A Study of Avastin (Bevacizumab) in Combination With mFOL... | NCT00778102

ID	Type	Description	Link
2007-007863-26

Label	Type	Description	Intervention Names
1	Experimental		Drug: 5-FU Drug: Leucovorin Drug: Oxaliplatin Drug: bevacizumab [Avastin]
2	Active Comparator		Drug: 5-FU Drug: Irinotecan Drug: Leucovorin Drug: Oxaliplatin Drug: bevacizumab [Avastin]

Name	Type	Description	Arm Group Labels	Other Names
5-FU	Drug	Bolus 400mg/m2, day 1 every 2 weeks	1
5-FU

Measure	Description	Time Frame
Percentage of Participants With Complete Resection or Residual (Microscopic or Macroscopic) Tumor	Following resective surgery, participants were evaluated for complete resection (R0) or the presence of microscopic (R1) or macroscopic (R2) residual tumor. The percentage of participants within each residual tumor classification was calculated as [number of participants with R0, R1, and/or R2 divided by the total number of participants] multiplied by 100. Associated 95% confidence intervals were calculated for one-sample binomial using the Clopper-Pearson method.	Up to 5 years (at Screening; every 6 weeks, and within 4 weeks prior to surgery; and at time of/after surgery)

Measure	Description	Time Frame
Time to Resection	Time to resection was defined as the time from randomization to the date of first resective surgery. For participants who did not undergo resective surgery, time to resection was censored at Day 1. Time to resection was estimated by Kaplan-Meier analysis.	Up to 5 years (at Screening; prior to each cycle, and within 7 days prior to surgery; and at time of surgery)

Name	Affiliation	Role
Clinical Trials	Hoffmann-La Roche	Study Director

PubMed Identifier	Type	Citation	Retractions
32816630	Derived	Cremolini C, Antoniotti C, Stein A, Bendell J, Gruenberger T, Rossini D, Masi G, Ongaro E, Hurwitz H, Falcone A, Schmoll HJ, Di Maio M. Individual Patient Data Meta-Analysis of FOLFOXIRI Plus Bevacizumab Versus Doublets Plus Bevacizumab as Initial Therapy of Unresectable Metastatic Colorectal Cancer. J Clin Oncol. 2020 Aug 20:JCO2001225. doi: 10.1200/JCO.20.01225. Online ahead of print.
25538173

ID	Title	Description
FG000	Bevacizumab + mFOLFOX-6	Participants received a chemotherapy regimen of bevacizumab plus oxaliplatin, leucovorin, and 5-fluorouracil (5-FU) (mFOLFOX-6). Each drug was administered on Day 1 of each 2-week cycle. Dosing was as follows: bevacizumab 5 milligrams per kilogram (mg/kg) via intravenous (IV) infusion; oxaliplatin 85 milligrams per meter-squared (mg/m^2) via IV infusion; leucovorin 400 mg/m^2 via IV infusion; 5-FU 400 mg/m^2 via IV bolus; and 5-FU 2400 mg/m^2 via continuous 46-hour IV infusion. Following completion of 12 cycles, participants could discontinue oxaliplatin and continue with bevacizumab, leucovorin, and 5-FU. Treatment was continued until resectability, progressive disease (PD), unacceptable toxicity, or participant refusal.

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

Percentage of Participants With Complete Resection or Residual (Microscopic or Macroscopic) Tumor

Following resective surgery, participants were evaluated for complete resection (R0) or the presence of microscopic (R1) or macroscopic (R2) residual tumor. The percentage of participants within each residual tumor classification was calculated as [number of participants with R0, R1, and/or R2 divided by the total number of participants] multiplied by 100. Associated 95% confidence intervals were calculated for one-sample binomial using the Clopper-Pearson method.

ITT Population

Posted

Number

95% Confidence Interval

percentage of participants

Up to 5 years (at Screening; every 6 weeks, and within 4 weeks prior to surgery; and at time of/after surgery)

ID	Title	Description
OG000	Bevacizumab + mFOLFOX-6	Participants received a chemotherapy regimen of bevacizumab plus mFOLFOX-6. Each drug was administered on Day 1 of each 2-week cycle. Dosing was as follows: bevacizumab 5 mg/kg via IV infusion; oxaliplatin 85 mg/m^2 via IV infusion; leucovorin 400 mg/m^2 via IV infusion; 5-FU 400 mg/m^2 via IV bolus; and 5-FU 2400 mg/m^2 via continuous 46-hour IV infusion. Following completion of 12 cycles, participants could discontinue oxaliplatin and continue with bevacizumab, leucovorin, and 5-FU. Treatment was continued until resectability, PD, unacceptable toxicity, or participant refusal.
OG001	Bevacizumab + FOLFOXIRI	Participants received a chemotherapy regimen of bevacizumab plus FOLFOXIRI. Each drug was administered on Day 1 of each 2-week cycle. Dosing was as follows: bevacizumab 5 mg/kg via IV infusion; oxaliplatin 85 mg/m^2 via IV infusion; irinotecan 165 mg/m^2 via IV infusion; leucovorin 200 mg/m^2 via IV infusion; and 5-FU 3200 mg/m^2 via continuous 46-hour IV infusion. Following completion of 12 cycles, participants were to discontinue either irinotecan, oxaliplatin, or both. Treatment was continued until resectability, PD, unacceptable toxicity, or participant refusal.

Units	Counts
Participants	OG00039 OG00141

Title

Denominators

Categories

R0, R1, or R2

Title	Measurements
	OG00048.7(32.4 to 65.2) OG00161.0(44.5 to 75.8)

R0 or R1

Title	Measurements
	OG000

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	CI Lower Limit Comment	CI Upper Limit Comment	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type	Non-Inferiority Comment	Other Analysis Description
OG000 OG001	Difference between groups in the collective percentage of participants with R0, R1, or R2.	Chi-squared		0.2707		Difference in Resection Rate	12.3			2-Sided	95	-11.0	35.5			Confidence interval calculated for difference based on Hauck-Anderson method.	No	Superiority or Other

Secondary

Time to Resection

Time to resection was defined as the time from randomization to the date of first resective surgery. For participants who did not undergo resective surgery, time to resection was censored at Day 1. Time to resection was estimated by Kaplan-Meier analysis.

ITT Population

Posted

Median

95% Confidence Interval

months

Up to 5 years (at Screening; prior to each cycle, and within 7 days prior to surgery; and at time of surgery)

ID	Title	Description
OG000	Bevacizumab + mFOLFOX-6	Participants received a chemotherapy regimen of bevacizumab plus mFOLFOX-6. Each drug was administered on Day 1 of each 2-week cycle. Dosing was as follows: bevacizumab 5 mg/kg via IV infusion; oxaliplatin 85 mg/m^2 via IV infusion; leucovorin 400 mg/m^2 via IV infusion; 5-FU 400 mg/m^2 via IV bolus; and 5-FU 2400 mg/m^2 via continuous 46-hour IV infusion. Following completion of 12 cycles, participants could discontinue oxaliplatin and continue with bevacizumab, leucovorin, and 5-FU. Treatment was continued until resectability, PD, unacceptable toxicity, or participant refusal.
OG001	Bevacizumab + FOLFOXIRI	Participants received a chemotherapy regimen of bevacizumab plus FOLFOXIRI. Each drug was administered on Day 1 of each 2-week cycle. Dosing was as follows: bevacizumab 5 mg/kg via IV infusion; oxaliplatin 85 mg/m^2 via IV infusion; irinotecan 165 mg/m^2 via IV infusion; leucovorin 200 mg/m^2 via IV infusion; and 5-FU 3200 mg/m^2 via continuous 46-hour IV infusion. Following completion of 12 cycles, participants were to discontinue either irinotecan, oxaliplatin, or both. Treatment was continued until resectability, PD, unacceptable toxicity, or participant refusal.

Secondary

Percentage of Participants With Histopathological Response

At the time of resective surgery, participants were evaluated for histopathological response as defined through pathologist review of the resected metastatic lesions, including assessment of margin status and tumor cell viability. Histopathological response classification was based upon the percentage of viable tumor cells, where 'Complete response' was considered for those with 0 percent (%) viable tumor cells, 'Major response' for those with 1% to 49% viable tumor cells, 'Minor response' for 50% to 99% viable tumor cells, and 'No response' for 100% viable tumor cells. The response could not be determined in some cases and was documented as 'Unknown.' The percentage of participants within each response category was calculated as [number of participants with a given response divided by the number of participants who completed the assessment] multiplied by 100.

ITT Population; only participants with a histopathological assessment after the first resective surgery were included in the analysis.

Posted

Number

percentage of participants

Up to 5 years (at Screening; every 6 weeks, and within 4 weeks prior to surgery; and at time of/after surgery)

ID	Title	Description
OG000	Bevacizumab + mFOLFOX-6	Participants received a chemotherapy regimen of bevacizumab plus mFOLFOX-6. Each drug was administered on Day 1 of each 2-week cycle. Dosing was as follows: bevacizumab 5 mg/kg via IV infusion; oxaliplatin 85 mg/m^2 via IV infusion; leucovorin 400 mg/m^2 via IV infusion; 5-FU 400 mg/m^2 via IV bolus; and 5-FU 2400 mg/m^2 via continuous 46-hour IV infusion. Following completion of 12 cycles, participants could discontinue oxaliplatin and continue with bevacizumab, leucovorin, and 5-FU. Treatment was continued until resectability, PD, unacceptable toxicity, or participant refusal.

Secondary

Percentage of Participants With Complete or Major Histopathological Response

At the time of resective surgery, participants were evaluated for histopathological response as defined through pathologist review of the resected metastatic lesions, including assessment of margin status and tumor cell viability. Histopathological response classification was based upon the percentage of viable tumor cells, as described previously. The collective percentage of participants assessed as having a complete or major response was calculated as [number of participants with complete or major response divided by the number of participants who completed the assessment] multiplied by 100. Associated 95% confidence intervals were calculated for one-sample binomial using the Clopper-Pearson method.

ITT Population; only participants with a histopathological assessment after the first resective surgery were included in the analysis.

Posted

Number

95% Confidence Interval

percentage of participants

Up to 5 years (at Screening; every 6 weeks, and within 4 weeks prior to surgery; and at time of/after surgery)

ID	Title	Description
OG000	Bevacizumab + mFOLFOX-6	Participants received a chemotherapy regimen of bevacizumab plus mFOLFOX-6. Each drug was administered on Day 1 of each 2-week cycle. Dosing was as follows: bevacizumab 5 mg/kg via IV infusion; oxaliplatin 85 mg/m^2 via IV infusion; leucovorin 400 mg/m^2 via IV infusion; 5-FU 400 mg/m^2 via IV bolus; and 5-FU 2400 mg/m^2 via continuous 46-hour IV infusion. Following completion of 12 cycles, participants could discontinue oxaliplatin and continue with bevacizumab, leucovorin, and 5-FU. Treatment was continued until resectability, PD, unacceptable toxicity, or participant refusal.

Secondary

Percentage of Participants Experiencing Relapse Following Curative Resection

Among participants with curative resection (complete resection [R0] or microscopic residual tumor [R1]), relapse was defined as the first new occurrence of cancer or death. The percentage of participants who experienced relapse was calculated as [number of participants with a relapse event divided by the number of participants initially classified as R0 or R1 following resective surgery] multiplied by 100.

ITT Population; only participants with a residual tumor classification of R0 or R1 after first resection were included in the analysis.

Posted

Number

percentage of participants

Up to 5 years (at time of surgery; 48 hours and 4 and 12 weeks after surgery; within 4 weeks after completion of treatment; every 3 to 6 months for 1 year; then annually)

ID	Title	Description
OG000	Bevacizumab + mFOLFOX-6	Participants received a chemotherapy regimen of bevacizumab plus mFOLFOX-6. Each drug was administered on Day 1 of each 2-week cycle. Dosing was as follows: bevacizumab 5 mg/kg via IV infusion; oxaliplatin 85 mg/m^2 via IV infusion; leucovorin 400 mg/m^2 via IV infusion; 5-FU 400 mg/m^2 via IV bolus; and 5-FU 2400 mg/m^2 via continuous 46-hour IV infusion. Following completion of 12 cycles, participants could discontinue oxaliplatin and continue with bevacizumab, leucovorin, and 5-FU. Treatment was continued until resectability, PD, unacceptable toxicity, or participant refusal.
OG001	Bevacizumab + FOLFOXIRI

Secondary

Relapse-Free Survival (RFS)

RFS was defined as the time from curative resection (complete resection [R0] or microscopic residual tumor [R1]) to the date of first diagnosis of relapse. For participants with curative resection and without relapse, RFS was censored at the last known relapse-free assessment. RFS was estimated by Kaplan-Meier analysis.

ITT Population; only participants with a residual tumor classification of R0 or R1 after first resection were included in the analysis.

Posted

Median

95% Confidence Interval

months

Up to 5 years (at time of surgery; 48 hours and 4 and 12 weeks after surgery; within 4 weeks after completion of treatment; every 3 to 6 months for 1 year; then annually)

ID	Title	Description
OG000	Bevacizumab + mFOLFOX-6	Participants received a chemotherapy regimen of bevacizumab plus mFOLFOX-6. Each drug was administered on Day 1 of each 2-week cycle. Dosing was as follows: bevacizumab 5 mg/kg via IV infusion; oxaliplatin 85 mg/m^2 via IV infusion; leucovorin 400 mg/m^2 via IV infusion; 5-FU 400 mg/m^2 via IV bolus; and 5-FU 2400 mg/m^2 via continuous 46-hour IV infusion. Following completion of 12 cycles, participants could discontinue oxaliplatin and continue with bevacizumab, leucovorin, and 5-FU. Treatment was continued until resectability, PD, unacceptable toxicity, or participant refusal.
OG001	Bevacizumab + FOLFOXIRI	Participants received a chemotherapy regimen of bevacizumab plus FOLFOXIRI. Each drug was administered on Day 1 of each 2-week cycle. Dosing was as follows: bevacizumab 5 mg/kg via IV infusion; oxaliplatin 85 mg/m^2 via IV infusion; irinotecan 165 mg/m^2 via IV infusion; leucovorin 200 mg/m^2 via IV infusion; and 5-FU 3200 mg/m^2 via continuous 46-hour IV infusion. Following completion of 12 cycles, participants were to discontinue either irinotecan, oxaliplatin, or both. Treatment was continued until resectability, PD, unacceptable toxicity, or participant refusal.

Secondary

Percentage of Participants Experiencing Death or Disease Progression

PD was defined, using Response Evaluation Criteria in Solid Tumors (RECIST) version 1.0, as at least a 20% increase in the sum of the longest diameter of target lesions, or the appearance of one or more new lesions. The percentage of participants experiencing PD or death was calculated as [number of participants with event divided by the number of participants analyzed] multiplied by 100.

ITT Population

Posted

Number

percentage of participants

Up to 5 years (at Screening; every 6 weeks, and within 4 weeks prior to surgery; 4 and 12 weeks after surgery; and at the end of Cycles 4 and 8 if assessed as R0 or R1, or every 6 weeks until progression or resectability if assessed as R2)

ID	Title	Description
OG000	Bevacizumab + mFOLFOX-6	Participants received a chemotherapy regimen of bevacizumab plus mFOLFOX-6. Each drug was administered on Day 1 of each 2-week cycle. Dosing was as follows: bevacizumab 5 mg/kg via IV infusion; oxaliplatin 85 mg/m^2 via IV infusion; leucovorin 400 mg/m^2 via IV infusion; 5-FU 400 mg/m^2 via IV bolus; and 5-FU 2400 mg/m^2 via continuous 46-hour IV infusion. Following completion of 12 cycles, participants could discontinue oxaliplatin and continue with bevacizumab, leucovorin, and 5-FU. Treatment was continued until resectability, PD, unacceptable toxicity, or participant refusal.
OG001	Bevacizumab + FOLFOXIRI	Participants received a chemotherapy regimen of bevacizumab plus FOLFOXIRI. Each drug was administered on Day 1 of each 2-week cycle. Dosing was as follows: bevacizumab 5 mg/kg via IV infusion; oxaliplatin 85 mg/m^2 via IV infusion; irinotecan 165 mg/m^2 via IV infusion; leucovorin 200 mg/m^2 via IV infusion; and 5-FU 3200 mg/m^2 via continuous 46-hour IV infusion. Following completion of 12 cycles, participants were to discontinue either irinotecan, oxaliplatin, or both. Treatment was continued until resectability, PD, unacceptable toxicity, or participant refusal.

Secondary

Progression-Free Survival (PFS)

PFS was defined, using RECIST version 1.0, as the time from randomization to the date of first documented PD or death from any cause. PD was defined as at least a 20% increase in the sum of the longest diameter of target lesions, or the appearance of one or more new lesions. For participants without documented PD or death, PFS was censored at the time of last tumor assessment. PFS was estimated by Kaplan-Meier analysis.

ITT Population

Posted

Median

95% Confidence Interval

months

ID	Title	Description
OG000	Bevacizumab + mFOLFOX-6	Participants received a chemotherapy regimen of bevacizumab plus mFOLFOX-6. Each drug was administered on Day 1 of each 2-week cycle. Dosing was as follows: bevacizumab 5 mg/kg via IV infusion; oxaliplatin 85 mg/m^2 via IV infusion; leucovorin 400 mg/m^2 via IV infusion; 5-FU 400 mg/m^2 via IV bolus; and 5-FU 2400 mg/m^2 via continuous 46-hour IV infusion. Following completion of 12 cycles, participants could discontinue oxaliplatin and continue with bevacizumab, leucovorin, and 5-FU. Treatment was continued until resectability, PD, unacceptable toxicity, or participant refusal.
OG001	Bevacizumab + FOLFOXIRI	Participants received a chemotherapy regimen of bevacizumab plus FOLFOXIRI. Each drug was administered on Day 1 of each 2-week cycle. Dosing was as follows: bevacizumab 5 mg/kg via IV infusion; oxaliplatin 85 mg/m^2 via IV infusion; irinotecan 165 mg/m^2 via IV infusion; leucovorin 200 mg/m^2 via IV infusion; and 5-FU 3200 mg/m^2 via continuous 46-hour IV infusion. Following completion of 12 cycles, participants were to discontinue either irinotecan, oxaliplatin, or both. Treatment was continued until resectability, PD, unacceptable toxicity, or participant refusal.

Secondary

Percentage of Participants Who Died

ITT Population

Posted

Number

percentage of participants

Up to 5 years (prior to each cycle, and within 7 days prior to surgery; at time of surgery; 48 hours and 4 and 12 weeks after surgery; within 4 weeks after completion of treatment; every 3 to 6 months for 1 year; then annually)

ID	Title	Description
OG000	Bevacizumab + mFOLFOX-6	Participants received a chemotherapy regimen of bevacizumab plus mFOLFOX-6. Each drug was administered on Day 1 of each 2-week cycle. Dosing was as follows: bevacizumab 5 mg/kg via IV infusion; oxaliplatin 85 mg/m^2 via IV infusion; leucovorin 400 mg/m^2 via IV infusion; 5-FU 400 mg/m^2 via IV bolus; and 5-FU 2400 mg/m^2 via continuous 46-hour IV infusion. Following completion of 12 cycles, participants could discontinue oxaliplatin and continue with bevacizumab, leucovorin, and 5-FU. Treatment was continued until resectability, PD, unacceptable toxicity, or participant refusal.
OG001	Bevacizumab + FOLFOXIRI	Participants received a chemotherapy regimen of bevacizumab plus FOLFOXIRI. Each drug was administered on Day 1 of each 2-week cycle. Dosing was as follows: bevacizumab 5 mg/kg via IV infusion; oxaliplatin 85 mg/m^2 via IV infusion; irinotecan 165 mg/m^2 via IV infusion; leucovorin 200 mg/m^2 via IV infusion; and 5-FU 3200 mg/m^2 via continuous 46-hour IV infusion. Following completion of 12 cycles, participants were to discontinue either irinotecan, oxaliplatin, or both. Treatment was continued until resectability, PD, unacceptable toxicity, or participant refusal.

Secondary

Overall Survival (OS)

OS was defined as the time from randomization to death from any cause. For participants without an event of death, OS was censored at the last-known alive date. OS was estimated by Kaplan-Meier analysis.

ITT Population

Posted

Median

95% Confidence Interval

months

ID	Title	Description
OG000	Bevacizumab + mFOLFOX-6	Participants received a chemotherapy regimen of bevacizumab plus mFOLFOX-6. Each drug was administered on Day 1 of each 2-week cycle. Dosing was as follows: bevacizumab 5 mg/kg via IV infusion; oxaliplatin 85 mg/m^2 via IV infusion; leucovorin 400 mg/m^2 via IV infusion; 5-FU 400 mg/m^2 via IV bolus; and 5-FU 2400 mg/m^2 via continuous 46-hour IV infusion. Following completion of 12 cycles, participants could discontinue oxaliplatin and continue with bevacizumab, leucovorin, and 5-FU. Treatment was continued until resectability, PD, unacceptable toxicity, or participant refusal.
OG001	Bevacizumab + FOLFOXIRI	Participants received a chemotherapy regimen of bevacizumab plus FOLFOXIRI. Each drug was administered on Day 1 of each 2-week cycle. Dosing was as follows: bevacizumab 5 mg/kg via IV infusion; oxaliplatin 85 mg/m^2 via IV infusion; irinotecan 165 mg/m^2 via IV infusion; leucovorin 200 mg/m^2 via IV infusion; and 5-FU 3200 mg/m^2 via continuous 46-hour IV infusion. Following completion of 12 cycles, participants were to discontinue either irinotecan, oxaliplatin, or both. Treatment was continued until resectability, PD, unacceptable toxicity, or participant refusal.

Secondary

Percentage of Participants With a Confirmed Best Overall Response of Complete Response (CR) or Partial Response (PR) According to RECIST Version 1.0

Using RECIST version 1.0, participants were considered to have achieved CR upon the disappearance of all target and non-target lesions. Participants who achieved PR demonstrated at least a 30% decrease in the sum of the largest diameter of target lesions, taking as reference the Screening sum largest diameter. Responses were confirmed by repeat assessments no less than 4 weeks after criteria for response were first met. The collective percentage of participants with confirmed best overall response of CR or PR was calculated as [number of participants meeting RECIST criteria for CR or PR divided by the number of participants analyzed] multiplied by 100. Associated 95% confidence intervals were calculated for one-sample binomial using the Clopper-Pearson method.

ITT Population

Posted

Number

95% Confidence Interval

percentage of participants

ID	Title	Description
OG000	Bevacizumab + mFOLFOX-6	Participants received a chemotherapy regimen of bevacizumab plus mFOLFOX-6. Each drug was administered on Day 1 of each 2-week cycle. Dosing was as follows: bevacizumab 5 mg/kg via IV infusion; oxaliplatin 85 mg/m^2 via IV infusion; leucovorin 400 mg/m^2 via IV infusion; 5-FU 400 mg/m^2 via IV bolus; and 5-FU 2400 mg/m^2 via continuous 46-hour IV infusion. Following completion of 12 cycles, participants could discontinue oxaliplatin and continue with bevacizumab, leucovorin, and 5-FU. Treatment was continued until resectability, PD, unacceptable toxicity, or participant refusal.

Secondary

Time to Response

Time to response according to RECIST version 1.0 was defined as the time from randomization to the date of first documented CR or PR. Participants were considered to have achieved CR upon the disappearance of all target and non-target lesions. Participants who achieved PR demonstrated at least a 30% decrease in the sum of the largest diameter of target lesions, taking as reference the Screening sum largest diameter. Responses were confirmed by repeat assessments no less than 4 weeks after criteria for response were first met. For participants who did not complete a confirmatory tumor assessment, time to response was censored at the date of last tumor assessment, or if unavailable, at the date of first dose. Time to response was estimated by Kaplan-Meier analysis.

ITT Population

Posted

Median

95% Confidence Interval

months

ID	Title	Description
OG000	Bevacizumab + mFOLFOX-6	Participants received a chemotherapy regimen of bevacizumab plus mFOLFOX-6. Each drug was administered on Day 1 of each 2-week cycle. Dosing was as follows: bevacizumab 5 mg/kg via IV infusion; oxaliplatin 85 mg/m^2 via IV infusion; leucovorin 400 mg/m^2 via IV infusion; 5-FU 400 mg/m^2 via IV bolus; and 5-FU 2400 mg/m^2 via continuous 46-hour IV infusion. Following completion of 12 cycles, participants could discontinue oxaliplatin and continue with bevacizumab, leucovorin, and 5-FU. Treatment was continued until resectability, PD, unacceptable toxicity, or participant refusal.

Secondary

Percentage of Participants With Complications Related to First Resective Surgery

Complications related to the first resective surgery were evaluated using the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 3.0, and classified according to severity. The NCI-CTCAE severity classification criteria are as follows: Grade 5 equals (=) resulting in death; Grade 4 = life-threatening; Grade 3 = severe; Grade 2 = moderate; and Grade 1 = mild. The percentage of participants experiencing a given adverse event (AE) by severity grade was calculated as [number of participants with an AE divided by the number of participants who underwent first resective surgery] multiplied by 100.

Safety Population (First Surgery Subpopulation): All participants who underwent a first resective surgery and who received at least one dose of trial medication, whether prematurely withdrawn or not. Participants were analyzed according to the actual treatment they received.

Posted

Number

percentage of participants

Up to 5 years (at time of surgery; 48 hours and 4 and 12 weeks after surgery; within 4 weeks after completion of treatment; every 3 to 6 months for 1 year; then annually)

ID	Title	Description
OG000	Bevacizumab + mFOLFOX-6	Participants received a chemotherapy regimen of bevacizumab plus mFOLFOX-6. Each drug was administered on Day 1 of each 2-week cycle. Dosing was as follows: bevacizumab 5 mg/kg via IV infusion; oxaliplatin 85 mg/m^2 via IV infusion; leucovorin 400 mg/m^2 via IV infusion; 5-FU 400 mg/m^2 via IV bolus; and 5-FU 2400 mg/m^2 via continuous 46-hour IV infusion. Following completion of 12 cycles, participants could discontinue oxaliplatin and continue with bevacizumab, leucovorin, and 5-FU. Treatment was continued until resectability, PD, unacceptable toxicity, or participant refusal.

Secondary

Percentage of Participants With Complications Related to Second Resective Surgery

Complications related to the second resective surgery were evaluated using the NCI-CTCAE version 3.0, and classified according to severity. The NCI-CTCAE severity classification criteria are as follows: Grade 5 = resulting in death; Grade 4 = life-threatening; Grade 3 = severe; Grade 2 = moderate; and Grade 1 = mild. The percentage of participants experiencing a given AE by severity grade was calculated as [number of participants with an AE divided by the number of participants who underwent second resective surgery] multiplied by 100.

Safety Population (Second Surgery Subpopulation): All participants who underwent a second resective surgery and who received at least one dose of trial medication, whether prematurely withdrawn or not. Participants were analyzed according to the actual treatment they received.

Posted

Number

percentage of participants

Up to 5 years (at time of surgery; 48 hours and 4 and 12 weeks after surgery; within 4 weeks after completion of treatment; every 3 to 6 months for 1 year; then annually)

ID	Title	Description
OG000	Bevacizumab + mFOLFOX-6	Participants received a chemotherapy regimen of bevacizumab plus mFOLFOX-6. Each drug was administered on Day 1 of each 2-week cycle. Dosing was as follows: bevacizumab 5 mg/kg via IV infusion; oxaliplatin 85 mg/m^2 via IV infusion; leucovorin 400 mg/m^2 via IV infusion; 5-FU 400 mg/m^2 via IV bolus; and 5-FU 2400 mg/m^2 via continuous 46-hour IV infusion. Following completion of 12 cycles, participants could discontinue oxaliplatin and continue with bevacizumab, leucovorin, and 5-FU. Treatment was continued until resectability, PD, unacceptable toxicity, or participant refusal.

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Abdominal pain	Gastrointestinal disorders	MedDRA (15.0)	Non-systematic Assessment	EG0001 affected37 at risk EG0011 affected40 at risk
Diarrhoea	Gastrointestinal disorders	MedDRA (15.0)	Non-systematic Assessment	EG0001 affected37 at risk EG0016 affected40 at risk
Ileus	Gastrointestinal disorders	MedDRA (15.0)	Non-systematic Assessment	EG0001 affected37 at risk EG0011 affected40 at risk
Abdominal pain upper	Gastrointestinal disorders	MedDRA (15.0)	Non-systematic Assessment	EG0001 affected37 at risk EG0010 affected40 at risk
Gastrointestinal haemorrhage	Gastrointestinal disorders	MedDRA (15.0)	Non-systematic Assessment	EG0001 affected37 at risk EG0010 affected40 at risk
Gastrointestinal hypomotility	Gastrointestinal disorders	MedDRA (15.0)	Non-systematic Assessment	EG0000 affected37 at risk EG0011 affected40 at risk
Intestinal obstruction	Gastrointestinal disorders	MedDRA (15.0)	Non-systematic Assessment	EG0000 affected37 at risk EG0011 affected40 at risk
Large intestinal obstruction	Gastrointestinal disorders	MedDRA (15.0)	Non-systematic Assessment	EG0001 affected37 at risk EG0010 affected40 at risk
Large intestine perforation	Gastrointestinal disorders	MedDRA (15.0)	Non-systematic Assessment	EG0000 affected37 at risk EG0011 affected40 at risk
Localised intraabdominal fluid collection	Gastrointestinal disorders	MedDRA (15.0)	Non-systematic Assessment	EG0000 affected37 at risk EG0011 affected40 at risk
Nausea	Gastrointestinal disorders	MedDRA (15.0)	Non-systematic Assessment	EG0000 affected37 at risk EG0011 affected40 at risk
Peritoneal haemorrhage	Gastrointestinal disorders	MedDRA (15.0)	Non-systematic Assessment	EG0000 affected37 at risk EG0011 affected40 at risk
Retroperitoneal haematoma	Gastrointestinal disorders	MedDRA (15.0)	Non-systematic Assessment	EG0001 affected37 at risk EG0010 affected40 at risk
Vomiting	Gastrointestinal disorders	MedDRA (15.0)	Non-systematic Assessment	EG0001 affected37 at risk EG0010 affected40 at risk
Febrile neutropenia	Blood and lymphatic system disorders	MedDRA (15.0)	Non-systematic Assessment	EG0003 affected37 at risk EG0016 affected40 at risk
Neutropenia	Blood and lymphatic system disorders	MedDRA (15.0)	Non-systematic Assessment	EG0003 affected37 at risk EG0014 affected40 at risk
Disseminated intravascular coagulation	Blood and lymphatic system disorders	MedDRA (15.0)	Non-systematic Assessment	EG0000 affected37 at risk EG0011 affected40 at risk
Peritonitis	Infections and infestations	MedDRA (15.0)	Non-systematic Assessment	EG0000 affected37 at risk EG0012 affected40 at risk
Bacterial sepsis	Infections and infestations	MedDRA (15.0)	Non-systematic Assessment	EG0001 affected37 at risk EG0010 affected40 at risk
Campylobacter infection	Infections and infestations	MedDRA (15.0)	Non-systematic Assessment	EG0000 affected37 at risk EG0011 affected40 at risk
Cholecystitis infective	Infections and infestations	MedDRA (15.0)	Non-systematic Assessment	EG0000 affected37 at risk EG0011 affected40 at risk
Device related infection	Infections and infestations	MedDRA (15.0)	Non-systematic Assessment	EG0001 affected37 at risk EG0010 affected40 at risk
Infection	Infections and infestations	MedDRA (15.0)	Non-systematic Assessment	EG0000 affected37 at risk EG0011 affected40 at risk
Liver abscess	Infections and infestations	MedDRA (15.0)	Non-systematic Assessment	EG0001 affected37 at risk EG0010 affected40 at risk
Lower respiratory tract infection	Infections and infestations	MedDRA (15.0)	Non-systematic Assessment	EG0000 affected37 at risk EG0011 affected40 at risk
Lung infection	Infections and infestations	MedDRA (15.0)	Non-systematic Assessment	EG0000 affected37 at risk EG0011 affected40 at risk
Neutropenic sepsis	Infections and infestations	MedDRA (15.0)	Non-systematic Assessment	EG0001 affected37 at risk EG0010 affected40 at risk
Wound infection	Infections and infestations	MedDRA (15.0)	Non-systematic Assessment	EG0001 affected37 at risk EG0010 affected40 at risk
Pulmonary embolism	Respiratory, thoracic and mediastinal disorders	MedDRA (15.0)	Non-systematic Assessment	EG0002 affected37 at risk EG0011 affected40 at risk
Epistaxis	Respiratory, thoracic and mediastinal disorders	MedDRA (15.0)	Non-systematic Assessment	EG0000 affected37 at risk EG0011 affected40 at risk
Pleural effusion	Respiratory, thoracic and mediastinal disorders	MedDRA (15.0)	Non-systematic Assessment	EG0001 affected37 at risk EG0010 affected40 at risk
Pneumothorax	Respiratory, thoracic and mediastinal disorders	MedDRA (15.0)	Non-systematic Assessment	EG0001 affected37 at risk EG0010 affected40 at risk
Deep vein thrombosis	Vascular disorders	MedDRA (15.0)	Non-systematic Assessment	EG0002 affected37 at risk EG0012 affected40 at risk
Thrombosis	Vascular disorders	MedDRA (15.0)	Non-systematic Assessment	EG0001 affected37 at risk EG0010 affected40 at risk
Pyrexia	General disorders	MedDRA (15.0)	Non-systematic Assessment	EG0000 affected37 at risk EG0012 affected40 at risk
General physical health deterioration	General disorders	MedDRA (15.0)	Non-systematic Assessment	EG0001 affected37 at risk EG0010 affected40 at risk
Impaired healing	General disorders	MedDRA (15.0)	Non-systematic Assessment	EG0000 affected37 at risk EG0011 affected40 at risk
Hepatic failure	Hepatobiliary disorders	MedDRA (15.0)	Non-systematic Assessment	EG0002 affected37 at risk EG0010 affected40 at risk
Cholangitis	Hepatobiliary disorders	MedDRA (15.0)	Non-systematic Assessment	EG0001 affected37 at risk EG0010 affected40 at risk
Portal vein thrombosis	Hepatobiliary disorders	MedDRA (15.0)	Non-systematic Assessment	EG0001 affected37 at risk EG0010 affected40 at risk
Wound dehiscence	Injury, poisoning and procedural complications	MedDRA (15.0)	Non-systematic Assessment	EG0000 affected37 at risk EG0013 affected40 at risk
Failure to anastomose	Injury, poisoning and procedural complications	MedDRA (15.0)	Non-systematic Assessment	EG0001 affected37 at risk EG0010 affected40 at risk
Angina pectoris	Cardiac disorders	MedDRA (15.0)	Non-systematic Assessment	EG0001 affected37 at risk EG0011 affected40 at risk
Atrial fibrillation	Cardiac disorders	MedDRA (15.0)	Non-systematic Assessment	EG0001 affected37 at risk EG0010 affected40 at risk
Endoscopic retrograde cholangiopancreatography	Investigations	MedDRA (15.0)	Non-systematic Assessment	EG0001 affected37 at risk EG0010 affected40 at risk
Gamma-glutamyltransferase increased	Investigations	MedDRA (15.0)	Non-systematic Assessment	EG0001 affected37 at risk EG0010 affected40 at risk
Muscle spasms	Musculoskeletal and connective tissue disorders	MedDRA (15.0)	Non-systematic Assessment	EG0000 affected37 at risk EG0011 affected40 at risk
Musculoskeletal disorder	Musculoskeletal and connective tissue disorders	MedDRA (15.0)	Non-systematic Assessment	EG0001 affected37 at risk EG0010 affected40 at risk
Paraesthesia	Nervous system disorders	MedDRA (15.0)	Non-systematic Assessment	EG0000 affected37 at risk EG0011 affected40 at risk
Drug hypersensitivity	Immune system disorders	MedDRA (15.0)	Non-systematic Assessment	EG0001 affected37 at risk EG0010 affected40 at risk
Pelvic fluid collection	Reproductive system and breast disorders	MedDRA (15.0)	Non-systematic Assessment	EG0000 affected37 at risk EG0011 affected40 at risk

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Diarrhoea	Gastrointestinal disorders	MedDRA (15.0)	Non-systematic Assessment	EG00020 affected37 at risk EG00133 affected40 at risk
Nausea	Gastrointestinal disorders	MedDRA (15.0)	Non-systematic Assessment	EG00023 affected37 at risk EG00121 affected40 at risk
Vomiting	Gastrointestinal disorders	MedDRA (15.0)	Non-systematic Assessment	EG00014 affected37 at risk EG00125 affected40 at risk
Constipation	Gastrointestinal disorders	MedDRA (15.0)	Non-systematic Assessment	EG00018 affected37 at risk EG00115 affected40 at risk
Abdominal pain	Gastrointestinal disorders	MedDRA (15.0)	Non-systematic Assessment	EG00015 affected37 at risk EG00115 affected40 at risk
Dry mouth	Gastrointestinal disorders	MedDRA (15.0)	Non-systematic Assessment	EG0007 affected37 at risk EG0018 affected40 at risk
Abdominal pain upper	Gastrointestinal disorders	MedDRA (15.0)	Non-systematic Assessment	EG0008 affected37 at risk EG0015 affected40 at risk
Stomatitis	Gastrointestinal disorders	MedDRA (15.0)	Non-systematic Assessment	EG0005 affected37 at risk EG0013 affected40 at risk
Toothache	Gastrointestinal disorders	MedDRA (15.0)	Non-systematic Assessment	EG0004 affected37 at risk EG0012 affected40 at risk
Dyspepsia	Gastrointestinal disorders	MedDRA (15.0)	Non-systematic Assessment	EG0002 affected37 at risk EG0012 affected40 at risk
Proctalgia	Gastrointestinal disorders	MedDRA (15.0)	Non-systematic Assessment	EG0001 affected37 at risk EG0012 affected40 at risk
Haemorrhoids	Gastrointestinal disorders	MedDRA (15.0)	Non-systematic Assessment	EG0001 affected37 at risk EG0012 affected40 at risk
Flatulence	Gastrointestinal disorders	MedDRA (15.0)	Non-systematic Assessment	EG0002 affected37 at risk EG0010 affected40 at risk
Neuropathy peripheral	Nervous system disorders	MedDRA (15.0)	Non-systematic Assessment	EG00022 affected37 at risk EG00119 affected40 at risk
Paraesthesia	Nervous system disorders	MedDRA (15.0)	Non-systematic Assessment	EG00012 affected37 at risk EG0017 affected40 at risk
Peripheral sensory neuropathy	Nervous system disorders	MedDRA (15.0)	Non-systematic Assessment	EG0004 affected37 at risk EG0014 affected40 at risk
Headache	Nervous system disorders	MedDRA (15.0)	Non-systematic Assessment	EG0009 affected37 at risk EG0017 affected40 at risk
Dysgeusia	Nervous system disorders	MedDRA (15.0)	Non-systematic Assessment	EG0005 affected37 at risk EG00110 affected40 at risk
Lethargy	Nervous system disorders	MedDRA (15.0)	Non-systematic Assessment	EG0003 affected37 at risk EG0012 affected40 at risk
Dysaesthesia	Nervous system disorders	MedDRA (15.0)	Non-systematic Assessment	EG0003 affected37 at risk EG0012 affected40 at risk
Dizziness	Nervous system disorders	MedDRA (15.0)	Non-systematic Assessment	EG0003 affected37 at risk EG0011 affected40 at risk
Polyneuropathy	Nervous system disorders	MedDRA (15.0)	Non-systematic Assessment	EG0003 affected37 at risk EG0011 affected40 at risk
Asthenia	General disorders	MedDRA (15.0)	Non-systematic Assessment	EG00014 affected37 at risk EG00116 affected40 at risk
Mucosal inflammation	General disorders	MedDRA (15.0)	Non-systematic Assessment	EG00020 affected37 at risk EG00117 affected40 at risk
Fatigue	General disorders	MedDRA (15.0)	Non-systematic Assessment	EG00010 affected37 at risk EG00112 affected40 at risk
Pyrexia	General disorders	MedDRA (15.0)	Non-systematic Assessment	EG0007 affected37 at risk EG00112 affected40 at risk
Catheter site pain	General disorders	MedDRA (15.0)	Non-systematic Assessment	EG0002 affected37 at risk EG0011 affected40 at risk
Pain	General disorders	MedDRA (15.0)	Non-systematic Assessment	EG0001 affected37 at risk EG0012 affected40 at risk
Chest pain	General disorders	MedDRA (15.0)	Non-systematic Assessment	EG0002 affected37 at risk EG0010 affected40 at risk
Oedema peripheral	General disorders	MedDRA (15.0)	Non-systematic Assessment	EG0000 affected37 at risk EG0012 affected40 at risk
Neutropenia	Blood and lymphatic system disorders	MedDRA (15.0)	Non-systematic Assessment	EG00020 affected37 at risk EG00126 affected40 at risk
Thrombocytopenia	Blood and lymphatic system disorders	MedDRA (15.0)	Non-systematic Assessment	EG0004 affected37 at risk EG0018 affected40 at risk
Anaemia	Blood and lymphatic system disorders	MedDRA (15.0)	Non-systematic Assessment	EG0004 affected37 at risk EG0016 affected40 at risk
Leukopenia	Blood and lymphatic system disorders	MedDRA (15.0)	Non-systematic Assessment	EG0001 affected37 at risk EG0014 affected40 at risk
Lymphopenia	Blood and lymphatic system disorders	MedDRA (15.0)	Non-systematic Assessment	EG0002 affected37 at risk EG0010 affected40 at risk
Epistaxis	Respiratory, thoracic and mediastinal disorders	MedDRA (15.0)	Non-systematic Assessment	EG00013 affected37 at risk EG00116 affected40 at risk
Cough	Respiratory, thoracic and mediastinal disorders	MedDRA (15.0)	Non-systematic Assessment	EG0003 affected37 at risk EG0015 affected40 at risk
Rhinorrhoea	Respiratory, thoracic and mediastinal disorders	MedDRA (15.0)	Non-systematic Assessment	EG0003 affected37 at risk EG0013 affected40 at risk
Dyspnoea	Respiratory, thoracic and mediastinal disorders	MedDRA (15.0)	Non-systematic Assessment	EG0003 affected37 at risk EG0012 affected40 at risk
Dysphonia	Respiratory, thoracic and mediastinal disorders	MedDRA (15.0)	Non-systematic Assessment	EG0002 affected37 at risk EG0012 affected40 at risk
Dyspnoea exertional	Respiratory, thoracic and mediastinal disorders	MedDRA (15.0)	Non-systematic Assessment	EG0002 affected37 at risk EG0012 affected40 at risk
Oropharyngeal pain	Respiratory, thoracic and mediastinal disorders	MedDRA (15.0)	Non-systematic Assessment	EG0001 affected37 at risk EG0014 affected40 at risk
Nasal congestion	Respiratory, thoracic and mediastinal disorders	MedDRA (15.0)	Non-systematic Assessment	EG0001 affected37 at risk EG0012 affected40 at risk
Platelet count decreased	Investigations	MedDRA (15.0)	Non-systematic Assessment	EG0005 affected37 at risk EG0013 affected40 at risk
Haemoglobin decreased	Investigations	MedDRA (15.0)	Non-systematic Assessment	EG0002 affected37 at risk EG0012 affected40 at risk
White blood cell count decreased	Investigations	MedDRA (15.0)	Non-systematic Assessment	EG0002 affected37 at risk EG0011 affected40 at risk
Gamma-glutamyltransferase increased	Investigations	MedDRA (15.0)	Non-systematic Assessment	EG0003 affected37 at risk EG0011 affected40 at risk
Blood lactate dehydrogenase increased	Investigations	MedDRA (15.0)	Non-systematic Assessment	EG0002 affected37 at risk EG0010 affected40 at risk
Alanine aminotransferase increased	Investigations	MedDRA (15.0)	Non-systematic Assessment	EG0002 affected37 at risk EG0011 affected40 at risk
Aspartate aminotransferase increased	Investigations	MedDRA (15.0)	Non-systematic Assessment	EG0002 affected37 at risk EG0011 affected40 at risk
Weight decreased	Investigations	MedDRA (15.0)	Non-systematic Assessment	EG0002 affected37 at risk EG0011 affected40 at risk
Blood alkaline phosphatase increased	Investigations	MedDRA (15.0)	Non-systematic Assessment	EG0002 affected37 at risk EG0010 affected40 at risk
Back pain	Musculoskeletal and connective tissue disorders	MedDRA (15.0)	Non-systematic Assessment	EG0008 affected37 at risk EG0017 affected40 at risk
Musculoskeletal pain	Musculoskeletal and connective tissue disorders	MedDRA (15.0)	Non-systematic Assessment	EG0003 affected37 at risk EG0014 affected40 at risk
Pain in extremity	Musculoskeletal and connective tissue disorders	MedDRA (15.0)	Non-systematic Assessment	EG0002 affected37 at risk EG0016 affected40 at risk
Neck pain	Musculoskeletal and connective tissue disorders	MedDRA (15.0)	Non-systematic Assessment	EG0004 affected37 at risk EG0011 affected40 at risk
Arthralgia	Musculoskeletal and connective tissue disorders	MedDRA (15.0)	Non-systematic Assessment	EG0000 affected37 at risk EG0014 affected40 at risk
Muscle spasms	Musculoskeletal and connective tissue disorders	MedDRA (15.0)	Non-systematic Assessment	EG0001 affected37 at risk EG0012 affected40 at risk
Myalgia	Musculoskeletal and connective tissue disorders	MedDRA (15.0)	Non-systematic Assessment	EG0002 affected37 at risk EG0011 affected40 at risk
Musculoskeletal chest pain	Musculoskeletal and connective tissue disorders	MedDRA (15.0)	Non-systematic Assessment	EG0002 affected37 at risk EG0010 affected40 at risk
Decreased appetite	Metabolism and nutrition disorders	MedDRA (15.0)	Non-systematic Assessment	EG0008 affected37 at risk EG00113 affected40 at risk
Hypokalaemia	Metabolism and nutrition disorders	MedDRA (15.0)	Non-systematic Assessment	EG0002 affected37 at risk EG0016 affected40 at risk
Hypocalcaemia	Metabolism and nutrition disorders	MedDRA (15.0)	Non-systematic Assessment	EG0000 affected37 at risk EG0013 affected40 at risk
Hypophosphataemia	Metabolism and nutrition disorders	MedDRA (15.0)	Non-systematic Assessment	EG0000 affected37 at risk EG0012 affected40 at risk
Alopecia	Skin and subcutaneous tissue disorders	MedDRA (15.0)	Non-systematic Assessment	EG0002 affected37 at risk EG00112 affected40 at risk
Pruritus	Skin and subcutaneous tissue disorders	MedDRA (15.0)	Non-systematic Assessment	EG0002 affected37 at risk EG0013 affected40 at risk
Rash	Skin and subcutaneous tissue disorders	MedDRA (15.0)	Non-systematic Assessment	EG0005 affected37 at risk EG0012 affected40 at risk
Palmar-plantar erythrodysaesthesia syndrome	Skin and subcutaneous tissue disorders	MedDRA (15.0)	Non-systematic Assessment	EG0002 affected37 at risk EG0013 affected40 at risk
Skin hyperpigmentation	Skin and subcutaneous tissue disorders	MedDRA (15.0)	Non-systematic Assessment	EG0002 affected37 at risk EG0012 affected40 at risk
Skin lesion	Skin and subcutaneous tissue disorders	MedDRA (15.0)	Non-systematic Assessment	EG0002 affected37 at risk EG0010 affected40 at risk
Urinary tract infection	Infections and infestations	MedDRA (15.0)	Non-systematic Assessment	EG0004 affected37 at risk EG0014 affected40 at risk
Nasopharyngitis	Infections and infestations	MedDRA (15.0)	Non-systematic Assessment	EG0004 affected37 at risk EG0011 affected40 at risk
Oral herpes	Infections and infestations	MedDRA (15.0)	Non-systematic Assessment	EG0003 affected37 at risk EG0013 affected40 at risk
Rhinitis	Infections and infestations	MedDRA (15.0)	Non-systematic Assessment	EG0001 affected37 at risk EG0012 affected40 at risk
Device related infection	Infections and infestations	MedDRA (15.0)	Non-systematic Assessment	EG0002 affected37 at risk EG0011 affected40 at risk
Lower respiratory tract infection	Infections and infestations	MedDRA (15.0)	Non-systematic Assessment	EG0000 affected37 at risk EG0013 affected40 at risk
Candida infection	Infections and infestations	MedDRA (15.0)	Non-systematic Assessment	EG0002 affected37 at risk EG0010 affected40 at risk
Tracheitis	Infections and infestations	MedDRA (15.0)	Non-systematic Assessment	EG0000 affected37 at risk EG0012 affected40 at risk
Hypertension	Vascular disorders	MedDRA (15.0)	Non-systematic Assessment	EG0008 affected37 at risk EG0015 affected40 at risk
Hypotension	Vascular disorders	MedDRA (15.0)	Non-systematic Assessment	EG0002 affected37 at risk EG0010 affected40 at risk
Insomnia	Psychiatric disorders	MedDRA (15.0)	Non-systematic Assessment	EG0007 affected37 at risk EG0012 affected40 at risk
Anxiety	Psychiatric disorders	MedDRA (15.0)	Non-systematic Assessment	EG0002 affected37 at risk EG0011 affected40 at risk
Hypersensitivity	Immune system disorders	MedDRA (15.0)	Non-systematic Assessment	EG0003 affected37 at risk EG0013 affected40 at risk
Vertigo	Ear and labyrinth disorders	MedDRA (15.0)	Non-systematic Assessment	EG0002 affected37 at risk EG0012 affected40 at risk
Proteinuria	Renal and urinary disorders	MedDRA (15.0)	Non-systematic Assessment	EG0002 affected37 at risk EG0014 affected40 at risk
Procedural pain	Injury, poisoning and procedural complications	MedDRA (15.0)	Non-systematic Assessment	EG0001 affected37 at risk EG0013 affected40 at risk

Facility	Status	City	State	ZIP	Country	Contacts
		Vienna		1090	Austria

ID	Term
D007414	Intestinal Neoplasms
D005770	Gastrointestinal Neoplasms
D004067	Digestive System Neoplasms
D009371	Neoplasms by Site
D009369	Neoplasms
D004066	Digestive System Diseases
D005767	Gastrointestinal Diseases
D003108	Colonic Diseases
D007410	Intestinal Diseases
D012002	Rectal Diseases

ID	Term
D014498	Uracil
D011744	Pyrimidinones
D011743	Pyrimidines
D006573	Heterocyclic Compounds, 1-Ring
D006571	Heterocyclic Compounds
D002166	Camptothecin
D000470	Alkaloids
D005575	Formyltetrahydrofolates
D013763	Tetrahydrofolates
D005492	Folic Acid
D011622	Pterins
D011621	Pteridines
D006574	Heterocyclic Compounds, 2-Ring
D000072471	Heterocyclic Compounds, Fused-Ring
D003067	Coenzymes
D045762	Enzymes and Coenzymes
D056831	Coordination Complexes
D009930	Organic Chemicals
D061067	Antibodies, Monoclonal, Humanized
D000911	Antibodies, Monoclonal
D000906	Antibodies
D007136	Immunoglobulins
D007162	Immunoproteins
D001798	Blood Proteins
D011506	Proteins
D000602	Amino Acids, Peptides, and Proteins
D012712	Serum Globulins
D005916	Globulins

ID	Title	Description
BG000	Bevacizumab + mFOLFOX-6	Participants received a chemotherapy regimen of bevacizumab plus mFOLFOX-6. Each drug was administered on Day 1 of each 2-week cycle. Dosing was as follows: bevacizumab 5 mg/kg via IV infusion; oxaliplatin 85 mg/m^2 via IV infusion; leucovorin 400 mg/m^2 via IV infusion; 5-FU 400 mg/m^2 via IV bolus; and 5-FU 2400 mg/m^2 via continuous 46-hour IV infusion. Following completion of 12 cycles, participants could discontinue oxaliplatin and continue with bevacizumab, leucovorin, and 5-FU. Treatment was continued until resectability, PD, unacceptable toxicity, or participant refusal.
BG001	Bevacizumab + FOLFOXIRI	Participants received a chemotherapy regimen of bevacizumab plus FOLFOXIRI. Each drug was administered on Day 1 of each 2-week cycle. Dosing was as follows: bevacizumab 5 mg/kg via IV infusion; oxaliplatin 85 mg/m^2 via IV infusion; irinotecan 165 mg/m^2 via IV infusion; leucovorin 200 mg/m^2 via IV infusion; and 5-FU 3200 mg/m^2 via continuous 46-hour IV infusion. Following completion of 12 cycles, participants were to discontinue either irinotecan, oxaliplatin, or both. Treatment was continued until resectability, PD, unacceptable toxicity, or participant refusal.
BG002	Total	Total of all reporting groups

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Bevacizumab + mFOLFOX-6	Participants received a chemotherapy regimen of bevacizumab plus mFOLFOX-6. Each drug was administered on Day 1 of each 2-week cycle. Dosing was as follows: bevacizumab 5 mg/kg via IV infusion; oxaliplatin 85 mg/m^2 via IV infusion; leucovorin 400 mg/m^2 via IV infusion; 5-FU 400 mg/m^2 via IV bolus; and 5-FU 2400 mg/m^2 via continuous 46-hour IV infusion. Following completion of 12 cycles, participants could discontinue oxaliplatin and continue with bevacizumab, leucovorin, and 5-FU. Treatment was continued until resectability, PD, unacceptable toxicity, or participant refusal.			24	37	36	37
EG001	Bevacizumab + FOLFOXIRI	Participants received a chemotherapy regimen of bevacizumab plus FOLFOXIRI. Each drug was administered on Day 1 of each 2-week cycle. Dosing was as follows: bevacizumab 5 mg/kg via IV infusion; oxaliplatin 85 mg/m^2 via IV infusion; irinotecan 165 mg/m^2 via IV infusion; leucovorin 200 mg/m^2 via IV infusion; and 5-FU 3200 mg/m^2 via continuous 46-hour IV infusion. Following completion of 12 cycles, participants were to discontinue either irinotecan, oxaliplatin, or both. Treatment was continued until resectability, PD, unacceptable toxicity, or participant refusal.			24	40	40	40

ID	Term
D005472	Fluorouracil
D000077146	Irinotecan
D002955	Leucovorin
D000077150	Oxaliplatin
D000068258	Bevacizumab