Cetuximab and/or Bevacizumab Combined With Combination Chemotherapy in Treating Patients With Metastatic Colorectal Cancer

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ClinicalTrials.gov Identifier: NCT00265850

Recruitment Status : Completed

First Posted : December 15, 2005

Results First Posted : April 26, 2017

Last Update Posted : May 7, 2020

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Sponsor:

Collaborators:

National Cancer Institute (NCI)

SWOG Cancer Research Network

Bristol-Myers Squibb

Aptuit

Information provided by (Responsible Party):

Alliance for Clinical Trials in Oncology

Study Type	Interventional
Study Design	Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment
Condition	Colorectal Cancer
Interventions	Biological: bevacizumab Biological: cetuximab Drug: FOLFOX or Drug: FOLFIRI
Enrollment	2334

Participant Flow

Recruitment Details
Pre-assignment Details	From 5/2005 to 9/2009, patients were randomized 1:1:1 to Arms A, B and C. Study was amended in 2009 to include only KRAS wild type patients; then Arm C was closed based on data showing no benefit from chemo with the combination of Bevacizumab and an EGFR antibody. Thereafter, only KRAS wild type patients were randomized 1:1 to Arm A and B.


Arm/Group Title	Arm A: FOLFOX or FOLFIRI + Bevacizumab	Arm B: FOLFOX or FOLFIRI + Cetuximab	Arm C: FOLFOX or FOLFIRI + Cetuximab + Bevacizumab
Arm/Group Description	Patients receive bevacizumab 5 mg/k...	Patients receive cetuximab 400mg/m^...	Patients receive cetuximab 400mg/m^...
Arm/Group Description	Patients receive bevacizumab 5 mg/kg IV every two weeks and then receive either FOLFOX or FOLFIRI every two weeks as described in the intervention section. One cycle is defined as 8 weeks of treatment. Treatment continues until disease progression, unacceptable toxicity or surgery with curative intent as planned. FOLFOX or: Patients receive oxaliplatin 85 mg/m^2 IV infused over two hours followed by leucovorin 400 mg/m^2 IV over 2 hours followed by 5-FU 400 mg/m^2 IV bolus, then 2400 mg/m^2 continuous IV infusion over 46-48 hours FOLFIRI: Patients receive irinotecan 180 mg/m^2 IV infused over 90 minutes followed by leucovorin 400 mg/m^2 IV over 2 hours followed by 5-FU 400 mg/m^2 IV bolus following leucovorin then 2400 mg/m^2 continuous IV infusion over 46-48 hours.	Patients receive cetuximab 400mg/m^2 IV over 2 hours on the first day of treatment, then 250 mg/m^2 IV over 1 hour weekly thereafter. Patients also receive either FOLFOX or FOLFIRI every two weeks as described in the intervention section. One cycle is defined as 8 weeks of treatment. Treatment continues until disease progression, unacceptable toxicity or surgery with curative intent as planned. FOLFOX or: Patients receive oxaliplatin 85 mg/m^2 IV infused over two hours followed by leucovorin 400 mg/m^2 IV over 2 hours followed by 5-FU 400 mg/m^2 IV bolus, then 2400 mg/m^2 continuous IV infusion over 46-48 hours FOLFIRI: Patients receive irinotecan 180 mg/m^2 IV infused over 90 minutes followed by leucovorin 400 mg/m^2 IV over 2 hours followed by 5-FU 400 mg/m^2 IV bolus following leucovorin then 2400 mg/m^2 continuous IV infusion over 46-48 hours.	Patients receive cetuximab 400mg/m^2 IV over 2 hours on the first day of treatment, then 250 mg/m^2 IV over 1 hour weekly thereafter. Also, patients receive bevacizumab 5 mg/kg IV every two weeks and then receive either FOLFOX or FOLFIRI every two weeks as described in the intervention section. One cycle is defined as 8 weeks of treatment. Treatment continues until disease progression, unacceptable toxicity or surgery with curative intent as planned. FOLFOX or: Patients receive oxaliplatin 85 mg/m^2 IV infused over two hours followed by leucovorin 400 mg/m^2 IV over 2 hours followed by 5-FU 400 mg/m^2 IV bolus, then 2400 mg/m^2 continuous IV infusion over 46-48 hours FOLFIRI: Patients receive irinotecan 180 mg/m^2 IV infused over 90 minutes followed by leucovorin 400 mg/m^2 IV over 2 hours followed by 5-FU 400 mg/m^2 IV bolus following leucovorin then 2400 mg/m^2 continuous IV infusion over 46-48 hours.
Period Title: Overall Study
Started	899	902	533
Completed	899	902	533
Not Completed	0	0	0

Baseline Characteristics

Arm/Group Title		Arm A: FOLFOX or FOLFIRI + Bevacizumab	Arm B: FOLFOX or FOLFIRI + Cetuximab	Arm C: FOLFOX or FOLFIRI + Cetuximab + Bevacizumab	Total
Arm/Group Description		Patients receive bevacizumab 5 mg/k...	Patients receive cetuximab 400mg/m^...	Patients receive cetuximab 400mg/m^...	Total of all reporting groups
Arm/Group Description		Patients receive bevacizumab 5 mg/kg IV every two weeks and then receive either FOLFOX or FOLFIRI every two weeks as described in the intervention section. One cycle is defined as 8 weeks of treatment. Treatment continues until disease progression, unacceptable toxicity or surgery with curative intent as planned. FOLFOX or: Patients receive oxaliplatin 85 mg/m^2 IV infused over two hours followed by leucovorin 400 mg/m^2 IV over 2 hours followed by 5-FU 400 mg/m^2 IV bolus, then 2400 mg/m^2 continuous IV infusion over 46-48 hours FOLFIRI: Patients receive irinotecan 180 mg/m^2 IV infused over 90 minutes followed by leucovorin 400 mg/m^2 IV over 2 hours followed by 5-FU 400 mg/m^2 IV bolus following leucovorin then 2400 mg/m^2 continuous IV infusion over 46-48 hours.	Patients receive cetuximab 400mg/m^2 IV over 2 hours on the first day of treatment, then 250 mg/m^2 IV over 1 hour weekly thereafter. Patients also receive either FOLFOX or FOLFIRI every two weeks as described in the intervention section. One cycle is defined as 8 weeks of treatment. Treatment continues until disease progression, unacceptable toxicity or surgery with curative intent as planned. FOLFOX or: Patients receive oxaliplatin 85 mg/m^2 IV infused over two hours followed by leucovorin 400 mg/m^2 IV over 2 hours followed by 5-FU 400 mg/m^2 IV bolus, then 2400 mg/m^2 continuous IV infusion over 46-48 hours FOLFIRI: Patients receive irinotecan 180 mg/m^2 IV infused over 90 minutes followed by leucovorin 400 mg/m^2 IV over 2 hours followed by 5-FU 400 mg/m^2 IV bolus following leucovorin then 2400 mg/m^2 continuous IV infusion over 46-48 hours.	Patients receive cetuximab 400mg/m^2 IV over 2 hours on the first day of treatment, then 250 mg/m^2 IV over 1 hour weekly thereafter. Also, patients receive bevacizumab 5 mg/kg IV every two weeks and then receive either FOLFOX or FOLFIRI every two weeks as described in the intervention section. One cycle is defined as 8 weeks of treatment. Treatment continues until disease progression, unacceptable toxicity or surgery with curative intent as planned. FOLFOX or: Patients receive oxaliplatin 85 mg/m^2 IV infused over two hours followed by leucovorin 400 mg/m^2 IV over 2 hours followed by 5-FU 400 mg/m^2 IV bolus, then 2400 mg/m^2 continuous IV infusion over 46-48 hours FOLFIRI: Patients receive irinotecan 180 mg/m^2 IV infused over 90 minutes followed by leucovorin 400 mg/m^2 IV over 2 hours followed by 5-FU 400 mg/m^2 IV bolus following leucovorin then 2400 mg/m^2 continuous IV infusion over 46-48 hours.	Total of all reporting groups
Overall Number of Baseline Participants		559	578	0	1137
Baseline Analysis Population Description		...
Baseline Analysis Population Description		During the trial, it was learned that KRAS mutation predicted for lack of efficacy of EGFR antibodies; also studies showed no benefit from chemo combined with both Bevacizumab and an EGFR antibody. The trial was amended to 2 arms limited to KRAS wild type patients. Only confirmed and consented KRAS wild type patients were analyzed.
Age, Continuous Median (Full Range) Unit of measure: Years
	Number Analyzed	559 participants	578 participants	0 participants	1137 participants
		59 (21.8 to 85)	59.2 (20.8 to 89.5)		59.1 (20.8 to 89.5)
Sex: Female, Male Measure Type: Count of Participants Unit of measure: Participants
	Number Analyzed	559 participants	578 participants	0 participants	1137 participants
	Female	211 37.7%	229 39.6%		440 38.7%
	Male	348 62.3%	349 60.4%		697 61.3%
Region of Enrollment Measure Type: Number Unit of measure: Participants	Number Analyzed	559 participants	578 participants	0 participants	1137 participants
Canada		32	32		64
United States		527	546		1073

Outcome Measures

1.Primary Outcome


Title	Overall Survival
Description	Survival time will be defined as the time from registration to death. ...
Description	Survival time will be defined as the time from registration to death. Time to event distributions will be estimated using the Kaplan-Meier method. Overall Survival (OS) will be compared between Arm A and Arm B.
Time Frame	Up to 5 years post-treatment

Outcome Measure Data

Analysis Population Description

All eligible KRAS wild type patients that began treatment were included in this endpoint.


Arm/Group Title	Arm A: FOLFOX or FOLFIRI + Bevacizumab	Arm B: FOLFOX or FOLFIRI + Cetuximab	Arm C: FOLFOX or FOLFIRI + Cetuximab + Bevacizumab
Arm/Group Description:	Patients receive bevacizumab 5 mg/k...	Patients receive cetuximab 400mg/m^...	Patients receive cetuximab 400mg/m^...
Arm/Group Description:	Patients receive bevacizumab 5 mg/kg IV every two weeks and then receive either FOLFOX or FOLFIRI every two weeks as described in the intervention section. One cycle is defined as 8 weeks of treatment. Treatment continues until disease progression, unacceptable toxicity or surgery with curative intent as planned. FOLFOX or: Patients receive oxaliplatin 85 mg/m^2 IV infused over two hours followed by leucovorin 400 mg/m^2 IV over 2 hours followed by 5-FU 400 mg/m^2 IV bolus, then 2400 mg/m^2 continuous IV infusion over 46-48 hours FOLFIRI: Patients receive irinotecan 180 mg/m^2 IV infused over 90 minutes followed by leucovorin 400 mg/m^2 IV over 2 hours followed by 5-FU 400 mg/m^2 IV bolus following leucovorin then 2400 mg/m^2 continuous IV infusion over 46-48 hours.	Patients receive cetuximab 400mg/m^2 IV over 2 hours on the first day of treatment, then 250 mg/m^2 IV over 1 hour weekly thereafter. Patients also receive either FOLFOX or FOLFIRI every two weeks as described in the intervention section. One cycle is defined as 8 weeks of treatment. Treatment continues until disease progression, unacceptable toxicity or surgery with curative intent as planned. FOLFOX or: Patients receive oxaliplatin 85 mg/m^2 IV infused over two hours followed by leucovorin 400 mg/m^2 IV over 2 hours followed by 5-FU 400 mg/m^2 IV bolus, then 2400 mg/m^2 continuous IV infusion over 46-48 hours FOLFIRI: Patients receive irinotecan 180 mg/m^2 IV infused over 90 minutes followed by leucovorin 400 mg/m^2 IV over 2 hours followed by 5-FU 400 mg/m^2 IV bolus following leucovorin then 2400 mg/m^2 continuous IV infusion over 46-48 hours.	Patients receive cetuximab 400mg/m^2 IV over 2 hours on the first day of treatment, then 250 mg/m^2 IV over 1 hour weekly thereafter. Also, patients receive bevacizumab 5 mg/kg IV every two weeks and then receive either FOLFOX or FOLFIRI every two weeks as described in the intervention section. One cycle is defined as 8 weeks of treatment. Treatment continues until disease progression, unacceptable toxicity or surgery with curative intent as planned. FOLFOX or: Patients receive oxaliplatin 85 mg/m^2 IV infused over two hours followed by leucovorin 400 mg/m^2 IV over 2 hours followed by 5-FU 400 mg/m^2 IV bolus, then 2400 mg/m^2 continuous IV infusion over 46-48 hours FOLFIRI: Patients receive irinotecan 180 mg/m^2 IV infused over 90 minutes followed by leucovorin 400 mg/m^2 IV over 2 hours followed by 5-FU 400 mg/m^2 IV bolus following leucovorin then 2400 mg/m^2 continuous IV infusion over 46-48 hours.
Overall Number of Participants Analyzed	559	578	0
Median (95% Confidence Interval) Unit of Measure: months
	29.0 (25.6 to 31.2)	30.0 (27.5 to 32.8)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Arm A: FOLFOX or FOLFIRI + Bevacizumab, Arm B: FOLFOX or FOLFIRI + Cetuximab
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]

Statistical Test of Hypothesis	P-Value	0.08
	Comments	[Not Specified]
	Method	Log Rank
	Comments	[Not Specified]

Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.88
	Confidence Interval	(2-Sided) 95% 0.77 to 1.01
	Estimation Comments	[Not Specified]

2.Secondary Outcome


Title	Progression-free Survival (PFS)
Description	PFS will be measured from study entry until first documented progressi...
Description	PFS will be measured from study entry until first documented progression or death from any cause. Time to event distributions will be estimated using the Kaplan-Meier method. PFS will be compared between Arm A and Arm B.
Time Frame	Up to 5 years post-treatment

Outcome Measure Data

Analysis Population Description

All eligible KRAS wild type patients were included in this analysis.


Arm/Group Title	Arm A: FOLFOX or FOLFIRI + Bevacizumab	Arm B: FOLFOX or FOLFIRI + Cetuximab	Arm C: FOLFOX or FOLFIRI + Cetuximab + Bevacizumab
Arm/Group Description:	Patients receive bevacizumab 5 mg/k...	Patients receive cetuximab 400mg/m^...	Patients receive cetuximab 400mg/m^...
Arm/Group Description:	Patients receive bevacizumab 5 mg/kg IV every two weeks and then receive either FOLFOX or FOLFIRI every two weeks as described in the intervention section. One cycle is defined as 8 weeks of treatment. Treatment continues until disease progression, unacceptable toxicity or surgery with curative intent as planned. FOLFOX or: Patients receive oxaliplatin 85 mg/m^2 IV infused over two hours followed by leucovorin 400 mg/m^2 IV over 2 hours followed by 5-FU 400 mg/m^2 IV bolus, then 2400 mg/m^2 continuous IV infusion over 46-48 hours FOLFIRI: Patients receive irinotecan 180 mg/m^2 IV infused over 90 minutes followed by leucovorin 400 mg/m^2 IV over 2 hours followed by 5-FU 400 mg/m^2 IV bolus following leucovorin then 2400 mg/m^2 continuous IV infusion over 46-48 hours.	Patients receive cetuximab 400mg/m^2 IV over 2 hours on the first day of treatment, then 250 mg/m^2 IV over 1 hour weekly thereafter. Patients also receive either FOLFOX or FOLFIRI every two weeks as described in the intervention section. One cycle is defined as 8 weeks of treatment. Treatment continues until disease progression, unacceptable toxicity or surgery with curative intent as planned. FOLFOX or: Patients receive oxaliplatin 85 mg/m^2 IV infused over two hours followed by leucovorin 400 mg/m^2 IV over 2 hours followed by 5-FU 400 mg/m^2 IV bolus, then 2400 mg/m^2 continuous IV infusion over 46-48 hours FOLFIRI: Patients receive irinotecan 180 mg/m^2 IV infused over 90 minutes followed by leucovorin 400 mg/m^2 IV over 2 hours followed by 5-FU 400 mg/m^2 IV bolus following leucovorin then 2400 mg/m^2 continuous IV infusion over 46-48 hours.	Patients receive cetuximab 400mg/m^2 IV over 2 hours on the first day of treatment, then 250 mg/m^2 IV over 1 hour weekly thereafter. Also, patients receive bevacizumab 5 mg/kg IV every two weeks and then receive either FOLFOX or FOLFIRI every two weeks as described in the intervention section. One cycle is defined as 8 weeks of treatment. Treatment continues until disease progression, unacceptable toxicity or surgery with curative intent as planned. FOLFOX or: Patients receive oxaliplatin 85 mg/m^2 IV infused over two hours followed by leucovorin 400 mg/m^2 IV over 2 hours followed by 5-FU 400 mg/m^2 IV bolus, then 2400 mg/m^2 continuous IV infusion over 46-48 hours FOLFIRI: Patients receive irinotecan 180 mg/m^2 IV infused over 90 minutes followed by leucovorin 400 mg/m^2 IV over 2 hours followed by 5-FU 400 mg/m^2 IV bolus following leucovorin then 2400 mg/m^2 continuous IV infusion over 46-48 hours.
Overall Number of Participants Analyzed	559	578	0
Median (95% Confidence Interval) Unit of Measure: months
	10.6 (9.5 to 11.1)	10.5 (9.5 to 11.3)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Arm A: FOLFOX or FOLFIRI + Bevacizumab, Arm B: FOLFOX or FOLFIRI + Cetuximab
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]

Statistical Test of Hypothesis	P-Value	0.45
	Comments	[Not Specified]
	Method	Log Rank
	Comments	[Not Specified]

Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.95
	Confidence Interval	(2-Sided) 95% 0.84 to 1.08
	Estimation Comments	[Not Specified]

3.Secondary Outcome


Title	Time to Treatment Failure
Description	[Not Specified]
Description	[Not Specified]
Time Frame	Up to 5 years post-treatment

Outcome Measure Data Not Reported

4.Secondary Outcome


Title	Duration of Tumor Response
Description	[Not Specified]
Description	[Not Specified]
Time Frame	Up to 5 years post-treatment

Outcome Measure Data Not Reported

Adverse Events

Time Frame	[Not Specified]
Adverse Event Reporting Description	Analysis was conducted on all KRAS wild type patients that were treated and assessed for adverse events.

Arm/Group Title	Arm A: FOLFOX or FOLFIRI + Bevacizumab		Arm B: FOLFOX or FOLFIRI + Cetuximab
Arm/Group Description	Patients receive bevacizumab 5 mg/k...		Patients receive cetuximab 400mg/m^...
Arm/Group Description	Patients receive bevacizumab 5 mg/kg IV every two weeks and then receive either FOLFOX or FOLFIRI every two weeks as described in the intervention section. One cycle is defined as 8 weeks of treatment. Treatment continues until disease progression, unacceptable toxicity or surgery with curative intent as planned. FOLFOX or: Patients receive oxaliplatin 85 mg/m^2 IV infused over two hours followed by leucovorin 400 mg/m^2 IV over 2 hours followed by 5-FU 400 mg/m^2 IV bolus, then 2400 mg/m^2 continuous IV infusion over 46-48 hours FOLFIRI: Patients receive irinotecan 180 mg/m^2 IV infused over 90 minutes followed by leucovorin 400 mg/m^2 IV over 2 hours followed by 5-FU 400 mg/m^2 IV bolus following leucovorin then 2400 mg/m^2 continuous IV infusion over 46-48 hours.		Patients receive cetuximab 400mg/m^2 IV over 2 hours on the first day of treatment, then 250 mg/m^2 IV over 1 hour weekly thereafter. Patients also receive either FOLFOX or FOLFIRI every two weeks as described in the intervention section. One cycle is defined as 8 weeks of treatment. Treatment continues until disease progression, unacceptable toxicity or surgery with curative intent as planned. FOLFOX or: Patients receive oxaliplatin 85 mg/m^2 IV infused over two hours followed by leucovorin 400 mg/m^2 IV over 2 hours followed by 5-FU 400 mg/m^2 IV bolus, then 2400 mg/m^2 continuous IV infusion over 46-48 hours FOLFIRI: Patients receive irinotecan 180 mg/m^2 IV infused over 90 minutes followed by leucovorin 400 mg/m^2 IV over 2 hours followed by 5-FU 400 mg/m^2 IV bolus following leucovorin then 2400 mg/m^2 continuous IV infusion over 46-48 hours.
All-Cause Mortality
	Arm A: FOLFOX or FOLFIRI + Bevacizumab		Arm B: FOLFOX or FOLFIRI + Cetuximab
	Affected / at Risk (%)		Affected / at Risk (%)
Total	--/--		--/--
Serious Adverse Events Serious Adverse Events
	Arm A: FOLFOX or FOLFIRI + Bevacizumab		Arm B: FOLFOX or FOLFIRI + Cetuximab
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	98/559 (17.53%)		111/578 (19.20%)
Blood and lymphatic system disorders
Febrile neutropenia ^† 1	1/559 (0.18%)	1	2/578 (0.35%)	2
Hemoglobin decreased ^† 1	1/559 (0.18%)	1	0/578 (0.00%)	0
Thrombotic microangiopathy ^† 1	0/559 (0.00%)	0	1/578 (0.17%)	1
Cardiac disorders
Arrhythmia supraventricular ^† 1	0/559 (0.00%)	0	1/578 (0.17%)	1
Left ventricular failure ^† 1	1/559 (0.18%)	1	0/578 (0.00%)	0
Myocardial ischemia ^† 1	3/559 (0.54%)	3	1/578 (0.17%)	1
Eye disorders
Eye disorder ^† 1	0/559 (0.00%)	0	1/578 (0.17%)	1
Gastrointestinal disorders
Abdominal pain ^† 1	3/559 (0.54%)	3	2/578 (0.35%)	2
Ascites ^† 1	1/559 (0.18%)	1	0/578 (0.00%)	0
Colitis ^† 1	0/559 (0.00%)	0	1/578 (0.17%)	1
Colonic obstruction ^† 1	0/559 (0.00%)	0	3/578 (0.52%)	3
Colonic perforation ^† 1	3/559 (0.54%)	3	0/578 (0.00%)	0
Constipation ^† 1	0/559 (0.00%)	0	1/578 (0.17%)	1
Diarrhea ^† 1	1/559 (0.18%)	1	0/578 (0.00%)	0
Duodenal hemorrhage ^† 1	0/559 (0.00%)	0	1/578 (0.17%)	1
Ear, nose and throat examination abnormal ^† 1	0/559 (0.00%)	0	1/578 (0.17%)	1
Esophagitis ^† 1	1/559 (0.18%)	1	0/578 (0.00%)	0
Gastric hemorrhage ^† 1	1/559 (0.18%)	1	0/578 (0.00%)	0
Gastrointestinal disorder ^† 1	0/559 (0.00%)	0	1/578 (0.17%)	1
Ileal obstruction ^† 1	1/559 (0.18%)	1	1/578 (0.17%)	1
Ileus ^† 1	1/559 (0.18%)	1	0/578 (0.00%)	0
Jejunal perforation ^† 1	1/559 (0.18%)	1	0/578 (0.00%)	0
Obstruction gastric ^† 1	0/559 (0.00%)	0	1/578 (0.17%)	1
Rectal hemorrhage ^† 1	1/559 (0.18%)	1	0/578 (0.00%)	0
Rectal pain ^† 1	0/559 (0.00%)	0	1/578 (0.17%)	1
Small intestinal obstruction ^† 1	1/559 (0.18%)	1	0/578 (0.00%)	0
Small intestinal perforation ^† 1	1/559 (0.18%)	1	1/578 (0.17%)	1
Vomiting ^† 1	1/559 (0.18%)	1	0/578 (0.00%)	0
General disorders
Death NOS ^† 1	5/559 (0.89%)	5	2/578 (0.35%)	2
Disease progression ^† 1	2/559 (0.36%)	2	0/578 (0.00%)	0
Fatigue ^† 1	4/559 (0.72%)	4	3/578 (0.52%)	3
Sudden death ^† 1	2/559 (0.36%)	2	2/578 (0.35%)	2
Hepatobiliary disorders
Hepatic failure ^† 1	1/559 (0.18%)	1	0/578 (0.00%)	0
Immune system disorders
Cytokine release syndrome ^† 1	0/559 (0.00%)	0	1/578 (0.17%)	1
Hypersensitivity ^† 1	2/559 (0.36%)	2	1/578 (0.17%)	1
Infections and infestations
Abdominal infection ^† 1	0/559 (0.00%)	0	1/578 (0.17%)	1
Ileal infection ^† 1	0/559 (0.00%)	0	1/578 (0.17%)	1
Infection ^† 1	1/559 (0.18%)	1	2/578 (0.35%)	2
Sepsis ^† 1	0/559 (0.00%)	0	4/578 (0.69%)	4
Injury, poisoning and procedural complications
Arterial injury ^† 1	0/559 (0.00%)	0	1/578 (0.17%)	1
Vascular access complication ^† 1	2/559 (0.36%)	3	7/578 (1.21%)	9
Wound dehiscence ^† 1	0/559 (0.00%)	0	1/578 (0.17%)	1
Investigations
Blood bilirubin increased ^† 1	1/559 (0.18%)	1	0/578 (0.00%)	0
Carbon monoxide diffusing capacity decreased ^† 1	0/559 (0.00%)	0	2/578 (0.35%)	2
Cardiac troponin I increased ^† 1	2/559 (0.36%)	2	1/578 (0.17%)	1
Creatinine increased ^† 1	1/559 (0.18%)	1	0/578 (0.00%)	0
Leukocyte count decreased ^† 1	2/559 (0.36%)	2	2/578 (0.35%)	2
Lymphocyte count decreased ^† 1	0/559 (0.00%)	0	1/578 (0.17%)	1
Neutrophil count decreased ^† 1	35/559 (6.26%)	38	36/578 (6.23%)	43
Platelet count decreased ^† 1	2/559 (0.36%)	2	3/578 (0.52%)	3
Serum cholesterol increased ^† 1	1/559 (0.18%)	1	0/578 (0.00%)	0
Metabolism and nutrition disorders
Anorexia ^† 1	1/559 (0.18%)	1	0/578 (0.00%)	0
Blood glucose increased ^† 1	1/559 (0.18%)	1	4/578 (0.69%)	5
Blood uric acid increased ^† 1	1/559 (0.18%)	1	0/578 (0.00%)	0
Dehydration ^† 1	0/559 (0.00%)	0	2/578 (0.35%)	2
Serum glucose decreased ^† 1	1/559 (0.18%)	1	1/578 (0.17%)	1
Serum magnesium decreased ^† 1	0/559 (0.00%)	0	5/578 (0.87%)	12
Serum phosphate decreased ^† 1	0/559 (0.00%)	0	1/578 (0.17%)	1
Serum potassium decreased ^† 1	2/559 (0.36%)	2	2/578 (0.35%)	2
Serum potassium increased ^† 1	1/559 (0.18%)	2	1/578 (0.17%)	1
Serum sodium decreased ^† 1	0/559 (0.00%)	0	1/578 (0.17%)	1
Serum sodium increased ^† 1	0/559 (0.00%)	0	1/578 (0.17%)	1
Musculoskeletal and connective tissue disorders
Back pain ^† 1	0/559 (0.00%)	0	1/578 (0.17%)	1
Nervous system disorders
Intracranial hemorrhage ^† 1	1/559 (0.18%)	1	1/578 (0.17%)	1
Ischemia cerebrovascular ^† 1	2/559 (0.36%)	2	1/578 (0.17%)	1
Peripheral sensory neuropathy ^† 1	3/559 (0.54%)	3	1/578 (0.17%)	1
Seizure ^† 1	0/559 (0.00%)	0	1/578 (0.17%)	1
Psychiatric disorders
Confusion ^† 1	1/559 (0.18%)	1	0/578 (0.00%)	0
Depression ^† 1	0/559 (0.00%)	0	1/578 (0.17%)	1
Psychosis ^† 1	0/559 (0.00%)	0	1/578 (0.17%)	1
Renal and urinary disorders
Proteinuria ^† 1	1/559 (0.18%)	1	1/578 (0.17%)	1
Renal failure ^† 1	0/559 (0.00%)	0	1/578 (0.17%)	1
Respiratory, thoracic and mediastinal disorders
Dyspnea ^† 1	1/559 (0.18%)	1	1/578 (0.17%)	1
Hypoxia ^† 1	0/559 (0.00%)	0	1/578 (0.17%)	1
Pneumonitis ^† 1	1/559 (0.18%)	1	1/578 (0.17%)	1
Respiratory disorder ^† 1	0/559 (0.00%)	0	4/578 (0.69%)	4
Skin and subcutaneous tissue disorders
Hand-and-foot syndrome ^† 1	1/559 (0.18%)	1	1/578 (0.17%)	1
Rash desquamating ^† 1	0/559 (0.00%)	0	1/578 (0.17%)	1
Vascular disorders
Hypertension ^† 1	0/559 (0.00%)	0	1/578 (0.17%)	1
Hypotension ^† 1	0/559 (0.00%)	0	2/578 (0.35%)	2
Thrombosis ^† 1	14/559 (2.50%)	14	22/578 (3.81%)	39
† Indicates events were collected by systematic assessment 1 Term from vocabulary, MedDRA 5
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	0%
	Arm A: FOLFOX or FOLFIRI + Bevacizumab		Arm B: FOLFOX or FOLFIRI + Cetuximab
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	531/559 (94.99%)		548/578 (94.81%)
Blood and lymphatic system disorders
Blood disorder ^† 1	0/559 (0.00%)	0	4/578 (0.69%)	4
Disseminated intravascular coagulation ^† 1	0/559 (0.00%)	0	1/578 (0.17%)	1
Febrile neutropenia ^† 1	5/559 (0.89%)	5	10/578 (1.73%)	10
Hemoglobin decreased ^† 1	95/559 (16.99%)	161	83/578 (14.36%)	145
Hemolysis ^† 1	7/559 (1.25%)	7	5/578 (0.87%)	6
Lymph node pain ^† 1	0/559 (0.00%)	0	1/578 (0.17%)	1
Lymphatic disorder ^† 1	1/559 (0.18%)	1	1/578 (0.17%)	1
Cardiac disorders
Atrial fibrillation ^† 1	3/559 (0.54%)	3	5/578 (0.87%)	5
Atrial flutter ^† 1	0/559 (0.00%)	0	1/578 (0.17%)	1
Atrial tachycardia ^† 1	1/559 (0.18%)	1	0/578 (0.00%)	0
Cardiac disorder ^† 1	5/559 (0.89%)	5	1/578 (0.17%)	1
Cardiac pain ^† 1	4/559 (0.72%)	4	5/578 (0.87%)	5
Conduction disorder ^† 1	0/559 (0.00%)	0	1/578 (0.17%)	1
Left ventricular failure ^† 1	2/559 (0.36%)	2	3/578 (0.52%)	6
Myocardial ischemia ^† 1	3/559 (0.54%)	3	5/578 (0.87%)	5
Myocarditis ^† 1	1/559 (0.18%)	1	0/578 (0.00%)	0
Nodal arrhythmia ^† 1	0/559 (0.00%)	0	1/578 (0.17%)	1
Palpitations ^† 1	2/559 (0.36%)	2	3/578 (0.52%)	3
Pericarditis ^† 1	1/559 (0.18%)	1	0/578 (0.00%)	0
Sinus bradycardia ^† 1	2/559 (0.36%)	2	2/578 (0.35%)	2
Sinus tachycardia ^† 1	2/559 (0.36%)	2	5/578 (0.87%)	5
Supraventricular tachycardia ^† 1	1/559 (0.18%)	1	2/578 (0.35%)	2
Ventricular trigeminy ^† 1	1/559 (0.18%)	1	1/578 (0.17%)	1
Ear and labyrinth disorders
Ear disorder ^† 1	1/559 (0.18%)	1	1/578 (0.17%)	1
Ear pain ^† 1	1/559 (0.18%)	2	1/578 (0.17%)	1
External ear inflammation ^† 1	0/559 (0.00%)	0	1/578 (0.17%)	1
Hearing impaired ^† 1	0/559 (0.00%)	0	1/578 (0.17%)	2
Hearing test abnormal ^† 1	0/559 (0.00%)	0	1/578 (0.17%)	2
Middle ear inflammation ^† 1	1/559 (0.18%)	1	1/578 (0.17%)	1
Tinnitus ^† 1	4/559 (0.72%)	5	4/578 (0.69%)	7
Endocrine disorders
Adrenal insufficiency ^† 1	1/559 (0.18%)	1	0/578 (0.00%)	0
Cushingoid ^† 1	0/559 (0.00%)	0	1/578 (0.17%)	1
Hyperthyroidism ^† 1	1/559 (0.18%)	2	1/578 (0.17%)	1
Hypothyroidism ^† 1	1/559 (0.18%)	2	1/578 (0.17%)	1
Eye disorders
Cataract ^† 1	3/559 (0.54%)	3	1/578 (0.17%)	3
Conjunctivitis ^† 1	3/559 (0.54%)	4	12/578 (2.08%)	23
Diplopia ^† 1	1/559 (0.18%)	1	1/578 (0.17%)	1
Dry eye syndrome ^† 1	1/559 (0.18%)	1	1/578 (0.17%)	3
Extraocular muscle paresis ^† 1	0/559 (0.00%)	0	1/578 (0.17%)	2
Eye disorder ^† 1	0/559 (0.00%)	0	4/578 (0.69%)	7
Eye pain ^† 1	1/559 (0.18%)	1	1/578 (0.17%)	1
Eyelid function disorder ^† 1	0/559 (0.00%)	0	2/578 (0.35%)	6
Glaucoma ^† 1	0/559 (0.00%)	0	1/578 (0.17%)	2
Keratitis ^† 1	0/559 (0.00%)	0	1/578 (0.17%)	1
Retinopathy ^† 1	0/559 (0.00%)	0	1/578 (0.17%)	1
Vision blurred ^† 1	3/559 (0.54%)	5	2/578 (0.35%)	10
Watering eyes ^† 1	1/559 (0.18%)	1	4/578 (0.69%)	8
Gastrointestinal disorders
Abdominal distension ^† 1	4/559 (0.72%)	4	4/578 (0.69%)	4
Abdominal pain ^† 1	189/559 (33.81%)	377	186/578 (32.18%)	327
Anal exam abnormal ^† 1	2/559 (0.36%)	2	1/578 (0.17%)	1
Anal fistula ^† 1	1/559 (0.18%)	2	0/578 (0.00%)	0
Anal hemorrhage ^† 1	2/559 (0.36%)	2	0/578 (0.00%)	0
Anal mucositis ^† 1	0/559 (0.00%)	0	1/578 (0.17%)	3
Anal pain ^† 1	3/559 (0.54%)	5	3/578 (0.52%)	6
Ascites ^† 1	3/559 (0.54%)	3	2/578 (0.35%)	2
Cheilitis ^† 1	2/559 (0.36%)	3	5/578 (0.87%)	5
Colitis ^† 1	1/559 (0.18%)	1	3/578 (0.52%)	3
Colonic fistula ^† 1	2/559 (0.36%)	5	1/578 (0.17%)	1
Colonic hemorrhage ^† 1	1/559 (0.18%)	1	0/578 (0.00%)	0
Colonic obstruction ^† 1	5/559 (0.89%)	5	6/578 (1.04%)	6
Colonic perforation ^† 1	2/559 (0.36%)	2	0/578 (0.00%)	0
Constipation ^† 1	41/559 (7.33%)	57	58/578 (10.03%)	91
Diarrhea ^† 1	304/559 (54.38%)	751	346/578 (59.86%)	804
Dry mouth ^† 1	1/559 (0.18%)	2	7/578 (1.21%)	10
Duodenal fistula ^† 1	0/559 (0.00%)	0	1/578 (0.17%)	1
Duodenal hemorrhage ^† 1	0/559 (0.00%)	0	1/578 (0.17%)	1
Duodenal obstruction ^† 1	1/559 (0.18%)	1	0/578 (0.00%)	0
Duodenal ulcer ^† 1	0/559 (0.00%)	0	1/578 (0.17%)	1
Dyspepsia ^† 1	23/559 (4.11%)	27	19/578 (3.29%)	57
Dysphagia ^† 1	9/559 (1.61%)	9	6/578 (1.04%)	6
Ear, nose and throat examination abnormal ^† 1	21/559 (3.76%)	28	54/578 (9.34%)	71
Endoscopy small intestine abnormal ^† 1	1/559 (0.18%)	1	1/578 (0.17%)	3
Enteritis ^† 1	1/559 (0.18%)	1	2/578 (0.35%)	2
Esophageal hemorrhage ^† 1	1/559 (0.18%)	1	0/578 (0.00%)	0
Esophageal ulcer ^† 1	1/559 (0.18%)	1	0/578 (0.00%)	0
Esophagitis ^† 1	3/559 (0.54%)	5	4/578 (0.69%)	4
Fecal incontinence ^† 1	0/559 (0.00%)	0	2/578 (0.35%)	2
Fistula of small intestine ^† 1	2/559 (0.36%)	3	0/578 (0.00%)	0
Flatulence ^† 1	6/559 (1.07%)	11	11/578 (1.90%)	12
Gastric hemorrhage ^† 1	1/559 (0.18%)	1	0/578 (0.00%)	0
Gastric stenosis ^† 1	0/559 (0.00%)	0	1/578 (0.17%)	1
Gastric ulcer ^† 1	2/559 (0.36%)	2	0/578 (0.00%)	0
Gastritis ^† 1	4/559 (0.72%)	7	6/578 (1.04%)	25
Gastrointestinal disorder ^† 1	6/559 (1.07%)	11	8/578 (1.38%)	9
Gingival pain ^† 1	1/559 (0.18%)	1	0/578 (0.00%)	0
Hemorrhoids ^† 1	12/559 (2.15%)	18	13/578 (2.25%)	16
Ileal obstruction ^† 1	1/559 (0.18%)	1	0/578 (0.00%)	0
Ileus ^† 1	6/559 (1.07%)	8	1/578 (0.17%)	1
Intestinal necrosis ^† 1	1/559 (0.18%)	1	0/578 (0.00%)	0
Jejunal obstruction ^† 1	0/559 (0.00%)	0	1/578 (0.17%)	1
Lip pain ^† 1	0/559 (0.00%)	0	1/578 (0.17%)	2
Mucositis oral ^† 1	44/559 (7.87%)	57	59/578 (10.21%)	102
Nausea ^† 1	90/559 (16.10%)	114	100/578 (17.30%)	154
Obstruction gastric ^† 1	1/559 (0.18%)	1	0/578 (0.00%)	0
Oral hemorrhage ^† 1	1/559 (0.18%)	1	0/578 (0.00%)	0
Oral pain ^† 1	2/559 (0.36%)	3	4/578 (0.69%)	5
Pancreatitis ^† 1	0/559 (0.00%)	0	2/578 (0.35%)	2
Periodontal disease ^† 1	1/559 (0.18%)	3	2/578 (0.35%)	6
Peritoneal hemorrhage ^† 1	0/559 (0.00%)	0	1/578 (0.17%)	1
Proctitis ^† 1	3/559 (0.54%)	3	0/578 (0.00%)	0
Rectal hemorrhage ^† 1	5/559 (0.89%)	6	3/578 (0.52%)	3
Rectal mucositis ^† 1	1/559 (0.18%)	1	0/578 (0.00%)	0
Rectal pain ^† 1	15/559 (2.68%)	27	7/578 (1.21%)	12
Rectal stenosis ^† 1	1/559 (0.18%)	1	0/578 (0.00%)	0
Rectal ulcer ^† 1	0/559 (0.00%)	0	1/578 (0.17%)	2
Salivary gland disorder ^† 1	2/559 (0.36%)	4	0/578 (0.00%)	0
Small intestinal mucositis ^† 1	1/559 (0.18%)	1	0/578 (0.00%)	0
Small intestinal necrosis ^† 1	0/559 (0.00%)	0	1/578 (0.17%)	1
Small intestinal obstruction ^† 1	7/559 (1.25%)	7	7/578 (1.21%)	7
Small intestinal perforation ^† 1	1/559 (0.18%)	1	0/578 (0.00%)	0
Small intestine ulcer ^† 1	1/559 (0.18%)	1	0/578 (0.00%)	0
Stomach pain ^† 1	0/559 (0.00%)	0	2/578 (0.35%)	4
Tooth disorder ^† 1	1/559 (0.18%)	2	4/578 (0.69%)	4
Toothache ^† 1	4/559 (0.72%)	4	3/578 (0.52%)	3
Upper gastrointestinal hemorrhage ^† 1	1/559 (0.18%)	1	2/578 (0.35%)	2
Vomiting ^† 1	174/559 (31.13%)	284	185/578 (32.01%)	265
General disorders
Chest pain ^† 1	11/559 (1.97%)	15	7/578 (1.21%)	7
Chills ^† 1	43/559 (7.69%)	51	62/578 (10.73%)	88
Edema limbs ^† 1	7/559 (1.25%)	7	9/578 (1.56%)	15
Facial pain ^† 1	1/559 (0.18%)	1	5/578 (0.87%)	5
Fatigue ^† 1	397/559 (71.02%)	1213	418/578 (72.32%)	1315
Fever ^† 1	75/559 (13.42%)	101	67/578 (11.59%)	83
Flu-like symptoms ^† 1	0/559 (0.00%)	0	2/578 (0.35%)	2
Gait abnormal ^† 1	1/559 (0.18%)	1	1/578 (0.17%)	1
General symptom ^† 1	6/559 (1.07%)	7	5/578 (0.87%)	8
Injection site reaction ^† 1	2/559 (0.36%)	3	3/578 (0.52%)	3
Localized edema ^† 1	2/559 (0.36%)	3	1/578 (0.17%)	1
Pain ^† 1	28/559 (5.01%)	39	30/578 (5.19%)	32
Pericardial pain ^† 1	0/559 (0.00%)	0	1/578 (0.17%)	1
Hepatobiliary disorders
Bile duct stenosis ^† 1	0/559 (0.00%)	0	1/578 (0.17%)	1
Cholecystitis ^† 1	2/559 (0.36%)	2	0/578 (0.00%)	0
Gallbladder pain ^† 1	1/559 (0.18%)	2	0/578 (0.00%)	0
Hepatic failure ^† 1	0/559 (0.00%)	0	1/578 (0.17%)	1
Hepatobiliary disease ^† 1	2/559 (0.36%)	2	0/578 (0.00%)	0
Portal hypertension ^† 1	0/559 (0.00%)	0	3/578 (0.52%)	3
Immune system disorders
Cytokine release syndrome ^† 1	22/559 (3.94%)	29	56/578 (9.69%)	61
Hypersensitivity ^† 1	13/559 (2.33%)	14	15/578 (2.60%)	20
Infections and infestations
Abdominal infection ^† 1	2/559 (0.36%)	2	0/578 (0.00%)	0
Anal infection ^† 1	1/559 (0.18%)	3	2/578 (0.35%)	3
Anorectal infection ^† 1	2/559 (0.36%)	2	0/578 (0.00%)	0
Biliary tract infection ^† 1	0/559 (0.00%)	0	1/578 (0.17%)	1
Bladder infection ^† 1	10/559 (1.79%)	14	7/578 (1.21%)	8
Bone infection ^† 1	1/559 (0.18%)	1	0/578 (0.00%)	0
Bronchitis ^† 1	4/559 (0.72%)	7	1/578 (0.17%)	1
Catheter related infection ^† 1	14/559 (2.50%)	17	10/578 (1.73%)	10
Colitis, infectious (e.g., Clostridium difficile) ^† 1	1/559 (0.18%)	1	1/578 (0.17%)	1
Conjunctivitis infective ^† 1	1/559 (0.18%)	1	6/578 (1.04%)	7
Device related infection ^† 1	1/559 (0.18%)	1	2/578 (0.35%)	2
Esophageal infection ^† 1	0/559 (0.00%)	0	1/578 (0.17%)	1
Eye infection ^† 1	2/559 (0.36%)	2	2/578 (0.35%)	5
Gingival infection ^† 1	5/559 (0.89%)	6	0/578 (0.00%)	0
Infection ^† 1	16/559 (2.86%)	19	17/578 (2.94%)	22
Infection with unknown ANC ^† 1	0/559 (0.00%)	0	1/578 (0.17%)	1
Infection without neutropenia ^† 1	2/559 (0.36%)	2	2/578 (0.35%)	3
Infectious colitis ^† 1	1/559 (0.18%)	1	3/578 (0.52%)	3
Infectious meningitis ^† 1	0/559 (0.00%)	0	1/578 (0.17%)	1
Joint infection ^† 1	0/559 (0.00%)	0	1/578 (0.17%)	1
Kidney infection ^† 1	1/559 (0.18%)	1	0/578 (0.00%)	0
Laryngitis ^† 1	1/559 (0.18%)	1	0/578 (0.00%)	0
Lip infection ^† 1	2/559 (0.36%)	2	2/578 (0.35%)	2
Lymph gland infection ^† 1	0/559 (0.00%)	0	1/578 (0.17%)	1
Mediastinal infection ^† 1	1/559 (0.18%)	1	0/578 (0.00%)	0
Mucosal infection ^† 1	0/559 (0.00%)	0	2/578 (0.35%)	2
Nail infection ^† 1	0/559 (0.00%)	0	16/578 (2.77%)	30
Opportunistic infection ^† 1	3/559 (0.54%)	3	1/578 (0.17%)	1
Otitis externa ^† 1	0/559 (0.00%)	0	1/578 (0.17%)	2
Otitis media ^† 1	3/559 (0.54%)	3	1/578 (0.17%)	1
Paranasal sinus infection ^† 1	1/559 (0.18%)	2	0/578 (0.00%)	0
Pelvic infection ^† 1	1/559 (0.18%)	1	0/578 (0.00%)	0
Penile infection ^† 1	0/559 (0.00%)	0	1/578 (0.17%)	1
Peripheral nerve infection ^† 1	1/559 (0.18%)	1	0/578 (0.00%)	0
Peritoneal infection ^† 1	3/559 (0.54%)	3	1/578 (0.17%)	1
Pharyngitis ^† 1	2/559 (0.36%)	2	1/578 (0.17%)	1
Pneumonia ^† 1	7/559 (1.25%)	7	8/578 (1.38%)	10
Rhinitis infective ^† 1	2/559 (0.36%)	2	1/578 (0.17%)	1
Salivary gland infection ^† 1	0/559 (0.00%)	0	1/578 (0.17%)	1
Scrotal infection ^† 1	1/559 (0.18%)	1	0/578 (0.00%)	0
Sepsis ^† 1	3/559 (0.54%)	3	5/578 (0.87%)	5
Sinusitis ^† 1	7/559 (1.25%)	9	3/578 (0.52%)	4
Skin infection ^† 1	5/559 (0.89%)	6	19/578 (3.29%)	24
Small intestine infection ^† 1	1/559 (0.18%)	1	1/578 (0.17%)	1
Soft tissue infection ^† 1	1/559 (0.18%)	1	1/578 (0.17%)	1
Stoma site infection ^† 1	0/559 (0.00%)	0	1/578 (0.17%)	1
Tooth infection ^† 1	8/559 (1.43%)	11	4/578 (0.69%)	5
Upper aerodigestive tract infection ^† 1	1/559 (0.18%)	1	0/578 (0.00%)	0
Upper respiratory infection ^† 1	10/559 (1.79%)	16	7/578 (1.21%)	9
Urethral infection ^† 1	1/559 (0.18%)	1	0/578 (0.00%)	0
Urinary tract infection ^† 1	24/559 (4.29%)	27	19/578 (3.29%)	21
Vaginal infection ^† 1	3/559 (0.54%)	4	0/578 (0.00%)	0
Wound infection ^† 1	4/559 (0.72%)	5	6/578 (1.04%)	7
Wound-infectious ^† 1	0/559 (0.00%)	0	1/578 (0.17%)	1
Injury, poisoning and procedural complications
Aortic injury ^† 1	0/559 (0.00%)	0	1/578 (0.17%)	1
Arterial injury ^† 1	1/559 (0.18%)	1	0/578 (0.00%)	0
Esophageal anastomotic leak ^† 1	0/559 (0.00%)	0	1/578 (0.17%)	1
Fracture ^† 1	3/559 (0.54%)	3	5/578 (0.87%)	6
Intestinal stoma site bleeding ^† 1	2/559 (0.36%)	2	0/578 (0.00%)	0
Intraoperative gastrointestinal injury ^† 1	1/559 (0.18%)	1	0/578 (0.00%)	0
Radiation recall reaction (dermatologic) ^† 1	0/559 (0.00%)	0	5/578 (0.87%)	5
Seroma ^† 1	1/559 (0.18%)	1	0/578 (0.00%)	0
Vascular access complication ^† 1	14/559 (2.50%)	24	21/578 (3.63%)	33
Wound dehiscence ^† 1	5/559 (0.89%)	7	1/578 (0.17%)	2
Investigations
Activated partial thromboplastin time prolonged ^† 1	0/559 (0.00%)	0	3/578 (0.52%)	3
Alanine aminotransferase increased ^† 1	16/559 (2.86%)	29	23/578 (3.98%)	38
Alkaline phosphatase ^† 1	1/559 (0.18%)	1	1/578 (0.17%)	1
Alkaline phosphatase increased ^† 1	32/559 (5.72%)	49	35/578 (6.06%)	58
Amylase increased ^† 1	1/559 (0.18%)	1	2/578 (0.35%)	2
Aspartate aminotransferase increased ^† 1	11/559 (1.97%)	15	21/578 (3.63%)	34
Blood bilirubin increased ^† 1	45/559 (8.05%)	84	57/578 (9.86%)	108
Blood gonadotrophin abnormal ^† 1	1/559 (0.18%)	2	0/578 (0.00%)	0
CD4 lymphocytes decreased ^† 1	0/559 (0.00%)	0	1/578 (0.17%)	4
Cardiac troponin T increased ^† 1	0/559 (0.00%)	0	1/578 (0.17%)	1
Coagulopathy ^† 1	0/559 (0.00%)	0	2/578 (0.35%)	6
Creatinine increased ^† 1	21/559 (3.76%)	25	7/578 (1.21%)	8
Electrocardiogram QTc interval prolonged ^† 1	0/559 (0.00%)	0	1/578 (0.17%)	1
Fibrinogen decreased ^† 1	0/559 (0.00%)	0	1/578 (0.17%)	1
Gamma-glutamyltransferase increased ^† 1	0/559 (0.00%)	0	4/578 (0.69%)	9
INR increased ^† 1	10/559 (1.79%)	14	18/578 (3.11%)	40
Laboratory test abnormal ^† 1	2/559 (0.36%)	2	7/578 (1.21%)	8
Leukocyte count decreased ^† 1	79/559 (14.13%)	144	98/578 (16.96%)	150
Lipase increased ^† 1	1/559 (0.18%)	1	4/578 (0.69%)	4
Lymphocyte count decreased ^† 1	29/559 (5.19%)	68	31/578 (5.36%)	60
Neutrophil count decreased ^† 1	316/559 (56.53%)	716	334/578 (57.79%)	792
Platelet count decreased ^† 1	208/559 (37.21%)	541	210/578 (36.33%)	575
Serum cholesterol increased ^† 1	1/559 (0.18%)	2	3/578 (0.52%)	11
Weight gain ^† 1	10/559 (1.79%)	30	9/578 (1.56%)	21
Weight loss ^† 1	35/559 (6.26%)	49	63/578 (10.90%)	113
Metabolism and nutrition disorders
Anorexia ^† 1	71/559 (12.70%)	92	100/578 (17.30%)	142
Blood bicarbonate decreased ^† 1	0/559 (0.00%)	0	2/578 (0.35%)	2
Blood glucose increased ^† 1	75/559 (13.42%)	141	80/578 (13.84%)	161
Dehydration ^† 1	53/559 (9.48%)	62	53/578 (9.17%)	66
Glucose intolerance ^† 1	1/559 (0.18%)	1	2/578 (0.35%)	4
Serum albumin decreased ^† 1	64/559 (11.45%)	87	62/578 (10.73%)	90
Serum calcium decreased ^† 1	25/559 (4.47%)	26	36/578 (6.23%)	51
Serum calcium increased ^† 1	1/559 (0.18%)	1	1/578 (0.17%)	1
Serum glucose decreased ^† 1	5/559 (0.89%)	7	5/578 (0.87%)	6
Serum magnesium decreased ^† 1	56/559 (10.02%)	97	231/578 (39.97%)	685
Serum magnesium increased ^† 1	1/559 (0.18%)	2	0/578 (0.00%)	0
Serum phosphate decreased ^† 1	10/559 (1.79%)	14	25/578 (4.33%)	35
Serum potassium decreased ^† 1	29/559 (5.19%)	37	56/578 (9.69%)	72
Serum potassium increased ^† 1	4/559 (0.72%)	4	10/578 (1.73%)	11
Serum sodium decreased ^† 1	16/559 (2.86%)	24	10/578 (1.73%)	11
Serum sodium increased ^† 1	3/559 (0.54%)	3	3/578 (0.52%)	3
Serum triglycerides increased ^† 1	0/559 (0.00%)	0	1/578 (0.17%)	2
Musculoskeletal and connective tissue disorders
Arthralgia ^† 1	27/559 (4.83%)	56	14/578 (2.42%)	18
Arthritis ^† 1	1/559 (0.18%)	2	3/578 (0.52%)	4
Back pain ^† 1	29/559 (5.19%)	56	29/578 (5.02%)	45
Bone pain ^† 1	6/559 (1.07%)	12	9/578 (1.56%)	13
Buttock pain ^† 1	1/559 (0.18%)	1	0/578 (0.00%)	0
Chest wall pain ^† 1	2/559 (0.36%)	2	3/578 (0.52%)	3
Joint disorder ^† 1	1/559 (0.18%)	1	0/578 (0.00%)	0
Joint effusion ^† 1	0/559 (0.00%)	0	1/578 (0.17%)	1
Muscle weakness ^† 1	4/559 (0.72%)	4	15/578 (2.60%)	17
Muscle weakness lower limb ^† 1	4/559 (0.72%)	5	4/578 (0.69%)	5
Musculoskeletal disorder ^† 1	3/559 (0.54%)	3	5/578 (0.87%)	9
Myalgia ^† 1	10/559 (1.79%)	12	11/578 (1.90%)	17
Neck pain ^† 1	5/559 (0.89%)	7	4/578 (0.69%)	4
Osteoporosis ^† 1	0/559 (0.00%)	0	1/578 (0.17%)	5
Pain in extremity ^† 1	20/559 (3.58%)	36	21/578 (3.63%)	28
Soft tissue necrosis upper limb ^† 1	1/559 (0.18%)	1	0/578 (0.00%)	0
Trismus ^† 1	1/559 (0.18%)	1	0/578 (0.00%)	0
Upper extremity dysfunction ^† 1	1/559 (0.18%)	2	0/578 (0.00%)	0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Tumor pain ^† 1	1/559 (0.18%)	1	3/578 (0.52%)	7
Nervous system disorders
Ataxia ^† 1	3/559 (0.54%)	3	7/578 (1.21%)	10
Cognitive disturbance ^† 1	1/559 (0.18%)	1	0/578 (0.00%)	0
Depressed level of consciousness ^† 1	4/559 (0.72%)	4	2/578 (0.35%)	2
Dizziness ^† 1	19/559 (3.40%)	25	28/578 (4.84%)	31
Dysgeusia ^† 1	24/559 (4.29%)	37	33/578 (5.71%)	47
Extrapyramidal disorder ^† 1	2/559 (0.36%)	2	2/578 (0.35%)	11
Facial nerve disorder ^† 1	0/559 (0.00%)	0	1/578 (0.17%)	2
Headache ^† 1	98/559 (17.53%)	209	80/578 (13.84%)	165
Ischemia cerebrovascular ^† 1	2/559 (0.36%)	2	4/578 (0.69%)	4
Memory impairment ^† 1	1/559 (0.18%)	1	2/578 (0.35%)	2
Mini mental status examination abnormal ^† 1	1/559 (0.18%)	1	0/578 (0.00%)	0
Neuralgia ^† 1	1/559 (0.18%)	2	1/578 (0.17%)	1
Neurological disorder NOS ^† 1	5/559 (0.89%)	5	3/578 (0.52%)	3
Peripheral motor neuropathy ^† 1	9/559 (1.61%)	33	12/578 (2.08%)	20
Peripheral sensory neuropathy ^† 1	355/559 (63.51%)	1131	344/578 (59.52%)	1176
Recurrent laryngeal nerve palsy ^† 1	1/559 (0.18%)	1	0/578 (0.00%)	0
Seizure ^† 1	2/559 (0.36%)	2	5/578 (0.87%)	5
Sinus pain ^† 1	0/559 (0.00%)	0	1/578 (0.17%)	1
Speech disorder ^† 1	5/559 (0.89%)	7	3/578 (0.52%)	4
Syncope ^† 1	10/559 (1.79%)	10	17/578 (2.94%)	19
Syncope vasovagal ^† 1	1/559 (0.18%)	1	2/578 (0.35%)	2
Tremor ^† 1	1/559 (0.18%)	1	3/578 (0.52%)	5
Trigeminal nerve disorder ^† 1	1/559 (0.18%)	1	0/578 (0.00%)	0
Psychiatric disorders
Agitation ^† 1	1/559 (0.18%)	1	3/578 (0.52%)	3
Anxiety ^† 1	22/559 (3.94%)	47	12/578 (2.08%)	18
Confusion ^† 1	6/559 (1.07%)	6	5/578 (0.87%)	5
Depression ^† 1	16/559 (2.86%)	19	23/578 (3.98%)	36
Insomnia ^† 1	26/559 (4.65%)	34	36/578 (6.23%)	65
Libido decreased ^† 1	1/559 (0.18%)	1	0/578 (0.00%)	0
Psychosis ^† 1	0/559 (0.00%)	0	1/578 (0.17%)	1
Renal and urinary disorders
Bladder hemorrhage ^† 1	2/559 (0.36%)	2	1/578 (0.17%)	1
Bladder pain ^† 1	0/559 (0.00%)	0	2/578 (0.35%)	2
Bladder spasm ^† 1	0/559 (0.00%)	0	1/578 (0.17%)	1
Cystitis ^† 1	0/559 (0.00%)	0	3/578 (0.52%)	3
Glomerular filtration rate decreased ^† 1	0/559 (0.00%)	0	2/578 (0.35%)	2
Hemoglobin urine positive ^† 1	2/559 (0.36%)	3	0/578 (0.00%)	0
Hemorrhage urinary tract ^† 1	2/559 (0.36%)	3	2/578 (0.35%)	2
Kidney pain ^† 1	1/559 (0.18%)	1	0/578 (0.00%)	0
Kidney perforation ^† 1	1/559 (0.18%)	2	0/578 (0.00%)	0
Proteinuria ^† 1	159/559 (28.44%)	335	43/578 (7.44%)	62
Renal failure ^† 1	7/559 (1.25%)	7	3/578 (0.52%)	3
Renal hemorrhage ^† 1	0/559 (0.00%)	0	1/578 (0.17%)	1
Ureteric hemorrhage ^† 1	0/559 (0.00%)	0	1/578 (0.17%)	1
Ureteric obstruction ^† 1	0/559 (0.00%)	0	2/578 (0.35%)	7
Ureteric stenosis ^† 1	1/559 (0.18%)	1	0/578 (0.00%)	0
Urinary frequency ^† 1	6/559 (1.07%)	8	4/578 (0.69%)	4
Urinary incontinence ^† 1	0/559 (0.00%)	0	5/578 (0.87%)	9
Urinary retention ^† 1	5/559 (0.89%)	8	2/578 (0.35%)	3
Urogenital disorder ^† 1	1/559 (0.18%)	1	1/578 (0.17%)	1
Reproductive system and breast disorders
Erectile dysfunction ^† 1	2/559 (0.36%)	3	1/578 (0.17%)	4
Gynecomastia ^† 1	1/559 (0.18%)	2	0/578 (0.00%)	0
Pelvic pain ^† 1	0/559 (0.00%)	0	3/578 (0.52%)	3
Prostatic obstruction ^† 1	0/559 (0.00%)	0	1/578 (0.17%)	1
Vaginal dryness ^† 1	1/559 (0.18%)	1	0/578 (0.00%)	0
Vaginal fistula ^† 1	1/559 (0.18%)	1	0/578 (0.00%)	0
Vaginal hemorrhage ^† 1	2/559 (0.36%)	3	3/578 (0.52%)	4
Vaginal inflammation ^† 1	1/559 (0.18%)	3	1/578 (0.17%)	1
Vaginal mucositis ^† 1	0/559 (0.00%)	0	1/578 (0.17%)	1
Respiratory, thoracic and mediastinal disorders
Allergic rhinitis ^† 1	9/559 (1.61%)	16	4/578 (0.69%)	4
Apnea ^† 1	1/559 (0.18%)	2	1/578 (0.17%)	1
Aspiration ^† 1	1/559 (0.18%)	1	0/578 (0.00%)	0
Bronchospasm ^† 1	2/559 (0.36%)	2	2/578 (0.35%)	4
Cough ^† 1	17/559 (3.04%)	21	11/578 (1.90%)	29
Dyspnea ^† 1	33/559 (5.90%)	53	37/578 (6.40%)	61
Dyspnea (shortness of breath) ^† 1	1/559 (0.18%)	9	1/578 (0.17%)	1
Epistaxis ^† 1	18/559 (3.22%)	29	2/578 (0.35%)	2
Hiccups ^† 1	9/559 (1.61%)	12	4/578 (0.69%)	5
Hypoxia ^† 1	4/559 (0.72%)	6	8/578 (1.38%)	8
Laryngeal edema ^† 1	1/559 (0.18%)	1	0/578 (0.00%)	0
Nasal congestion ^† 1	3/559 (0.54%)	3	3/578 (0.52%)	4
Pharyngeal examination abnormal ^† 1	2/559 (0.36%)	2	2/578 (0.35%)	4
Pharyngeal mucositis ^† 1	1/559 (0.18%)	1	1/578 (0.17%)	1
Pharyngolaryngeal pain ^† 1	3/559 (0.54%)	3	0/578 (0.00%)	0
Pleural effusion ^† 1	0/559 (0.00%)	0	2/578 (0.35%)	2
Pleural hemorrhage ^† 1	0/559 (0.00%)	0	1/578 (0.17%)	1
Pleuritic pain ^† 1	1/559 (0.18%)	1	1/578 (0.17%)	1
Pneumonitis ^† 1	5/559 (0.89%)	6	9/578 (1.56%)	9
Pneumothorax ^† 1	0/559 (0.00%)	0	1/578 (0.17%)	1
Respiratory disorder ^† 1	1/559 (0.18%)	1	1/578 (0.17%)	1
Respiratory tract hemorrhage ^† 1	1/559 (0.18%)	1	0/578 (0.00%)	0
Tracheoscopy abnormal ^† 1	0/559 (0.00%)	0	1/578 (0.17%)	2
Voice alteration ^† 1	4/559 (0.72%)	12	2/578 (0.35%)	2
Skin and subcutaneous tissue disorders
Alopecia ^† 1	16/559 (2.86%)	35	18/578 (3.11%)	27
Body odor ^† 1	1/559 (0.18%)	1	0/578 (0.00%)	0
Decubitus ulcer ^† 1	1/559 (0.18%)	1	5/578 (0.87%)	7
Dry skin ^† 1	6/559 (1.07%)	12	38/578 (6.57%)	74
Erythema multiforme ^† 1	3/559 (0.54%)	3	11/578 (1.90%)	18
Hand-and-foot syndrome ^† 1	24/559 (4.29%)	53	46/578 (7.96%)	71
Nail disorder ^† 1	6/559 (1.07%)	8	20/578 (3.46%)	40
Pain of skin ^† 1	2/559 (0.36%)	2	7/578 (1.21%)	7
Pruritus ^† 1	3/559 (0.54%)	4	23/578 (3.98%)	27
Rash acneiform ^† 1	9/559 (1.61%)	15	123/578 (21.28%)	271
Rash desquamating ^† 1	13/559 (2.33%)	16	66/578 (11.42%)	110
Rash/dermatitis associated with high-dose chemotherapy or BMT studies. ^† 1	0/559 (0.00%)	0	1/578 (0.17%)	1
Scalp pain ^† 1	0/559 (0.00%)	0	2/578 (0.35%)	2
Skin disorder ^† 1	5/559 (0.89%)	6	31/578 (5.36%)	53
Skin hyperpigmentation ^† 1	6/559 (1.07%)	15	6/578 (1.04%)	16
Skin hypopigmentation ^† 1	0/559 (0.00%)	0	1/578 (0.17%)	1
Skin induration ^† 1	0/559 (0.00%)	0	1/578 (0.17%)	1
Skin ulceration ^† 1	3/559 (0.54%)	3	5/578 (0.87%)	5
Sweating ^† 1	9/559 (1.61%)	12	7/578 (1.21%)	21
Urticaria ^† 1	3/559 (0.54%)	4	0/578 (0.00%)	0
Vascular disorders
Flushing ^† 1	1/559 (0.18%)	1	1/578 (0.17%)	1
Hot flashes ^† 1	1/559 (0.18%)	1	4/578 (0.69%)	8
Hypertension ^† 1	179/559 (32.02%)	402	80/578 (13.84%)	184
Hypotension ^† 1	23/559 (4.11%)	25	35/578 (6.06%)	40
Lymph leakage ^† 1	1/559 (0.18%)	1	0/578 (0.00%)	0
Lymphedema ^† 1	1/559 (0.18%)	1	0/578 (0.00%)	0
Phlebitis ^† 1	2/559 (0.36%)	3	2/578 (0.35%)	2
Thrombosis ^† 1	44/559 (7.87%)	97	50/578 (8.65%)	95
Vascular disorder ^† 1	2/559 (0.36%)	2	3/578 (0.52%)	5
† Indicates events were collected by systematic assessment 1 Term from vocabulary, MedDRA 5

Limitations and Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

Results Point of Contact

Layout table for Results Point of Contact information

Name/Title:	Alan Venook, M.D.
Organization:	Alliance for Clinical Trials in Oncology
EMail:	Venook@cc.ucsf.edu

Publications of Results:

Venook AP, Blanke CD, Niedzwiecki D, Lenz HJ, Taylor JR, Hollis DR, Sutherland S, Goldberg RM. Revisiting the Cancer and Leukemia Group B/Southwest Oncology Group 80405 Trial: a phase III trial of chemotherapy and biologic agents for patients with untreated advanced colorectal adenocarcinoma. Clin Colorectal Cancer. 2007 May;6(7):536-8. doi: 10.3816/CCC.2007.n.021. No abstract available.

Venook AP, Blanke CD, Niedzwiecki D, Lenz HJ, Taylor JR, Hollis DR, Sutherland S, Goldberg RM. Cancer and Leukemia Group B/Southwest Oncology Group trial 80405: a phase III trial of chemotherapy and biologics for patients with untreated advanced colorectal adenocarcinoma. Clin Colorectal Cancer. 2005 Nov;5(4):292-4. doi: 10.3816/ccc.2005.n.043. No abstract available.

Other Publications:

Schrag D, Naughton M, Kesselheim A, et al.: Clinical trial participants' strategies for coping with prescription drug costs: A companion study to CALGB 80405. [Abstract] J Clin Oncol 27 (Suppl 15): A-9503, 2009.

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Yuan C, Sato K, Hollis BW, Zhang S, Niedzwiecki D, Ou FS, Chang IW, O'Neil BH, Innocenti F, Lenz HJ, Blanke CD, Goldberg RM, Venook AP, Mayer RJ, Fuchs CS, Meyerhardt JA, Ng K. Plasma 25-Hydroxyvitamin D Levels and Survival in Patients with Advanced or Metastatic Colorectal Cancer: Findings from CALGB/SWOG 80405 (Alliance). Clin Cancer Res. 2019 Dec 15;25(24):7497-7505. doi: 10.1158/1078-0432.CCR-19-0877. Epub 2019 Sep 23.

Guercio BJ, Zhang S, Ou FS, Venook AP, Niedzwiecki D, Lenz HJ, Innocenti F, O'Neil BH, Shaw JE, Polite BN, Hochster HS, Atkins JN, Goldberg RM, Sato K, Ng K, Van Blarigan E, Mayer RJ, Blanke CD, O'Reilly EM, Fuchs CS, Meyerhardt JA. Associations of Physical Activity With Survival and Progression in Metastatic Colorectal Cancer: Results From Cancer and Leukemia Group B (Alliance)/SWOG 80405. J Clin Oncol. 2019 Oct 10;37(29):2620-2631. doi: 10.1200/JCO.19.01019. Epub 2019 Aug 13.

Lenz HJ, Ou FS, Venook AP, Hochster HS, Niedzwiecki D, Goldberg RM, Mayer RJ, Bertagnolli MM, Blanke CD, Zemla T, Qu X, Wirapati P, Tejpar S, Innocenti F, Kabbarah O. Impact of Consensus Molecular Subtype on Survival in Patients With Metastatic Colorectal Cancer: Results From CALGB/SWOG 80405 (Alliance). J Clin Oncol. 2019 Aug 1;37(22):1876-1885. doi: 10.1200/JCO.18.02258. Epub 2019 May 1. Erratum In: J Clin Oncol. 2020 Feb 20;38(6):656.

Venook AP, Niedzwiecki D, Lenz HJ, Innocenti F, Fruth B, Meyerhardt JA, Schrag D, Greene C, O'Neil BH, Atkins JN, Berry S, Polite BN, O'Reilly EM, Goldberg RM, Hochster HS, Schilsky RL, Bertagnolli MM, El-Khoueiry AB, Watson P, Benson AB 3rd, Mulkerin DL, Mayer RJ, Blanke C. Effect of First-Line Chemotherapy Combined With Cetuximab or Bevacizumab on Overall Survival in Patients With KRAS Wild-Type Advanced or Metastatic Colorectal Cancer: A Randomized Clinical Trial. JAMA. 2017 Jun 20;317(23):2392-2401. doi: 10.1001/jama.2017.7105.

Layout table for additonal information

Responsible Party:	Alliance for Clinical Trials in Oncology
ClinicalTrials.gov Identifier:	NCT00265850
Other Study ID Numbers:	CALGB 80405 U10CA037447 ( U.S. NIH Grant/Contract ) CDR0000455161 ( Other Identifier: Physician Data Query ) NCI-2009-00434 ( Registry Identifier: NCI Clinical Trial Reporting Program Office )
First Submitted:	December 14, 2005
First Posted:	December 15, 2005
Results First Submitted:	March 13, 2017
Results First Posted:	April 26, 2017
Last Update Posted:	May 7, 2020

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