Trial Outcomes & Findings for A Translational Study of Bevacizumab in Participants With Metastatic Colorectal Cancer (NCT NCT01588990)
NCT ID: NCT01588990
Last Updated: 2019-01-22
Results Overview
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.
Recruitment status
COMPLETED
Study phase
PHASE4
Target enrollment
128 participants
Primary outcome timeframe
Baseline up to disease progression, death or end of study (up to 4 years)
Results posted on
2019-01-22
Participant Flow
Participant milestones
| Measure |
Bevacizumab: Phase A and Phase B
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.
|
|---|---|
|
Phase A
STARTED
|
128
|
|
Phase A
COMPLETED
|
58
|
|
Phase A
NOT COMPLETED
|
70
|
|
Phase B
STARTED
|
53
|
|
Phase B
COMPLETED
|
37
|
|
Phase B
NOT COMPLETED
|
16
|
Reasons for withdrawal
| Measure |
Bevacizumab: Phase A and Phase B
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.
|
|---|---|
|
Phase A
Withdrawal by Subject
|
5
|
|
Phase A
Physician Decision
|
11
|
|
Phase A
Other
|
14
|
|
Phase A
Lost to Follow-up
|
1
|
|
Phase A
Death
|
5
|
|
Phase A
Adverse Event
|
28
|
|
Phase A
Still on therapy at end of study
|
6
|
|
Phase B
Adverse Event
|
2
|
|
Phase B
Still on therapy at end of study
|
5
|
|
Phase B
Withdrawal by Subject
|
3
|
|
Phase B
Physician Decision
|
4
|
|
Phase B
Other
|
2
|
Baseline Characteristics
A Translational Study of Bevacizumab in Participants With Metastatic Colorectal Cancer
Baseline characteristics by cohort
| Measure |
Bevacizumab: Phase A and Phase B
n=128 Participants
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.
|
|---|---|
|
Age, Continuous
|
61.9 years
STANDARD_DEVIATION 11.66 • n=5 Participants
|
|
Sex: Female, Male
Female
|
70 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
58 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: Baseline up to disease progression, death or end of study (up to 4 years)Population: FAS population. "Overall Number of Participants Analyzed" = participants who were evaluable for this outcome.
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.
Outcome measures
| Measure |
Bevacizumab: Phase A and Phase B
n=127 Participants
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.
|
|---|---|
|
Association Between Neutrophil to Lymphocyte Ratio (NLR) [NLR ≤5 Versus NLR >5] and Progression-Free Survival (PFS) as Assessed by Hazard Ratio
|
1.4 hazard ratio
Interval 0.9 to 2.2
|
SECONDARY outcome
Timeframe: Baseline up to first disease progression, death or end of study (up to 4 years)Population: FAS population.
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.
Outcome measures
| Measure |
Bevacizumab: Phase A and Phase B
n=128 Participants
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.
|
|---|---|
|
PFS Until First Disease Progression as Assessed by the Investigator Based on Routine Clinical Practice: Phase A
|
9.2 months
Interval 7.9 to 10.8
|
SECONDARY outcome
Timeframe: From the start of Phase B treatment to disease progression, death or end of study (up to 4 years)Population: Phase B FAS population included participants who received at least 1 dose of bevacizumab in Phase B.
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.
Outcome measures
| Measure |
Bevacizumab: Phase A and Phase B
n=53 Participants
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.
|
|---|---|
|
PFS Until Second Disease Progression as Assessed by the Investigator Based on Routine Clinical Practice: Phase B
|
6.7 months
Interval 3.0 to 8.2
|
SECONDARY outcome
Timeframe: Baseline up to disease progression, death or end of study (up to 4 years)Population: FAS population.
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.
Outcome measures
| Measure |
Bevacizumab: Phase A and Phase B
n=128 Participants
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.
|
|---|---|
|
Time to Failure of Strategy (TFS): Overall
|
14.8 months
Interval 13.1 to 19.4
|
SECONDARY outcome
Timeframe: Baseline up to disease progression, death or end of study (up to 4 years)Population: FAS population.
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.
Outcome measures
| Measure |
Bevacizumab: Phase A and Phase B
n=128 Participants
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.
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|---|---|
|
Duration of Disease Control (DDC) as Assessed by the Investigator Based on Routine Clinical Practice: Overall
|
14.0 months
Interval 10.8 to 16.6
|
SECONDARY outcome
Timeframe: Baseline until death or end of study (up to 4 years)Population: FAS population.
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.
Outcome measures
| Measure |
Bevacizumab: Phase A and Phase B
n=128 Participants
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 Survival (OS) From the Start of Treatment to Study Completion: Overall
|
25.0 months
Interval 19.2 to 29.7
|
SECONDARY outcome
Timeframe: Baseline until death or end of study (up to 4 years)Population: FAS population. "Overall Number of Participants Analyzed" = participants who were evaluable for this outcome.
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.
Outcome measures
| Measure |
Bevacizumab: Phase A and Phase B
n=101 Participants
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.
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|---|---|
|
Survival Beyond First Disease Progression: Overall
|
12.6 months
Interval 8.8 to 15.9
|
SECONDARY outcome
Timeframe: From the start of Phase B treatment death or end of study (up to 4 years)Population: Phase B FAS population.
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.
Outcome measures
| Measure |
Bevacizumab: Phase A and Phase B
n=53 Participants
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.
|
|---|---|
|
OS: Phase B
|
14.9 months
Interval 8.2 to 17.5
|
SECONDARY outcome
Timeframe: Baseline up to disease progression, death or end of study (up to 4 years)Population: FAS population.
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.
Outcome measures
| Measure |
Bevacizumab: Phase A and Phase B
n=128 Participants
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.
|
|---|---|
|
Percentage of Participants With Confirmed Complete or Partial Response as Assessed by the Investigator Based on Routine Clinical Practice: Phase A
Complete response
|
3.1 percentage of participants
|
|
Percentage of Participants With Confirmed Complete or Partial Response as Assessed by the Investigator Based on Routine Clinical Practice: Phase A
Partial response
|
8.6 percentage of participants
|
SECONDARY outcome
Timeframe: From the start of Phase B treatment to disease progression, death or end of study (up to 4 years)Population: Phase B FAS population.
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.
Outcome measures
| Measure |
Bevacizumab: Phase A and Phase B
n=53 Participants
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.
|
|---|---|
|
Percentage of Participants With Confirmed Complete or Partial Response as Assessed by the Investigator Based on Routine Clinical Practice: Phase B
Complete response
|
0 percentage of participants
|
|
Percentage of Participants With Confirmed Complete or Partial Response as Assessed by the Investigator Based on Routine Clinical Practice: Phase B
Partial response
|
0 percentage of participants
|
SECONDARY outcome
Timeframe: Baseline up to disease progression, death or end of study (up to 4 years)Population: FAS population.
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.
Outcome measures
| Measure |
Bevacizumab: Phase A and Phase B
n=128 Participants
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.
|
|---|---|
|
Percentage of Participants With Confirmed Complete or Partial Response as Assessed by the Investigator Based on Routine Clinical Practice: Overall
Complete response
|
3.1 percentage of participants
|
|
Percentage of Participants With Confirmed Complete or Partial Response as Assessed by the Investigator Based on Routine Clinical Practice: Overall
Partial response
|
8.6 percentage of participants
|
SECONDARY outcome
Timeframe: Baseline up to disease progression, death or end of study (up to 4 years)Population: FAS population.
The results include percentage of participants who underwent potentially curative liver resection.
Outcome measures
| Measure |
Bevacizumab: Phase A and Phase B
n=128 Participants
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.
|
|---|---|
|
Percentage of Participants Who Underwent Liver Resection: Overall
|
1.6 percentage of participants
|
SECONDARY outcome
Timeframe: Baseline up to disease progression, death or end of study (up to 4 years)Population: FAS population. "Overall Number of Participants Analyzed" = participants who were evaluable for this outcome.
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.
Outcome measures
| Measure |
Bevacizumab: Phase A and Phase B
n=127 Participants
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.
|
|---|---|
|
Association Between NLR (NLR ≤5 Versus NLR >5) and OS as Assessed by Hazard Ratio
|
1.6 hazard ratio
Interval 1.0 to 2.7
|
SECONDARY outcome
Timeframe: Baseline up to disease progression, death or end of study (up to 4 years)Population: FAS population. "Overall Number of Participants Analyzed" = participants who were evaluable for this outcome.
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.
Outcome measures
| Measure |
Bevacizumab: Phase A and Phase B
n=127 Participants
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.
|
|---|---|
|
Association Between NLR Normalization (First NLR Post-Baseline ≤5 Versus NLR >5) and PFS as Assessed by Hazard Ratio
|
0.9 hazard ratio
Interval 0.5 to 1.8
|
SECONDARY outcome
Timeframe: Baseline up to disease progression, death or end of study (up to 4 years)Population: FAS population. "Overall Number of Participants Analyzed" = participants who were evaluable for this outcome.
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.
Outcome measures
| Measure |
Bevacizumab: Phase A and Phase B
n=127 Participants
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.
|
|---|---|
|
Association Between Longitudinal NLR (Longitudinal NLR ≤5 Versus NLR >5) and PFS as Assessed by Hazard Ratio
|
1.3 hazard ratio
Interval 0.9 to 1.9
|
SECONDARY outcome
Timeframe: Baseline up to death or end of study (up to 4 years)Population: FAS population. "Overall Number of Participants Analyzed" = participants who were evaluable for this outcome.
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.
Outcome measures
| Measure |
Bevacizumab: Phase A and Phase B
n=127 Participants
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.
|
|---|---|
|
Association Between Longitudinal NLR (Longitudinal NLR ≤5 Versus NLR >5) and OS as Assessed by Hazard Ratio
|
2.2 hazard ratio
Interval 1.2 to 4.0
|
SECONDARY outcome
Timeframe: 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]Population: FAS population. "Number Analyzed" = participants who were evaluable at the specified time point for this outcome.
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.
Outcome measures
| Measure |
Bevacizumab: Phase A and Phase B
n=128 Participants
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.
|
|---|---|
|
European Quality of Life 5-Dimension (EuroQol-5D) Utility Score: Phase A
Phase A Baseline
|
0.830 units on a scale
Standard Deviation 0.1590
|
|
European Quality of Life 5-Dimension (EuroQol-5D) Utility Score: Phase A
Phase A Visit 2 (Weeks 8-9)
|
0.857 units on a scale
Standard Deviation 0.1392
|
|
European Quality of Life 5-Dimension (EuroQol-5D) Utility Score: Phase A
Phase A Visit 3 (Weeks 16-17)
|
0.865 units on a scale
Standard Deviation 0.1074
|
|
European Quality of Life 5-Dimension (EuroQol-5D) Utility Score: Phase A
Phase A Visit 4 (Weeks 24-25)
|
0.853 units on a scale
Standard Deviation 0.1206
|
|
European Quality of Life 5-Dimension (EuroQol-5D) Utility Score: Phase A
Phase A Visit 5 (Weeks 32-33)
|
0.869 units on a scale
Standard Deviation 0.1381
|
|
European Quality of Life 5-Dimension (EuroQol-5D) Utility Score: Phase A
Phase A Visit 6 (Weeks 40-41)
|
0.892 units on a scale
Standard Deviation 0.1013
|
|
European Quality of Life 5-Dimension (EuroQol-5D) Utility Score: Phase A
Phase A Visit 7 (Weeks 48-49)
|
0.872 units on a scale
Standard Deviation 0.1332
|
|
European Quality of Life 5-Dimension (EuroQol-5D) Utility Score: Phase A
Phase A Visit 8 (Weeks 56-57)
|
0.881 units on a scale
Standard Deviation 0.1058
|
|
European Quality of Life 5-Dimension (EuroQol-5D) Utility Score: Phase A
Phase A Visit 9 (Weeks 64-65)
|
0.894 units on a scale
Standard Deviation 0.1081
|
|
European Quality of Life 5-Dimension (EuroQol-5D) Utility Score: Phase A
Phase A Visit 10 (Weeks 72-73)
|
0.843 units on a scale
Standard Deviation 0.1466
|
|
European Quality of Life 5-Dimension (EuroQol-5D) Utility Score: Phase A
Phase A Visit 11 (Weeks 80-81)
|
0.898 units on a scale
Standard Deviation 0.0952
|
|
European Quality of Life 5-Dimension (EuroQol-5D) Utility Score: Phase A
Phase A Visit 12 (Weeks 88-89)
|
0.915 units on a scale
Standard Deviation 0.1033
|
|
European Quality of Life 5-Dimension (EuroQol-5D) Utility Score: Phase A
Phase A Visit 13 (Weeks 96-97)
|
0.844 units on a scale
Standard Deviation 0.1463
|
|
European Quality of Life 5-Dimension (EuroQol-5D) Utility Score: Phase A
Phase A Visit 14 (Weeks 104-105)
|
0.899 units on a scale
Standard Deviation 0.1398
|
|
European Quality of Life 5-Dimension (EuroQol-5D) Utility Score: Phase A
Phase A Visit 15 (Weeks 112-113)
|
0.878 units on a scale
Standard Deviation 0.0861
|
|
European Quality of Life 5-Dimension (EuroQol-5D) Utility Score: Phase A
Phase A Visit 16 (Weeks 120-121)
|
0.899 units on a scale
Standard Deviation 0.0852
|
|
European Quality of Life 5-Dimension (EuroQol-5D) Utility Score: Phase A
Phase A Visit 17 (Weeks 128-129)
|
0.873 units on a scale
Standard Deviation 0.1734
|
|
European Quality of Life 5-Dimension (EuroQol-5D) Utility Score: Phase A
Phase A Visit 18 (Weeks 136-137)
|
0.909 units on a scale
Standard Deviation 0.0876
|
|
European Quality of Life 5-Dimension (EuroQol-5D) Utility Score: Phase A
Phase A Visit 19 (Weeks 144-145)
|
0.947 units on a scale
Standard Deviation 0.0914
|
|
European Quality of Life 5-Dimension (EuroQol-5D) Utility Score: Phase A
Phase A Visit 20 (Weeks 152-153)
|
0.852 units on a scale
Standard Deviation 0.0718
|
|
European Quality of Life 5-Dimension (EuroQol-5D) Utility Score: Phase A
Phase A Visit 21 (Weeks 160-161)
|
0.933 units on a scale
Standard Deviation 0.1156
|
|
European Quality of Life 5-Dimension (EuroQol-5D) Utility Score: Phase A
Phase A Visit 22 (Weeks 168-169)
|
0.813 units on a scale
Standard Deviation 0.0193
|
|
European Quality of Life 5-Dimension (EuroQol-5D) Utility Score: Phase A
Phase A Visit 23 (Weeks 176-177)
|
0.900 units on a scale
Standard Deviation 0.1416
|
|
European Quality of Life 5-Dimension (EuroQol-5D) Utility Score: Phase A
Phase A EOT Visit (up to 4 years)
|
0.817 units on a scale
Standard Deviation 0.1423
|
|
European Quality of Life 5-Dimension (EuroQol-5D) Utility Score: Phase A
Survival Follow-Up 1 (up to 4 years)
|
0.768 units on a scale
Standard Deviation 0.1414
|
|
European Quality of Life 5-Dimension (EuroQol-5D) Utility Score: Phase A
Survival Follow-Up 2 (up to 4 years)
|
0.901 units on a scale
Standard Deviation 0.0860
|
|
European Quality of Life 5-Dimension (EuroQol-5D) Utility Score: Phase A
Survival Follow-Up 3 (up to 4 years)
|
0.819 units on a scale
Standard Deviation 0.0583
|
|
European Quality of Life 5-Dimension (EuroQol-5D) Utility Score: Phase A
Survival Follow-Up 4 (up to 4 years)
|
0.843 units on a scale
|
|
European Quality of Life 5-Dimension (EuroQol-5D) Utility Score: Phase A
Survival Follow-Up 5 (up to 4 years)
|
1.000 units on a scale
|
|
European Quality of Life 5-Dimension (EuroQol-5D) Utility Score: Phase A
Survival Follow-Up 6 (up to 4 years)
|
0.835 units on a scale
Standard Deviation 0.0229
|
|
European Quality of Life 5-Dimension (EuroQol-5D) Utility Score: Phase A
Survival Follow-Up 7 (up to 4 years)
|
0.816 units on a scale
|
SECONDARY outcome
Timeframe: 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]Population: Phase B FAS population. "Number Analyzed" = participants who were evaluable at the specified time point for this outcome.
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.
Outcome measures
| Measure |
Bevacizumab: Phase A and Phase B
n=53 Participants
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.
|
|---|---|
|
EuroQol-5D Utility Score: Phase B
Phase B Baseline
|
0.814 units on a scale
Standard Deviation 0.1566
|
|
EuroQol-5D Utility Score: Phase B
Phase B Visit 2 (up to 4 years)
|
0.859 units on a scale
Standard Deviation 0.1376
|
|
EuroQol-5D Utility Score: Phase B
Phase B Visit 3 (up to 4 years)
|
0.894 units on a scale
Standard Deviation 0.1108
|
|
EuroQol-5D Utility Score: Phase B
Phase B Visit 4 (up to 4 years)
|
0.897 units on a scale
Standard Deviation 0.1012
|
|
EuroQol-5D Utility Score: Phase B
Phase B Visit 5 (up to 4 years)
|
0.866 units on a scale
Standard Deviation 0.1299
|
|
EuroQol-5D Utility Score: Phase B
Phase B Visit 6 (up to 4 years)
|
0.837 units on a scale
Standard Deviation 0.1710
|
|
EuroQol-5D Utility Score: Phase B
Phase B Visit 7 (up to 4 years)
|
0.876 units on a scale
Standard Deviation 0.0986
|
|
EuroQol-5D Utility Score: Phase B
Phase B Visit 8 (up to 4 years)
|
0.874 units on a scale
Standard Deviation 0.1141
|
|
EuroQol-5D Utility Score: Phase B
Phase B Visit 9 (up to 4 years)
|
0.908 units on a scale
Standard Deviation 0.1299
|
|
EuroQol-5D Utility Score: Phase B
Phase B Visit 10 (up to 4 years)
|
0.811 units on a scale
Standard Deviation 0.0466
|
|
EuroQol-5D Utility Score: Phase B
Phase B Visit 11 (up to 4 years)
|
0.806 units on a scale
Standard Deviation 0.0539
|
|
EuroQol-5D Utility Score: Phase B
Phase B Visit 12 (up to 4 years)
|
0.844 units on a scale
|
|
EuroQol-5D Utility Score: Phase B
Phase B Visit 13 (up to 4 years)
|
1.000 units on a scale
|
|
EuroQol-5D Utility Score: Phase B
Phase B Visit 14 (up to 4 years)
|
1.000 units on a scale
|
|
EuroQol-5D Utility Score: Phase B
Phase B Visit 15 (up to 4 years)
|
0.844 units on a scale
|
|
EuroQol-5D Utility Score: Phase B
Phase B Visit 16 (up to 4 years)
|
0.833 units on a scale
|
|
EuroQol-5D Utility Score: Phase B
Phase B Visit 17 (up to 4 years)
|
0.844 units on a scale
|
|
EuroQol-5D Utility Score: Phase B
Phase B Visit 18 (up to 4 years)
|
0.833 units on a scale
|
|
EuroQol-5D Utility Score: Phase B
Phase B Visit 19 (up to 4 years)
|
0.827 units on a scale
|
|
EuroQol-5D Utility Score: Phase B
Phase B Visit 20 (up to 4 years)
|
0.816 units on a scale
|
|
EuroQol-5D Utility Score: Phase B
Phase B Visit 21 (up to 4 years)
|
0.844 units on a scale
|
|
EuroQol-5D Utility Score: Phase B
Phase B Visit 22 (up to 4 years)
|
0.844 units on a scale
|
|
EuroQol-5D Utility Score: Phase B
Phase B Visit 23 (up to 4 years)
|
0.827 units on a scale
|
|
EuroQol-5D Utility Score: Phase B
Phase B Visit 24 (up to 4 years)
|
0.844 units on a scale
|
|
EuroQol-5D Utility Score: Phase B
Phase B EOT Visit (up to 4 years)
|
0.809 units on a scale
Standard Deviation 0.1585
|
|
EuroQol-5D Utility Score: Phase B
Survival Follow-Up 1 (up to 4 years)
|
0.740 units on a scale
Standard Deviation 0.1035
|
|
EuroQol-5D Utility Score: Phase B
Survival Follow-Up 2 (up to 4 years)
|
0.772 units on a scale
Standard Deviation 0.0782
|
|
EuroQol-5D Utility Score: Phase B
Survival Follow-Up 3 (up to 4 years)
|
0.827 units on a scale
|
|
EuroQol-5D Utility Score: Phase B
Survival Follow-Up 4 (up to 4 years)
|
0.827 units on a scale
|
|
EuroQol-5D Utility Score: Phase B
Survival Follow-Up 6 (up to 4 years)
|
1.000 units on a scale
|
SECONDARY outcome
Timeframe: 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]Population: FAS population. "Number Analyzed" = participants who were evaluable at the specified time point for this outcome.
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).
Outcome measures
| Measure |
Bevacizumab: Phase A and Phase B
n=128 Participants
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.
|
|---|---|
|
Assessment of Quality of Life - Eight Dimensions (AQoL-8D) Global Utility Score: Phase A
Phase A Visit 15 (Weeks 112-113)
|
0.871 units on a scale
Standard Deviation 0.0877
|
|
Assessment of Quality of Life - Eight Dimensions (AQoL-8D) Global Utility Score: Phase A
Phase A Baseline
|
0.747 units on a scale
Standard Deviation 0.1819
|
|
Assessment of Quality of Life - Eight Dimensions (AQoL-8D) Global Utility Score: Phase A
Phase A Visit 2 (Weeks 8-9)
|
0.760 units on a scale
Standard Deviation 0.1710
|
|
Assessment of Quality of Life - Eight Dimensions (AQoL-8D) Global Utility Score: Phase A
Phase A Visit 3 (Weeks 16-17)
|
0.767 units on a scale
Standard Deviation 0.1691
|
|
Assessment of Quality of Life - Eight Dimensions (AQoL-8D) Global Utility Score: Phase A
Phase A Visit 4 (Weeks 24-25)
|
0.796 units on a scale
Standard Deviation 0.1650
|
|
Assessment of Quality of Life - Eight Dimensions (AQoL-8D) Global Utility Score: Phase A
Phase A Visit 5 (Weeks 32-33)
|
0.800 units on a scale
Standard Deviation 0.1762
|
|
Assessment of Quality of Life - Eight Dimensions (AQoL-8D) Global Utility Score: Phase A
Phase A Visit 6 (Weeks 40-41)
|
0.831 units on a scale
Standard Deviation 0.1578
|
|
Assessment of Quality of Life - Eight Dimensions (AQoL-8D) Global Utility Score: Phase A
Phase A Visit 7 (Weeks 48-49)
|
0.818 units on a scale
Standard Deviation 0.1455
|
|
Assessment of Quality of Life - Eight Dimensions (AQoL-8D) Global Utility Score: Phase A
Phase A Visit 8 (Weeks 56-57)
|
0.851 units on a scale
Standard Deviation 0.1043
|
|
Assessment of Quality of Life - Eight Dimensions (AQoL-8D) Global Utility Score: Phase A
Phase A Visit 9 (Weeks 64-65)
|
0.822 units on a scale
Standard Deviation 0.1304
|
|
Assessment of Quality of Life - Eight Dimensions (AQoL-8D) Global Utility Score: Phase A
Phase A Visit 10 (Weeks 72-73)
|
0.827 units on a scale
Standard Deviation 0.1426
|
|
Assessment of Quality of Life - Eight Dimensions (AQoL-8D) Global Utility Score: Phase A
Phase A Visit 11 (Weeks 80-81)
|
0.839 units on a scale
Standard Deviation 0.1272
|
|
Assessment of Quality of Life - Eight Dimensions (AQoL-8D) Global Utility Score: Phase A
Phase A Visit 12 (Weeks 88-89)
|
0.856 units on a scale
Standard Deviation 0.1295
|
|
Assessment of Quality of Life - Eight Dimensions (AQoL-8D) Global Utility Score: Phase A
Phase A Visit 13 (Weeks 96-97)
|
0.831 units on a scale
Standard Deviation 0.1482
|
|
Assessment of Quality of Life - Eight Dimensions (AQoL-8D) Global Utility Score: Phase A
Phase A Visit 14 (Weeks 104-105)
|
0.815 units on a scale
Standard Deviation 0.1788
|
|
Assessment of Quality of Life - Eight Dimensions (AQoL-8D) Global Utility Score: Phase A
Phase A Visit 16 (Weeks 120-121)
|
0.869 units on a scale
Standard Deviation 0.1428
|
|
Assessment of Quality of Life - Eight Dimensions (AQoL-8D) Global Utility Score: Phase A
Phase A Visit 17 (Weeks 128-129)
|
0.859 units on a scale
Standard Deviation 0.1430
|
|
Assessment of Quality of Life - Eight Dimensions (AQoL-8D) Global Utility Score: Phase A
Phase A Visit 18 (Weeks 136-137)
|
0.880 units on a scale
Standard Deviation 0.1048
|
|
Assessment of Quality of Life - Eight Dimensions (AQoL-8D) Global Utility Score: Phase A
Phase A Visit 19 (Weeks 144-145)
|
0.915 units on a scale
Standard Deviation 0.0883
|
|
Assessment of Quality of Life - Eight Dimensions (AQoL-8D) Global Utility Score: Phase A
Phase A Visit 20 (Weeks 152-153)
|
0.864 units on a scale
Standard Deviation 0.1266
|
|
Assessment of Quality of Life - Eight Dimensions (AQoL-8D) Global Utility Score: Phase A
Phase A Visit 21 (Weeks 160-161)
|
0.806 units on a scale
Standard Deviation 0.1422
|
|
Assessment of Quality of Life - Eight Dimensions (AQoL-8D) Global Utility Score: Phase A
Phase A Visit 22 (Weeks 168-169)
|
0.811 units on a scale
Standard Deviation 0.2238
|
|
Assessment of Quality of Life - Eight Dimensions (AQoL-8D) Global Utility Score: Phase A
Phase A Visit 23 (Weeks 176-177)
|
0.709 units on a scale
Standard Deviation 0.3336
|
|
Assessment of Quality of Life - Eight Dimensions (AQoL-8D) Global Utility Score: Phase A
Phase A EOT Visit (up to 4 years)
|
0.739 units on a scale
Standard Deviation 0.1882
|
|
Assessment of Quality of Life - Eight Dimensions (AQoL-8D) Global Utility Score: Phase A
Survival Follow-Up 1 (up to 4 years)
|
0.718 units on a scale
Standard Deviation 0.1600
|
|
Assessment of Quality of Life - Eight Dimensions (AQoL-8D) Global Utility Score: Phase A
Survival Follow-Up 2 (up to 4 years)
|
0.792 units on a scale
Standard Deviation 0.1977
|
|
Assessment of Quality of Life - Eight Dimensions (AQoL-8D) Global Utility Score: Phase A
Survival Follow-Up 3 (up to 4 years)
|
0.696 units on a scale
Standard Deviation 0.1684
|
|
Assessment of Quality of Life - Eight Dimensions (AQoL-8D) Global Utility Score: Phase A
Survival Follow-Up 4 (up to 4 years)
|
0.620 units on a scale
|
|
Assessment of Quality of Life - Eight Dimensions (AQoL-8D) Global Utility Score: Phase A
Survival Follow-Up 5 (up to 4 years)
|
0.800 units on a scale
|
|
Assessment of Quality of Life - Eight Dimensions (AQoL-8D) Global Utility Score: Phase A
Survival Follow-Up 6 (up to 4 years)
|
0.810 units on a scale
Standard Deviation 0.0531
|
|
Assessment of Quality of Life - Eight Dimensions (AQoL-8D) Global Utility Score: Phase A
Survival Follow-Up 7 (up to 4 years)
|
0.874 units on a scale
|
SECONDARY outcome
Timeframe: 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]Population: Phase B FAS population. "Number Analyzed" = participants who were evaluable at the specified time point for this outcome.
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).
Outcome measures
| Measure |
Bevacizumab: Phase A and Phase B
n=53 Participants
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.
|
|---|---|
|
AQoL-8D Global Utility Score: Phase B
Phase B Baseline
|
0.736 units on a scale
Standard Deviation 0.1943
|
|
AQoL-8D Global Utility Score: Phase B
Phase B Visit 2 (up to 4 years)
|
0.773 units on a scale
Standard Deviation 0.1821
|
|
AQoL-8D Global Utility Score: Phase B
Phase B Visit 3 (up to 4 years)
|
0.813 units on a scale
Standard Deviation 0.1610
|
|
AQoL-8D Global Utility Score: Phase B
Phase B Visit 4 (up to 4 years)
|
0.878 units on a scale
Standard Deviation 0.1154
|
|
AQoL-8D Global Utility Score: Phase B
Phase B Visit 5 (up to 4 years)
|
0.808 units on a scale
Standard Deviation 0.1630
|
|
AQoL-8D Global Utility Score: Phase B
Phase B Visit 6 (up to 4 years)
|
0.809 units on a scale
Standard Deviation 0.1717
|
|
AQoL-8D Global Utility Score: Phase B
Phase B Visit 7 (up to 4 years)
|
0.825 units on a scale
Standard Deviation 0.1682
|
|
AQoL-8D Global Utility Score: Phase B
Phase B Visit 8 (up to 4 years)
|
0.910 units on a scale
Standard Deviation 0.1023
|
|
AQoL-8D Global Utility Score: Phase B
Phase B Visit 9 (up to 4 years)
|
0.819 units on a scale
Standard Deviation 0.1986
|
|
AQoL-8D Global Utility Score: Phase B
Phase B Visit 10 (up to 4 years)
|
0.856 units on a scale
Standard Deviation 0.1589
|
|
AQoL-8D Global Utility Score: Phase B
Phase B Visit 11 (up to 4 years)
|
0.730 units on a scale
Standard Deviation 0.2906
|
|
AQoL-8D Global Utility Score: Phase B
Phase B Visit 12 (up to 4 years)
|
0.960 units on a scale
|
|
AQoL-8D Global Utility Score: Phase B
Phase B Visit 13 (up to 4 years)
|
0.965 units on a scale
|
|
AQoL-8D Global Utility Score: Phase B
Phase B Visit 14 (up to 4 years)
|
0.958 units on a scale
|
|
AQoL-8D Global Utility Score: Phase B
Phase B Visit 15 (up to 4 years)
|
0.967 units on a scale
|
|
AQoL-8D Global Utility Score: Phase B
Phase B Visit 16 (up to 4 years)
|
0.942 units on a scale
|
|
AQoL-8D Global Utility Score: Phase B
Phase B Visit 17 (up to 4 years)
|
0.927 units on a scale
|
|
AQoL-8D Global Utility Score: Phase B
Phase B Visit 18 (up to 4 years)
|
0.931 units on a scale
|
|
AQoL-8D Global Utility Score: Phase B
Phase B Visit 19 (up to 4 years)
|
0.866 units on a scale
|
|
AQoL-8D Global Utility Score: Phase B
Phase B Visit 20 (up to 4 years)
|
0.887 units on a scale
|
|
AQoL-8D Global Utility Score: Phase B
Phase B Visit 21 (up to 4 years)
|
0.940 units on a scale
|
|
AQoL-8D Global Utility Score: Phase B
Phase B Visit 22 (up to 4 years)
|
0.919 units on a scale
|
|
AQoL-8D Global Utility Score: Phase B
Phase B Visit 23 (up to 4 years)
|
0.937 units on a scale
|
|
AQoL-8D Global Utility Score: Phase B
Phase B Visit 24 (up to 4 years)
|
0.950 units on a scale
|
|
AQoL-8D Global Utility Score: Phase B
Phase B EOT Visit (up to 4 years)
|
0.708 units on a scale
Standard Deviation 0.2229
|
|
AQoL-8D Global Utility Score: Phase B
Survival Follow-Up 1 (up to 4 years)
|
0.788 units on a scale
Standard Deviation 0.0895
|
|
AQoL-8D Global Utility Score: Phase B
Survival Follow-Up 2 (up to 4 years)
|
0.791 units on a scale
Standard Deviation 0.1829
|
|
AQoL-8D Global Utility Score: Phase B
Survival Follow-Up 3 (up to 4 years)
|
0.989 units on a scale
|
|
AQoL-8D Global Utility Score: Phase B
Survival Follow-Up 4 (up to 4 years)
|
0.981 units on a scale
|
|
AQoL-8D Global Utility Score: Phase B
Survival Follow-Up 6 (up to 4 years)
|
0.875 units on a scale
|
SECONDARY outcome
Timeframe: 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]Population: FAS population. "Number Analyzed" = participants who were evaluable at the specified time point for this outcome.
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.
Outcome measures
| Measure |
Bevacizumab: Phase A and Phase B
n=128 Participants
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.
|
|---|---|
|
Functional Assessment of Cancer Therapy-Colorectal (FACT-C) Score: Phase A
Phase A Baseline
|
103.84 units on a scale
Standard Deviation 16.615
|
|
Functional Assessment of Cancer Therapy-Colorectal (FACT-C) Score: Phase A
Phase A Visit 2 (Weeks 8-9)
|
103.33 units on a scale
Standard Deviation 16.065
|
|
Functional Assessment of Cancer Therapy-Colorectal (FACT-C) Score: Phase A
Phase A Visit 3 (Weeks 16-17)
|
106.34 units on a scale
Standard Deviation 15.318
|
|
Functional Assessment of Cancer Therapy-Colorectal (FACT-C) Score: Phase A
Phase A Visit 4 (Weeks 24-25)
|
109.66 units on a scale
Standard Deviation 15.038
|
|
Functional Assessment of Cancer Therapy-Colorectal (FACT-C) Score: Phase A
Phase A Visit 5 (Weeks 32-33)
|
109.39 units on a scale
Standard Deviation 16.727
|
|
Functional Assessment of Cancer Therapy-Colorectal (FACT-C) Score: Phase A
Phase A Visit 6 (Weeks 40-41)
|
111.30 units on a scale
Standard Deviation 16.420
|
|
Functional Assessment of Cancer Therapy-Colorectal (FACT-C) Score: Phase A
Phase A Visit 7 (Weeks 48-49)
|
111.40 units on a scale
Standard Deviation 13.506
|
|
Functional Assessment of Cancer Therapy-Colorectal (FACT-C) Score: Phase A
Phase A Visit 8 (Weeks 56-57)
|
113.51 units on a scale
Standard Deviation 10.777
|
|
Functional Assessment of Cancer Therapy-Colorectal (FACT-C) Score: Phase A
Phase A Visit 9 (Weeks 64-65)
|
113.92 units on a scale
Standard Deviation 12.239
|
|
Functional Assessment of Cancer Therapy-Colorectal (FACT-C) Score: Phase A
Phase A Visit 10 (Weeks 72-73)
|
115.11 units on a scale
Standard Deviation 15.473
|
|
Functional Assessment of Cancer Therapy-Colorectal (FACT-C) Score: Phase A
Phase A Visit 11 (Weeks 80-81)
|
114.00 units on a scale
Standard Deviation 13.230
|
|
Functional Assessment of Cancer Therapy-Colorectal (FACT-C) Score: Phase A
Phase A Visit 12 (Weeks 88-89)
|
115.99 units on a scale
Standard Deviation 12.844
|
|
Functional Assessment of Cancer Therapy-Colorectal (FACT-C) Score: Phase A
Phase A Visit 13 (Weeks 96-97)
|
113.54 units on a scale
Standard Deviation 12.298
|
|
Functional Assessment of Cancer Therapy-Colorectal (FACT-C) Score: Phase A
Phase A Visit 14 (Weeks 104-105)
|
112.36 units on a scale
Standard Deviation 15.443
|
|
Functional Assessment of Cancer Therapy-Colorectal (FACT-C) Score: Phase A
Phase A Visit 15 (Weeks 112-113)
|
119.48 units on a scale
Standard Deviation 11.542
|
|
Functional Assessment of Cancer Therapy-Colorectal (FACT-C) Score: Phase A
Phase A Visit 16 (Weeks 120-121)
|
116.38 units on a scale
Standard Deviation 15.214
|
|
Functional Assessment of Cancer Therapy-Colorectal (FACT-C) Score: Phase A
Phase A Visit 17 (Weeks 128-129)
|
113.69 units on a scale
Standard Deviation 17.816
|
|
Functional Assessment of Cancer Therapy-Colorectal (FACT-C) Score: Phase A
Phase A Visit 18 (Weeks 136-137)
|
112.94 units on a scale
Standard Deviation 16.931
|
|
Functional Assessment of Cancer Therapy-Colorectal (FACT-C) Score: Phase A
Phase A Visit 19 (Weeks 144-145)
|
117.55 units on a scale
Standard Deviation 10.397
|
|
Functional Assessment of Cancer Therapy-Colorectal (FACT-C) Score: Phase A
Phase A Visit 20 (Weeks 152-153)
|
115.86 units on a scale
Standard Deviation 13.120
|
|
Functional Assessment of Cancer Therapy-Colorectal (FACT-C) Score: Phase A
Phase A Visit 21 (Weeks 160-161)
|
106.00 units on a scale
Standard Deviation 20.664
|
|
Functional Assessment of Cancer Therapy-Colorectal (FACT-C) Score: Phase A
Phase A Visit 22 (Weeks 168-169)
|
112.00 units on a scale
Standard Deviation 26.870
|
|
Functional Assessment of Cancer Therapy-Colorectal (FACT-C) Score: Phase A
Phase A Visit 23 (Weeks 176-177)
|
105.00 units on a scale
Standard Deviation 36.770
|
|
Functional Assessment of Cancer Therapy-Colorectal (FACT-C) Score: Phase A
Phase A EOT Visit (up to 4 years)
|
103.94 units on a scale
Standard Deviation 17.429
|
|
Functional Assessment of Cancer Therapy-Colorectal (FACT-C) Score: Phase A
Survival Follow-Up 1 (up to 4 years)
|
102.89 units on a scale
Standard Deviation 18.086
|
|
Functional Assessment of Cancer Therapy-Colorectal (FACT-C) Score: Phase A
Survival Follow-Up 2 (up to 4 years)
|
104.00 units on a scale
Standard Deviation 8.047
|
|
Functional Assessment of Cancer Therapy-Colorectal (FACT-C) Score: Phase A
Survival Follow-Up 3 (up to 4 years)
|
105.50 units on a scale
Standard Deviation 10.607
|
|
Functional Assessment of Cancer Therapy-Colorectal (FACT-C) Score: Phase A
Survival Follow-Up 4 (up to 4 years)
|
109.00 units on a scale
|
|
Functional Assessment of Cancer Therapy-Colorectal (FACT-C) Score: Phase A
Survival Follow-Up 5 (up to 4 years)
|
119.00 units on a scale
|
|
Functional Assessment of Cancer Therapy-Colorectal (FACT-C) Score: Phase A
Survival Follow-Up 6 (up to 4 years)
|
103.61 units on a scale
Standard Deviation 4.945
|
|
Functional Assessment of Cancer Therapy-Colorectal (FACT-C) Score: Phase A
Survival Follow-Up 7 (up to 4 years)
|
115.00 units on a scale
|
SECONDARY outcome
Timeframe: 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]Population: Phase B FAS population. "Number Analyzed" = participants who were evaluable at the specified time point for this outcome.
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.
Outcome measures
| Measure |
Bevacizumab: Phase A and Phase B
n=53 Participants
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.
|
|---|---|
|
FACT-C Score: Phase B
Phase B Visit 8 (up to 4 years)
|
120.39 units on a scale
Standard Deviation 9.007
|
|
FACT-C Score: Phase B
Phase B Visit 9 (up to 4 years)
|
108.08 units on a scale
Standard Deviation 18.267
|
|
FACT-C Score: Phase B
Phase B Visit 10 (up to 4 years)
|
110.50 units on a scale
Standard Deviation 17.678
|
|
FACT-C Score: Phase B
Phase B Visit 11 (up to 4 years)
|
109.33 units on a scale
Standard Deviation 19.328
|
|
FACT-C Score: Phase B
Phase B Visit 12 (up to 4 years)
|
125.00 units on a scale
|
|
FACT-C Score: Phase B
Phase B Visit 13 (up to 4 years)
|
119.00 units on a scale
|
|
FACT-C Score: Phase B
Phase B Visit 14 (up to 4 years)
|
117.00 units on a scale
|
|
FACT-C Score: Phase B
Phase B Visit 15 (up to 4 years)
|
126.00 units on a scale
|
|
FACT-C Score: Phase B
Phase B Visit 16 (up to 4 years)
|
123.00 units on a scale
|
|
FACT-C Score: Phase B
Phase B Visit 17 (up to 4 years)
|
127.00 units on a scale
|
|
FACT-C Score: Phase B
Phase B Visit 18 (up to 4 years)
|
126.00 units on a scale
|
|
FACT-C Score: Phase B
Phase B Visit 19 (up to 4 years)
|
127.00 units on a scale
|
|
FACT-C Score: Phase B
Phase B Visit 20 (up to 4 years)
|
126.00 units on a scale
|
|
FACT-C Score: Phase B
Phase B Visit 21 (up to 4 years)
|
123.00 units on a scale
|
|
FACT-C Score: Phase B
Phase B Visit 22 (up to 4 years)
|
124.00 units on a scale
|
|
FACT-C Score: Phase B
Phase B Visit 23 (up to 4 years)
|
126.00 units on a scale
|
|
FACT-C Score: Phase B
Phase B Visit 24 (up to 4 years)
|
130.00 units on a scale
|
|
FACT-C Score: Phase B
Phase B EOT Visit (up to 4 years)
|
101.67 units on a scale
Standard Deviation 19.023
|
|
FACT-C Score: Phase B
Survival Follow-Up 1 (up to 4 years)
|
98.72 units on a scale
Standard Deviation 20.024
|
|
FACT-C Score: Phase B
Survival Follow-Up 2 (up to 4 years)
|
102.50 units on a scale
Standard Deviation 17.705
|
|
FACT-C Score: Phase B
Survival Follow-Up 3 (up to 4 years)
|
126.33 units on a scale
|
|
FACT-C Score: Phase B
Survival Follow-Up 4 (up to 4 years)
|
125.00 units on a scale
|
|
FACT-C Score: Phase B
Survival Follow-Up 6 (up to 4 years)
|
124.67 units on a scale
|
|
FACT-C Score: Phase B
Phase B Baseline
|
103.47 units on a scale
Standard Deviation 18.284
|
|
FACT-C Score: Phase B
Phase B Visit 2 (up to 4 years)
|
108.71 units on a scale
Standard Deviation 17.387
|
|
FACT-C Score: Phase B
Phase B Visit 3 (up to 4 years)
|
108.19 units on a scale
Standard Deviation 16.541
|
|
FACT-C Score: Phase B
Phase B Visit 4 (up to 4 years)
|
114.89 units on a scale
Standard Deviation 14.467
|
|
FACT-C Score: Phase B
Phase B Visit 5 (up to 4 years)
|
110.60 units on a scale
Standard Deviation 15.592
|
|
FACT-C Score: Phase B
Phase B Visit 6 (up to 4 years)
|
111.28 units on a scale
Standard Deviation 14.121
|
|
FACT-C Score: Phase B
Phase B Visit 7 (up to 4 years)
|
114.78 units on a scale
Standard Deviation 12.640
|
Adverse Events
Bevacizumab: Phase A and Phase B
Serious events: 86 serious events
Other events: 128 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Bevacizumab: Phase A and Phase B
n=128 participants at risk
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.
|
|---|---|
|
Blood and lymphatic system disorders
Febrile neutropenia
|
1.6%
2/128 • Baseline up to end of study (up to 4 years)
FAS population.
|
|
Blood and lymphatic system disorders
Neutropenia
|
0.78%
1/128 • Baseline up to end of study (up to 4 years)
FAS population.
|
|
Cardiac disorders
Angina pectoris
|
2.3%
3/128 • Baseline up to end of study (up to 4 years)
FAS population.
|
|
Eye disorders
Visual impairment
|
0.78%
1/128 • Baseline up to end of study (up to 4 years)
FAS population.
|
|
Gastrointestinal disorders
Abdominal pain
|
4.7%
6/128 • Baseline up to end of study (up to 4 years)
FAS population.
|
|
Gastrointestinal disorders
Abdominal pain upper
|
1.6%
2/128 • Baseline up to end of study (up to 4 years)
FAS population.
|
|
Gastrointestinal disorders
Anal fissure
|
0.78%
1/128 • Baseline up to end of study (up to 4 years)
FAS population.
|
|
Gastrointestinal disorders
Colitis
|
0.78%
1/128 • Baseline up to end of study (up to 4 years)
FAS population.
|
|
Gastrointestinal disorders
Colonic obstruction
|
0.78%
1/128 • Baseline up to end of study (up to 4 years)
FAS population.
|
|
Gastrointestinal disorders
Constipation
|
1.6%
2/128 • Baseline up to end of study (up to 4 years)
FAS population.
|
|
Gastrointestinal disorders
Diarrhoea
|
6.2%
8/128 • Baseline up to end of study (up to 4 years)
FAS population.
|
|
Gastrointestinal disorders
Dysphagia
|
0.78%
1/128 • Baseline up to end of study (up to 4 years)
FAS population.
|
|
Gastrointestinal disorders
Enterovesical fistula
|
1.6%
2/128 • Baseline up to end of study (up to 4 years)
FAS population.
|
|
Gastrointestinal disorders
Gastritis
|
0.78%
1/128 • Baseline up to end of study (up to 4 years)
FAS population.
|
|
Gastrointestinal disorders
Gastrointestinal haemorrhage
|
0.78%
1/128 • Baseline up to end of study (up to 4 years)
FAS population.
|
|
Gastrointestinal disorders
Gastrointestinal perforation
|
0.78%
1/128 • Baseline up to end of study (up to 4 years)
FAS population.
|
|
Gastrointestinal disorders
Gastrooesophageal reflux disease
|
0.78%
1/128 • Baseline up to end of study (up to 4 years)
FAS population.
|
|
Gastrointestinal disorders
Ileus
|
0.78%
1/128 • Baseline up to end of study (up to 4 years)
FAS population.
|
|
Gastrointestinal disorders
Inguinal hernia
|
0.78%
1/128 • Baseline up to end of study (up to 4 years)
FAS population.
|
|
Gastrointestinal disorders
Intestinal obstruction
|
4.7%
6/128 • Baseline up to end of study (up to 4 years)
FAS population.
|
|
Gastrointestinal disorders
Intestinal perforation
|
0.78%
1/128 • Baseline up to end of study (up to 4 years)
FAS population.
|
|
Gastrointestinal disorders
Large intestinal obstruction
|
0.78%
1/128 • Baseline up to end of study (up to 4 years)
FAS population.
|
|
Gastrointestinal disorders
Large intestine perforation
|
0.78%
1/128 • Baseline up to end of study (up to 4 years)
FAS population.
|
|
Gastrointestinal disorders
Melaena
|
0.78%
1/128 • Baseline up to end of study (up to 4 years)
FAS population.
|
|
Gastrointestinal disorders
Nausea
|
3.9%
5/128 • Baseline up to end of study (up to 4 years)
FAS population.
|
|
Gastrointestinal disorders
Neutropenic colitis
|
0.78%
1/128 • Baseline up to end of study (up to 4 years)
FAS population.
|
|
Gastrointestinal disorders
Rectal haemorrhage
|
2.3%
3/128 • Baseline up to end of study (up to 4 years)
FAS population.
|
|
Gastrointestinal disorders
Rectal perforation
|
0.78%
1/128 • Baseline up to end of study (up to 4 years)
FAS population.
|
|
Gastrointestinal disorders
Small intestinal obstruction
|
2.3%
3/128 • Baseline up to end of study (up to 4 years)
FAS population.
|
|
Gastrointestinal disorders
Vomiting
|
7.8%
10/128 • Baseline up to end of study (up to 4 years)
FAS population.
|
|
General disorders
Catheter site pain
|
0.78%
1/128 • Baseline up to end of study (up to 4 years)
FAS population.
|
|
General disorders
Extravasation
|
0.78%
1/128 • Baseline up to end of study (up to 4 years)
FAS population.
|
|
General disorders
Non-cardiac chest pain
|
0.78%
1/128 • Baseline up to end of study (up to 4 years)
FAS population.
|
|
General disorders
Pyrexia
|
9.4%
12/128 • Baseline up to end of study (up to 4 years)
FAS population.
|
|
Hepatobiliary disorders
Cholecystitis acute
|
0.78%
1/128 • Baseline up to end of study (up to 4 years)
FAS population.
|
|
Infections and infestations
Abscess limb
|
0.78%
1/128 • Baseline up to end of study (up to 4 years)
FAS population.
|
|
Infections and infestations
Anal abscess
|
1.6%
2/128 • Baseline up to end of study (up to 4 years)
FAS population.
|
|
Infections and infestations
Bronchitis
|
1.6%
2/128 • Baseline up to end of study (up to 4 years)
FAS population.
|
|
Infections and infestations
Clostridium difficile colitis
|
0.78%
1/128 • Baseline up to end of study (up to 4 years)
FAS population.
|
|
Infections and infestations
Device related infection
|
0.78%
1/128 • Baseline up to end of study (up to 4 years)
FAS population.
|
|
Infections and infestations
Ear infection
|
0.78%
1/128 • Baseline up to end of study (up to 4 years)
FAS population.
|
|
Infections and infestations
Enterocolitis infectious
|
0.78%
1/128 • Baseline up to end of study (up to 4 years)
FAS population.
|
|
Infections and infestations
Eyelid infection
|
0.78%
1/128 • Baseline up to end of study (up to 4 years)
FAS population.
|
|
Infections and infestations
Gangrene
|
0.78%
1/128 • Baseline up to end of study (up to 4 years)
FAS population.
|
|
Infections and infestations
Gastroenteritis
|
2.3%
3/128 • Baseline up to end of study (up to 4 years)
FAS population.
|
|
Infections and infestations
Gastroenteritis viral
|
0.78%
1/128 • Baseline up to end of study (up to 4 years)
FAS population.
|
|
Infections and infestations
Infected dermal cyst
|
0.78%
1/128 • Baseline up to end of study (up to 4 years)
FAS population.
|
|
Infections and infestations
Infective exacerbation of chronic obstructive airways disease
|
0.78%
1/128 • Baseline up to end of study (up to 4 years)
FAS population.
|
|
Infections and infestations
Lobar pneumonia
|
0.78%
1/128 • Baseline up to end of study (up to 4 years)
FAS population.
|
|
Infections and infestations
Lower respiratory tract infection
|
2.3%
3/128 • Baseline up to end of study (up to 4 years)
FAS population.
|
|
Infections and infestations
Muscle abscess
|
0.78%
1/128 • Baseline up to end of study (up to 4 years)
FAS population.
|
|
Infections and infestations
Pharyngitis
|
0.78%
1/128 • Baseline up to end of study (up to 4 years)
FAS population.
|
|
Infections and infestations
Pilonidal cyst
|
0.78%
1/128 • Baseline up to end of study (up to 4 years)
FAS population.
|
|
Infections and infestations
Pneumonia
|
2.3%
3/128 • Baseline up to end of study (up to 4 years)
FAS population.
|
|
Infections and infestations
Pneumonia streptococcal
|
0.78%
1/128 • Baseline up to end of study (up to 4 years)
FAS population.
|
|
Infections and infestations
Sepsis
|
5.5%
7/128 • Baseline up to end of study (up to 4 years)
FAS population.
|
|
Infections and infestations
Upper respiratory tract infection
|
0.78%
1/128 • Baseline up to end of study (up to 4 years)
FAS population.
|
|
Infections and infestations
Urinary tract infection
|
1.6%
2/128 • Baseline up to end of study (up to 4 years)
FAS population.
|
|
Infections and infestations
Urosepsis
|
0.78%
1/128 • Baseline up to end of study (up to 4 years)
FAS population.
|
|
Infections and infestations
Wound infection
|
0.78%
1/128 • Baseline up to end of study (up to 4 years)
FAS population.
|
|
Injury, poisoning and procedural complications
Fall
|
0.78%
1/128 • Baseline up to end of study (up to 4 years)
FAS population.
|
|
Injury, poisoning and procedural complications
Infusion related reaction
|
0.78%
1/128 • Baseline up to end of study (up to 4 years)
FAS population.
|
|
Injury, poisoning and procedural complications
Laceration
|
0.78%
1/128 • Baseline up to end of study (up to 4 years)
FAS population.
|
|
Injury, poisoning and procedural complications
Procedural pain
|
0.78%
1/128 • Baseline up to end of study (up to 4 years)
FAS population.
|
|
Injury, poisoning and procedural complications
Procedural site reaction
|
0.78%
1/128 • Baseline up to end of study (up to 4 years)
FAS population.
|
|
Injury, poisoning and procedural complications
Radius fracture
|
0.78%
1/128 • Baseline up to end of study (up to 4 years)
FAS population.
|
|
Metabolism and nutrition disorders
Dehydration
|
5.5%
7/128 • Baseline up to end of study (up to 4 years)
FAS population.
|
|
Metabolism and nutrition disorders
Hypomagnesaemia
|
0.78%
1/128 • Baseline up to end of study (up to 4 years)
FAS population.
|
|
Metabolism and nutrition disorders
Hypophagia
|
0.78%
1/128 • Baseline up to end of study (up to 4 years)
FAS population.
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
0.78%
1/128 • Baseline up to end of study (up to 4 years)
FAS population.
|
|
Musculoskeletal and connective tissue disorders
Flank pain
|
2.3%
3/128 • Baseline up to end of study (up to 4 years)
FAS population.
|
|
Musculoskeletal and connective tissue disorders
Musculoskeletal chest pain
|
0.78%
1/128 • Baseline up to end of study (up to 4 years)
FAS population.
|
|
Musculoskeletal and connective tissue disorders
Neck pain
|
0.78%
1/128 • Baseline up to end of study (up to 4 years)
FAS population.
|
|
Nervous system disorders
Cerebrovascular accident
|
0.78%
1/128 • Baseline up to end of study (up to 4 years)
FAS population.
|
|
Nervous system disorders
Dizziness
|
1.6%
2/128 • Baseline up to end of study (up to 4 years)
FAS population.
|
|
Nervous system disorders
Hemiparesis
|
0.78%
1/128 • Baseline up to end of study (up to 4 years)
FAS population.
|
|
Nervous system disorders
Syncope
|
0.78%
1/128 • Baseline up to end of study (up to 4 years)
FAS population.
|
|
Nervous system disorders
Transient ischaemic attack
|
0.78%
1/128 • Baseline up to end of study (up to 4 years)
FAS population.
|
|
Psychiatric disorders
Acute psychosis
|
0.78%
1/128 • Baseline up to end of study (up to 4 years)
FAS population.
|
|
Psychiatric disorders
Confusional state
|
1.6%
2/128 • Baseline up to end of study (up to 4 years)
FAS population.
|
|
Renal and urinary disorders
Haematuria
|
0.78%
1/128 • Baseline up to end of study (up to 4 years)
FAS population.
|
|
Renal and urinary disorders
Hydronephrosis
|
0.78%
1/128 • Baseline up to end of study (up to 4 years)
FAS population.
|
|
Renal and urinary disorders
Renal failure acute
|
2.3%
3/128 • Baseline up to end of study (up to 4 years)
FAS population.
|
|
Renal and urinary disorders
Urinary incontinence
|
0.78%
1/128 • Baseline up to end of study (up to 4 years)
FAS population.
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea
|
1.6%
2/128 • Baseline up to end of study (up to 4 years)
FAS population.
|
|
Respiratory, thoracic and mediastinal disorders
Pleural effusion
|
0.78%
1/128 • Baseline up to end of study (up to 4 years)
FAS population.
|
|
Respiratory, thoracic and mediastinal disorders
Pleuritic pain
|
0.78%
1/128 • Baseline up to end of study (up to 4 years)
FAS population.
|
|
Respiratory, thoracic and mediastinal disorders
Pneumonia aspiration
|
0.78%
1/128 • Baseline up to end of study (up to 4 years)
FAS population.
|
|
Respiratory, thoracic and mediastinal disorders
Pulmonary embolism
|
10.2%
13/128 • Baseline up to end of study (up to 4 years)
FAS population.
|
|
Vascular disorders
Hypertension
|
1.6%
2/128 • Baseline up to end of study (up to 4 years)
FAS population.
|
|
Vascular disorders
Hypotension
|
1.6%
2/128 • Baseline up to end of study (up to 4 years)
FAS population.
|
|
Vascular disorders
Jugular vein thrombosis
|
0.78%
1/128 • Baseline up to end of study (up to 4 years)
FAS population.
|
|
Vascular disorders
Orthostatic hypotension
|
0.78%
1/128 • Baseline up to end of study (up to 4 years)
FAS population.
|
|
Vascular disorders
Thrombophlebitis superficial
|
0.78%
1/128 • Baseline up to end of study (up to 4 years)
FAS population.
|
Other adverse events
| Measure |
Bevacizumab: Phase A and Phase B
n=128 participants at risk
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.
|
|---|---|
|
Blood and lymphatic system disorders
Anaemia
|
11.7%
15/128 • Baseline up to end of study (up to 4 years)
FAS population.
|
|
Blood and lymphatic system disorders
Neutropenia
|
25.0%
32/128 • Baseline up to end of study (up to 4 years)
FAS population.
|
|
Blood and lymphatic system disorders
Thrombocytopenia
|
12.5%
16/128 • Baseline up to end of study (up to 4 years)
FAS population.
|
|
Gastrointestinal disorders
Abdominal distension
|
7.0%
9/128 • Baseline up to end of study (up to 4 years)
FAS population.
|
|
Gastrointestinal disorders
Abdominal pain
|
31.2%
40/128 • Baseline up to end of study (up to 4 years)
FAS population.
|
|
Gastrointestinal disorders
Abdominal pain upper
|
10.2%
13/128 • Baseline up to end of study (up to 4 years)
FAS population.
|
|
Gastrointestinal disorders
Constipation
|
39.8%
51/128 • Baseline up to end of study (up to 4 years)
FAS population.
|
|
Gastrointestinal disorders
Diarrhoea
|
54.7%
70/128 • Baseline up to end of study (up to 4 years)
FAS population.
|
|
Gastrointestinal disorders
Dyspepsia
|
10.2%
13/128 • Baseline up to end of study (up to 4 years)
FAS population.
|
|
Gastrointestinal disorders
Gastrooesophageal reflux disease
|
20.3%
26/128 • Baseline up to end of study (up to 4 years)
FAS population.
|
|
Gastrointestinal disorders
Mouth ulceration
|
12.5%
16/128 • Baseline up to end of study (up to 4 years)
FAS population.
|
|
Gastrointestinal disorders
Nausea
|
68.0%
87/128 • Baseline up to end of study (up to 4 years)
FAS population.
|
|
Gastrointestinal disorders
Rectal haemorrhage
|
7.0%
9/128 • Baseline up to end of study (up to 4 years)
FAS population.
|
|
Gastrointestinal disorders
Stomatitis
|
17.2%
22/128 • Baseline up to end of study (up to 4 years)
FAS population.
|
|
Gastrointestinal disorders
Vomiting
|
28.1%
36/128 • Baseline up to end of study (up to 4 years)
FAS population.
|
|
Gastrointestinal disorders
Toothache
|
7.0%
9/128 • Baseline up to end of study (up to 4 years)
FAS population.
|
|
General disorders
Fatigue
|
62.5%
80/128 • Baseline up to end of study (up to 4 years)
FAS population.
|
|
General disorders
Mucosal inflammation
|
24.2%
31/128 • Baseline up to end of study (up to 4 years)
FAS population.
|
|
General disorders
Non-cardiac chest pain
|
6.2%
8/128 • Baseline up to end of study (up to 4 years)
FAS population.
|
|
General disorders
Oedema peripheral
|
10.9%
14/128 • Baseline up to end of study (up to 4 years)
FAS population.
|
|
General disorders
Pyrexia
|
9.4%
12/128 • Baseline up to end of study (up to 4 years)
FAS population.
|
|
Infections and infestations
Oral candidiasis
|
5.5%
7/128 • Baseline up to end of study (up to 4 years)
FAS population.
|
|
Infections and infestations
Oral herpes
|
5.5%
7/128 • Baseline up to end of study (up to 4 years)
FAS population.
|
|
Infections and infestations
Upper respiratory tract infection
|
14.1%
18/128 • Baseline up to end of study (up to 4 years)
FAS population.
|
|
Infections and infestations
Urinary tract infection
|
15.6%
20/128 • Baseline up to end of study (up to 4 years)
FAS population.
|
|
Injury, poisoning and procedural complications
Fall
|
7.8%
10/128 • Baseline up to end of study (up to 4 years)
FAS population.
|
|
Investigations
Weight decreased
|
10.9%
14/128 • Baseline up to end of study (up to 4 years)
FAS population.
|
|
Metabolism and nutrition disorders
Decreased appetite
|
21.9%
28/128 • Baseline up to end of study (up to 4 years)
FAS population.
|
|
Metabolism and nutrition disorders
Dehydration
|
6.2%
8/128 • Baseline up to end of study (up to 4 years)
FAS population.
|
|
Metabolism and nutrition disorders
Hypoalbuminaemia
|
5.5%
7/128 • Baseline up to end of study (up to 4 years)
FAS population.
|
|
Metabolism and nutrition disorders
Hypokalaemia
|
5.5%
7/128 • Baseline up to end of study (up to 4 years)
FAS population.
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
13.3%
17/128 • Baseline up to end of study (up to 4 years)
FAS population.
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
17.2%
22/128 • Baseline up to end of study (up to 4 years)
FAS population.
|
|
Musculoskeletal and connective tissue disorders
Muscle spasms
|
5.5%
7/128 • Baseline up to end of study (up to 4 years)
FAS population.
|
|
Musculoskeletal and connective tissue disorders
Musculoskeletal pain
|
10.9%
14/128 • Baseline up to end of study (up to 4 years)
FAS population.
|
|
Musculoskeletal and connective tissue disorders
Neck pain
|
7.0%
9/128 • Baseline up to end of study (up to 4 years)
FAS population.
|
|
Musculoskeletal and connective tissue disorders
Pain in extremity
|
14.1%
18/128 • Baseline up to end of study (up to 4 years)
FAS population.
|
|
Nervous system disorders
Dizziness
|
10.2%
13/128 • Baseline up to end of study (up to 4 years)
FAS population.
|
|
Nervous system disorders
Dysaesthesia
|
11.7%
15/128 • Baseline up to end of study (up to 4 years)
FAS population.
|
|
Nervous system disorders
Dysgeusia
|
15.6%
20/128 • Baseline up to end of study (up to 4 years)
FAS population.
|
|
Nervous system disorders
Headache
|
18.8%
24/128 • Baseline up to end of study (up to 4 years)
FAS population.
|
|
Nervous system disorders
Lethargy
|
7.0%
9/128 • Baseline up to end of study (up to 4 years)
FAS population.
|
|
Nervous system disorders
Neuropathy peripheral
|
62.5%
80/128 • Baseline up to end of study (up to 4 years)
FAS population.
|
|
Nervous system disorders
Paraesthesia
|
20.3%
26/128 • Baseline up to end of study (up to 4 years)
FAS population.
|
|
Psychiatric disorders
Anxiety
|
7.8%
10/128 • Baseline up to end of study (up to 4 years)
FAS population.
|
|
Psychiatric disorders
Depression
|
9.4%
12/128 • Baseline up to end of study (up to 4 years)
FAS population.
|
|
Psychiatric disorders
Insomnia
|
19.5%
25/128 • Baseline up to end of study (up to 4 years)
FAS population.
|
|
Renal and urinary disorders
Proteinuria
|
7.8%
10/128 • Baseline up to end of study (up to 4 years)
FAS population.
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
10.2%
13/128 • Baseline up to end of study (up to 4 years)
FAS population.
|
|
Respiratory, thoracic and mediastinal disorders
Dysphonia
|
8.6%
11/128 • Baseline up to end of study (up to 4 years)
FAS population.
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea
|
10.2%
13/128 • Baseline up to end of study (up to 4 years)
FAS population.
|
|
Respiratory, thoracic and mediastinal disorders
Epistaxis
|
23.4%
30/128 • Baseline up to end of study (up to 4 years)
FAS population.
|
|
Respiratory, thoracic and mediastinal disorders
Oropharyngeal pain
|
6.2%
8/128 • Baseline up to end of study (up to 4 years)
FAS population.
|
|
Respiratory, thoracic and mediastinal disorders
Rhinorrhoea
|
6.2%
8/128 • Baseline up to end of study (up to 4 years)
FAS population.
|
|
Skin and subcutaneous tissue disorders
Alopecia
|
20.3%
26/128 • Baseline up to end of study (up to 4 years)
FAS population.
|
|
Skin and subcutaneous tissue disorders
Dry skin
|
7.8%
10/128 • Baseline up to end of study (up to 4 years)
FAS population.
|
|
Skin and subcutaneous tissue disorders
Nail disorder
|
5.5%
7/128 • Baseline up to end of study (up to 4 years)
FAS population.
|
|
Skin and subcutaneous tissue disorders
Palmar-plantar erythrodysaesthesia syndrome
|
29.7%
38/128 • Baseline up to end of study (up to 4 years)
FAS population.
|
|
Skin and subcutaneous tissue disorders
Rash
|
16.4%
21/128 • Baseline up to end of study (up to 4 years)
FAS population.
|
|
Vascular disorders
Hypertension
|
18.0%
23/128 • Baseline up to end of study (up to 4 years)
FAS population.
|
|
Vascular disorders
Hypotension
|
5.5%
7/128 • Baseline up to end of study (up to 4 years)
FAS population.
|
|
Gastrointestinal disorders
Haemorrhoids
|
5.5%
7/128 • Baseline up to end of study (up to 4 years)
FAS population.
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee 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.
- Publication restrictions are in place
Restriction type: OTHER