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A Translational Study of Bevacizumab in Participants With Metastatic Colorectal Cancer (ASCENT)

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ClinicalTrials.gov Identifier: NCT01588990
Recruitment Status : Completed
First Posted : May 1, 2012
Results First Posted : January 21, 2019
Last Update Posted : January 21, 2019
Sponsor:
Information provided by (Responsible Party):
Hoffmann-La Roche

Study Type Interventional
Study Design Intervention Model: Single Group Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Colorectal Neoplasms
Interventions Drug: Oxaliplatin
Drug: Capecitabine
Drug: Bevacizumab
Drug: Leucovorin
Drug: 5-Fluouracil
Drug: Irinotecan
Enrollment 128
Recruitment Details  
Pre-assignment Details  
Arm/Group Title Bevacizumab: Phase A and Phase B
Hide Arm/Group Description The trial consisted of 2 phases of treatment. Phase A: Participants received bevacizumab 7.5 mg/kg IV on Day 1 every 3 weeks in combination with XELOX (oral capecitabine 1000 mg/m^2 twice daily Days 1-14, oxaliplatin 130 mg/m^2 IV Day 1) or bevacizumab 5 mg/kg IV on Day 1 every 2 weeks in combination with mFOLFOX6 (oxaliplatin 85 mg/m^2 IV Day 1, leucovorin 400 mg/m^2 IV Day 1, 5-fluouracil 400 mg/m^2 IV loading dose then 2400 mg/m^2 continuous IV infusion over 46 hours Day 1) until first disease progression or occurrence of unmanageable toxicity. Phase B: Upon documented first disease progression, participants continued receiving bevacizumab 5 mg/kg IV on Day 1 every 2 weeks in combination with FOLFIRI (irinotecan 180 mg/m^2 IV Day 1, leucovorin and 5-fluouracil [same regimen as of mFOLFOX6]) until second disease progression or occurrence of unmanageable toxicity. Phase B treatment had to commence within 4 weeks of the date of documented first disease progression.
Period Title: Phase A
Started 128
Completed 58 [1]
Not Completed 70
Reason Not Completed
Withdrawal by Subject             5
Physician Decision             11
Other             14
Lost to Follow-up             1
Death             5
Adverse Event             28
Still on therapy at end of study             6
[1]
A total of 58 participants had disease progression in Phase A and ended Phase A.
Period Title: Phase B
Started 53 [1]
Completed 37 [2]
Not Completed 16
Reason Not Completed
Adverse Event             2
Still on therapy at end of study             5
Withdrawal by Subject             3
Physician Decision             4
Other             2
[1]
Of 58 participants who had documented disease progression in Phase A, 53 entered in Phase B.
[2]
A total of 37 participants had disease progression in Phase B and ended Phase B.
Arm/Group Title Bevacizumab: Phase A and Phase B
Hide Arm/Group Description The trial consisted of 2 phases of treatment. Phase A: Participants received bevacizumab 7.5 mg/kg intravenously (IV) on Day 1 every 3 weeks in combination with XELOX (oral capecitabine 1000 mg/m^2 twice daily Days 1-14, oxaliplatin 130 mg/m^2 IV Day 1) or bevacizumab 5 mg/kg IV on Day 1 every 2 weeks in combination with mFOLFOX6 (oxaliplatin 85 mg/m^2 IV Day 1, leucovorin 400 mg/m^2 IV Day 1, 5-fluouracil 400 mg/m^2 IV loading dose then 2400 mg/m^2 continuous IV infusion over 46 hours Day 1) until first disease progression or occurrence of unmanageable toxicity. Phase B: Upon documented first disease progression, participants continued receiving bevacizumab 5 mg/kg IV on Day 1 every 2 weeks in combination with FOLFIRI (irinotecan 180 mg/m^2 IV Day 1, leucovorin and 5-fluouracil [same regimen as of mFOLFOX6]) until second disease progression or occurrence of unmanageable toxicity. Phase B treatment had to commence within 4 weeks of the date of documented first disease progression.
Overall Number of Baseline Participants 128
Hide Baseline Analysis Population Description
Full Analysis Set (FAS) included all participants who received at least 1 dose of bevacizumab.
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 128 participants
61.9  (11.66)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 128 participants
Female
70
  54.7%
Male
58
  45.3%
1.Primary Outcome
Title Association Between Neutrophil to Lymphocyte Ratio (NLR) [NLR ≤5 Versus NLR >5] and Progression-Free Survival (PFS) as Assessed by Hazard Ratio
Hide Description NLR was calculated from the laboratory values as the ratio of Neutrophils to Lymphocytes. PFS was defined as the time from the start of initial treatment to documentation of first disease progression or death from any cause, whichever occurred first. Disease progression was determined according to standard practice based on radiological, biochemical (carcinoembryonic antigen [CEA]) or clinical factors. Determination of disease progression was to be unequivocal and was defined as any of the following: an unequivocal and clinically meaningful increase in the size of known tumors, the appearance of one or more new lesions, death due to disease without prior objective documentation of progression, elevated CEA accompanied by other radiological or clinical evidence of progression, or symptomatic deterioration. The association between NLR (NLR less than or equal to [≤] 5 vs greater than [>] 5) and PFS was reported as hazard ratio.
Time Frame Baseline up to disease progression, death or end of study (up to 4 years)
Hide Outcome Measure Data
Hide Analysis Population Description
FAS population. “Overall Number of Participants Analyzed” = participants who were evaluable for this outcome.
Arm/Group Title Bevacizumab: Phase A and Phase B
Hide Arm/Group Description:
The trial consisted of 2 phases of treatment. Phase A: Participants received bevacizumab 7.5 mg/kg intravenously (IV) on Day 1 every 3 weeks in combination with XELOX (oral capecitabine 1000 mg/m^2 twice daily Days 1-14, oxaliplatin 130 mg/m^2 IV Day 1) or bevacizumab 5 mg/kg IV on Day 1 every 2 weeks in combination with mFOLFOX6 (oxaliplatin 85 mg/m^2 IV Day 1, leucovorin 400 mg/m^2 IV Day 1, 5-fluouracil 400 mg/m^2 IV loading dose then 2400 mg/m^2 continuous IV infusion over 46 hours Day 1) until first disease progression or occurrence of unmanageable toxicity. Phase B: Upon documented first disease progression, participants continued receiving bevacizumab 5 mg/kg IV on Day 1 every 2 weeks in combination with FOLFIRI (irinotecan 180 mg/m^2 IV Day 1, leucovorin and 5-fluouracil [same regimen as of mFOLFOX6]) until second disease progression or occurrence of unmanageable toxicity. Phase B treatment had to commence within 4 weeks of the date of documented first disease progression.
Overall Number of Participants Analyzed 127
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: hazard ratio
1.4
(0.9 to 2.2)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Bevacizumab: Phase A and Phase B
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.101
Comments [Not Specified]
Method Cox Proportional Hazards Model
Comments [Not Specified]
2.Secondary Outcome
Title PFS Until First Disease Progression as Assessed by the Investigator Based on Routine Clinical Practice: Phase A
Hide Description PFS until first progression was defined as the time from the start of initial treatment to documentation of first disease progression or death from any cause, whichever occurred first. Disease progression was determined according to standard practice based on radiological, biochemical (CEA) or clinical factors. Determination of disease progression was to be unequivocal and was defined as any of the following: an unequivocal and clinically meaningful increase in the size of known tumors, the appearance of one or more new lesions, death due to disease without prior objective documentation of progression, elevated CEA accompanied by other radiological or clinical evidence of progression, or symptomatic deterioration. Kaplan-Meier methodology was used to estimate PFS.
Time Frame Baseline up to first disease progression, death or end of study (up to 4 years)
Hide Outcome Measure Data
Hide Analysis Population Description
FAS population.
Arm/Group Title Bevacizumab: Phase A
Hide Arm/Group Description:
In Phase A, participants received bevacizumab 7.5 milligrams per kilogram (mg/kg) IV on Day 1 every 3 weeks in combination with XELOX (oral capecitabine 1000 milligrams per square meter [mg/m^2] twice daily Days 1-14, oxaliplatin 130 mg/m^2 IV Day 1) or bevacizumab 5 mg/kg IV on Day 1 every 2 weeks in combination with mFOLFOX6 (oxaliplatin 85 mg/m^2 IV Day 1, leucovorin 400 mg/m^2 IV Day 1, 5-fluouracil 400 mg/m^2 IV loading dose then 2400 mg/m^2 continuous IV infusion over 46 hours Day 1) until first disease progression or occurrence of unmanageable toxicity.
Overall Number of Participants Analyzed 128
Median (95% Confidence Interval)
Unit of Measure: months
9.2
(7.9 to 10.8)
3.Secondary Outcome
Title PFS Until Second Disease Progression as Assessed by the Investigator Based on Routine Clinical Practice: Phase B
Hide Description PFS in Phase B (PFS-B) was defined as the time from the start of Phase B treatment to documentation of second disease progression or death from any cause, whichever occurred first. Disease progression was determined according to standard practice based on radiological, biochemical (CEA) or clinical factors. Determination of disease progression was to be unequivocal and was defined as any of the following: an unequivocal and clinically meaningful increase in the size of known tumors, the appearance of one or more new lesions, death due to disease without prior objective documentation of progression, elevated CEA accompanied by other radiological or clinical evidence of progression, or symptomatic deterioration. Kaplan-Meier methodology was used to estimate PFS.
Time Frame From the start of Phase B treatment to disease progression, death or end of study (up to 4 years)
Hide Outcome Measure Data
Hide Analysis Population Description
Phase B FAS population included participants who received at least 1 dose of bevacizumab in Phase B.
Arm/Group Title Bevacizumab: Phase B
Hide Arm/Group Description:
Upon documented first disease progression in Phase A, participants continued receiving bevacizumab 5 mg/kg IV on Day 1 every 2 weeks in combination with FOLFIRI (irinotecan 180 mg/m^2 IV Day 1, leucovorin 400 mg/m^2 IV Day 1, and 5-fluouracil 400 mg/m^2 IV loading dose then 2400 mg/m^2 continuous IV infusion over 46 hours Day 1) in Phase B until second disease progression or occurrence of unmanageable toxicity. Phase B treatment had to commence within 4 weeks of the date of documented first disease progression.
Overall Number of Participants Analyzed 53
Median (95% Confidence Interval)
Unit of Measure: months
6.7
(3.0 to 8.2)
4.Secondary Outcome
Title Time to Failure of Strategy (TFS): Overall
Hide Description TFS was defined as time from the start of initial treatment to documentation of first disease progression without entering Phase B, or second disease progression having entered Phase B. Disease progression was determined according to standard practice based on radiological, biochemical (CEA) or clinical factors. Determination of disease progression was to be unequivocal and was defined as any of the following: an unequivocal and clinically meaningful increase in the size of known tumors, the appearance of one or more new lesions, death due to disease without prior objective documentation of progression, elevated CEA accompanied by other radiological or clinical evidence of progression, or symptomatic deterioration. Kaplan-Meier methodology was used to estimate TFS.
Time Frame Baseline up to disease progression, death or end of study (up to 4 years)
Hide Outcome Measure Data
Hide Analysis Population Description
FAS population.
Arm/Group Title Bevacizumab: Phase A and Phase B
Hide Arm/Group Description:
The trial consisted of 2 phases of treatment. Phase A: Participants received bevacizumab 7.5 mg/kg intravenously (IV) on Day 1 every 3 weeks in combination with XELOX (oral capecitabine 1000 mg/m^2 twice daily Days 1-14, oxaliplatin 130 mg/m^2 IV Day 1) or bevacizumab 5 mg/kg IV on Day 1 every 2 weeks in combination with mFOLFOX6 (oxaliplatin 85 mg/m^2 IV Day 1, leucovorin 400 mg/m^2 IV Day 1, 5-fluouracil 400 mg/m^2 IV loading dose then 2400 mg/m^2 continuous IV infusion over 46 hours Day 1) until first disease progression or occurrence of unmanageable toxicity. Phase B: Upon documented first disease progression, participants continued receiving bevacizumab 5 mg/kg IV on Day 1 every 2 weeks in combination with FOLFIRI (irinotecan 180 mg/m^2 IV Day 1, leucovorin and 5-fluouracil [same regimen as of mFOLFOX6]) until second disease progression or occurrence of unmanageable toxicity. Phase B treatment had to commence within 4 weeks of the date of documented first disease progression.
Overall Number of Participants Analyzed 128
Median (95% Confidence Interval)
Unit of Measure: months
14.8
(13.1 to 19.4)
5.Secondary Outcome
Title Duration of Disease Control (DDC) as Assessed by the Investigator Based on Routine Clinical Practice: Overall
Hide Description DDC was defined as PFS + PFS-B. In cases where a participant did not enter Phase B, then DDC was defined as PFS. PFS was defined as time from start of initial treatment to documentation of first disease progression or death from any cause, whichever occurred first. PFS-B was time from start of Phase B treatment to documentation of second disease progression or death from any cause, whichever occurred first. Disease progression was determined according to standard practice based on radiological, biochemical (CEA) or clinical factors. Determination of disease progression was to be unequivocal and was defined as any of the following: an unequivocal and clinically meaningful increase in the size of known tumors, appearance of one or more new lesions, death due to disease without prior objective documentation of progression, elevated CEA accompanied by other radiological or clinical evidence of progression, or symptomatic deterioration. Kaplan-Meier methodology was used to estimate DDC.
Time Frame Baseline up to disease progression, death or end of study (up to 4 years)
Hide Outcome Measure Data
Hide Analysis Population Description
FAS population.
Arm/Group Title Bevacizumab: Phase A and Phase B
Hide Arm/Group Description:
The trial consisted of 2 phases of treatment. Phase A: Participants received bevacizumab 7.5 mg/kg IV on Day 1 every 3 weeks in combination with XELOX (oral capecitabine 1000 mg/m^2 twice daily Days 1-14, oxaliplatin 130 mg/m^2 IV Day 1) or bevacizumab 5 mg/kg IV on Day 1 every 2 weeks in combination with mFOLFOX6 (oxaliplatin 85 mg/m^2 IV Day 1, leucovorin 400 mg/m^2 IV Day 1, 5-fluouracil 400 mg/m^2 IV loading dose then 2400 mg/m^2 continuous IV infusion over 46 hours Day 1) until first disease progression or occurrence of unmanageable toxicity. Phase B: Upon documented first disease progression, participants continued receiving bevacizumab 5 mg/kg IV on Day 1 every 2 weeks in combination with FOLFIRI (irinotecan 180 mg/m^2 IV Day 1, leucovorin and 5-fluouracil [same regimen as of mFOLFOX6]) until second disease progression or occurrence of unmanageable toxicity. Phase B treatment had to commence within 4 weeks of the date of documented first disease progression.
Overall Number of Participants Analyzed 128
Median (95% Confidence Interval)
Unit of Measure: months
14.0
(10.8 to 16.6)
6.Secondary Outcome
Title Overall Survival (OS) From the Start of Treatment to Study Completion: Overall
Hide Description OS was defined as the time from the start of initial treatment to the date of death, regardless of the cause of death. Kaplan-Meier methodology was used to estimate OS.
Time Frame Baseline until death or end of study (up to 4 years)
Hide Outcome Measure Data
Hide Analysis Population Description
FAS population.
Arm/Group Title Bevacizumab: Phase A and Phase B
Hide Arm/Group Description:
The trial consisted of 2 phases of treatment. Phase A: Participants received bevacizumab 7.5 mg/kg IV on Day 1 every 3 weeks in combination with XELOX (oral capecitabine 1000 mg/m^2 twice daily Days 1-14, oxaliplatin 130 mg/m^2 IV Day 1) or bevacizumab 5 mg/kg IV on Day 1 every 2 weeks in combination with mFOLFOX6 (oxaliplatin 85 mg/m^2 IV Day 1, leucovorin 400 mg/m^2 IV Day 1, 5-fluouracil 400 mg/m^2 IV loading dose then 2400 mg/m^2 continuous IV infusion over 46 hours Day 1) until first disease progression or occurrence of unmanageable toxicity. Phase B: Upon documented first disease progression, participants continued receiving bevacizumab 5 mg/kg IV on Day 1 every 2 weeks in combination with FOLFIRI (irinotecan 180 mg/m^2 IV Day 1, leucovorin and 5-fluouracil [same regimen as of mFOLFOX6]) until second disease progression or occurrence of unmanageable toxicity. Phase B treatment had to commence within 4 weeks of the date of documented first disease progression.
Overall Number of Participants Analyzed 128
Median (95% Confidence Interval)
Unit of Measure: months
25.0
(19.2 to 29.7)
7.Secondary Outcome
Title Survival Beyond First Disease Progression: Overall
Hide Description Survival beyond first progression was defined as the time from the date of first disease progression to death due to any cause. Disease progression was determined according to standard practice based on radiological, biochemical (CEA) or clinical factors. Determination of disease progression was to be unequivocal and was defined as any of the following: an unequivocal and clinically meaningful increase in the size of known tumors, the appearance of one or more new lesions, death due to disease without prior objective documentation of progression, elevated CEA accompanied by other radiological or clinical evidence of progression, or symptomatic deterioration. Kaplan-Meier methodology was used to estimate survival beyond first disease progression.
Time Frame Baseline until death or end of study (up to 4 years)
Hide Outcome Measure Data
Hide Analysis Population Description
FAS population. “Overall Number of Participants Analyzed” = participants who were evaluable for this outcome.
Arm/Group Title Bevacizumab: Phase A and Phase B
Hide Arm/Group Description:
The trial consisted of 2 phases of treatment. Phase A: Participants received bevacizumab 7.5 mg/kg IV on Day 1 every 3 weeks in combination with XELOX (oral capecitabine 1000 mg/m^2 twice daily Days 1-14, oxaliplatin 130 mg/m^2 IV Day 1) or bevacizumab 5 mg/kg IV on Day 1 every 2 weeks in combination with mFOLFOX6 (oxaliplatin 85 mg/m^2 IV Day 1, leucovorin 400 mg/m^2 IV Day 1, 5-fluouracil 400 mg/m^2 IV loading dose then 2400 mg/m^2 continuous IV infusion over 46 hours Day 1) until first disease progression or occurrence of unmanageable toxicity. Phase B: Upon documented first disease progression, participants continued receiving bevacizumab 5 mg/kg IV on Day 1 every 2 weeks in combination with FOLFIRI (irinotecan 180 mg/m^2 IV Day 1, leucovorin and 5-fluouracil [same regimen as of mFOLFOX6]) until second disease progression or occurrence of unmanageable toxicity. Phase B treatment had to commence within 4 weeks of the date of documented first disease progression.
Overall Number of Participants Analyzed 101
Median (95% Confidence Interval)
Unit of Measure: months
12.6
(8.8 to 15.9)
8.Secondary Outcome
Title OS: Phase B
Hide Description Overall Survival in Phase B was defined as the time from the start of treatment in Phase B to death due to any cause. Kaplan-Meier methodology was used to estimate OS.
Time Frame From the start of Phase B treatment death or end of study (up to 4 years)
Hide Outcome Measure Data
Hide Analysis Population Description
Phase B FAS population.
Arm/Group Title Bevacizumab: Phase B
Hide Arm/Group Description:
Upon documented first disease progression in Phase A, participants continued receiving bevacizumab 5 mg/kg IV on Day 1 every 2 weeks in combination with FOLFIRI (irinotecan 180 mg/m^2 IV Day 1, leucovorin 400 mg/m^2 IV Day 1, and 5-fluouracil 400 mg/m^2 IV loading dose then 2400 mg/m^2 continuous IV infusion over 46 hours Day 1) in Phase B until second disease progression or occurrence of unmanageable toxicity. Phase B treatment had to commence within 4 weeks of the date of documented first disease progression.
Overall Number of Participants Analyzed 53
Median (95% Confidence Interval)
Unit of Measure: months
14.9
(8.2 to 17.5)
9.Secondary Outcome
Title Percentage of Participants With Confirmed Complete or Partial Response as Assessed by the Investigator Based on Routine Clinical Practice: Phase A
Hide Description Percentage of participants with best overall response of confirmed complete response or partial response based on the investigator assessment of the response as per routine clinical practice was reported. The confirmation of response must be no less than 4 weeks after initial assessment.
Time Frame Baseline up to disease progression, death or end of study (up to 4 years)
Hide Outcome Measure Data
Hide Analysis Population Description
FAS population.
Arm/Group Title Bevacizumab: Phase A
Hide Arm/Group Description:
In Phase A, participants received bevacizumab 7.5 mg/kg IV on Day 1 every 3 weeks in combination with XELOX (oral capecitabine 1000 mg/m^2 twice daily Days 1-14, oxaliplatin 130 mg/m^2 IV Day 1) or bevacizumab 5 mg/kg IV on Day 1 every 2 weeks in combination with mFOLFOX6 (oxaliplatin 85 mg/m^2 IV Day 1, leucovorin 400 mg/m^2 IV Day 1, 5-fluouracil 400 mg/m^2 IV loading dose then 2400 mg/m^2 continuous IV infusion over 46 hours Day 1) until first disease progression or occurrence of unmanageable toxicity.
Overall Number of Participants Analyzed 128
Measure Type: Number
Unit of Measure: percentage of participants
Complete response 3.1
Partial response 8.6
10.Secondary Outcome
Title Percentage of Participants With Confirmed Complete or Partial Response as Assessed by the Investigator Based on Routine Clinical Practice: Phase B
Hide Description Percentage of participants with best overall response of confirmed complete response or partial response based on the investigator assessment of the response as per routine clinical practice was reported. The confirmation of response must be no less than 4 weeks after initial assessment.
Time Frame From the start of Phase B treatment to disease progression, death or end of study (up to 4 years)
Hide Outcome Measure Data
Hide Analysis Population Description
Phase B FAS population.
Arm/Group Title Bevacizumab: Phase B
Hide Arm/Group Description:
Upon documented first disease progression in Phase A, participants continued receiving bevacizumab 5 mg/kg IV on Day 1 every 2 weeks in combination with FOLFIRI (irinotecan 180 mg/m^2 IV Day 1, leucovorin 400 mg/m^2 IV Day 1, and 5-fluouracil 400 mg/m^2 IV loading dose then 2400 mg/m^2 continuous IV infusion over 46 hours Day 1) in Phase B until second disease progression or occurrence of unmanageable toxicity. Phase B treatment had to commence within 4 weeks of the date of documented first disease progression.
Overall Number of Participants Analyzed 53
Measure Type: Number
Unit of Measure: percentage of participants
Complete response 0
Partial response 0
11.Secondary Outcome
Title Percentage of Participants With Confirmed Complete or Partial Response as Assessed by the Investigator Based on Routine Clinical Practice: Overall
Hide Description Percentage of participants with best overall response of confirmed complete response or partial response based on the investigator assessment of the response as per routine clinical practice was reported. The confirmation of response must be no less than 4 weeks after initial assessment.
Time Frame Baseline up to disease progression, death or end of study (up to 4 years)
Hide Outcome Measure Data
Hide Analysis Population Description
FAS population.
Arm/Group Title Bevacizumab: Phase A and Phase B
Hide Arm/Group Description:
The trial consisted of 2 phases of treatment. Phase A: Participants received bevacizumab 7.5 mg/kg IV on Day 1 every 3 weeks in combination with XELOX (oral capecitabine 1000 mg/m^2 twice daily Days 1-14, oxaliplatin 130 mg/m^2 IV Day 1) or bevacizumab 5 mg/kg IV on Day 1 every 2 weeks in combination with mFOLFOX6 (oxaliplatin 85 mg/m^2 IV Day 1, leucovorin 400 mg/m^2 IV Day 1, 5-fluouracil 400 mg/m^2 IV loading dose then 2400 mg/m^2 continuous IV infusion over 46 hours Day 1) until first disease progression or occurrence of unmanageable toxicity. Phase B: Upon documented first disease progression, participants continued receiving bevacizumab 5 mg/kg IV on Day 1 every 2 weeks in combination with FOLFIRI (irinotecan 180 mg/m^2 IV Day 1, leucovorin and 5-fluouracil [same regimen as of mFOLFOX6]) until second disease progression or occurrence of unmanageable toxicity. Phase B treatment had to commence within 4 weeks of the date of documented first disease progression.
Overall Number of Participants Analyzed 128
Measure Type: Number
Unit of Measure: percentage of participants
Complete response 3.1
Partial response 8.6
12.Secondary Outcome
Title Percentage of Participants Who Underwent Liver Resection: Overall
Hide Description The results include percentage of participants who underwent potentially curative liver resection.
Time Frame Baseline up to disease progression, death or end of study (up to 4 years)
Hide Outcome Measure Data
Hide Analysis Population Description
FAS population.
Arm/Group Title Bevacizumab: Phase A and Phase B
Hide Arm/Group Description:
The trial consisted of 2 phases of treatment. Phase A: Participants received bevacizumab 7.5 mg/kg IV on Day 1 every 3 weeks in combination with XELOX (oral capecitabine 1000 mg/m^2 twice daily Days 1-14, oxaliplatin 130 mg/m^2 IV Day 1) or bevacizumab 5 mg/kg IV on Day 1 every 2 weeks in combination with mFOLFOX6 (oxaliplatin 85 mg/m^2 IV Day 1, leucovorin 400 mg/m^2 IV Day 1, 5-fluouracil 400 mg/m^2 IV loading dose then 2400 mg/m^2 continuous IV infusion over 46 hours Day 1) until first disease progression or occurrence of unmanageable toxicity. Phase B: Upon documented first disease progression, participants continued receiving bevacizumab 5 mg/kg IV on Day 1 every 2 weeks in combination with FOLFIRI (irinotecan 180 mg/m^2 IV Day 1, leucovorin and 5-fluouracil [same regimen as of mFOLFOX6]) until second disease progression or occurrence of unmanageable toxicity. Phase B treatment had to commence within 4 weeks of the date of documented first disease progression.
Overall Number of Participants Analyzed 128
Measure Type: Number
Unit of Measure: percentage of participants
1.6
13.Secondary Outcome
Title Association Between NLR (NLR ≤5 Versus NLR >5) and OS as Assessed by Hazard Ratio
Hide Description NLR was calculated from the laboratory values as the ratio of Neutrophils to Lymphocytes. OS was defined as the time from the start of initial treatment to the date of death, regardless of the cause of death. The association between NLR (NLR ≤ 5 vs > 5) and OS was reported as hazard ratio.
Time Frame Baseline up to disease progression, death or end of study (up to 4 years)
Hide Outcome Measure Data
Hide Analysis Population Description
FAS population. “Overall Number of Participants Analyzed” = participants who were evaluable for this outcome.
Arm/Group Title Bevacizumab: Phase A and Phase B
Hide Arm/Group Description:
The trial consisted of 2 phases of treatment. Phase A: Participants received bevacizumab 7.5 mg/kg IV on Day 1 every 3 weeks in combination with XELOX (oral capecitabine 1000 mg/m^2 twice daily Days 1-14, oxaliplatin 130 mg/m^2 IV Day 1) or bevacizumab 5 mg/kg IV on Day 1 every 2 weeks in combination with mFOLFOX6 (oxaliplatin 85 mg/m^2 IV Day 1, leucovorin 400 mg/m^2 IV Day 1, 5-fluouracil 400 mg/m^2 IV loading dose then 2400 mg/m^2 continuous IV infusion over 46 hours Day 1) until first disease progression or occurrence of unmanageable toxicity. Phase B: Upon documented first disease progression, participants continued receiving bevacizumab 5 mg/kg IV on Day 1 every 2 weeks in combination with FOLFIRI (irinotecan 180 mg/m^2 IV Day 1, leucovorin and 5-fluouracil [same regimen as of mFOLFOX6]) until second disease progression or occurrence of unmanageable toxicity. Phase B treatment had to commence within 4 weeks of the date of documented first disease progression.
Overall Number of Participants Analyzed 127
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: hazard ratio
1.6
(1.0 to 2.7)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Bevacizumab: Phase A and Phase B
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.052
Comments [Not Specified]
Method Cox Proportional Hazards Model
Comments [Not Specified]
14.Secondary Outcome
Title Association Between NLR Normalization (First NLR Post-Baseline ≤5 Versus NLR >5) and PFS as Assessed by Hazard Ratio
Hide Description NLR was calculated from laboratory values as ratio of Neutrophils to Lymphocytes. NLR normalization was assessed by adding first post-baseline measurement of NLR to the primary model. This is equivalent to testing whether first change in NLR is significantly associated with outcome. PFS was defined as time from start of initial treatment to documentation of first disease progression or death from any cause. Disease progression was determined according to standard practice based on radiological, biochemical (CEA) or clinical factors. Determination of disease progression was defined as: an unequivocal and clinically meaningful increase in size of known tumors, appearance of ≥1 new lesions, death due to disease without prior objective documentation of progression, elevated CEA accompanied by other radiological or clinical evidence of progression, or symptomatic deterioration.The association between NLR normalization (first NLR post-baseline ≤5 vs >5) and PFS was reported as hazard ratio.
Time Frame Baseline up to disease progression, death or end of study (up to 4 years)
Hide Outcome Measure Data
Hide Analysis Population Description
FAS population. “Overall Number of Participants Analyzed” = participants who were evaluable for this outcome.
Arm/Group Title Bevacizumab: Phase A and Phase B
Hide Arm/Group Description:
The trial consisted of 2 phases of treatment. Phase A: Participants received bevacizumab 7.5 mg/kg IV on Day 1 every 3 weeks in combination with XELOX (oral capecitabine 1000 mg/m^2 twice daily Days 1-14, oxaliplatin 130 mg/m^2 IV Day 1) or bevacizumab 5 mg/kg IV on Day 1 every 2 weeks in combination with mFOLFOX6 (oxaliplatin 85 mg/m^2 IV Day 1, leucovorin 400 mg/m^2 IV Day 1, 5-fluouracil 400 mg/m^2 IV loading dose then 2400 mg/m^2 continuous IV infusion over 46 hours Day 1) until first disease progression or occurrence of unmanageable toxicity. Phase B: Upon documented first disease progression, participants continued receiving bevacizumab 5 mg/kg IV on Day 1 every 2 weeks in combination with FOLFIRI (irinotecan 180 mg/m^2 IV Day 1, leucovorin and 5-fluouracil [same regimen as of mFOLFOX6]) until second disease progression or occurrence of unmanageable toxicity. Phase B treatment had to commence within 4 weeks of the date of documented first disease progression.
Overall Number of Participants Analyzed 127
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: hazard ratio
0.9
(0.5 to 1.8)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Bevacizumab: Phase A and Phase B
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.797
Comments [Not Specified]
Method Cox Proportional Hazards Model
Comments [Not Specified]
15.Secondary Outcome
Title Association Between Longitudinal NLR (Longitudinal NLR ≤5 Versus NLR >5) and PFS as Assessed by Hazard Ratio
Hide Description NLR was calculated from the laboratory values as the ratio of Neutrophils to Lymphocytes. Longitudinal NLR was assessed by treating the NLR measurements taken over the time-course of treatment as a time-dependent covariate. PFS was defined as time from the start of initial treatment to documentation of first disease progression or death from any cause, whichever occurred first. Disease progression was determined according to standard practice based on radiological, biochemical (CEA) or clinical factors. Determination of disease progression was to be unequivocal and was defined as: an unequivocal and clinically meaningful increase in size of known tumors, appearance of one or more new lesions, death due to disease without prior objective documentation of progression, elevated CEA accompanied by other radiological or clinical evidence of progression, or symptomatic deterioration. The association between longitudinal NLR (longitudinal NLR ≤5 vs N>5) and PFS was reported as hazard ratio.
Time Frame Baseline up to disease progression, death or end of study (up to 4 years)
Hide Outcome Measure Data
Hide Analysis Population Description
FAS population. “Overall Number of Participants Analyzed” = participants who were evaluable for this outcome.
Arm/Group Title Bevacizumab: Phase A and Phase B
Hide Arm/Group Description:
The trial consisted of 2 phases of treatment. Phase A: Participants received bevacizumab 7.5 mg/kg IV on Day 1 every 3 weeks in combination with XELOX (oral capecitabine 1000 mg/m^2 twice daily Days 1-14, oxaliplatin 130 mg/m^2 IV Day 1) or bevacizumab 5 mg/kg IV on Day 1 every 2 weeks in combination with mFOLFOX6 (oxaliplatin 85 mg/m^2 IV Day 1, leucovorin 400 mg/m^2 IV Day 1, 5-fluouracil 400 mg/m^2 IV loading dose then 2400 mg/m^2 continuous IV infusion over 46 hours Day 1) until first disease progression or occurrence of unmanageable toxicity. Phase B: Upon documented first disease progression, participants continued receiving bevacizumab 5 mg/kg IV on Day 1 every 2 weeks in combination with FOLFIRI (irinotecan 180 mg/m^2 IV Day 1, leucovorin and 5-fluouracil [same regimen as of mFOLFOX6]) until second disease progression or occurrence of unmanageable toxicity. Phase B treatment had to commence within 4 weeks of the date of documented first disease progression.
Overall Number of Participants Analyzed 127
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: hazard ratio
1.3
(0.9 to 1.9)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Bevacizumab: Phase A and Phase B
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.188
Comments [Not Specified]
Method Cox Proportional Hazards Model
Comments [Not Specified]
16.Secondary Outcome
Title Association Between Longitudinal NLR (Longitudinal NLR ≤5 Versus NLR >5) and OS as Assessed by Hazard Ratio
Hide Description NLR was calculated from the laboratory values as the ratio of Neutrophils to Lymphocytes. Longitudinal NLR was assessed by treating the NLR measurements taken over the time-course of treatment as a time-dependent covariate. OS was defined as the time from the start of initial treatment to the date of death, regardless of the cause of death. The association between longitudinal NLR (longitudinal NLR ≤5 vs NLR >5) and OS was reported as hazard ratio.
Time Frame Baseline up to death or end of study (up to 4 years)
Hide Outcome Measure Data
Hide Analysis Population Description
FAS population. “Overall Number of Participants Analyzed” = participants who were evaluable for this outcome.
Arm/Group Title Bevacizumab: Phase A and Phase B
Hide Arm/Group Description:
The trial consisted of 2 phases of treatment. Phase A: Participants received bevacizumab 7.5 mg/kg IV on Day 1 every 3 weeks in combination with XELOX (oral capecitabine 1000 mg/m^2 twice daily Days 1-14, oxaliplatin 130 mg/m^2 IV Day 1) or bevacizumab 5 mg/kg IV on Day 1 every 2 weeks in combination with mFOLFOX6 (oxaliplatin 85 mg/m^2 IV Day 1, leucovorin 400 mg/m^2 IV Day 1, 5-fluouracil 400 mg/m^2 IV loading dose then 2400 mg/m^2 continuous IV infusion over 46 hours Day 1) until first disease progression or occurrence of unmanageable toxicity. Phase B: Upon documented first disease progression, participants continued receiving bevacizumab 5 mg/kg IV on Day 1 every 2 weeks in combination with FOLFIRI (irinotecan 180 mg/m^2 IV Day 1, leucovorin and 5-fluouracil [same regimen as of mFOLFOX6]) until second disease progression or occurrence of unmanageable toxicity. Phase B treatment had to commence within 4 weeks of the date of documented first disease progression.
Overall Number of Participants Analyzed 127
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: hazard ratio
2.2
(1.2 to 4.0)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Bevacizumab: Phase A and Phase B
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.016
Comments [Not Specified]
Method Cox Proportional Hazards Model
Comments [Not Specified]
17.Secondary Outcome
Title European Quality of Life 5-Dimension (EuroQol-5D) Utility Score: Phase A
Hide Description EQ-5D is a standardized generic preference based health related quality of life instrument. It records how one’s health is “today” and consists of a descriptive system. The descriptive system is comprised of 5 dimensions: mobility, self-care, usual activities, pain/discomfort, anxiety/depression. Each dimension on the EQ-5D involves a 3-point response scale which indicates the level of impairment (level 1 = no problem; level 2 = some or moderate problem[s] and level 3 = unable, or extreme problems). Level of problem reported in each EQ-5D dimension determines a unique health state which is converted into a weighted health state index by applying scores from EQ-5D preference weights elicited from general population samples. This generates a unique description of the subjects’ health status, which is valued between 0 (representing death) and 1 (representing perfect health). Higher the score, the better the quality of life.
Time Frame Baseline, every 8-9 weeks thereafter, end of treatment (EOT) (30 days after disease progression [up to 4 years]), survival follow-up 12-weekly visits (up to 4 years) [Detailed time points are presented in the category titles]
Hide Outcome Measure Data
Hide Analysis Population Description
FAS population. "Number Analyzed" = participants who were evaluable at the specified time point for this outcome.
Arm/Group Title Bevacizumab: Phase A
Hide Arm/Group Description:
In Phase A, participants received bevacizumab 7.5 mg/kg IV on Day 1 every 3 weeks in combination with XELOX (oral capecitabine 1000 mg/m^2 twice daily Days 1-14, oxaliplatin 130 mg/m^2 IV Day 1) or bevacizumab 5 mg/kg IV on Day 1 every 2 weeks in combination with mFOLFOX6 (oxaliplatin 85 mg/m^2 IV Day 1, leucovorin 400 mg/m^2 IV Day 1, 5-fluouracil 400 mg/m^2 IV loading dose then 2400 mg/m^2 continuous IV infusion over 46 hours Day 1) until first disease progression or occurrence of unmanageable toxicity.
Overall Number of Participants Analyzed 128
Mean (Standard Deviation)
Unit of Measure: units on a scale
Phase A Baseline Number Analyzed 127 participants
0.830  (0.1590)
Phase A Visit 2 (Weeks 8-9) Number Analyzed 100 participants
0.857  (0.1392)
Phase A Visit 3 (Weeks 16-17) Number Analyzed 79 participants
0.865  (0.1074)
Phase A Visit 4 (Weeks 24-25) Number Analyzed 62 participants
0.853  (0.1206)
Phase A Visit 5 (Weeks 32-33) Number Analyzed 42 participants
0.869  (0.1381)
Phase A Visit 6 (Weeks 40-41) Number Analyzed 30 participants
0.892  (0.1013)
Phase A Visit 7 (Weeks 48-49) Number Analyzed 23 participants
0.872  (0.1332)
Phase A Visit 8 (Weeks 56-57) Number Analyzed 18 participants
0.881  (0.1058)
Phase A Visit 9 (Weeks 64-65) Number Analyzed 19 participants
0.894  (0.1081)
Phase A Visit 10 (Weeks 72-73) Number Analyzed 15 participants
0.843  (0.1466)
Phase A Visit 11 (Weeks 80-81) Number Analyzed 14 participants
0.898  (0.0952)
Phase A Visit 12 (Weeks 88-89) Number Analyzed 14 participants
0.915  (0.1033)
Phase A Visit 13 (Weeks 96-97) Number Analyzed 12 participants
0.844  (0.1463)
Phase A Visit 14 (Weeks 104-105) Number Analyzed 12 participants
0.899  (0.1398)
Phase A Visit 15 (Weeks 112-113) Number Analyzed 10 participants
0.878  (0.0861)
Phase A Visit 16 (Weeks 120-121) Number Analyzed 8 participants
0.899  (0.0852)
Phase A Visit 17 (Weeks 128-129) Number Analyzed 10 participants
0.873  (0.1734)
Phase A Visit 18 (Weeks 136-137) Number Analyzed 9 participants
0.909  (0.0876)
Phase A Visit 19 (Weeks 144-145) Number Analyzed 7 participants
0.947  (0.0914)
Phase A Visit 20 (Weeks 152-153) Number Analyzed 7 participants
0.852  (0.0718)
Phase A Visit 21 (Weeks 160-161) Number Analyzed 3 participants
0.933  (0.1156)
Phase A Visit 22 (Weeks 168-169) Number Analyzed 2 participants
0.813  (0.0193)
Phase A Visit 23 (Weeks 176-177) Number Analyzed 2 participants
0.900  (0.1416)
Phase A EOT Visit (up to 4 years) Number Analyzed 78 participants
0.817  (0.1423)
Survival Follow-Up 1 (up to 4 years) Number Analyzed 10 participants
0.768  (0.1414)
Survival Follow-Up 2 (up to 4 years) Number Analyzed 3 participants
0.901  (0.0860)
Survival Follow-Up 3 (up to 4 years) Number Analyzed 2 participants
0.819  (0.0583)
Survival Follow-Up 4 (up to 4 years) Number Analyzed 1 participants
0.843
Survival Follow-Up 5 (up to 4 years) Number Analyzed 1 participants
1.000
Survival Follow-Up 6 (up to 4 years) Number Analyzed 3 participants
0.835  (0.0229)
Survival Follow-Up 7 (up to 4 years) Number Analyzed 1 participants
0.816
18.Secondary Outcome
Title EuroQol-5D Utility Score: Phase B
Hide Description EQ-5D is a standardized generic preference based health related quality of life instrument. It records how one’s health is “today” and consists of a descriptive system. The descriptive system is comprised of 5 dimensions: mobility, self-care, usual activities, pain/discomfort, anxiety/depression. Each dimension on the EQ-5D involves a 3-point response scale which indicates the level of impairment (level 1 = no problem; level 2 = some or moderate problem[s] and level 3 = unable, or extreme problems). Level of problem reported in each EQ-5D dimension determines a unique health state which is converted into a weighted health state index by applying scores from EQ-5D preference weights elicited from general population samples. This generates a unique description of the subjects’ health status, which is valued between 0 (representing death) and 1 (representing perfect health). Higher the score, the better the quality of life.
Time Frame Baseline, every 8-9 weeks thereafter, EOT (30 days after disease progression [up to 4 years]), survival follow-up 12-weekly visits (up to 4 years) [Detailed time points are presented in the category titles]
Hide Outcome Measure Data
Hide Analysis Population Description
Phase B FAS population. "Number Analyzed" = participants who were evaluable at the specified time point for this outcome.
Arm/Group Title Bevacizumab: Phase B
Hide Arm/Group Description:
Upon documented first disease progression in Phase A, participants continued receiving bevacizumab 5 mg/kg IV on Day 1 every 2 weeks in combination with FOLFIRI (irinotecan 180 mg/m^2 IV Day 1, leucovorin 400 mg/m^2 IV Day 1, and 5-fluouracil 400 mg/m^2 IV loading dose then 2400 mg/m^2 continuous IV infusion over 46 hours Day 1) in Phase B until second disease progression or occurrence of unmanageable toxicity. Phase B treatment had to commence within 4 weeks of the date of documented first disease progression.
Overall Number of Participants Analyzed 53
Mean (Standard Deviation)
Unit of Measure: units on a scale
Phase B Baseline Number Analyzed 53 participants
0.814  (0.1566)
Phase B Visit 2 (up to 4 years) Number Analyzed 32 participants
0.859  (0.1376)
Phase B Visit 3 (up to 4 years) Number Analyzed 25 participants
0.894  (0.1108)
Phase B Visit 4 (up to 4 years) Number Analyzed 20 participants
0.897  (0.1012)
Phase B Visit 5 (up to 4 years) Number Analyzed 13 participants
0.866  (0.1299)
Phase B Visit 6 (up to 4 years) Number Analyzed 12 participants
0.837  (0.1710)
Phase B Visit 7 (up to 4 years) Number Analyzed 6 participants
0.876  (0.0986)
Phase B Visit 8 (up to 4 years) Number Analyzed 3 participants
0.874  (0.1141)
Phase B Visit 9 (up to 4 years) Number Analyzed 2 participants
0.908  (0.1299)
Phase B Visit 10 (up to 4 years) Number Analyzed 2 participants
0.811  (0.0466)
Phase B Visit 11 (up to 4 years) Number Analyzed 2 participants
0.806  (0.0539)
Phase B Visit 12 (up to 4 years) Number Analyzed 1 participants
0.844
Phase B Visit 13 (up to 4 years) Number Analyzed 1 participants
1.000
Phase B Visit 14 (up to 4 years) Number Analyzed 1 participants
1.000
Phase B Visit 15 (up to 4 years) Number Analyzed 1 participants
0.844
Phase B Visit 16 (up to 4 years) Number Analyzed 1 participants
0.833
Phase B Visit 17 (up to 4 years) Number Analyzed 1 participants
0.844
Phase B Visit 18 (up to 4 years) Number Analyzed 1 participants
0.833
Phase B Visit 19 (up to 4 years) Number Analyzed 1 participants
0.827
Phase B Visit 20 (up to 4 years) Number Analyzed 1 participants
0.816
Phase B Visit 21 (up to 4 years) Number Analyzed 1 participants
0.844
Phase B Visit 22 (up to 4 years) Number Analyzed 1 participants
0.844
Phase B Visit 23 (up to 4 years) Number Analyzed 1 participants
0.827
Phase B Visit 24 (up to 4 years) Number Analyzed 1 participants
0.844
Phase B EOT Visit (up to 4 years) Number Analyzed 31 participants
0.809  (0.1585)
Survival Follow-Up 1 (up to 4 years) Number Analyzed 3 participants
0.740  (0.1035)
Survival Follow-Up 2 (up to 4 years) Number Analyzed 4 participants
0.772  (0.0782)
Survival Follow-Up 3 (up to 4 years) Number Analyzed 1 participants
0.827
Survival Follow-Up 4 (up to 4 years) Number Analyzed 1 participants
0.827
Survival Follow-Up 6 (up to 4 years) Number Analyzed 1 participants
1.000
19.Secondary Outcome
Title Assessment of Quality of Life - Eight Dimensions (AQoL-8D) Global Utility Score: Phase A
Hide Description AQoL-8D provides a global utility score and comprised of 35 questions from which 8 dimensions (Independent Living, Life Satisfaction, Mental Health, Coping, Relationships, Self Worth, Pain, and Senses) are derived. Each of the 8 scales is calculated based on the answers to 3 questions. Each question is given an answer dependent utility score (0 [worst] to 1 [best]) and then these scores are combined using a multiplicative model to get the normalized scale score value, each scale ranging between 0.0 (representing death) and 1.0 (representing full health).
Time Frame Baseline, every 8-9 weeks thereafter, EOT (30 days after disease progression [up to 4 years]), survival follow-up 12-weekly visits (up to 4 years) [Detailed time points are presented in the category titles]
Hide Outcome Measure Data
Hide Analysis Population Description
FAS population. "Number Analyzed" = participants who were evaluable at the specified time point for this outcome.
Arm/Group Title Bevacizumab: Phase A
Hide Arm/Group Description:
In Phase A, participants received bevacizumab 7.5 mg/kg IV on Day 1 every 3 weeks in combination with XELOX (oral capecitabine 1000 mg/m^2 twice daily Days 1-14, oxaliplatin 130 mg/m^2 IV Day 1) or bevacizumab 5 mg/kg IV on Day 1 every 2 weeks in combination with mFOLFOX6 (oxaliplatin 85 mg/m^2 IV Day 1, leucovorin 400 mg/m^2 IV Day 1, 5-fluouracil 400 mg/m^2 IV loading dose then 2400 mg/m^2 continuous IV infusion over 46 hours Day 1) until first disease progression or occurrence of unmanageable toxicity.
Overall Number of Participants Analyzed 128
Mean (Standard Deviation)
Unit of Measure: units on a scale
Phase A Baseline Number Analyzed 123 participants
0.747  (0.1819)
Phase A Visit 2 (Weeks 8-9) Number Analyzed 100 participants
0.760  (0.1710)
Phase A Visit 3 (Weeks 16-17) Number Analyzed 81 participants
0.767  (0.1691)
Phase A Visit 4 (Weeks 24-25) Number Analyzed 61 participants
0.796  (0.1650)
Phase A Visit 5 (Weeks 32-33) Number Analyzed 43 participants
0.800  (0.1762)
Phase A Visit 6 (Weeks 40-41) Number Analyzed 28 participants
0.831  (0.1578)
Phase A Visit 7 (Weeks 48-49) Number Analyzed 23 participants
0.818  (0.1455)
Phase A Visit 8 (Weeks 56-57) Number Analyzed 18 participants
0.851  (0.1043)
Phase A Visit 9 (Weeks 64-65) Number Analyzed 19 participants
0.822  (0.1304)
Phase A Visit 10 (Weeks 72-73) Number Analyzed 15 participants
0.827  (0.1426)
Phase A Visit 11 (Weeks 80-81) Number Analyzed 14 participants
0.839  (0.1272)
Phase A Visit 12 (Weeks 88-89) Number Analyzed 14 participants
0.856  (0.1295)
Phase A Visit 13 (Weeks 96-97) Number Analyzed 12 participants
0.831  (0.1482)
Phase A Visit 14 (Weeks 104-105) Number Analyzed 12 participants
0.815  (0.1788)
Phase A Visit 15 (Weeks 112-113) Number Analyzed 10 participants
0.871  (0.0877)
Phase A Visit 16 (Weeks 120-121) Number Analyzed 8 participants
0.869  (0.1428)
Phase A Visit 17 (Weeks 128-129) Number Analyzed 10 participants
0.859  (0.1430)
Phase A Visit 18 (Weeks 136-137) Number Analyzed 9 participants
0.880  (0.1048)
Phase A Visit 19 (Weeks 144-145) Number Analyzed 7 participants
0.915  (0.0883)
Phase A Visit 20 (Weeks 152-153) Number Analyzed 7 participants
0.864  (0.1266)
Phase A Visit 21 (Weeks 160-161) Number Analyzed 3 participants
0.806  (0.1422)
Phase A Visit 22 (Weeks 168-169) Number Analyzed 2 participants
0.811  (0.2238)
Phase A Visit 23 (Weeks 176-177) Number Analyzed 2 participants
0.709  (0.3336)
Phase A EOT Visit (up to 4 years) Number Analyzed 80 participants
0.739  (0.1882)
Survival Follow-Up 1 (up to 4 years) Number Analyzed 9 participants
0.718  (0.1600)
Survival Follow-Up 2 (up to 4 years) Number Analyzed 3 participants
0.792  (0.1977)
Survival Follow-Up 3 (up to 4 years) Number Analyzed 2 participants
0.696  (0.1684)
Survival Follow-Up 4 (up to 4 years) Number Analyzed 1 participants
0.620
Survival Follow-Up 5 (up to 4 years) Number Analyzed 1 participants
0.800
Survival Follow-Up 6 (up to 4 years) Number Analyzed 2 participants
0.810  (0.0531)
Survival Follow-Up 7 (up to 4 years) Number Analyzed 1 participants
0.874
20.Secondary Outcome
Title AQoL-8D Global Utility Score: Phase B
Hide Description AQoL-8D provides a global utility score and consists of 8 separately scored dimensions including Independent Living, Life Satisfaction, Mental Health, Coping, Relationships, Self Worth, Pain, and Senses. Each of the 8 scales is calculated based on the answers to 3 questions. Each question is given an answer dependent utility score (0 [worst] to 1 [best]) and then these scores are combined using a multiplicative model to get the normalized scale score value, each scale ranging between 0.0 (representing death) and 1.0 (representing full health).
Time Frame Baseline, every 8-9 weeks thereafter, EOT (30 days after disease progression [up to 4 years]), survival follow-up 12-weekly visits (up to 4 years) [Detailed time points are presented in the category titles]
Hide Outcome Measure Data
Hide Analysis Population Description
Phase B FAS population. "Number Analyzed" = participants who were evaluable at the specified time point for this outcome.
Arm/Group Title Bevacizumab: Phase B
Hide Arm/Group Description:
Upon documented first disease progression in Phase A, participants continued receiving bevacizumab 5 mg/kg IV on Day 1 every 2 weeks in combination with FOLFIRI (irinotecan 180 mg/m^2 IV Day 1, leucovorin 400 mg/m^2 IV Day 1, and 5-fluouracil 400 mg/m^2 IV loading dose then 2400 mg/m^2 continuous IV infusion over 46 hours Day 1) in Phase B until second disease progression or occurrence of unmanageable toxicity. Phase B treatment had to commence within 4 weeks of the date of documented first disease progression.
Overall Number of Participants Analyzed 53
Mean (Standard Deviation)
Unit of Measure: units on a scale
Phase B Baseline Number Analyzed 53 participants
0.736  (0.1943)
Phase B Visit 2 (up to 4 years) Number Analyzed 32 participants
0.773  (0.1821)
Phase B Visit 3 (up to 4 years) Number Analyzed 23 participants
0.813  (0.1610)
Phase B Visit 4 (up to 4 years) Number Analyzed 18 participants
0.878  (0.1154)
Phase B Visit 5 (up to 4 years) Number Analyzed 13 participants
0.808  (0.1630)
Phase B Visit 6 (up to 4 years) Number Analyzed 12 participants
0.809  (0.1717)
Phase B Visit 7 (up to 4 years) Number Analyzed 6 participants
0.825  (0.1682)
Phase B Visit 8 (up to 4 years) Number Analyzed 3 participants
0.910  (0.1023)
Phase B Visit 9 (up to 4 years) Number Analyzed 2 participants
0.819  (0.1986)
Phase B Visit 10 (up to 4 years) Number Analyzed 2 participants
0.856  (0.1589)
Phase B Visit 11 (up to 4 years) Number Analyzed 2 participants
0.730  (0.2906)
Phase B Visit 12 (up to 4 years) Number Analyzed 1 participants
0.960
Phase B Visit 13 (up to 4 years) Number Analyzed 1 participants
0.965
Phase B Visit 14 (up to 4 years) Number Analyzed 1 participants
0.958
Phase B Visit 15 (up to 4 years) Number Analyzed 1 participants
0.967
Phase B Visit 16 (up to 4 years) Number Analyzed 1 participants
0.942
Phase B Visit 17 (up to 4 years) Number Analyzed 1 participants
0.927
Phase B Visit 18 (up to 4 years) Number Analyzed 1 participants
0.931
Phase B Visit 19 (up to 4 years) Number Analyzed 1 participants
0.866
Phase B Visit 20 (up to 4 years) Number Analyzed 1 participants
0.887
Phase B Visit 21 (up to 4 years) Number Analyzed 1 participants
0.940
Phase B Visit 22 (up to 4 years) Number Analyzed 1 participants
0.919
Phase B Visit 23 (up to 4 years) Number Analyzed 1 participants
0.937
Phase B Visit 24 (up to 4 years) Number Analyzed 1 participants
0.950
Phase B EOT Visit (up to 4 years) Number Analyzed 32 participants
0.708  (0.2229)
Survival Follow-Up 1 (up to 4 years) Number Analyzed 3 participants
0.788  (0.0895)
Survival Follow-Up 2 (up to 4 years) Number Analyzed 4 participants
0.791  (0.1829)
Survival Follow-Up 3 (up to 4 years) Number Analyzed 1 participants
0.989
Survival Follow-Up 4 (up to 4 years) Number Analyzed 1 participants
0.981
Survival Follow-Up 6 (up to 4 years) Number Analyzed 1 participants
0.875
21.Secondary Outcome
Title Functional Assessment of Cancer Therapy-Colorectal (FACT-C) Score: Phase A
Hide Description FACT-C is one part of the Functional Assessment of Chronic Illness Therapy (FACIT) Measurement System, which comprehensively assesses the health-related QoL of cancer participants and participants with other chronic illnesses. It is composed of 27 items of the general version of the FACT-C as a general core QoL measure and has a disease-specific subscale containing 9 colorectal cancer-specific items. It consists of total 36 items, summarized to 5 subscales: physical well-being (7 items), functional well-being (7 items), social/family well-being (7 items); all 3 subscales range from 0 to 28, emotional well-being (6 items) range from 0 to 24, colorectal cancer subscale (9 items) range from 0 to 36; higher subscale score=better QoL. All single-item measures range from 0='Not at all' to 4='Very much'. Total possible score range: 0 to 144. High scale score represents a better QoL.
Time Frame Baseline, every 8-9 weeks thereafter, EOT (30 days after disease progression [up to 4 years]), survival follow-up 12-weekly visits (up to 4 years) [Detailed time points are presented in the category titles]
Hide Outcome Measure Data
Hide Analysis Population Description
FAS population. "Number Analyzed" = participants who were evaluable at the specified time point for this outcome.
Arm/Group Title Bevacizumab: Phase A
Hide Arm/Group Description:
In Phase A, participants received bevacizumab 7.5 mg/kg IV on Day 1 every 3 weeks in combination with XELOX (oral capecitabine 1000 mg/m^2 twice daily Days 1-14, oxaliplatin 130 mg/m^2 IV Day 1) or bevacizumab 5 mg/kg IV on Day 1 every 2 weeks in combination with mFOLFOX6 (oxaliplatin 85 mg/m^2 IV Day 1, leucovorin 400 mg/m^2 IV Day 1, 5-fluouracil 400 mg/m^2 IV loading dose then 2400 mg/m^2 continuous IV infusion over 46 hours Day 1) until first disease progression or occurrence of unmanageable toxicity.
Overall Number of Participants Analyzed 128
Mean (Standard Deviation)
Unit of Measure: units on a scale
Phase A Baseline Number Analyzed 121 participants
103.84  (16.615)
Phase A Visit 2 (Weeks 8-9) Number Analyzed 98 participants
103.33  (16.065)
Phase A Visit 3 (Weeks 16-17) Number Analyzed 78 participants
106.34  (15.318)
Phase A Visit 4 (Weeks 24-25) Number Analyzed 61 participants
109.66  (15.038)
Phase A Visit 5 (Weeks 32-33) Number Analyzed 43 participants
109.39  (16.727)
Phase A Visit 6 (Weeks 40-41) Number Analyzed 30 participants
111.30  (16.420)
Phase A Visit 7 (Weeks 48-49) Number Analyzed 23 participants
111.40  (13.506)
Phase A Visit 8 (Weeks 56-57) Number Analyzed 17 participants
113.51  (10.777)
Phase A Visit 9 (Weeks 64-65) Number Analyzed 19 participants
113.92  (12.239)
Phase A Visit 10 (Weeks 72-73) Number Analyzed 15 participants
115.11  (15.473)
Phase A Visit 11 (Weeks 80-81) Number Analyzed 14 participants
114.00  (13.230)
Phase A Visit 12 (Weeks 88-89) Number Analyzed 14 participants
115.99  (12.844)
Phase A Visit 13 (Weeks 96-97) Number Analyzed 12 participants
113.54  (12.298)
Phase A Visit 14 (Weeks 104-105) Number Analyzed 12 participants
112.36  (15.443)
Phase A Visit 15 (Weeks 112-113) Number Analyzed 10 participants
119.48  (11.542)
Phase A Visit 16 (Weeks 120-121) Number Analyzed 7 participants
116.38  (15.214)
Phase A Visit 17 (Weeks 128-129) Number Analyzed 9 participants
113.69  (17.816)
Phase A Visit 18 (Weeks 136-137) Number Analyzed 9 participants
112.94  (16.931)
Phase A Visit 19 (Weeks 144-145) Number Analyzed 7 participants
117.55  (10.397)
Phase A Visit 20 (Weeks 152-153) Number Analyzed 7 participants
115.86  (13.120)
Phase A Visit 21 (Weeks 160-161) Number Analyzed 3 participants
106.00  (20.664)
Phase A Visit 22 (Weeks 168-169) Number Analyzed 2 participants
112.00  (26.870)
Phase A Visit 23 (Weeks 176-177) Number Analyzed 2 participants
105.00  (36.770)
Phase A EOT Visit (up to 4 years) Number Analyzed 79 participants
103.94  (17.429)
Survival Follow-Up 1 (up to 4 years) Number Analyzed 9 participants
102.89  (18.086)
Survival Follow-Up 2 (up to 4 years) Number Analyzed 3 participants
104.00  (8.047)
Survival Follow-Up 3 (up to 4 years) Number Analyzed 2 participants
105.50  (10.607)
Survival Follow-Up 4 (up to 4 years) Number Analyzed 1 participants
109.00
Survival Follow-Up 5 (up to 4 years) Number Analyzed 1 participants
119.00
Survival Follow-Up 6 (up to 4 years) Number Analyzed 3 participants
103.61  (4.945)
Survival Follow-Up 7 (up to 4 years) Number Analyzed 1 participants
115.00
22.Secondary Outcome
Title FACT-C Score: Phase B
Hide Description FACT-C is one part of the FACIT Measurement System, which comprehensively assesses the health-related QoL of cancer participants and participants with other chronic illnesses. It is composed of 27 items of the general version of the FACT-C as a general core QoL measure and has a disease-specific subscale containing 9 colorectal cancer-specific items. It consists of total 36 items, summarized to 5 subscales: physical well-being (7 items), functional well-being (7 items), social/family well-being (7 items); all 3 subscales range from 0 to 28, emotional well-being (6 items) range from 0 to 24, colorectal cancer subscale (9 items) range from 0 to 36; higher subscale score=better QoL. All single-item measures range from 0='Not at all' to 4='Very much'. Total possible score range: 0 to 144. High scale score represents a better QoL.
Time Frame Baseline, every 8-9 weeks thereafter, EOT (30 days after disease progression [up to 4 years]), survival follow-up 12-weekly visits (up to 4 years) [Detailed time points are presented in the category titles]
Hide Outcome Measure Data
Hide Analysis Population Description
Phase B FAS population. "Number Analyzed" = participants who were evaluable at the specified time point for this outcome.
Arm/Group Title Bevacizumab: Phase B
Hide Arm/Group Description:
Upon documented first disease progression in Phase A, participants continued receiving bevacizumab 5 mg/kg IV on Day 1 every 2 weeks in combination with FOLFIRI (irinotecan 180 mg/m^2 IV Day 1, leucovorin 400 mg/m^2 IV Day 1, and 5-fluouracil 400 mg/m^2 IV loading dose then 2400 mg/m^2 continuous IV infusion over 46 hours Day 1) in Phase B until second disease progression or occurrence of unmanageable toxicity. Phase B treatment had to commence within 4 weeks of the date of documented first disease progression.
Overall Number of Participants Analyzed 53
Mean (Standard Deviation)
Unit of Measure: units on a scale
Phase B Baseline Number Analyzed 53 participants
103.47  (18.284)
Phase B Visit 2 (up to 4 years) Number Analyzed 30 participants
108.71  (17.387)
Phase B Visit 3 (up to 4 years) Number Analyzed 25 participants
108.19  (16.541)
Phase B Visit 4 (up to 4 years) Number Analyzed 19 participants
114.89  (14.467)
Phase B Visit 5 (up to 4 years) Number Analyzed 13 participants
110.60  (15.592)
Phase B Visit 6 (up to 4 years) Number Analyzed 12 participants
111.28  (14.121)
Phase B Visit 7 (up to 4 years) Number Analyzed 6 participants
114.78  (12.640)
Phase B Visit 8 (up to 4 years) Number Analyzed 3 participants
120.39  (9.007)
Phase B Visit 9 (up to 4 years) Number Analyzed 2 participants
108.08  (18.267)
Phase B Visit 10 (up to 4 years) Number Analyzed 2 participants
110.50  (17.678)
Phase B Visit 11 (up to 4 years) Number Analyzed 2 participants
109.33  (19.328)
Phase B Visit 12 (up to 4 years) Number Analyzed 1 participants
125.00
Phase B Visit 13 (up to 4 years) Number Analyzed 1 participants
119.00
Phase B Visit 14 (up to 4 years) Number Analyzed 1 participants
117.00
Phase B Visit 15 (up to 4 years) Number Analyzed 1 participants
126.00
Phase B Visit 16 (up to 4 years) Number Analyzed 1 participants
123.00
Phase B Visit 17 (up to 4 years) Number Analyzed 1 participants
127.00
Phase B Visit 18 (up to 4 years) Number Analyzed 1 participants
126.00
Phase B Visit 19 (up to 4 years) Number Analyzed 1 participants
127.00
Phase B Visit 20 (up to 4 years) Number Analyzed 1 participants
126.00
Phase B Visit 21 (up to 4 years) Number Analyzed 1 participants
123.00
Phase B Visit 22 (up to 4 years) Number Analyzed 1 participants
124.00
Phase B Visit 23 (up to 4 years) Number Analyzed 1 participants
126.00
Phase B Visit 24 (up to 4 years) Number Analyzed 1 participants
130.00
Phase B EOT Visit (up to 4 years) Number Analyzed 33 participants
101.67  (19.023)
Survival Follow-Up 1 (up to 4 years) Number Analyzed 3 participants
98.72  (20.024)
Survival Follow-Up 2 (up to 4 years) Number Analyzed 4 participants
102.50  (17.705)
Survival Follow-Up 3 (up to 4 years) Number Analyzed 1 participants
126.33
Survival Follow-Up 4 (up to 4 years) Number Analyzed 1 participants
125.00
Survival Follow-Up 6 (up to 4 years) Number Analyzed 1 participants
124.67
Time Frame Baseline up to end of study (up to 4 years)
Adverse Event Reporting Description FAS population.
 
Arm/Group Title Bevacizumab: Phase A and Phase B
Hide Arm/Group Description The trial consisted of 2 phases of treatment. Phase A: Participants received bevacizumab 7.5 mg/kg intravenously (IV) on Day 1 every 3 weeks in combination with XELOX (oral capecitabine 1000 mg/m^2 twice daily Days 1-14, oxaliplatin 130 mg/m^2 IV Day 1) or bevacizumab 5 mg/kg IV on Day 1 every 2 weeks in combination with mFOLFOX6 (oxaliplatin 85 mg/m^2 IV Day 1, leucovorin 400 mg/m^2 IV Day 1, 5-fluouracil 400 mg/m^2 IV loading dose then 2400 mg/m^2 continuous IV infusion over 46 hours Day 1) until first disease progression or occurrence of unmanageable toxicity. Phase B: Upon documented first disease progression, participants continued receiving bevacizumab 5 mg/kg IV on Day 1 every 2 weeks in combination with FOLFIRI (irinotecan 180 mg/m^2 IV Day 1, leucovorin and 5-fluouracil [same regimen as of mFOLFOX6]) until second disease progression or occurrence of unmanageable toxicity. Phase B treatment had to commence within 4 weeks of the date of documented first disease progression.
All-Cause Mortality
Bevacizumab: Phase A and Phase B
Affected / at Risk (%)
Total   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
Bevacizumab: Phase A and Phase B
Affected / at Risk (%)
Total   86/128 (67.19%) 
Blood and lymphatic system disorders   
Febrile neutropenia * 1  2/128 (1.56%) 
Neutropenia * 1  1/128 (0.78%) 
Cardiac disorders   
Angina pectoris * 1  3/128 (2.34%) 
Eye disorders   
Visual impairment * 1  1/128 (0.78%) 
Gastrointestinal disorders   
Abdominal pain * 1  6/128 (4.69%) 
Abdominal pain upper * 1  2/128 (1.56%) 
Anal fissure * 1  1/128 (0.78%) 
Colitis * 1  1/128 (0.78%) 
Colonic obstruction * 1  1/128 (0.78%) 
Constipation * 1  2/128 (1.56%) 
Diarrhoea * 1  8/128 (6.25%) 
Dysphagia * 1  1/128 (0.78%) 
Enterovesical fistula * 1  2/128 (1.56%) 
Gastritis * 1  1/128 (0.78%) 
Gastrointestinal haemorrhage * 1  1/128 (0.78%) 
Gastrointestinal perforation * 1  1/128 (0.78%) 
Gastrooesophageal reflux disease * 1  1/128 (0.78%) 
Ileus * 1  1/128 (0.78%) 
Inguinal hernia * 1  1/128 (0.78%) 
Intestinal obstruction * 1  6/128 (4.69%) 
Intestinal perforation * 1  1/128 (0.78%) 
Large intestinal obstruction * 1  1/128 (0.78%) 
Large intestine perforation * 1  1/128 (0.78%) 
Melaena * 1  1/128 (0.78%) 
Nausea * 1  5/128 (3.91%) 
Neutropenic colitis * 1  1/128 (0.78%) 
Rectal haemorrhage * 1  3/128 (2.34%) 
Rectal perforation * 1  1/128 (0.78%) 
Small intestinal obstruction * 1  3/128 (2.34%) 
Vomiting * 1  10/128 (7.81%) 
General disorders   
Catheter site pain * 1  1/128 (0.78%) 
Extravasation * 1  1/128 (0.78%) 
Non-cardiac chest pain * 1  1/128 (0.78%) 
Pyrexia * 1  12/128 (9.38%) 
Hepatobiliary disorders   
Cholecystitis acute * 1  1/128 (0.78%) 
Infections and infestations   
Abscess limb * 1  1/128 (0.78%) 
Anal abscess * 1  2/128 (1.56%) 
Bronchitis * 1  2/128 (1.56%) 
Clostridium difficile colitis * 1  1/128 (0.78%) 
Device related infection * 1  1/128 (0.78%) 
Ear infection * 1  1/128 (0.78%) 
Enterocolitis infectious * 1  1/128 (0.78%) 
Eyelid infection * 1  1/128 (0.78%) 
Gangrene * 1  1/128 (0.78%) 
Gastroenteritis * 1  3/128 (2.34%) 
Gastroenteritis viral * 1  1/128 (0.78%) 
Infected dermal cyst * 1  1/128 (0.78%) 
Infective exacerbation of chronic obstructive airways disease * 1  1/128 (0.78%) 
Lobar pneumonia * 1  1/128 (0.78%) 
Lower respiratory tract infection * 1  3/128 (2.34%) 
Muscle abscess * 1  1/128 (0.78%) 
Pharyngitis * 1  1/128 (0.78%) 
Pilonidal cyst * 1  1/128 (0.78%) 
Pneumonia * 1  3/128 (2.34%) 
Pneumonia streptococcal * 1  1/128 (0.78%) 
Sepsis * 1  7/128 (5.47%) 
Upper respiratory tract infection * 1  1/128 (0.78%) 
Urinary tract infection * 1  2/128 (1.56%) 
Urosepsis * 1  1/128 (0.78%) 
Wound infection * 1  1/128 (0.78%) 
Injury, poisoning and procedural complications   
Fall * 1  1/128 (0.78%) 
Infusion related reaction * 1  1/128 (0.78%) 
Laceration * 1  1/128 (0.78%) 
Procedural pain * 1  1/128 (0.78%) 
Procedural site reaction * 1  1/128 (0.78%) 
Radius fracture * 1  1/128 (0.78%) 
Metabolism and nutrition disorders   
Dehydration * 1  7/128 (5.47%) 
Hypomagnesaemia * 1  1/128 (0.78%) 
Hypophagia * 1  1/128 (0.78%) 
Musculoskeletal and connective tissue disorders   
Back pain * 1  1/128 (0.78%) 
Flank pain * 1  3/128 (2.34%) 
Musculoskeletal chest pain * 1  1/128 (0.78%) 
Neck pain * 1  1/128 (0.78%) 
Nervous system disorders   
Cerebrovascular accident * 1  1/128 (0.78%) 
Dizziness * 1  2/128 (1.56%) 
Hemiparesis * 1  1/128 (0.78%) 
Syncope * 1  1/128 (0.78%) 
Transient ischaemic attack * 1  1/128 (0.78%) 
Psychiatric disorders   
Acute psychosis * 1  1/128 (0.78%) 
Confusional state * 1  2/128 (1.56%) 
Renal and urinary disorders   
Haematuria * 1  1/128 (0.78%) 
Hydronephrosis * 1  1/128 (0.78%) 
Renal failure acute * 1  3/128 (2.34%) 
Urinary incontinence * 1  1/128 (0.78%) 
Respiratory, thoracic and mediastinal disorders   
Dyspnoea * 1  2/128 (1.56%) 
Pleural effusion * 1  1/128 (0.78%) 
Pleuritic pain * 1  1/128 (0.78%) 
Pneumonia aspiration * 1  1/128 (0.78%) 
Pulmonary embolism * 1  13/128 (10.16%) 
Vascular disorders   
Hypertension * 1  2/128 (1.56%) 
Hypotension * 1  2/128 (1.56%) 
Jugular vein thrombosis * 1  1/128 (0.78%) 
Orthostatic hypotension * 1  1/128 (0.78%) 
Thrombophlebitis superficial * 1  1/128 (0.78%) 
*
Indicates events were collected by non-systematic assessment
1
Term from vocabulary, MedDRA v15.0
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Bevacizumab: Phase A and Phase B
Affected / at Risk (%)
Total   128/128 (100.00%) 
Blood and lymphatic system disorders   
Anaemia * 1  15/128 (11.72%) 
Neutropenia * 1  32/128 (25.00%) 
Thrombocytopenia * 1  16/128 (12.50%) 
Gastrointestinal disorders   
Abdominal distension * 1  9/128 (7.03%) 
Abdominal pain * 1  40/128 (31.25%) 
Abdominal pain upper * 1  13/128 (10.16%) 
Constipation * 1  51/128 (39.84%) 
Diarrhoea * 1  70/128 (54.69%) 
Dyspepsia * 1  13/128 (10.16%) 
Gastrooesophageal reflux disease * 1  26/128 (20.31%) 
Mouth ulceration * 1  16/128 (12.50%) 
Nausea * 1  87/128 (67.97%) 
Rectal haemorrhage * 1  9/128 (7.03%) 
Stomatitis * 1  22/128 (17.19%) 
Vomiting * 1  36/128 (28.13%) 
Toothache * 1  9/128 (7.03%) 
Haemorrhoids * 1  7/128 (5.47%) 
General disorders   
Fatigue * 1  80/128 (62.50%) 
Mucosal inflammation * 1  31/128 (24.22%) 
Non-cardiac chest pain * 1  8/128 (6.25%) 
Oedema peripheral * 1  14/128 (10.94%) 
Pyrexia * 1  12/128 (9.38%) 
Infections and infestations   
Oral candidiasis * 1  7/128 (5.47%) 
Oral herpes * 1  7/128 (5.47%) 
Upper respiratory tract infection * 1  18/128 (14.06%) 
Urinary tract infection * 1  20/128 (15.63%) 
Injury, poisoning and procedural complications   
Fall * 1  10/128 (7.81%) 
Investigations   
Weight decreased * 1  14/128 (10.94%) 
Metabolism and nutrition disorders   
Decreased appetite * 1  28/128 (21.88%) 
Dehydration * 1  8/128 (6.25%) 
Hypoalbuminaemia * 1  7/128 (5.47%) 
Hypokalaemia * 1  7/128 (5.47%) 
Musculoskeletal and connective tissue disorders   
Arthralgia * 1  17/128 (13.28%) 
Back pain * 1  22/128 (17.19%) 
Muscle spasms * 1  7/128 (5.47%) 
Musculoskeletal pain * 1  14/128 (10.94%) 
Neck pain * 1  9/128 (7.03%) 
Pain in extremity * 1  18/128 (14.06%) 
Nervous system disorders   
Dizziness * 1  13/128 (10.16%) 
Dysaesthesia * 1  15/128 (11.72%) 
Dysgeusia * 1  20/128 (15.63%) 
Headache * 1  24/128 (18.75%) 
Lethargy * 1  9/128 (7.03%) 
Neuropathy peripheral * 1  80/128 (62.50%) 
Paraesthesia * 1  26/128 (20.31%) 
Psychiatric disorders   
Anxiety * 1  10/128 (7.81%) 
Depression * 1  12/128 (9.38%) 
Insomnia * 1  25/128 (19.53%) 
Renal and urinary disorders   
Proteinuria * 1  10/128 (7.81%) 
Respiratory, thoracic and mediastinal disorders   
Cough * 1  13/128 (10.16%) 
Dysphonia * 1  11/128 (8.59%) 
Dyspnoea * 1  13/128 (10.16%) 
Epistaxis * 1  30/128 (23.44%) 
Oropharyngeal pain * 1  8/128 (6.25%) 
Rhinorrhoea * 1  8/128 (6.25%) 
Skin and subcutaneous tissue disorders   
Alopecia * 1  26/128 (20.31%) 
Dry skin * 1  10/128 (7.81%) 
Nail disorder * 1  7/128 (5.47%) 
Palmar-plantar erythrodysaesthesia syndrome * 1  38/128 (29.69%) 
Rash * 1  21/128 (16.41%) 
Vascular disorders   
Hypertension * 1  23/128 (17.97%) 
Hypotension * 1  7/128 (5.47%) 
*
Indicates events were collected by non-systematic assessment
1
Term from vocabulary, MedDRA v15.0
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-La Roche
Phone: 800-821-8590
EMail: genentech@druginfo.com
Layout table for additonal information
Responsible Party: Hoffmann-La Roche
ClinicalTrials.gov Identifier: NCT01588990     History of Changes
Other Study ID Numbers: ML25753
First Submitted: April 27, 2012
First Posted: May 1, 2012
Results First Submitted: October 13, 2017
Results First Posted: January 21, 2019
Last Update Posted: January 21, 2019