRA (13.1)	Non-systematic Assessment	EG0000 affected97 at risk EG0011 affected101 at risk EG0020 affected97 at risk EG003
Urinary tract infection	Infections and infestations	MedDRA (13.1)	Non-systematic Assessment	EG0001 affected97 at risk EG0010 affected101 at risk EG0021 affected97 at risk EG003
Pyrexia	General disorders	MedDRA (13.1)	Non-systematic Assessment	EG0001 affected97 at risk EG0011 affected101 at risk EG0021 affected97 at risk EG003
Chest discomfort	General disorders	MedDRA (13.1)	Non-systematic Assessment	EG0000 affected97 at risk EG0011 affected101 at risk EG0020 affected97 at risk EG003
Device breakage	General disorders	MedDRA (13.1)	Non-systematic Assessment	EG0001 affected97 at risk EG0010 affected101 at risk EG0021 affected97 at risk EG003
Disease progression	General disorders	MedDRA (13.1)	Non-systematic Assessment	EG0000 affected97 at risk EG0011 affected101 at risk EG0021 affected97 at risk EG003
Mucosal inflammation	General disorders	MedDRA (13.1)	Non-systematic Assessment	EG0001 affected97 at risk EG0010 affected101 at risk EG0021 affected97 at risk EG003
Neutropenia	Blood and lymphatic system disorders	MedDRA (13.1)	Non-systematic Assessment	EG0002 affected97 at risk EG0010 affected101 at risk EG0022 affected97 at risk EG003
Anaemia	Blood and lymphatic system disorders	MedDRA (13.1)	Non-systematic Assessment	EG0000 affected97 at risk EG0011 affected101 at risk EG0020 affected97 at risk EG003
Febrile neutropenia	Blood and lymphatic system disorders	MedDRA (13.1)	Non-systematic Assessment	EG0001 affected97 at risk EG0010 affected101 at risk EG0021 affected97 at risk EG003
Pancytopenia	Blood and lymphatic system disorders	MedDRA (13.1)	Non-systematic Assessment	EG0001 affected97 at risk EG0010 affected101 at risk EG0021 affected97 at risk EG003
Thrombocytopenia	Blood and lymphatic system disorders	MedDRA (13.1)	Non-systematic Assessment	EG0000 affected97 at risk EG0011 affected101 at risk EG0020 affected97 at risk EG003
Renal failure	Renal and urinary disorders	MedDRA (13.1)	Non-systematic Assessment	EG0001 affected97 at risk EG0011 affected101 at risk EG0021 affected97 at risk EG003
Renal failure acute	Renal and urinary disorders	MedDRA (13.1)	Non-systematic Assessment	EG0002 affected97 at risk EG0010 affected101 at risk EG0022 affected97 at risk EG003
Renal impairment	Renal and urinary disorders	MedDRA (13.1)	Non-systematic Assessment	EG0000 affected97 at risk EG0011 affected101 at risk EG0020 affected97 at risk EG003
Pulmonary embolism	Respiratory, thoracic and mediastinal disorders	MedDRA (13.1)	Non-systematic Assessment	EG0001 affected97 at risk EG0012 affected101 at risk EG0021 affected97 at risk EG003
Acute respiratory failure	Respiratory, thoracic and mediastinal disorders	MedDRA (13.1)	Non-systematic Assessment	EG0001 affected97 at risk EG0010 affected101 at risk EG0021 affected97 at risk EG003
Bronchospasm	Respiratory, thoracic and mediastinal disorders	MedDRA (13.1)	Non-systematic Assessment	EG0001 affected97 at risk EG0010 affected101 at risk EG0021 affected97 at risk EG003
Atrial fibrillation	Cardiac disorders	MedDRA (13.1)	Non-systematic Assessment	EG0000 affected97 at risk EG0011 affected101 at risk EG0020 affected97 at risk EG003
Cardiovascular insufficiency	Cardiac disorders	MedDRA (13.1)	Non-systematic Assessment	EG0000 affected97 at risk EG0011 affected101 at risk EG0020 affected97 at risk EG003
Myocardial infarction	Cardiac disorders	MedDRA (13.1)	Non-systematic Assessment	EG0001 affected97 at risk EG0010 affected101 at risk EG0021 affected97 at risk EG003
Myocardial ischaemia	Cardiac disorders	MedDRA (13.1)	Non-systematic Assessment	EG0001 affected97 at risk EG0010 affected101 at risk EG0021 affected97 at risk EG003
Cerebral ischaemia	Nervous system disorders	MedDRA (13.1)	Non-systematic Assessment	EG0001 affected97 at risk EG0010 affected101 at risk EG0021 affected97 at risk EG003
Dizziness	Nervous system disorders	MedDRA (13.1)	Non-systematic Assessment	EG0001 affected97 at risk EG0010 affected101 at risk EG0021 affected97 at risk EG003
Ischaemic stroke	Nervous system disorders	MedDRA (13.1)	Non-systematic Assessment	EG0000 affected97 at risk EG0011 affected101 at risk EG0020 affected97 at risk EG003
Sciatica	Nervous system disorders	MedDRA (13.1)	Non-systematic Assessment	EG0000 affected97 at risk EG0011 affected101 at risk EG0020 affected97 at risk EG003
Axillary vein thrombosis	Vascular disorders	MedDRA (13.1)	Non-systematic Assessment	EG0001 affected97 at risk EG0010 affected101 at risk EG0021 affected97 at risk EG003
Circulatory collapse	Vascular disorders	MedDRA (13.1)	Non-systematic Assessment	EG0001 affected97 at risk EG0010 affected101 at risk EG0021 affected97 at risk EG003
Deep vein thrombosis	Vascular disorders	MedDRA (13.1)	Non-systematic Assessment	EG0000 affected97 at risk EG0011 affected101 at risk EG0020 affected97 at risk EG003
Thrombosis	Vascular disorders	MedDRA (13.1)	Non-systematic Assessment	EG0000 affected97 at risk EG0011 affected101 at risk EG0020 affected97 at risk EG003
Colorectal cancer	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA (13.1)	Non-systematic Assessment	EG0000 affected97 at risk EG0013 affected101 at risk EG0021 affected97 at risk EG003
Dermatitis allergic	Skin and subcutaneous tissue disorders	MedDRA (13.1)	Non-systematic Assessment	EG0001 affected97 at risk EG0010 affected101 at risk EG0021 affected97 at risk EG003
Palmar-plantar erythrodysaesthesia syndrome	Skin and subcutaneous tissue disorders	MedDRA (13.1)	Non-systematic Assessment	EG0001 affected97 at risk EG0010 affected101 at risk EG0021 affected97 at risk EG003
Skin ulcer	Skin and subcutaneous tissue disorders	MedDRA (13.1)	Non-systematic Assessment	EG0001 affected97 at risk EG0010 affected101 at risk EG0021 affected97 at risk EG003
Hepatic failure	Hepatobiliary disorders	MedDRA (13.1)	Non-systematic Assessment	EG0001 affected97 at risk EG0010 affected101 at risk EG0021 affected97 at risk EG003
Jaundice cholestatic	Hepatobiliary disorders	MedDRA (13.1)	Non-systematic Assessment	EG0001 affected97 at risk EG0010 affected101 at risk EG0021 affected97 at risk EG003
Blood amylase increased	Investigations	MedDRA (13.1)	Non-systematic Assessment	EG0000 affected97 at risk EG0011 affected101 at risk EG0020 affected97 at risk EG003
Blood creatinine increased	Investigations	MedDRA (13.1)	Non-systematic Assessment	EG0000 affected97 at risk EG0011 affected101 at risk EG0020 affected97 at risk EG003
Hyperglycaemia	Metabolism and nutrition disorders	MedDRA (13.1)	Non-systematic Assessment	EG0001 affected97 at risk EG0010 affected101 at risk EG0021 affected97 at risk EG003
Hypokalaemia	Metabolism and nutrition disorders	MedDRA (13.1)	Non-systematic Assessment	EG0000 affected97 at risk EG0011 affected101 at risk EG0020 affected97 at risk EG003
Arthropathy	Musculoskeletal and connective tissue disorders	MedDRA (13.1)	Non-systematic Assessment	EG0001 affected97 at risk EG0010 affected101 at risk EG0021 affected97 at risk EG003
Fistula	Musculoskeletal and connective tissue disorders	MedDRA (13.1)	Non-systematic Assessment	EG0001 affected97 at risk EG0010 affected101 at risk EG0021 affected97 at risk EG003
Retinal vein thrombosis	Eye disorders	MedDRA (13.1)	Non-systematic Assessment	EG0001 affected97 at risk EG0010 affected101 at risk EG0021 affected97 at risk EG003
Hypersensitivity	Immune system disorders	MedDRA (13.1)	Non-systematic Assessment	EG0000 affected97 at risk EG0011 affected101 at risk EG0020 affected97 at risk EG003
Cervical vertebral fracture	Injury, poisoning and procedural complications	MedDRA (13.1)	Non-systematic Assessment	EG0000 affected97 at risk EG0011 affected101 at risk EG0020 affected97 at risk EG003
Delirium	Psychiatric disorders	MedDRA (13.1)	Non-systematic Assessment	EG0001 affected97 at risk EG0010 affected101 at risk EG0021 affected97 at risk EG003
Metasteses to central nervous system	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA (13.1)	Non-systematic Assessment	EG0000 affected97 at risk EG0010 affected101 at risk EG0020 affected97 at risk EG003
Hepatic function abnormal	Hepatobiliary disorders	MedDRA (13.1)	Non-systematic Assessment	EG0000 affected97 at risk EG0010 affected101 at risk EG0020 affected97 at risk EG003

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Diarrhoea	Gastrointestinal disorders	MedDRA (13.1)	Non-systematic Assessment	EG00049 affected97 at risk EG00139 affected101 at risk EG00249 affected97 at risk EG00339 affected101 at risk
Nausea	Gastrointestinal disorders	MedDRA (13.1)	Non-systematic Assessment	EG00036 affected97 at risk EG00149 affected101 at risk EG00236 affected97 at risk EG003
Vomiting	Gastrointestinal disorders	MedDRA (13.1)	Non-systematic Assessment	EG00024 affected97 at risk EG00120 affected101 at risk EG00224 affected97 at risk EG003
Abdominal pain	Gastrointestinal disorders	MedDRA (13.1)	Non-systematic Assessment	EG00015 affected97 at risk EG00123 affected101 at risk EG00216 affected97 at risk EG003
Constipation	Gastrointestinal disorders	MedDRA (13.1)	Non-systematic Assessment	EG00012 affected97 at risk EG00121 affected101 at risk EG00212 affected97 at risk EG003
Stomatitis	Gastrointestinal disorders	MedDRA (13.1)	Non-systematic Assessment	EG00022 affected97 at risk EG0014 affected101 at risk EG00222 affected97 at risk EG003
Abdominal pain upper	Gastrointestinal disorders	MedDRA (13.1)	Non-systematic Assessment	EG0008 affected97 at risk EG0016 affected101 at risk EG0028 affected97 at risk EG003
Dyspepsia	Gastrointestinal disorders	MedDRA (13.1)	Non-systematic Assessment	EG0003 affected97 at risk EG0016 affected101 at risk EG0023 affected97 at risk EG003
Rectal haemorrhage	Gastrointestinal disorders	MedDRA (13.1)	Non-systematic Assessment	EG0005 affected97 at risk EG0014 affected101 at risk EG0025 affected97 at risk EG003
Abdominal pain lower	Gastrointestinal disorders	MedDRA (13.1)	Non-systematic Assessment	EG0002 affected97 at risk EG0015 affected101 at risk EG0022 affected97 at risk EG003
Abdominal distension	Gastrointestinal disorders	MedDRA (13.1)	Non-systematic Assessment	EG0001 affected97 at risk EG0015 affected101 at risk EG0021 affected97 at risk EG003
Proctalgia	Gastrointestinal disorders	MedDRA (13.1)	Non-systematic Assessment	EG0005 affected97 at risk EG0010 affected101 at risk EG0025 affected97 at risk EG003
Peripheral sensory neuropathy	Nervous system disorders	MedDRA (13.1)	Non-systematic Assessment	EG00022 affected97 at risk EG00125 affected101 at risk EG00222 affected97 at risk EG003
Dysaesthesia	Nervous system disorders	MedDRA (13.1)	Non-systematic Assessment	EG00016 affected97 at risk EG00121 affected101 at risk EG00216 affected97 at risk EG003
Neurotoxicity	Nervous system disorders	MedDRA (13.1)	Non-systematic Assessment	EG00019 affected97 at risk EG00113 affected101 at risk EG00219 affected97 at risk EG003
Paraesthesia	Nervous system disorders	MedDRA (13.1)	Non-systematic Assessment	EG00010 affected97 at risk EG00120 affected101 at risk EG00210 affected97 at risk EG003
Neuropathy peripheral	Nervous system disorders	MedDRA (13.1)	Non-systematic Assessment	EG00013 affected97 at risk EG0019 affected101 at risk EG00213 affected97 at risk EG003
Dysgeusia	Nervous system disorders	MedDRA (13.1)	Non-systematic Assessment	EG00012 affected97 at risk EG0016 affected101 at risk EG00212 affected97 at risk EG003
Hypoaesthesia	Nervous system disorders	MedDRA (13.1)	Non-systematic Assessment	EG0009 affected97 at risk EG0019 affected101 at risk EG0029 affected97 at risk EG003
Dizziness	Nervous system disorders	MedDRA (13.1)	Non-systematic Assessment	EG0006 affected97 at risk EG00110 affected101 at risk EG0026 affected97 at risk EG003
Headache	Nervous system disorders	MedDRA (13.1)	Non-systematic Assessment	EG0006 affected97 at risk EG0013 affected101 at risk EG0026 affected97 at risk EG003
Lethargy	Nervous system disorders	MedDRA (13.1)	Non-systematic Assessment	EG0002 affected97 at risk EG0015 affected101 at risk EG0022 affected97 at risk EG003
Asthenia	General disorders	MedDRA (13.1)	Non-systematic Assessment	EG00031 affected97 at risk EG00124 affected101 at risk EG00231 affected97 at risk EG003
Fatigue	General disorders	MedDRA (13.1)	Non-systematic Assessment	EG00022 affected97 at risk EG00124 affected101 at risk EG00222 affected97 at risk EG003
Mucosal inflammation	General disorders	MedDRA (13.1)	Non-systematic Assessment	EG00021 affected97 at risk EG00116 affected101 at risk EG00221 affected97 at risk EG003
Pyrexia	General disorders	MedDRA (13.1)	Non-systematic Assessment	EG00010 affected97 at risk EG00111 affected101 at risk EG00210 affected97 at risk EG003
Oedema peripheral	General disorders	MedDRA (13.1)	Non-systematic Assessment	EG0003 affected97 at risk EG0016 affected101 at risk EG0023 affected97 at risk EG003
Neutropenia	Blood and lymphatic system disorders	MedDRA (13.1)	Non-systematic Assessment	EG00060 affected97 at risk EG00139 affected101 at risk EG00260 affected97 at risk EG003
Thrombocytopenia	Blood and lymphatic system disorders	MedDRA (13.1)	Non-systematic Assessment	EG00018 affected97 at risk EG00125 affected101 at risk EG00218 affected97 at risk EG003
Anaemia	Blood and lymphatic system disorders	MedDRA (13.1)	Non-systematic Assessment	EG00023 affected97 at risk EG00115 affected101 at risk EG00223 affected97 at risk EG003
Leukopenia	Blood and lymphatic system disorders	MedDRA (13.1)	Non-systematic Assessment	EG00011 affected97 at risk EG0017 affected101 at risk EG00211 affected97 at risk EG003
Palmar-plantar erythrodysaesthesia syndrome	Skin and subcutaneous tissue disorders	MedDRA (13.1)	Non-systematic Assessment	EG00052 affected97 at risk EG00111 affected101 at risk EG00252 affected97 at risk EG003
Rash	Skin and subcutaneous tissue disorders	MedDRA (13.1)	Non-systematic Assessment	EG00023 affected97 at risk EG00110 affected101 at risk EG00224 affected97 at risk EG003
Alopecia	Skin and subcutaneous tissue disorders	MedDRA (13.1)	Non-systematic Assessment	EG00023 affected97 at risk EG0016 affected101 at risk EG00223 affected97 at risk EG003
Dry skin	Skin and subcutaneous tissue disorders	MedDRA (13.1)	Non-systematic Assessment	EG0007 affected97 at risk EG0018 affected101 at risk EG0027 affected97 at risk EG003
Erythema	Skin and subcutaneous tissue disorders	MedDRA (13.1)	Non-systematic Assessment	EG00011 affected97 at risk EG0014 affected101 at risk EG00212 affected97 at risk EG003
Pruritus	Skin and subcutaneous tissue disorders	MedDRA (13.1)	Non-systematic Assessment	EG0005 affected97 at risk EG0013 affected101 at risk EG0025 affected97 at risk EG003
Epistaxis	Respiratory, thoracic and mediastinal disorders	MedDRA (13.1)	Non-systematic Assessment	EG0009 affected97 at risk EG00110 affected101 at risk EG0029 affected97 at risk EG003
Cough	Respiratory, thoracic and mediastinal disorders	MedDRA (13.1)	Non-systematic Assessment	EG0009 affected97 at risk EG0018 affected101 at risk EG0029 affected97 at risk EG003
Dyspnoea	Respiratory, thoracic and mediastinal disorders	MedDRA (13.1)	Non-systematic Assessment	EG0006 affected97 at risk EG00110 affected101 at risk EG0026 affected97 at risk EG003
Dysaesthesia pharynx	Respiratory, thoracic and mediastinal disorders	MedDRA (13.1)	Non-systematic Assessment	EG0003 affected97 at risk EG0016 affected101 at risk EG0023 affected97 at risk EG003
Hiccups	Respiratory, thoracic and mediastinal disorders	MedDRA (13.1)	Non-systematic Assessment	EG0002 affected97 at risk EG0016 affected101 at risk EG0022 affected97 at risk EG003
Pulmonary embolism	Respiratory, thoracic and mediastinal disorders	MedDRA (13.1)	Non-systematic Assessment	EG0002 affected97 at risk EG0015 affected101 at risk EG0022 affected97 at risk EG003
Upper respiratory tract infection	Infections and infestations	MedDRA (13.1)	Non-systematic Assessment	EG0000 affected97 at risk EG0015 affected101 at risk EG0020 affected97 at risk EG003
Blood amylase increased	Investigations	MedDRA (13.1)	Non-systematic Assessment	EG0005 affected97 at risk EG00110 affected101 at risk EG0025 affected97 at risk EG003
Platelet count decreased	Investigations	MedDRA (13.1)	Non-systematic Assessment	EG0003 affected97 at risk EG0018 affected101 at risk EG0023 affected97 at risk EG003
Aspartate aminotransferase increased	Investigations	MedDRA (13.1)	Non-systematic Assessment	EG0005 affected97 at risk EG0015 affected101 at risk EG0025 affected97 at risk EG003
Lipase increased	Investigations	MedDRA (13.1)	Non-systematic Assessment	EG0006 affected97 at risk EG0014 affected101 at risk EG0026 affected97 at risk EG003
Alanine aminotransferase increased	Investigations	MedDRA (13.1)	Non-systematic Assessment	EG0004 affected97 at risk EG0015 affected101 at risk EG0024 affected97 at risk EG003
Weight decreased	Investigations	MedDRA (13.1)	Non-systematic Assessment	EG0005 affected97 at risk EG0011 affected101 at risk EG0025 affected97 at risk EG003
Neutrophil count decreased	Investigations	MedDRA (13.1)	Non-systematic Assessment	EG0000 affected97 at risk EG0015 affected101 at risk EG0020 affected97 at risk EG003
Decreased appetite	Metabolism and nutrition disorders	MedDRA (13.1)	Non-systematic Assessment	EG00013 affected97 at risk EG00116 affected101 at risk EG00213 affected97 at risk EG003
Hyperglycaemia	Metabolism and nutrition disorders	MedDRA (13.1)	Non-systematic Assessment	EG0005 affected97 at risk EG0016 affected101 at risk EG0025 affected97 at risk EG003
Hypertension	Vascular disorders	MedDRA (13.1)	Non-systematic Assessment	EG00020 affected97 at risk EG00110 affected101 at risk EG00220 affected97 at risk EG003
Phlebitis	Vascular disorders	MedDRA (13.1)	Non-systematic Assessment	EG0006 affected97 at risk EG0017 affected101 at risk EG0026 affected97 at risk EG003
Back pain	Musculoskeletal and connective tissue disorders	MedDRA (13.1)	Non-systematic Assessment	EG0006 affected97 at risk EG0017 affected101 at risk EG0026 affected97 at risk EG003
Pain in extremity	Musculoskeletal and connective tissue disorders	MedDRA (13.1)	Non-systematic Assessment	EG0004 affected97 at risk EG0015 affected101 at risk EG0024 affected97 at risk EG003
Proteinuria	Renal and urinary disorders	MedDRA (13.1)	Non-systematic Assessment	EG0006 affected97 at risk EG0015 affected101 at risk EG0026 affected97 at risk EG003
Blood bilirubin increased	Investigations	MedDRA (13.1)	Non-systematic Assessment	EG0001 affected97 at risk EG0013 affected101 at risk EG0020 affected97 at risk EG003
Intestinal obstruction	Gastrointestinal disorders	MedDRA (13.1)	Non-systematic Assessment	EG0001 affected97 at risk EG0013 affected101 at risk EG0022 affected97 at risk EG003

Facility	Status	City	State	ZIP	Country	Contacts
		Wichita	Kansas	67214	United States

ID	Term
D015179	Colorectal Neoplasms
D009362	Neoplasm Metastasis

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
D009385	Neoplastic Processes
D010335	Pathologic Processes
D013568	Pathological Conditions, Signs and Symptoms

ID	Term
D000077157	Sorafenib
D005472	Fluorouracil
D058766	Levoleucovorin
D000077150	Oxaliplatin

ID	Term
D010671	Phenylurea Compounds
D014508	Urea
D000577	Amides
D009930	Organic Chemicals
D001555	Benzene Derivatives
D006841	Hydrocarbons, Aromatic
D006844	Hydrocarbons, Cyclic
D006838	Hydrocarbons
D009536	Niacinamide
D009539	Nicotinic Acids
D000147	Acids, Heterocyclic
D006571	Heterocyclic Compounds
D011725	Pyridines
D006573	Heterocyclic Compounds, 1-Ring
D014498	Uracil
D011744	Pyrimidinones
D011743	Pyrimidines
D002955	Leucovorin
D005575	Formyltetrahydrofolates
D013763	Tetrahydrofolates
D005492	Folic Acid
D011622	Pterins
D011621	Pteridines
D006574	Heterocyclic Compounds, 2-Ring
D000072471	Heterocyclic Compounds, Fused-Ring
D056831	Coordination Complexes