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A Study of Avastin (Bevacizumab) in Combination With mFOLFOX-6 or FOLFOXIRI in Patients With Metastatic Colorectal Cancer.

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ClinicalTrials.gov Identifier: NCT00778102
Recruitment Status : Completed
First Posted : October 23, 2008
Results First Posted : August 7, 2015
Last Update Posted : November 2, 2016
Sponsor:
Information provided by (Responsible Party):
Hoffmann-La Roche

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Colorectal Cancer
Interventions Drug: 5-FU
Drug: Irinotecan
Drug: Leucovorin
Drug: Oxaliplatin
Drug: bevacizumab [Avastin]
Enrollment 80
Recruitment Details  
Pre-assignment Details  
Arm/Group Title Bevacizumab + mFOLFOX-6 Bevacizumab + FOLFOXIRI
Hide Arm/Group Description 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. Participants received a chemotherapy regimen of bevacizumab plus oxaliplatin, irinotecan, leucovorin, and 5-FU (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.
Period Title: Overall Study
Started 39 41
Completed 18 19
Not Completed 21 22
Reason Not Completed
Adverse Event             8             5
Death             1             1
Lost to Follow-up             1             0
Violation of Selection Criteria             1             1
Protocol Violation             0             1
Refused Treatment             2             3
Withdrawal by Subject             1             1
Administrative Reason             7             10
Arm/Group Title Bevacizumab + mFOLFOX-6 Bevacizumab + FOLFOXIRI Total
Hide Arm/Group Description 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. 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. Total of all reporting groups
Overall Number of Baseline Participants 39 41 80
Hide Baseline Analysis Population Description
Intent-to-Treat (ITT) Population: All randomized participants. Participants were analyzed according to which treatment group they were randomized, regardless of the treatment actually received.
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 39 participants 41 participants 80 participants
57.1  (10.32) 61.8  (11.02) 59.5  (10.87)
Gender  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 39 participants 41 participants 80 participants
Female
21
  53.8%
12
  29.3%
33
  41.3%
Male
18
  46.2%
29
  70.7%
47
  58.8%
1.Primary Outcome
Title Percentage of Participants With Complete Resection or Residual (Microscopic or Macroscopic) Tumor
Hide Description 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.
Time Frame Up to 5 years (at Screening; every 6 weeks, and within 4 weeks prior to surgery; and at time of/after surgery)
Hide Outcome Measure Data
Hide Analysis Population Description
ITT Population
Arm/Group Title Bevacizumab + mFOLFOX-6 Bevacizumab + FOLFOXIRI
Hide Arm/Group Description:
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.
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.
Overall Number of Participants Analyzed 39 41
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
R0, R1, or R2
48.7
(32.4 to 65.2)
61.0
(44.5 to 75.8)
R0 or R1
33.3
(19.1 to 50.2)
51.2
(35.1 to 67.1)
R0
23.1
(11.1 to 39.3)
48.8
(32.9 to 64.9)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Bevacizumab + mFOLFOX-6, Bevacizumab + FOLFOXIRI
Comments Difference between groups in the collective percentage of participants with R0, R1, or R2.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.2707
Comments [Not Specified]
Method Chi-squared
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference in Resection Rate
Estimated Value 12.3
Confidence Interval (2-Sided) 95%
-11.0 to 35.5
Estimation Comments Confidence interval calculated for difference based on Hauck-Anderson method.
2.Secondary Outcome
Title Time to Resection
Hide Description 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.
Time Frame Up to 5 years (at Screening; prior to each cycle, and within 7 days prior to surgery; and at time of surgery)
Hide Outcome Measure Data
Hide Analysis Population Description
ITT Population
Arm/Group Title Bevacizumab + mFOLFOX-6 Bevacizumab + FOLFOXIRI
Hide Arm/Group Description:
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.
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.
Overall Number of Participants Analyzed 39 41
Median (95% Confidence Interval)
Unit of Measure: months
4.4
(4.1 to 5.8)
4.3
(3.9 to 5.5)
3.Secondary Outcome
Title Percentage of Participants With Histopathological Response
Hide Description 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.
Time Frame Up to 5 years (at Screening; every 6 weeks, and within 4 weeks prior to surgery; and at time of/after surgery)
Hide Outcome Measure Data
Hide Analysis Population Description
ITT Population; only participants with a histopathological assessment after the first resective surgery were included in the analysis.
Arm/Group Title Bevacizumab + mFOLFOX-6 Bevacizumab + FOLFOXIRI
Hide Arm/Group Description:
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.
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.
Overall Number of Participants Analyzed 14 21
Measure Type: Number
Unit of Measure: percentage of participants
Complete response 0 4.8
Major response 57.1 47.6
Minor response 28.6 33.3
No response 0 0
Unknown 14.3 14.3
4.Secondary Outcome
Title Percentage of Participants With Complete or Major Histopathological Response
Hide Description 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.
Time Frame Up to 5 years (at Screening; every 6 weeks, and within 4 weeks prior to surgery; and at time of/after surgery)
Hide Outcome Measure Data
Hide Analysis Population Description
ITT Population; only participants with a histopathological assessment after the first resective surgery were included in the analysis.
Arm/Group Title Bevacizumab + mFOLFOX-6 Bevacizumab + FOLFOXIRI
Hide Arm/Group Description:
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.
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.
Overall Number of Participants Analyzed 14 21
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
57.1
(28.9 to 82.3)
52.4
(29.8 to 74.3)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Bevacizumab + mFOLFOX-6, Bevacizumab + FOLFOXIRI
Comments Difference between groups in the collective percentage of participants with complete or major histopathological response.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.7817
Comments [Not Specified]
Method Chi-squared
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference in Response Rate
Estimated Value -4.8
Confidence Interval (2-Sided) 95%
-43.0 to 33.5
Estimation Comments Confidence interval calculated for difference based on Hauck-Anderson method.
5.Secondary Outcome
Title Percentage of Participants Experiencing Relapse Following Curative Resection
Hide Description 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.
Time Frame 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)
Hide Outcome Measure Data
Hide Analysis Population Description
ITT Population; only participants with a residual tumor classification of R0 or R1 after first resection were included in the analysis.
Arm/Group Title Bevacizumab + mFOLFOX-6 Bevacizumab + FOLFOXIRI
Hide Arm/Group Description:
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.
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.
Overall Number of Participants Analyzed 13 21
Measure Type: Number
Unit of Measure: percentage of participants
76.9 57.1
6.Secondary Outcome
Title Relapse-Free Survival (RFS)
Hide Description 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.
Time Frame 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)
Hide Outcome Measure Data
Hide Analysis Population Description
ITT Population; only participants with a residual tumor classification of R0 or R1 after first resection were included in the analysis.
Arm/Group Title Bevacizumab + mFOLFOX-6 Bevacizumab + FOLFOXIRI
Hide Arm/Group Description:
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.
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.
Overall Number of Participants Analyzed 13 21
Median (95% Confidence Interval)
Unit of Measure: months
8.1
(3.8 to 11.7)
17.1 [1] 
(12.3 to NA)
[1]
Confidence interval upper limit was not reached due to insufficient follow-up.
7.Secondary Outcome
Title Percentage of Participants Experiencing Death or Disease Progression
Hide Description 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.
Time Frame 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)
Hide Outcome Measure Data
Hide Analysis Population Description
ITT Population
Arm/Group Title Bevacizumab + mFOLFOX-6 Bevacizumab + FOLFOXIRI
Hide Arm/Group Description:
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.
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.
Overall Number of Participants Analyzed 39 41
Measure Type: Number
Unit of Measure: percentage of participants
89.7 68.3
8.Secondary Outcome
Title Progression-Free Survival (PFS)
Hide Description 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.
Time Frame 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)
Hide Outcome Measure Data
Hide Analysis Population Description
ITT Population
Arm/Group Title Bevacizumab + mFOLFOX-6 Bevacizumab + FOLFOXIRI
Hide Arm/Group Description:
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.
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.
Overall Number of Participants Analyzed 39 41
Median (95% Confidence Interval)
Unit of Measure: months
11.5
(9.6 to 13.6)
18.6
(12.9 to 22.3)
9.Secondary Outcome
Title Percentage of Participants Who Died
Hide Description [Not Specified]
Time Frame 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)
Hide Outcome Measure Data
Hide Analysis Population Description
ITT Population
Arm/Group Title Bevacizumab + mFOLFOX-6 Bevacizumab + FOLFOXIRI
Hide Arm/Group Description:
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.
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.
Overall Number of Participants Analyzed 39 41
Measure Type: Number
Unit of Measure: percentage of participants
48.7 19.5
10.Secondary Outcome
Title Overall Survival (OS)
Hide Description 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.
Time Frame 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)
Hide Outcome Measure Data
Hide Analysis Population Description
ITT Population
Arm/Group Title Bevacizumab + mFOLFOX-6 Bevacizumab + FOLFOXIRI
Hide Arm/Group Description:
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.
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.
Overall Number of Participants Analyzed 39 41
Median (95% Confidence Interval)
Unit of Measure: months
32.2 [1] 
(21.5 to NA)
NA [2] 
(NA to NA)
[1]
Confidence interval upper limit was not reached due to insufficient follow-up.
[2]
Median and corresponding confidence interval were not reached due to insufficient follow-up.
11.Secondary Outcome
Title Percentage of Participants With a Confirmed Best Overall Response of Complete Response (CR) or Partial Response (PR) According to RECIST Version 1.0
Hide Description 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.
Time Frame 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)
Hide Outcome Measure Data
Hide Analysis Population Description
ITT Population
Arm/Group Title Bevacizumab + mFOLFOX-6 Bevacizumab + FOLFOXIRI
Hide Arm/Group Description:
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.
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.
Overall Number of Participants Analyzed 39 41
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
61.5
(44.6 to 76.6)
80.5
(65.1 to 91.2)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Bevacizumab + mFOLFOX-6, Bevacizumab + FOLFOXIRI
Comments Difference between groups in the collective percentage of participants with confirmed best overall response of CR or PR.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0612
Comments [Not Specified]
Method Chi-squared
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference in Response Rate (CR or PR)
Estimated Value 18.9
Confidence Interval (2-Sided) 95%
-2.1 to 40.0
Estimation Comments Confidence interval calculated for difference based on Hauck-Anderson method.
12.Secondary Outcome
Title Time to Response
Hide Description 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.
Time Frame 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)
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Hide Analysis Population Description
ITT Population
Arm/Group Title Bevacizumab + mFOLFOX-6 Bevacizumab + FOLFOXIRI
Hide Arm/Group Description:
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.
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.
Overall Number of Participants Analyzed 39 41
Median (95% Confidence Interval)
Unit of Measure: months
3.1
(2.7 to 8.6)
3.1
(1.9 to 3.9)
13.Secondary Outcome
Title Percentage of Participants With Complications Related to First Resective Surgery
Hide Description 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.
Time Frame 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)
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Hide Analysis Population Description
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.
Arm/Group Title Bevacizumab + mFOLFOX-6 Bevacizumab + FOLFOXIRI
Hide Arm/Group Description:
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.
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.
Overall Number of Participants Analyzed 19 25
Measure Type: Number
Unit of Measure: percentage of participants
Any complication, Total 73.7 52.0
Any complication, Grade 1 15.8 4.0
Any complication, Grade 2 36.8 12.0
Any complication, Grade 3 10.5 24.0
Any complication, Grade 4 0 12
Any complication, Grade 5 10.5 0
Bleeding, Total 15.8 8.0
Bleeding, Grade 1 5.3 0
Bleeding, Grade 2 5.3 4.0
Bleeding, Grade 3 5.3 4.0
Cardiovascular, Total 10.5 4.0
Cardiovascular, Grade 2 0 4
Cardiovascular, Grade 3 5.3 0
Cardiovascular, Grade 4 5.3 0
Infections, Total 26.3 32.0
Infections, Grade 1 10.5 12.0
Infections, Grade 2 5.3 0
Infections, Grade 3 5.3 16.0
Infections, Grade 4 5.3 4.0
Liver insufficiency, Total 10.5 0
Liver insufficiency, Grade 5 10.5 0
Neural disorder, Total 5.3 0
Neural disorder, Grade 2 5.3 0
Noninfected perihepatic fluid collections, Total 0 4
Noninfected perihepatic fluid collections, Grade 2 0 4
Other complication, Total 52.6 28.0
Other complication, Grade 1 26.3 8.0
Other complication, Grade 2 21.1 8.0
Other complication, Grade 3 0 12
Other complication, Grade 4 5.3 0
Pulmonary, Total 5.3 4.0
Pulmonary, Grade 3 5.3 4.0
Renal impairment, Total 10.5 4.0
Renal impairment, Grade 2 5.3 4.0
Renal impairment, Grade 4 5.3 0
Wound healing, Total 5.3 12.0
Wound healing, Grade 1 5.3 0
Wound healing, Grade 3 0 4
Wound healing, Grade 4 0 8
14.Secondary Outcome
Title Percentage of Participants With Complications Related to Second Resective Surgery
Hide Description 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.
Time Frame 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)
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Hide Analysis Population Description
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.
Arm/Group Title Bevacizumab + mFOLFOX-6 Bevacizumab + FOLFOXIRI
Hide Arm/Group Description:
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.
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.
Overall Number of Participants Analyzed 3 3
Measure Type: Number
Unit of Measure: percentage of participants
Any complication, Total 100.0 66.7
Any complication, Grade 1 0 33.3
Any complication, Grade 2 66.7 0
Any complication, Grade 3 0 33.3
Any complication, Grade 3a 33.3 0
Bleeding, Total 33.3 33.3
Bleeding, Grade 1 0 33.3
Bleeding, Grade 2 33.3 0
Time Frame Up to 5 years (at Screening; 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)
Adverse Event Reporting Description Safety Population: All participants who received at least one dose of trial medication, whether prematurely withdrawn or not.
 
Arm/Group Title Bevacizumab + mFOLFOX-6 Bevacizumab + FOLFOXIRI
Hide Arm/Group Description 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. 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.
All-Cause Mortality
Bevacizumab + mFOLFOX-6 Bevacizumab + FOLFOXIRI
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/-- 
Hide Serious Adverse Events
Bevacizumab + mFOLFOX-6 Bevacizumab + FOLFOXIRI
Affected / at Risk (%) Affected / at Risk (%)
Total   24/37 (64.86%)   24/40 (60.00%) 
Blood and lymphatic system disorders     
Febrile neutropenia * 1  3/37 (8.11%)  6/40 (15.00%) 
Neutropenia * 1  3/37 (8.11%)  4/40 (10.00%) 
Disseminated intravascular coagulation * 1  0/37 (0.00%)  1/40 (2.50%) 
Cardiac disorders     
Angina pectoris * 1  1/37 (2.70%)  1/40 (2.50%) 
Atrial fibrillation * 1  1/37 (2.70%)  0/40 (0.00%) 
Gastrointestinal disorders     
Abdominal pain * 1  1/37 (2.70%)  1/40 (2.50%) 
Diarrhoea * 1  1/37 (2.70%)  6/40 (15.00%) 
Ileus * 1  1/37 (2.70%)  1/40 (2.50%) 
Abdominal pain upper * 1  1/37 (2.70%)  0/40 (0.00%) 
Gastrointestinal haemorrhage * 1  1/37 (2.70%)  0/40 (0.00%) 
Gastrointestinal hypomotility * 1  0/37 (0.00%)  1/40 (2.50%) 
Intestinal obstruction * 1  0/37 (0.00%)  1/40 (2.50%) 
Large intestinal obstruction * 1  1/37 (2.70%)  0/40 (0.00%) 
Large intestine perforation * 1  0/37 (0.00%)  1/40 (2.50%) 
Localised intraabdominal fluid collection * 1  0/37 (0.00%)  1/40 (2.50%) 
Nausea * 1  0/37 (0.00%)  1/40 (2.50%) 
Peritoneal haemorrhage * 1  0/37 (0.00%)  1/40 (2.50%) 
Retroperitoneal haematoma * 1  1/37 (2.70%)  0/40 (0.00%) 
Vomiting * 1  1/37 (2.70%)  0/40 (0.00%) 
General disorders     
Pyrexia * 1  0/37 (0.00%)  2/40 (5.00%) 
General physical health deterioration * 1  1/37 (2.70%)  0/40 (0.00%) 
Impaired healing * 1  0/37 (0.00%)  1/40 (2.50%) 
Hepatobiliary disorders     
Hepatic failure * 1  2/37 (5.41%)  0/40 (0.00%) 
Cholangitis * 1  1/37 (2.70%)  0/40 (0.00%) 
Portal vein thrombosis * 1  1/37 (2.70%)  0/40 (0.00%) 
Immune system disorders     
Drug hypersensitivity * 1  1/37 (2.70%)  0/40 (0.00%) 
Infections and infestations     
Peritonitis * 1  0/37 (0.00%)  2/40 (5.00%) 
Bacterial sepsis * 1  1/37 (2.70%)  0/40 (0.00%) 
Campylobacter infection * 1  0/37 (0.00%)  1/40 (2.50%) 
Cholecystitis infective * 1  0/37 (0.00%)  1/40 (2.50%) 
Device related infection * 1  1/37 (2.70%)  0/40 (0.00%) 
Infection * 1  0/37 (0.00%)  1/40 (2.50%) 
Liver abscess * 1  1/37 (2.70%)  0/40 (0.00%) 
Lower respiratory tract infection * 1  0/37 (0.00%)  1/40 (2.50%) 
Lung infection * 1  0/37 (0.00%)  1/40 (2.50%) 
Neutropenic sepsis * 1  1/37 (2.70%)  0/40 (0.00%) 
Wound infection * 1  1/37 (2.70%)  0/40 (0.00%) 
Injury, poisoning and procedural complications     
Wound dehiscence * 1  0/37 (0.00%)  3/40 (7.50%) 
Failure to anastomose * 1  1/37 (2.70%)  0/40 (0.00%) 
Investigations     
Endoscopic retrograde cholangiopancreatography * 1  1/37 (2.70%)  0/40 (0.00%) 
Gamma-glutamyltransferase increased * 1  1/37 (2.70%)  0/40 (0.00%) 
Musculoskeletal and connective tissue disorders     
Muscle spasms * 1  0/37 (0.00%)  1/40 (2.50%) 
Musculoskeletal disorder * 1  1/37 (2.70%)  0/40 (0.00%) 
Nervous system disorders     
Paraesthesia * 1  0/37 (0.00%)  1/40 (2.50%) 
Reproductive system and breast disorders     
Pelvic fluid collection * 1  0/37 (0.00%)  1/40 (2.50%) 
Respiratory, thoracic and mediastinal disorders     
Pulmonary embolism * 1  2/37 (5.41%)  1/40 (2.50%) 
Epistaxis * 1  0/37 (0.00%)  1/40 (2.50%) 
Pleural effusion * 1  1/37 (2.70%)  0/40 (0.00%) 
Pneumothorax * 1  1/37 (2.70%)  0/40 (0.00%) 
Vascular disorders     
Deep vein thrombosis * 1  2/37 (5.41%)  2/40 (5.00%) 
Thrombosis * 1  1/37 (2.70%)  0/40 (0.00%) 
*
Indicates events were collected by non-systematic assessment
1
Term from vocabulary, MedDRA (15.0)
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Bevacizumab + mFOLFOX-6 Bevacizumab + FOLFOXIRI
Affected / at Risk (%) Affected / at Risk (%)
Total   36/37 (97.30%)   40/40 (100.00%) 
Blood and lymphatic system disorders     
Neutropenia * 1  20/37 (54.05%)  26/40 (65.00%) 
Thrombocytopenia * 1  4/37 (10.81%)  8/40 (20.00%) 
Anaemia * 1  4/37 (10.81%)  6/40 (15.00%) 
Leukopenia * 1  1/37 (2.70%)  4/40 (10.00%) 
Lymphopenia * 1  2/37 (5.41%)  0/40 (0.00%) 
Ear and labyrinth disorders     
Vertigo * 1  2/37 (5.41%)  2/40 (5.00%) 
Gastrointestinal disorders     
Diarrhoea * 1  20/37 (54.05%)  33/40 (82.50%) 
Nausea * 1  23/37 (62.16%)  21/40 (52.50%) 
Vomiting * 1  14/37 (37.84%)  25/40 (62.50%) 
Constipation * 1  18/37 (48.65%)  15/40 (37.50%) 
Abdominal pain * 1  15/37 (40.54%)  15/40 (37.50%) 
Dry mouth * 1  7/37 (18.92%)  8/40 (20.00%) 
Abdominal pain upper * 1  8/37 (21.62%)  5/40 (12.50%) 
Stomatitis * 1  5/37 (13.51%)  3/40 (7.50%) 
Toothache * 1  4/37 (10.81%)  2/40 (5.00%) 
Dyspepsia * 1  2/37 (5.41%)  2/40 (5.00%) 
Proctalgia * 1  1/37 (2.70%)  2/40 (5.00%) 
Haemorrhoids * 1  1/37 (2.70%)  2/40 (5.00%) 
Flatulence * 1  2/37 (5.41%)  0/40 (0.00%) 
General disorders     
Asthenia * 1  14/37 (37.84%)  16/40 (40.00%) 
Mucosal inflammation * 1  20/37 (54.05%)  17/40 (42.50%) 
Fatigue * 1  10/37 (27.03%)  12/40 (30.00%) 
Pyrexia * 1  7/37 (18.92%)  12/40 (30.00%) 
Catheter site pain * 1  2/37 (5.41%)  1/40 (2.50%) 
Pain * 1  1/37 (2.70%)  2/40 (5.00%) 
Chest pain * 1  2/37 (5.41%)  0/40 (0.00%) 
Oedema peripheral * 1  0/37 (0.00%)  2/40 (5.00%) 
Immune system disorders     
Hypersensitivity * 1  3/37 (8.11%)  3/40 (7.50%) 
Infections and infestations     
Urinary tract infection * 1  4/37 (10.81%)  4/40 (10.00%) 
Nasopharyngitis * 1  4/37 (10.81%)  1/40 (2.50%) 
Oral herpes * 1  3/37 (8.11%)  3/40 (7.50%) 
Rhinitis * 1  1/37 (2.70%)  2/40 (5.00%) 
Device related infection * 1  2/37 (5.41%)  1/40 (2.50%) 
Lower respiratory tract infection * 1  0/37 (0.00%)  3/40 (7.50%) 
Candida infection * 1  2/37 (5.41%)  0/40 (0.00%) 
Tracheitis * 1  0/37 (0.00%)  2/40 (5.00%) 
Injury, poisoning and procedural complications     
Procedural pain * 1  1/37 (2.70%)  3/40 (7.50%) 
Investigations     
Platelet count decreased * 1  5/37 (13.51%)  3/40 (7.50%) 
Haemoglobin decreased * 1  2/37 (5.41%)  2/40 (5.00%) 
White blood cell count decreased * 1  2/37 (5.41%)  1/40 (2.50%) 
Gamma-glutamyltransferase increased * 1  3/37 (8.11%)  1/40 (2.50%) 
Blood lactate dehydrogenase increased * 1  2/37 (5.41%)  0/40 (0.00%) 
Alanine aminotransferase increased * 1  2/37 (5.41%)  1/40 (2.50%) 
Aspartate aminotransferase increased * 1  2/37 (5.41%)  1/40 (2.50%) 
Weight decreased * 1  2/37 (5.41%)  1/40 (2.50%) 
Blood alkaline phosphatase increased * 1  2/37 (5.41%)  0/40 (0.00%) 
Metabolism and nutrition disorders     
Decreased appetite * 1  8/37 (21.62%)  13/40 (32.50%) 
Hypokalaemia * 1  2/37 (5.41%)  6/40 (15.00%) 
Hypocalcaemia * 1  0/37 (0.00%)  3/40 (7.50%) 
Hypophosphataemia * 1  0/37 (0.00%)  2/40 (5.00%) 
Musculoskeletal and connective tissue disorders     
Back pain * 1  8/37 (21.62%)  7/40 (17.50%) 
Musculoskeletal pain * 1  3/37 (8.11%)  4/40 (10.00%) 
Pain in extremity * 1  2/37 (5.41%)  6/40 (15.00%) 
Neck pain * 1  4/37 (10.81%)  1/40 (2.50%) 
Arthralgia * 1  0/37 (0.00%)  4/40 (10.00%) 
Muscle spasms * 1  1/37 (2.70%)  2/40 (5.00%) 
Myalgia * 1  2/37 (5.41%)  1/40 (2.50%) 
Musculoskeletal chest pain * 1  2/37 (5.41%)  0/40 (0.00%) 
Nervous system disorders     
Neuropathy peripheral * 1  22/37 (59.46%)  19/40 (47.50%) 
Paraesthesia * 1  12/37 (32.43%)  7/40 (17.50%) 
Peripheral sensory neuropathy * 1  4/37 (10.81%)  4/40 (10.00%) 
Headache * 1  9/37 (24.32%)  7/40 (17.50%) 
Dysgeusia * 1  5/37 (13.51%)  10/40 (25.00%) 
Lethargy * 1  3/37 (8.11%)  2/40 (5.00%) 
Dysaesthesia * 1  3/37 (8.11%)  2/40 (5.00%) 
Dizziness * 1  3/37 (8.11%)  1/40 (2.50%) 
Polyneuropathy * 1  3/37 (8.11%)  1/40 (2.50%) 
Psychiatric disorders     
Insomnia * 1  7/37 (18.92%)  2/40 (5.00%) 
Anxiety * 1  2/37 (5.41%)  1/40 (2.50%) 
Renal and urinary disorders     
Proteinuria * 1  2/37 (5.41%)  4/40 (10.00%) 
Respiratory, thoracic and mediastinal disorders     
Epistaxis * 1  13/37 (35.14%)  16/40 (40.00%) 
Cough * 1  3/37 (8.11%)  5/40 (12.50%) 
Rhinorrhoea * 1  3/37 (8.11%)  3/40 (7.50%) 
Dyspnoea * 1  3/37 (8.11%)  2/40 (5.00%) 
Dysphonia * 1  2/37 (5.41%)  2/40 (5.00%) 
Dyspnoea exertional * 1  2/37 (5.41%)  2/40 (5.00%) 
Oropharyngeal pain * 1  1/37 (2.70%)  4/40 (10.00%) 
Nasal congestion * 1  1/37 (2.70%)  2/40 (5.00%) 
Skin and subcutaneous tissue disorders     
Alopecia * 1  2/37 (5.41%)  12/40 (30.00%) 
Pruritus * 1  2/37 (5.41%)  3/40 (7.50%) 
Rash * 1  5/37 (13.51%)  2/40 (5.00%) 
Palmar-plantar erythrodysaesthesia syndrome * 1  2/37 (5.41%)  3/40 (7.50%) 
Skin hyperpigmentation * 1  2/37 (5.41%)  2/40 (5.00%) 
Skin lesion * 1  2/37 (5.41%)  0/40 (0.00%) 
Vascular disorders     
Hypertension * 1  8/37 (21.62%)  5/40 (12.50%) 
Hypotension * 1  2/37 (5.41%)  0/40 (0.00%) 
*
Indicates events were collected by non-systematic assessment
1
Term from vocabulary, MedDRA (15.0)
[Not Specified]
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
The Study being conducted under this Agreement is part of the Overall Study. Investigator is free to publish in reputable journals or to present at professional conferences the results of the Study, but only after the first publication or presentation that involves the Overall Study. The Sponsor may request that Confidential Information be deleted and/or the publication be postponed in order to protect the Sponsor's intellectual property rights.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Medical Communications
Organization: Hoffmann-LaRoche
Phone: 800-821-8590
EMail: genentech@druginfo.com
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Layout table for additonal information
Responsible Party: Hoffmann-La Roche
ClinicalTrials.gov Identifier: NCT00778102    
Other Study ID Numbers: MO18725
2007-007863-26
First Submitted: October 22, 2008
First Posted: October 23, 2008
Results First Submitted: July 10, 2015
Results First Posted: August 7, 2015
Last Update Posted: November 2, 2016