Trial Outcomes & Findings for Combination Chemotherapy Plus Bevacizumab With or Without Oxaliplatin in Treating Older Patients With Metastatic Colorectal Cancer (NCT NCT01279681)

Last Updated: 2017-12-08

Results Overview

Progression was defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions. Progression free survival was defined as the time (in months) from the date of randomization to the date of documented disease progression or death, whichever occurs first. Patients were followed until progression (and progression was declared) regardless of whether the patient was on the first line treatment or not. Patients who progress following a missed scan will have their date of progression back-dated to the date of missing scan. Patients without a progression who are still alive at the time of analysis will be censored at the date of last follow-up.

Recruitment status

TERMINATED

Study phase

PHASE3

Target enrollment

32 participants

Primary outcome timeframe

Up to 5 years

Results posted on

2017-12-08

Participant Flow

Thirty-two participants were enrolled between January 2011 and December 2012. The trial was terminated prematurely due to poor accrual and limited cooperative group resources. All follow-up was discontinued November 1, 2014.

Prior to randomization, physician chose fluoropyrimidine type \[ie, oral Capecitabine (Xeloda) or infusional 5FU\]. Patient was randomly assigned to arm A \[fluoropyrimidine + bevacizumab (BEV)\] or arm B \[fluoropyrimidine/oxaliplatin (OXAL) + BEV\] using chosen fluoropyrimidine. LV=Leucovorin, mFOLFOX7=5FU+LV+OXAL.

Participant milestones

Participant milestones
Measure	Arm A [Fluoropyrimidine + Bevacizumab (BEV)] Patients receive either 5FU/LV or Capecitabine, plus BEV. 5FU/LV + BEV is comprised of 5FU IV over 46-48 hours, LV calcium IV over 2 hours, and BEV IV over 10-90 minutes on day 1. Courses repeat every 14 days in the absence of disease progression or unacceptable toxicity. Capecitabine + BEV is comprised of capecitabine PO BID on days 1-14 and BEV IV over 30-90 minutes on day 1. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.	Arm B [Fluoropyrimidine/Oxaliplatin (OXAL) + BEV] Patients receive either mFOLFOX7 plus BEV, or Capecitabine + OXAL (XELOX) plus BEV. mFOLFOX7 + BEV is comprised of OXAL IV over 2 hours, LV calcium IV over 2 hours, and 5FU IV over 46-48 hours on day 1. Patients also receive BEV IV over 10-90 minutes on day 1. Courses repeat every 14 days in the absence of disease progression or unacceptable toxicity. XELOX + BEV is comprised of OXAL IV over 2 hours on day 1 and capecitabine PO BID on days 1-14. Patients also receive BEV IV over 30-90 minutes on day 1. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
Overall Study STARTED	15	17
Overall Study COMPLETED	0	0
Overall Study NOT COMPLETED	15	17

Reasons for withdrawal

Reasons for withdrawal
Measure	Arm A [Fluoropyrimidine + Bevacizumab (BEV)] Patients receive either 5FU/LV or Capecitabine, plus BEV. 5FU/LV + BEV is comprised of 5FU IV over 46-48 hours, LV calcium IV over 2 hours, and BEV IV over 10-90 minutes on day 1. Courses repeat every 14 days in the absence of disease progression or unacceptable toxicity. Capecitabine + BEV is comprised of capecitabine PO BID on days 1-14 and BEV IV over 30-90 minutes on day 1. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.	Arm B [Fluoropyrimidine/Oxaliplatin (OXAL) + BEV] Patients receive either mFOLFOX7 plus BEV, or Capecitabine + OXAL (XELOX) plus BEV. mFOLFOX7 + BEV is comprised of OXAL IV over 2 hours, LV calcium IV over 2 hours, and 5FU IV over 46-48 hours on day 1. Patients also receive BEV IV over 10-90 minutes on day 1. Courses repeat every 14 days in the absence of disease progression or unacceptable toxicity. XELOX + BEV is comprised of OXAL IV over 2 hours on day 1 and capecitabine PO BID on days 1-14. Patients also receive BEV IV over 30-90 minutes on day 1. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
Overall Study Disease Progression	9	6
Overall Study Withdrawal by Subject	3	4
Overall Study Adverse Event	2	3
Overall Study Death	0	1
Overall Study Withdrawal Prior to Beginning Treatment	0	1
Overall Study Physician Decision	1	0
Overall Study Other Reason	0	2

Baseline Characteristics

Combination Chemotherapy Plus Bevacizumab With or Without Oxaliplatin in Treating Older Patients With Metastatic Colorectal Cancer

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Arm A [Fluoropyrimidine + Bevacizumab (BEV)] n=15 Participants Patients receive either 5FU/LV or Capecitabine, plus BEV. 5FU/LV + BEV is comprised of 5FU IV over 46-48 hours, LV calcium IV over 2 hours, and BEV IV over 10-90 minutes on day 1. Courses repeat every 14 days in the absence of disease progression or unacceptable toxicity. Capecitabine + BEV is comprised of capecitabine PO BID on days 1-14 and BEV IV over 30-90 minutes on day 1. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.	Arm B [Fluoropyrimidine/Oxaliplatin (OXAL) + BEV] n=17 Participants Patients receive either mFOLFOX7 plus BEV, or Capecitabine + OXAL (XELOX) plus BEV. mFOLFOX7 + BEV is comprised of OXAL IV over 2 hours, LV calcium IV over 2 hours, and 5FU IV over 46-48 hours on day 1. Patients also receive BEV IV over 10-90 minutes on day 1. Courses repeat every 14 days in the absence of disease progression or unacceptable toxicity. XELOX + BEV is comprised of OXAL IV over 2 hours on day 1 and capecitabine PO BID on days 1-14. Patients also receive BEV IV over 30-90 minutes on day 1. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.	Total n=32 Participants Total of all reporting groups
Age, Continuous	75 years n=5 Participants	77 years n=7 Participants	75.5 years n=5 Participants
Age, Customized 70-74 years	7 Participants n=5 Participants	7 Participants n=7 Participants	14 Participants n=5 Participants
Age, Customized 75-79 years	7 Participants n=5 Participants	7 Participants n=7 Participants	14 Participants n=5 Participants
Age, Customized 80-84 years	1 Participants n=5 Participants	2 Participants n=7 Participants	3 Participants n=5 Participants
Age, Customized 85+ years	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Sex: Female, Male Female	6 Participants n=5 Participants	6 Participants n=7 Participants	12 Participants n=5 Participants
Sex: Female, Male Male	9 Participants n=5 Participants	11 Participants n=7 Participants	20 Participants n=5 Participants
Race/Ethnicity, Customized White	13 Participants n=5 Participants	17 Participants n=7 Participants	30 Participants n=5 Participants
Race/Ethnicity, Customized Black or African American	2 Participants n=5 Participants	0 Participants n=7 Participants	2 Participants n=5 Participants
Eastern Cooperative Oncology Group (ECOG) Performance Status 0-1	14 Participants n=5 Participants	15 Participants n=7 Participants	29 Participants n=5 Participants
Eastern Cooperative Oncology Group (ECOG) Performance Status 2	1 Participants n=5 Participants	2 Participants n=7 Participants	3 Participants n=5 Participants
Number of Metastatic Sites 1	5 Participants n=5 Participants	5 Participants n=7 Participants	10 Participants n=5 Participants
Number of Metastatic Sites >1	10 Participants n=5 Participants	12 Participants n=7 Participants	22 Participants n=5 Participants
Physician determined 5-FU choice prior to randomization Infusional	7 Participants n=5 Participants	13 Participants n=7 Participants	20 Participants n=5 Participants
Physician determined 5-FU choice prior to randomization Capecitabine	8 Participants n=5 Participants	4 Participants n=7 Participants	12 Participants n=5 Participants

PRIMARY outcome

Timeframe: Up to 5 years

Population: One participant who refused to initiate study treatment following randomization was excluded from the analysis.

Outcome measures

Outcome measures
Measure	Arm A [Fluoropyrimidine + Bevacizumab (BEV)] n=15 Participants Patients receive either 5FU/LV or Capecitabine, plus BEV. 5FU/LV + BEV is comprised of 5FU IV over 46-48 hours, LV calcium IV over 2 hours, and BEV IV over 10-90 minutes on day 1. Courses repeat every 14 days in the absence of disease progression or unacceptable toxicity. Capecitabine + BEV is comprised of capecitabine PO BID on days 1-14 and BEV IV over 30-90 minutes on day 1. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.	Arm B [Fluoropyrimidine/Oxaliplatin (OXAL) + BEV] n=16 Participants Patients receive either mFOLFOX7 plus BEV, or Capecitabine + OXAL (XELOX) plus BEV. mFOLFOX7 + BEV is comprised of OXAL IV over 2 hours, LV calcium IV over 2 hours, and 5FU IV over 46-48 hours on day 1. Patients also receive BEV IV over 10-90 minutes on day 1. Courses repeat every 14 days in the absence of disease progression or unacceptable toxicity. XELOX + BEV is comprised of OXAL IV over 2 hours on day 1 and capecitabine PO BID on days 1-14. Patients also receive BEV IV over 30-90 minutes on day 1. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
Progression-Free Survival	6.7 months Interval 5.7 to 13.4	6.7 months Interval 6.0 to 10.6

SECONDARY outcome

Timeframe: Up to 5 years

Population: One participant who refused to initiate study treatment following randomization was excluded from the analysis.

Overall survival was defined as the time (in months) from randomization to death.

Outcome measures

Outcome measures
Measure	Arm A [Fluoropyrimidine + Bevacizumab (BEV)] n=15 Participants Patients receive either 5FU/LV or Capecitabine, plus BEV. 5FU/LV + BEV is comprised of 5FU IV over 46-48 hours, LV calcium IV over 2 hours, and BEV IV over 10-90 minutes on day 1. Courses repeat every 14 days in the absence of disease progression or unacceptable toxicity. Capecitabine + BEV is comprised of capecitabine PO BID on days 1-14 and BEV IV over 30-90 minutes on day 1. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.	Arm B [Fluoropyrimidine/Oxaliplatin (OXAL) + BEV] n=16 Participants Patients receive either mFOLFOX7 plus BEV, or Capecitabine + OXAL (XELOX) plus BEV. mFOLFOX7 + BEV is comprised of OXAL IV over 2 hours, LV calcium IV over 2 hours, and 5FU IV over 46-48 hours on day 1. Patients also receive BEV IV over 10-90 minutes on day 1. Courses repeat every 14 days in the absence of disease progression or unacceptable toxicity. XELOX + BEV is comprised of OXAL IV over 2 hours on day 1 and capecitabine PO BID on days 1-14. Patients also receive BEV IV over 30-90 minutes on day 1. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
Overall Survival	18.8 months Interval 16.1 to 29.3	15.4 months Interval 9.9 to Upper limit of 95% CI is not attainable due to insufficient number of participants with events

SECONDARY outcome

Timeframe: Up to 5 years

Population: One participant who refused to initiate study treatment following randomization was excluded from the analysis.

Response was defined using Response Evaluation Criteria In Solid Tumors (RECIST) criteria: * Complete Response (CR): disappearance of all target lesions; * Partial Response (PR) 30% decrease in sum of longest diameter of target lesions; * Progressive Disease (PD): 20% increase in sum of longest diameter of target lesions; * Stable Disease (SD): small changes that do not meet above criteria. Response rate is reported as the percentage of participants who achieved Complete Response or Partial Response.

Outcome measures

Outcome measures
Measure	Arm A [Fluoropyrimidine + Bevacizumab (BEV)] n=15 Participants Patients receive either 5FU/LV or Capecitabine, plus BEV. 5FU/LV + BEV is comprised of 5FU IV over 46-48 hours, LV calcium IV over 2 hours, and BEV IV over 10-90 minutes on day 1. Courses repeat every 14 days in the absence of disease progression or unacceptable toxicity. Capecitabine + BEV is comprised of capecitabine PO BID on days 1-14 and BEV IV over 30-90 minutes on day 1. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.	Arm B [Fluoropyrimidine/Oxaliplatin (OXAL) + BEV] n=16 Participants Patients receive either mFOLFOX7 plus BEV, or Capecitabine + OXAL (XELOX) plus BEV. mFOLFOX7 + BEV is comprised of OXAL IV over 2 hours, LV calcium IV over 2 hours, and 5FU IV over 46-48 hours on day 1. Patients also receive BEV IV over 10-90 minutes on day 1. Courses repeat every 14 days in the absence of disease progression or unacceptable toxicity. XELOX + BEV is comprised of OXAL IV over 2 hours on day 1 and capecitabine PO BID on days 1-14. Patients also receive BEV IV over 30-90 minutes on day 1. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
Response Rate, Defined as the Percentage of Patients in Each Arm Who Have an Objective Status of Complete Response or Partial Response, Confirmed by a Second Assessment Measured at Least 6 Weeks From the Initial Assessment	47 percentage of participants Interval 21.0 to 73.0	38 percentage of participants Interval 15.0 to 65.0

SECONDARY outcome

Timeframe: Up to 42 days after treatment discontinuation

Population: One participant who refused to initiate study treatment following randomization was excluded from the analysis.

Adverse events were assessed using the NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0

Outcome measures

Outcome measures
Measure	Arm A [Fluoropyrimidine + Bevacizumab (BEV)] n=15 Participants Patients receive either 5FU/LV or Capecitabine, plus BEV. 5FU/LV + BEV is comprised of 5FU IV over 46-48 hours, LV calcium IV over 2 hours, and BEV IV over 10-90 minutes on day 1. Courses repeat every 14 days in the absence of disease progression or unacceptable toxicity. Capecitabine + BEV is comprised of capecitabine PO BID on days 1-14 and BEV IV over 30-90 minutes on day 1. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.	Arm B [Fluoropyrimidine/Oxaliplatin (OXAL) + BEV] n=16 Participants Patients receive either mFOLFOX7 plus BEV, or Capecitabine + OXAL (XELOX) plus BEV. mFOLFOX7 + BEV is comprised of OXAL IV over 2 hours, LV calcium IV over 2 hours, and 5FU IV over 46-48 hours on day 1. Patients also receive BEV IV over 10-90 minutes on day 1. Courses repeat every 14 days in the absence of disease progression or unacceptable toxicity. XELOX + BEV is comprised of OXAL IV over 2 hours on day 1 and capecitabine PO BID on days 1-14. Patients also receive BEV IV over 30-90 minutes on day 1. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
Number of Participants With Grade 3 Adverse Events At Least Possibly Related to Treatment Neutropenia	0 Participants	1 Participants
Number of Participants With Grade 3 Adverse Events At Least Possibly Related to Treatment Nausea	1 Participants	0 Participants
Number of Participants With Grade 3 Adverse Events At Least Possibly Related to Treatment Vomiting	0 Participants	1 Participants
Number of Participants With Grade 3 Adverse Events At Least Possibly Related to Treatment Mucositis	1 Participants	1 Participants
Number of Participants With Grade 3 Adverse Events At Least Possibly Related to Treatment Fatigue	2 Participants	1 Participants
Number of Participants With Grade 3 Adverse Events At Least Possibly Related to Treatment Peripheral sensory neuropathy	0 Participants	1 Participants
Number of Participants With Grade 3 Adverse Events At Least Possibly Related to Treatment Fall	1 Participants	0 Participants
Number of Participants With Grade 3 Adverse Events At Least Possibly Related to Treatment Anorexia	2 Participants	0 Participants
Number of Participants With Grade 3 Adverse Events At Least Possibly Related to Treatment Hyperglycemia	0 Participants	1 Participants
Number of Participants With Grade 3 Adverse Events At Least Possibly Related to Treatment Palmar-plantar erythrodysesthesia	5 Participants	1 Participants
Number of Participants With Grade 3 Adverse Events At Least Possibly Related to Treatment Hypertension	2 Participants	4 Participants
Number of Participants With Grade 3 Adverse Events At Least Possibly Related to Treatment Thromboembolic events	1 Participants	1 Participants
Number of Participants With Grade 3 Adverse Events At Least Possibly Related to Treatment Anemia	0 Participants	1 Participants
Number of Participants With Grade 3 Adverse Events At Least Possibly Related to Treatment Hyponatremia	2 Participants	1 Participants
Number of Participants With Grade 3 Adverse Events At Least Possibly Related to Treatment Dysesthesia	0 Participants	1 Participants
Number of Participants With Grade 3 Adverse Events At Least Possibly Related to Treatment Ejection fraction descreased	0 Participants	1 Participants
Number of Participants With Grade 3 Adverse Events At Least Possibly Related to Treatment Chronic kidney disease	0 Participants	1 Participants
Number of Participants With Grade 3 Adverse Events At Least Possibly Related to Treatment Back pain	0 Participants	1 Participants

Adverse Events

Arm A [Fluoropyrimidine + Bevacizumab (BEV)]

Serious events: 5 serious events

Other events: 15 other events

Deaths: 0 deaths

Arm B [Fluoropyrimidine/Oxaliplatin (OXAL) + BEV]

Serious events: 3 serious events

Other events: 16 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Additional Information

Joleen M. Hubbard, M.D.

Mayo Clinic

Phone: 507 284-3121

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Restriction type: LTE60

Measure	Arm A [Fluoropyrimidine + Bevacizumab (BEV)] n=15 participants at risk Patients receive either 5FU/LV or Capecitabine, plus BEV. 5FU/LV + BEV is comprised of 5FU IV over 46-48 hours, LV calcium IV over 2 hours, and BEV IV over 10-90 minutes on day 1. Courses repeat every 14 days in the absence of disease progression or unacceptable toxicity. Capecitabine + BEV is comprised of capecitabine PO BID on days 1-14 and BEV IV over 30-90 minutes on day 1. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.	Arm B [Fluoropyrimidine/Oxaliplatin (OXAL) + BEV] n=16 participants at risk Patients receive either mFOLFOX7 plus BEV, or Capecitabine + OXAL (XELOX) plus BEV. mFOLFOX7 + BEV is comprised of OXAL IV over 2 hours, LV calcium IV over 2 hours, and 5FU IV over 46-48 hours on day 1. Patients also receive BEV IV over 10-90 minutes on day 1. Courses repeat every 14 days in the absence of disease progression or unacceptable toxicity. XELOX + BEV is comprised of OXAL IV over 2 hours on day 1 and capecitabine PO BID on days 1-14. Patients also receive BEV IV over 30-90 minutes on day 1. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
Cardiac disorders Atrial fibrillation	0.00% 0/15 • Up to 3 years Excluded one participant who refused to initiate study treatment following randomization.	6.2% 1/16 • Number of events 1 • Up to 3 years Excluded one participant who refused to initiate study treatment following randomization.
Gastrointestinal disorders Abdominal pain	6.7% 1/15 • Number of events 1 • Up to 3 years Excluded one participant who refused to initiate study treatment following randomization.	0.00% 0/16 • Up to 3 years Excluded one participant who refused to initiate study treatment following randomization.
Gastrointestinal disorders Colonic obstruction	6.7% 1/15 • Number of events 1 • Up to 3 years Excluded one participant who refused to initiate study treatment following randomization.	6.2% 1/16 • Number of events 1 • Up to 3 years Excluded one participant who refused to initiate study treatment following randomization.
Gastrointestinal disorders Colonic perforation	0.00% 0/15 • Up to 3 years Excluded one participant who refused to initiate study treatment following randomization.	6.2% 1/16 • Number of events 1 • Up to 3 years Excluded one participant who refused to initiate study treatment following randomization.
Gastrointestinal disorders Constipation	6.7% 1/15 • Number of events 1 • Up to 3 years Excluded one participant who refused to initiate study treatment following randomization.	0.00% 0/16 • Up to 3 years Excluded one participant who refused to initiate study treatment following randomization.
Gastrointestinal disorders Diarrhea	0.00% 0/15 • Up to 3 years Excluded one participant who refused to initiate study treatment following randomization.	6.2% 1/16 • Number of events 1 • Up to 3 years Excluded one participant who refused to initiate study treatment following randomization.
Gastrointestinal disorders Mucositis oral	6.7% 1/15 • Number of events 1 • Up to 3 years Excluded one participant who refused to initiate study treatment following randomization.	0.00% 0/16 • Up to 3 years Excluded one participant who refused to initiate study treatment following randomization.
Gastrointestinal disorders Nausea	6.7% 1/15 • Number of events 1 • Up to 3 years Excluded one participant who refused to initiate study treatment following randomization.	0.00% 0/16 • Up to 3 years Excluded one participant who refused to initiate study treatment following randomization.
Gastrointestinal disorders Vomiting	0.00% 0/15 • Up to 3 years Excluded one participant who refused to initiate study treatment following randomization.	6.2% 1/16 • Number of events 1 • Up to 3 years Excluded one participant who refused to initiate study treatment following randomization.
General disorders Edema limbs	6.7% 1/15 • Number of events 2 • Up to 3 years Excluded one participant who refused to initiate study treatment following randomization.	0.00% 0/16 • Up to 3 years Excluded one participant who refused to initiate study treatment following randomization.
General disorders Fatigue	13.3% 2/15 • Number of events 2 • Up to 3 years Excluded one participant who refused to initiate study treatment following randomization.	0.00% 0/16 • Up to 3 years Excluded one participant who refused to initiate study treatment following randomization.
Immune system disorders Allergic reaction	0.00% 0/15 • Up to 3 years Excluded one participant who refused to initiate study treatment following randomization.	6.2% 1/16 • Number of events 1 • Up to 3 years Excluded one participant who refused to initiate study treatment following randomization.
Infections and infestations Skin infection	0.00% 0/15 • Up to 3 years Excluded one participant who refused to initiate study treatment following randomization.	6.2% 1/16 • Number of events 1 • Up to 3 years Excluded one participant who refused to initiate study treatment following randomization.
Metabolism and nutrition disorders Dehydration	6.7% 1/15 • Number of events 1 • Up to 3 years Excluded one participant who refused to initiate study treatment following randomization.	6.2% 1/16 • Number of events 1 • Up to 3 years Excluded one participant who refused to initiate study treatment following randomization.
Metabolism and nutrition disorders Hyperglycemia	6.7% 1/15 • Number of events 1 • Up to 3 years Excluded one participant who refused to initiate study treatment following randomization.	0.00% 0/16 • Up to 3 years Excluded one participant who refused to initiate study treatment following randomization.
Metabolism and nutrition disorders Hyponatremia	6.7% 1/15 • Number of events 1 • Up to 3 years Excluded one participant who refused to initiate study treatment following randomization.	0.00% 0/16 • Up to 3 years Excluded one participant who refused to initiate study treatment following randomization.
Musculoskeletal and connective tissue disorders Musculoskeletal and connective tissue disorder - Other, specify	6.7% 1/15 • Number of events 2 • Up to 3 years Excluded one participant who refused to initiate study treatment following randomization.	0.00% 0/16 • Up to 3 years Excluded one participant who refused to initiate study treatment following randomization.
Vascular disorders Hypertension	13.3% 2/15 • Number of events 3 • Up to 3 years Excluded one participant who refused to initiate study treatment following randomization.	0.00% 0/16 • Up to 3 years Excluded one participant who refused to initiate study treatment following randomization.
Vascular disorders Hypotension	0.00% 0/15 • Up to 3 years Excluded one participant who refused to initiate study treatment following randomization.	6.2% 1/16 • Number of events 1 • Up to 3 years Excluded one participant who refused to initiate study treatment following randomization.
Vascular disorders Vascular disorders - Other, specify	0.00% 0/15 • Up to 3 years Excluded one participant who refused to initiate study treatment following randomization.	6.2% 1/16 • Number of events 1 • Up to 3 years Excluded one participant who refused to initiate study treatment following randomization.

Measure	Arm A [Fluoropyrimidine + Bevacizumab (BEV)] n=15 participants at risk Patients receive either 5FU/LV or Capecitabine, plus BEV. 5FU/LV + BEV is comprised of 5FU IV over 46-48 hours, LV calcium IV over 2 hours, and BEV IV over 10-90 minutes on day 1. Courses repeat every 14 days in the absence of disease progression or unacceptable toxicity. Capecitabine + BEV is comprised of capecitabine PO BID on days 1-14 and BEV IV over 30-90 minutes on day 1. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.	Arm B [Fluoropyrimidine/Oxaliplatin (OXAL) + BEV] n=16 participants at risk Patients receive either mFOLFOX7 plus BEV, or Capecitabine + OXAL (XELOX) plus BEV. mFOLFOX7 + BEV is comprised of OXAL IV over 2 hours, LV calcium IV over 2 hours, and 5FU IV over 46-48 hours on day 1. Patients also receive BEV IV over 10-90 minutes on day 1. Courses repeat every 14 days in the absence of disease progression or unacceptable toxicity. XELOX + BEV is comprised of OXAL IV over 2 hours on day 1 and capecitabine PO BID on days 1-14. Patients also receive BEV IV over 30-90 minutes on day 1. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
Blood and lymphatic system disorders Anemia	0.00% 0/15 • Up to 3 years Excluded one participant who refused to initiate study treatment following randomization.	18.8% 3/16 • Number of events 6 • Up to 3 years Excluded one participant who refused to initiate study treatment following randomization.
Gastrointestinal disorders Abdominal pain	46.7% 7/15 • Number of events 13 • Up to 3 years Excluded one participant who refused to initiate study treatment following randomization.	12.5% 2/16 • Number of events 3 • Up to 3 years Excluded one participant who refused to initiate study treatment following randomization.
Gastrointestinal disorders Constipation	6.7% 1/15 • Number of events 1 • Up to 3 years Excluded one participant who refused to initiate study treatment following randomization.	0.00% 0/16 • Up to 3 years Excluded one participant who refused to initiate study treatment following randomization.
Gastrointestinal disorders Diarrhea	73.3% 11/15 • Number of events 73 • Up to 3 years Excluded one participant who refused to initiate study treatment following randomization.	68.8% 11/16 • Number of events 41 • Up to 3 years Excluded one participant who refused to initiate study treatment following randomization.
Gastrointestinal disorders Dysphagia	6.7% 1/15 • Number of events 1 • Up to 3 years Excluded one participant who refused to initiate study treatment following randomization.	0.00% 0/16 • Up to 3 years Excluded one participant who refused to initiate study treatment following randomization.
Gastrointestinal disorders Enterocolitis	6.7% 1/15 • Number of events 1 • Up to 3 years Excluded one participant who refused to initiate study treatment following randomization.	0.00% 0/16 • Up to 3 years Excluded one participant who refused to initiate study treatment following randomization.
Gastrointestinal disorders Esophagitis	13.3% 2/15 • Number of events 2 • Up to 3 years Excluded one participant who refused to initiate study treatment following randomization.	12.5% 2/16 • Number of events 3 • Up to 3 years Excluded one participant who refused to initiate study treatment following randomization.
Gastrointestinal disorders Mucositis oral	46.7% 7/15 • Number of events 33 • Up to 3 years Excluded one participant who refused to initiate study treatment following randomization.	37.5% 6/16 • Number of events 14 • Up to 3 years Excluded one participant who refused to initiate study treatment following randomization.
Gastrointestinal disorders Nausea	80.0% 12/15 • Number of events 33 • Up to 3 years Excluded one participant who refused to initiate study treatment following randomization.	50.0% 8/16 • Number of events 31 • Up to 3 years Excluded one participant who refused to initiate study treatment following randomization.
Gastrointestinal disorders Rectal perforation	0.00% 0/15 • Up to 3 years Excluded one participant who refused to initiate study treatment following randomization.	6.2% 1/16 • Number of events 2 • Up to 3 years Excluded one participant who refused to initiate study treatment following randomization.
Gastrointestinal disorders Vomiting	46.7% 7/15 • Number of events 12 • Up to 3 years Excluded one participant who refused to initiate study treatment following randomization.	18.8% 3/16 • Number of events 3 • Up to 3 years Excluded one participant who refused to initiate study treatment following randomization.
General disorders Edema limbs	6.7% 1/15 • Number of events 1 • Up to 3 years Excluded one participant who refused to initiate study treatment following randomization.	6.2% 1/16 • Number of events 1 • Up to 3 years Excluded one participant who refused to initiate study treatment following randomization.
General disorders Fatigue	93.3% 14/15 • Number of events 129 • Up to 3 years Excluded one participant who refused to initiate study treatment following randomization.	93.8% 15/16 • Number of events 106 • Up to 3 years Excluded one participant who refused to initiate study treatment following randomization.
General disorders Fever	6.7% 1/15 • Number of events 3 • Up to 3 years Excluded one participant who refused to initiate study treatment following randomization.	6.2% 1/16 • Number of events 1 • Up to 3 years Excluded one participant who refused to initiate study treatment following randomization.
General disorders Localized edema	0.00% 0/15 • Up to 3 years Excluded one participant who refused to initiate study treatment following randomization.	6.2% 1/16 • Number of events 1 • Up to 3 years Excluded one participant who refused to initiate study treatment following randomization.
Hepatobiliary disorders Cholecystitis	0.00% 0/15 • Up to 3 years Excluded one participant who refused to initiate study treatment following randomization.	6.2% 1/16 • Number of events 1 • Up to 3 years Excluded one participant who refused to initiate study treatment following randomization.
Infections and infestations Bladder infection	13.3% 2/15 • Number of events 4 • Up to 3 years Excluded one participant who refused to initiate study treatment following randomization.	0.00% 0/16 • Up to 3 years Excluded one participant who refused to initiate study treatment following randomization.
Infections and infestations Lung infection	6.7% 1/15 • Number of events 1 • Up to 3 years Excluded one participant who refused to initiate study treatment following randomization.	0.00% 0/16 • Up to 3 years Excluded one participant who refused to initiate study treatment following randomization.
Infections and infestations Pharyngitis	6.7% 1/15 • Number of events 1 • Up to 3 years Excluded one participant who refused to initiate study treatment following randomization.	0.00% 0/16 • Up to 3 years Excluded one participant who refused to initiate study treatment following randomization.
Infections and infestations Upper respiratory infection	6.7% 1/15 • Number of events 1 • Up to 3 years Excluded one participant who refused to initiate study treatment following randomization.	0.00% 0/16 • Up to 3 years Excluded one participant who refused to initiate study treatment following randomization.
Infections and infestations Urinary tract infection	0.00% 0/15 • Up to 3 years Excluded one participant who refused to initiate study treatment following randomization.	6.2% 1/16 • Number of events 1 • Up to 3 years Excluded one participant who refused to initiate study treatment following randomization.
Injury, poisoning and procedural complications Fall	6.7% 1/15 • Number of events 1 • Up to 3 years Excluded one participant who refused to initiate study treatment following randomization.	0.00% 0/16 • Up to 3 years Excluded one participant who refused to initiate study treatment following randomization.
Injury, poisoning and procedural complications Injury, poisoning and procedural complications - Other, specify	6.7% 1/15 • Number of events 1 • Up to 3 years Excluded one participant who refused to initiate study treatment following randomization.	0.00% 0/16 • Up to 3 years Excluded one participant who refused to initiate study treatment following randomization.
Injury, poisoning and procedural complications Wound dehiscence	6.7% 1/15 • Number of events 1 • Up to 3 years Excluded one participant who refused to initiate study treatment following randomization.	0.00% 0/16 • Up to 3 years Excluded one participant who refused to initiate study treatment following randomization.
Investigations Creatinine increased	0.00% 0/15 • Up to 3 years Excluded one participant who refused to initiate study treatment following randomization.	12.5% 2/16 • Number of events 2 • Up to 3 years Excluded one participant who refused to initiate study treatment following randomization.
Investigations Ejection fraction decreased	0.00% 0/15 • Up to 3 years Excluded one participant who refused to initiate study treatment following randomization.	6.2% 1/16 • Number of events 1 • Up to 3 years Excluded one participant who refused to initiate study treatment following randomization.
Investigations INR increased	0.00% 0/15 • Up to 3 years Excluded one participant who refused to initiate study treatment following randomization.	6.2% 1/16 • Number of events 1 • Up to 3 years Excluded one participant who refused to initiate study treatment following randomization.
Investigations Lymphocyte count decreased	13.3% 2/15 • Number of events 2 • Up to 3 years Excluded one participant who refused to initiate study treatment following randomization.	6.2% 1/16 • Number of events 1 • Up to 3 years Excluded one participant who refused to initiate study treatment following randomization.
Investigations Neutrophil count decreased	0.00% 0/15 • Up to 3 years Excluded one participant who refused to initiate study treatment following randomization.	18.8% 3/16 • Number of events 3 • Up to 3 years Excluded one participant who refused to initiate study treatment following randomization.
Investigations Weight loss	46.7% 7/15 • Number of events 24 • Up to 3 years Excluded one participant who refused to initiate study treatment following randomization.	43.8% 7/16 • Number of events 10 • Up to 3 years Excluded one participant who refused to initiate study treatment following randomization.
Investigations White blood cell decreased	0.00% 0/15 • Up to 3 years Excluded one participant who refused to initiate study treatment following randomization.	6.2% 1/16 • Number of events 1 • Up to 3 years Excluded one participant who refused to initiate study treatment following randomization.
Metabolism and nutrition disorders Anorexia	60.0% 9/15 • Number of events 44 • Up to 3 years Excluded one participant who refused to initiate study treatment following randomization.	50.0% 8/16 • Number of events 33 • Up to 3 years Excluded one participant who refused to initiate study treatment following randomization.
Metabolism and nutrition disorders Dehydration	0.00% 0/15 • Up to 3 years Excluded one participant who refused to initiate study treatment following randomization.	6.2% 1/16 • Number of events 1 • Up to 3 years Excluded one participant who refused to initiate study treatment following randomization.
Metabolism and nutrition disorders Hyperglycemia	6.7% 1/15 • Number of events 1 • Up to 3 years Excluded one participant who refused to initiate study treatment following randomization.	6.2% 1/16 • Number of events 1 • Up to 3 years Excluded one participant who refused to initiate study treatment following randomization.
Metabolism and nutrition disorders Hypoalbuminemia	0.00% 0/15 • Up to 3 years Excluded one participant who refused to initiate study treatment following randomization.	6.2% 1/16 • Number of events 1 • Up to 3 years Excluded one participant who refused to initiate study treatment following randomization.
Metabolism and nutrition disorders Hypocalcemia	0.00% 0/15 • Up to 3 years Excluded one participant who refused to initiate study treatment following randomization.	6.2% 1/16 • Number of events 1 • Up to 3 years Excluded one participant who refused to initiate study treatment following randomization.
Metabolism and nutrition disorders Hypokalemia	6.7% 1/15 • Number of events 1 • Up to 3 years Excluded one participant who refused to initiate study treatment following randomization.	6.2% 1/16 • Number of events 1 • Up to 3 years Excluded one participant who refused to initiate study treatment following randomization.
Metabolism and nutrition disorders Hypomagnesemia	0.00% 0/15 • Up to 3 years Excluded one participant who refused to initiate study treatment following randomization.	6.2% 1/16 • Number of events 1 • Up to 3 years Excluded one participant who refused to initiate study treatment following randomization.
Metabolism and nutrition disorders Hyponatremia	6.7% 1/15 • Number of events 1 • Up to 3 years Excluded one participant who refused to initiate study treatment following randomization.	12.5% 2/16 • Number of events 2 • Up to 3 years Excluded one participant who refused to initiate study treatment following randomization.
Musculoskeletal and connective tissue disorders Arthritis	6.7% 1/15 • Number of events 3 • Up to 3 years Excluded one participant who refused to initiate study treatment following randomization.	0.00% 0/16 • Up to 3 years Excluded one participant who refused to initiate study treatment following randomization.
Musculoskeletal and connective tissue disorders Back pain	6.7% 1/15 • Number of events 1 • Up to 3 years Excluded one participant who refused to initiate study treatment following randomization.	6.2% 1/16 • Number of events 1 • Up to 3 years Excluded one participant who refused to initiate study treatment following randomization.
Nervous system disorders Dysesthesia	20.0% 3/15 • Number of events 7 • Up to 3 years Excluded one participant who refused to initiate study treatment following randomization.	31.2% 5/16 • Number of events 23 • Up to 3 years Excluded one participant who refused to initiate study treatment following randomization.
Nervous system disorders Dysgeusia	6.7% 1/15 • Number of events 1 • Up to 3 years Excluded one participant who refused to initiate study treatment following randomization.	0.00% 0/16 • Up to 3 years Excluded one participant who refused to initiate study treatment following randomization.
Nervous system disorders Headache	6.7% 1/15 • Number of events 2 • Up to 3 years Excluded one participant who refused to initiate study treatment following randomization.	0.00% 0/16 • Up to 3 years Excluded one participant who refused to initiate study treatment following randomization.
Nervous system disorders Paresthesia	33.3% 5/15 • Number of events 57 • Up to 3 years Excluded one participant who refused to initiate study treatment following randomization.	50.0% 8/16 • Number of events 32 • Up to 3 years Excluded one participant who refused to initiate study treatment following randomization.
Nervous system disorders Peripheral sensory neuropathy	46.7% 7/15 • Number of events 77 • Up to 3 years Excluded one participant who refused to initiate study treatment following randomization.	56.2% 9/16 • Number of events 65 • Up to 3 years Excluded one participant who refused to initiate study treatment following randomization.
Nervous system disorders Stroke	0.00% 0/15 • Up to 3 years Excluded one participant who refused to initiate study treatment following randomization.	6.2% 1/16 • Number of events 1 • Up to 3 years Excluded one participant who refused to initiate study treatment following randomization.
Nervous system disorders Syncope	0.00% 0/15 • Up to 3 years Excluded one participant who refused to initiate study treatment following randomization.	18.8% 3/16 • Number of events 3 • Up to 3 years Excluded one participant who refused to initiate study treatment following randomization.
Psychiatric disorders Insomnia	0.00% 0/15 • Up to 3 years Excluded one participant who refused to initiate study treatment following randomization.	6.2% 1/16 • Number of events 1 • Up to 3 years Excluded one participant who refused to initiate study treatment following randomization.
Renal and urinary disorders Chronic kidney disease	6.7% 1/15 • Number of events 6 • Up to 3 years Excluded one participant who refused to initiate study treatment following randomization.	6.2% 1/16 • Number of events 1 • Up to 3 years Excluded one participant who refused to initiate study treatment following randomization.
Renal and urinary disorders Proteinuria	46.7% 7/15 • Number of events 22 • Up to 3 years Excluded one participant who refused to initiate study treatment following randomization.	25.0% 4/16 • Number of events 11 • Up to 3 years Excluded one participant who refused to initiate study treatment following randomization.
Renal and urinary disorders Urinary retention	0.00% 0/15 • Up to 3 years Excluded one participant who refused to initiate study treatment following randomization.	6.2% 1/16 • Number of events 2 • Up to 3 years Excluded one participant who refused to initiate study treatment following randomization.
Respiratory, thoracic and mediastinal disorders Cough	6.7% 1/15 • Number of events 1 • Up to 3 years Excluded one participant who refused to initiate study treatment following randomization.	0.00% 0/16 • Up to 3 years Excluded one participant who refused to initiate study treatment following randomization.
Respiratory, thoracic and mediastinal disorders Pharyngeal mucositis	6.7% 1/15 • Number of events 2 • Up to 3 years Excluded one participant who refused to initiate study treatment following randomization.	0.00% 0/16 • Up to 3 years Excluded one participant who refused to initiate study treatment following randomization.
Skin and subcutaneous tissue disorders Nail loss	6.7% 1/15 • Number of events 1 • Up to 3 years Excluded one participant who refused to initiate study treatment following randomization.	0.00% 0/16 • Up to 3 years Excluded one participant who refused to initiate study treatment following randomization.
Skin and subcutaneous tissue disorders Pain of skin	6.7% 1/15 • Number of events 1 • Up to 3 years Excluded one participant who refused to initiate study treatment following randomization.	6.2% 1/16 • Number of events 4 • Up to 3 years Excluded one participant who refused to initiate study treatment following randomization.
Skin and subcutaneous tissue disorders Palmar-plantar erythrodysesthesia syndrome	40.0% 6/15 • Number of events 24 • Up to 3 years Excluded one participant who refused to initiate study treatment following randomization.	6.2% 1/16 • Number of events 6 • Up to 3 years Excluded one participant who refused to initiate study treatment following randomization.
Skin and subcutaneous tissue disorders Skin and subcutaneous tissue disorders - Other, specify	0.00% 0/15 • Up to 3 years Excluded one participant who refused to initiate study treatment following randomization.	6.2% 1/16 • Number of events 3 • Up to 3 years Excluded one participant who refused to initiate study treatment following randomization.
Vascular disorders Hypertension	73.3% 11/15 • Number of events 79 • Up to 3 years Excluded one participant who refused to initiate study treatment following randomization.	56.2% 9/16 • Number of events 48 • Up to 3 years Excluded one participant who refused to initiate study treatment following randomization.
Vascular disorders Hypotension	0.00% 0/15 • Up to 3 years Excluded one participant who refused to initiate study treatment following randomization.	12.5% 2/16 • Number of events 2 • Up to 3 years Excluded one participant who refused to initiate study treatment following randomization.
Vascular disorders Thromboembolic event	20.0% 3/15 • Number of events 4 • Up to 3 years Excluded one participant who refused to initiate study treatment following randomization.	12.5% 2/16 • Number of events 2 • Up to 3 years Excluded one participant who refused to initiate study treatment following randomization.
Vascular disorders Vascular disorders - Other, specify	0.00% 0/15 • Up to 3 years Excluded one participant who refused to initiate study treatment following randomization.	6.2% 1/16 • Number of events 3 • Up to 3 years Excluded one participant who refused to initiate study treatment following randomization.