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OBELIX Study: A Study of Avastin (Bevacizumab) in Combination With XELOX in Patients With Metastatic Cancer of the Colon or Rectum.

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ClinicalTrials.gov Identifier: NCT00577031
Recruitment Status : Completed
First Posted : December 19, 2007
Results First Posted : August 18, 2015
Last Update Posted : August 18, 2015
Sponsor:
Information provided by (Responsible Party):
Hoffmann-La Roche

Study Type Interventional
Study Design Intervention Model: Single Group Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Colorectal Cancer
Interventions Drug: bevacizumab [Avastin]
Drug: Oxaliplatin
Drug: Xeloda
Enrollment 205
Recruitment Details  
Pre-assignment Details  
Arm/Group Title Bevacizumab+Oxaliplatin+Capecitabine/Bevacizumab
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Cycles 1-8 (3-week cycles): Participants received bevacizumab 7.5 milligrams per kilogram (mg/kg) intravenously (IV) and oxaliplatin 130 mg per square meter (mg/m^2) IV on Day 1 and capecitabine 1000 mg/m^2 tablets, orally, every 12 hours starting the evening of Day 1 for 14 days continuously; cycle was repeated until disease progression or for a maximum of 8 cycles.

Cycle 9 and beyond (3-week cycles): If the first 8 cycles were tolerated with no disease progression, participants received bevacizumab 7.5 mg/kg IV on Day 1; the cycle was repeated until disease progression.

Period Title: Overall Study
Started 205
Completed 0
Not Completed 205
Reason Not Completed
Adverse Event             52
Progression of disease             93
Protocol Violation             5
Participant withdrew consent             13
Participant non-compliance             5
Need for surgery             17
Medical decision             14
Death             6
Arm/Group Title Bevucizamab+Oxaliplatin+Capecitabine/Bevacizumab
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Cycles 1-8 (3-week cycles): Participants received bevacizumab 7.5 mg/kg IV and oxaliplatin 130 mg/m^2 IV on Day 1 and capecitabine 1000 mg/m^2 tablets, orally, every 12 hours starting the evening of Day 1 for 14 days continuously; cycle was repeated until disease progression or for a maximum of 8 cycles.

Cycle 9 and beyond (3-week cycles): If the first 8 cycles were tolerated with no disease progression participants received bevacizumab 7.5 mg/kg IV on Day 1; the cycle was repeated until disease progression.

Overall Number of Baseline Participants 197
Hide Baseline Analysis Population Description
Safety population: all enrolled participants who received at least 1 dose of all study medications.
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 197 participants
62.25  (9.94)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 197 participants
Female
86
  43.7%
Male
111
  56.3%
1.Primary Outcome
Title Progression-Free Survival (PFS): Percentage of Participants With Progressive Disease or Death
Hide Description PFS was defined as the time period in months from the start of study treatment to the first observation of disease progression or death from any cause, whichever occurred first. Data for participants with no tumor assessments after baseline but who were still alive at the time of the clinical cutoff were censored at Day 1. Participants who underwent surgery after experiencing a sufficient shrinkage of the tumor, had any relapse, new occurrence of colorectal cancer, or who died were all considered as having had an event. Participants who underwent surgery without any such event were censored at the date of the last tumor assessment that documented neither a relapse nor a new colorectal cancer had occurred. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20 percent (%) increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions.
Time Frame Baseline and Day 1 of every cycle until disease progression or death up to 5 years
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Hide Analysis Population Description
Intent-to-treat (ITT) population: all enrolled participants who received at least 1 dose of all study medications and had at least 1 measurable lesion according to the Response Evaluation Criteria In Solid Tumours (RECIST) criteria.
Arm/Group Title Bevucizamab+Oxaliplatin+Capecitabine/Bevacizumab
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Cycles 1-8 (3-week cycles): Participants received bevacizumab 7.5 mg/kg IV) and oxaliplatin 130 mg mg/m^2 IV on Day 1 and capecitabine 1000 mg/m^2 tablets, orally, every 12 hours starting the evening of Day 1 for 14 days continuously; cycle was repeated until disease progression or for a maximum of 8 cycles.

Cycle 9 and beyond (3-week cycles): If the first 8 cycles were tolerated with no disease progression participants received bevacizumab 7.5 mg/kg IV on Day 1; the cycle was repeated until disease progression.

Overall Number of Participants Analyzed 197
Measure Type: Number
Unit of Measure: percentage of participants
50.25
2.Primary Outcome
Title PFS: Time to Event
Hide Description PFS was defined as the time period in months from the start of study treatment to the first observation of disease progression or death from any cause, whichever occurred first. Data for participants with no tumor assessments after baseline but who were still alive at the time of the clinical cutoff were censored at Day 1. Participants who underwent surgery after experiencing a sufficient shrinkage of the tumor, had any relapse, new occurrence of colorectal cancer, or who died were all considered as having had an event. Participants who underwent surgery without any such event were censored at the date of the last tumor assessment that documented that neither a relapse nor a new colorectal cancer had occurred. Median PFS was estimated using the Kaplan-Meier method.
Time Frame Baseline and Day 1 of every cycle until disease progression or death up to 5 years
Hide Outcome Measure Data
Hide Analysis Population Description
ITT population.
Arm/Group Title Bevucizamab+Oxaliplatin+Capecitabine/Bevacizumab
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Cycles 1-8 (3-week cycles):

Participants received bevacizumab 7.5 mg/kg IV) and oxaliplatin 130 mg mg/m^2 IV on Day 1 and capecitabine 1000 mg/m^2 tablets, orally, every 12 hours starting the evening of Day

1 for 14 days continuously; cycle was repeated until disease progression or for a maximum of 8 cycles.

Cycle 9 and beyond (3-week cycles):

If the first 8 cycles were tolerated with no disease progression participants received bevacizumab 7.5 mg/kg IV on Day 1; the cycle was repeated until disease progression.

Overall Number of Participants Analyzed 197
Median (95% Confidence Interval)
Unit of Measure: months
9.70
(8.43 to 10.49)
3.Secondary Outcome
Title Percentage of Participants With a Best Overall Response of Complete Response (CR) or Partial Response (PR) Among Participants in the ITT Population Who Had at Least 1 Post-Baseline Assessment
Hide Description The percentage of participants with a best overall response of CR or PR according to RECIST. CR was defined as complete disappearance of all target lesions and non-target disease, with the exception of nodal disease. All nodes, both target and non-target, must have decreased to normal (short axis less than [<]10 millimeters [mm]). No new lesions. PR was defined as a greater than or equal to (≥) 30% decrease under baseline of the sum of diameters of all target lesions. The short axis was used in the sum for target nodes, while the longest diameter was used in the sum for all other target lesions. No unequivocal progression of non-target disease. No new lesions.
Time Frame Baseline, every 9 weeks (every 3 cycles) until end of treatment, disease progression, or withdrawal up to 5 years
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Hide Analysis Population Description
Subset of participants in the ITT population who had at least 1 post-baseline tumor assessment.
Arm/Group Title Bevucizamab+Oxaliplatin+Capecitabine/Bevacizumab
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Cycles 1-8 (3-week cycles): Participants received bevacizumab 7.5 mg/kg IV and oxaliplatin 130 mg/m^2 IV on Day 1 and capecitabine 1000 mg/m^2 tablets, orally, every 12 hours starting the evening of Day 1 for 14 days continuously; cycle was repeated until disease progression or for a maximum of 8 cycles.

Cycle 9 and beyond (3-week cycles): If the first 8 cycles were tolerated with no disease progression participants received bevacizumab 7.5 mg/kg IV on Day 1; the cycle was repeated until disease progression.

Overall Number of Participants Analyzed 165
Measure Type: Number
Unit of Measure: percentage of participants
58.79
4.Secondary Outcome
Title Percentage of Participants With a CR or PR Among Participants in the ITT Population
Hide Description CR and PR were defined using RECIST v1.0. CR was defined as complete disappearance of all target lesions and non-target disease, with the exception of nodal disease. All nodes, both target and non-target, must have decreased to normal (short axis <10 mm). No new lesions. PR was defined as a ≥30% decrease under baseline of the sum of diameters of all target lesions. The short axis was used in the sum for target nodes, while the longest diameter was used in the sum for all other target lesions. No unequivocal progression of non-target disease. No new lesions.
Time Frame Baseline, every 9 weeks (every 3 cycles) until end of treatment, disease progression, or withdrawal up to 5 years
Hide Outcome Measure Data
Hide Analysis Population Description
ITT population.
Arm/Group Title Bevucizamab+Oxaliplatin+Capecitabine/Bevacizumab
Hide Arm/Group Description:

Cycles 1-8 (3-week cycles): Participants received bevacizumab 7.5 mg/kg IV and oxaliplatin 130 mg/m^2 IV on Day 1 and capecitabine 1000 mg/m^2 tablets, orally, every 12 hours starting the evening of Day 1 for 14 days continuously; cycle was repeated until disease progression or for a maximum of 8 cycles.

Cycle 9 and beyond (3-week cycles): If the first 8 cycles were tolerated with no disease progression participants received bevacizumab 7.5 mg/kg IV on Day 1; the cycle was repeated until disease progression.

Overall Number of Participants Analyzed 197
Measure Type: Number
Unit of Measure: percentage of participants
49.24
5.Secondary Outcome
Title Time to CR or PR Overall Response - Time to Event
Hide Description Time to overall response (CR or PR) was calculated as the time between the date of start of treatment until first documented response (CR or PR defined per RECIST v1.0). Participants who did not achieve CR or PR were censored at the date of progression, death, or at last adequate tumor assessment date. Median time to CR or PR overall response was estimated using the Kaplan-Meier method.
Time Frame Baseline, every 9 weeks (every 3 cycles) until end of treatment, disease progression, or withdrawal up to 5 years
Hide Outcome Measure Data
Hide Analysis Population Description
ITT population.
Arm/Group Title Bevucizamab+Oxaliplatin+Capecitabine/Bevacizumab
Hide Arm/Group Description:

Cycles 1-8 (3-week cycles): Participants received bevacizumab 7.5 mg/kg IV and oxaliplatin 130 mg/m^2 IV on Day 1 and capecitabine 1000 mg/m^2 tablets, orally, every 12 hours starting the evening of Day 1 for 14 days continuously; cycle was repeated until disease progression or for a maximum of 8 cycles.

Cycle 9 and beyond (3-week cycles): If the first 8 cycles were tolerated with no disease progression participants received bevacizumab 7.5 mg/kg IV on Day 1; the cycle was repeated until disease progression.

Overall Number of Participants Analyzed 197
Median (95% Confidence Interval)
Unit of Measure: months
3.93
(2.56 to 4.66)
6.Secondary Outcome
Title Percentage of Participants With a Best Overall Response of CR or PR During First Line Treatment
Hide Description CR and PR were defined using RECIST v1.0 criteria. CR was defined as complete disappearance of all target lesions and non-target disease, with the exception of nodal disease. All nodes, both target and non-target, must have decreased to normal (short axis <10 mm). No new lesions. PR was defined as a ≥30% decrease under baseline of the sum of diameters of all target lesions. Short axis was used in sum for target nodes, while longest diameter was used in sum for all other target lesions. No unequivocal progression of non-target disease. No new lesions.
Time Frame Baseline, every 3 weeks (every cycle) to disease progression or death up to 5 years
Hide Outcome Measure Data
Hide Analysis Population Description
ITT population, only those participants who achieved a best overall response of CR or PR during first line treatment were included in the analysis.
Arm/Group Title Bevucizamab+Oxaliplatin+Capecitabine/Bevacizumab
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Cycles 1-8 (3-week cycles): Participants received bevacizumab 7.5 mg/kg IV and oxaliplatin 130 mg/m^2 IV on Day 1 and capecitabine 1000 mg/m^2 tablets, orally, every 12 hours starting the evening of Day 1 for 14 days continuously; cycle was repeated until disease progression or for a maximum of 8 cycles.

Cycle 9 and beyond (3-week cycles):If the first 8 cycles were tolerated with no disease progression participants received bevacizumab 7.5 mg/kg IV on Day 1; the cycle was repeated until disease progression.

Overall Number of Participants Analyzed 97
Measure Type: Number
Unit of Measure: percentage of participants
54.64
7.Secondary Outcome
Title Duration of Overall Response Among Participants Whose Best Response Was CR or PR During First Line Treatment - Time to Event
Hide Description For participants with a best overall response of CR or PR, the duration of overall response was measured from the time that the criteria for CR or PR (whichever occurred first) was met until the first date that progressive disease was objectively documented or until the date of death due to underlying cancer, whichever occurred first. Data for participants who did not have an event or who were alive without an objectively documented progressive disease were censored at the date of last adequate tumor assessment. Median duration of overall response was estimated using the Kaplan-Meier method.
Time Frame Baseline, every 3 weeks (every cycle) to disease progression or death up to 5 years
Hide Outcome Measure Data
Hide Analysis Population Description
ITT population, only those participants who achieved a best overall response of CR or PR during first line treatment were included in the analysis.
Arm/Group Title Bevucizamab+Oxaliplatin+Capecitabine/Bevacizumab
Hide Arm/Group Description:

Cycles 1-8 (3-week cycles): Participants received bevacizumab 7.5 mg/kg IV and oxaliplatin 130 mg/m^2 IV on Day 1 and capecitabine 1000 mg/m^2 tablets, orally, every 12 hours starting the evening of Day 1 for 14 days continuously; cycle was repeated until disease progression or for a maximum of 8 cycles.

Cycle 9 and beyond (3-week cycles):If the first 8 cycles were tolerated with no disease progression participants received bevacizumab 7.5 mg/kg IV on Day 1; the cycle was repeated until disease progression.

Overall Number of Participants Analyzed 97
Median (95% Confidence Interval)
Unit of Measure: months
8.52
(7.28 to 10.33)
8.Secondary Outcome
Title Percentage of Participants With a Stable Response During First Line Treatment
Hide Description Stable response defined as participants with a best overall response of CR, PR, or stable disease (SD), defined using RECIST v1.0 criteria. CR was defined as complete disappearance of all target lesions and non-target disease, with the exception of nodal disease. All nodes, both target and non-target, must have decreased to normal (short axis <10 mm). No new lesions. PR was defined as a ≥30% decrease under baseline of the sum of diameters of all target lesions. The short axis was used in the sum for target nodes, while the longest diameter was used in the sum for all other target lesions. No unequivocal progression of non-target disease. No new lesions. SD defined as neither sufficient shrinkage to qualify for partial response nor sufficient increase to qualify for progressive disease, taking as reference the smallest sum longest diameter since the treatment started.
Time Frame Baseline, every 3 weeks (every cycle) to disease progression or death up to 5 years
Hide Outcome Measure Data
Hide Analysis Population Description
ITT population, only participants who achieved a best overall response of CR, PR, or SD during first line treatment were included in the analysis.
Arm/Group Title Bevucizamab+Oxaliplatin+Capecitabine/Bevacizumab
Hide Arm/Group Description:

Cycles 1-8 (3-week cycles): Participants received bevacizumab 7.5 mg/kg IV and oxaliplatin 130 mg/m^2 IV on Day 1 and capecitabine 1000 mg/m^2 tablets, orally, every 12 hours starting the evening of Day 1 for 14 days continuously; cycle was repeated until disease progression or for a maximum of 8 cycles.

Cycle 9 and beyond (3-week cycles): If the first 8 cycles were tolerated with no disease progression participants received bevacizumab 7.5 mg/kg IV on Day 1; the cycle was repeated until disease progression.

Overall Number of Participants Analyzed 152
Measure Type: Number
Unit of Measure: percentage of participants
52.63
9.Secondary Outcome
Title Duration of Stable Response
Hide Description For participants with a best overall response of CR, PR, or SD during first line treatment, the duration of stable response was measured from the time that the criteria for CR, PR, or SD (whichever occurred first) was met until the first date that progressive disease was objectively documented or until the date of death due to underlying cancer, whichever occurred first. Data for participants who did not have an event or who were alive without an objectively documented progressive disease were censored at the date of last adequate tumor assessment. Median duration of stable response was estimated using the Kaplan-Meier method.
Time Frame Baseline, every 3 weeks (every cycle) to disease progression or death up to 5 years
Hide Outcome Measure Data
Hide Analysis Population Description
ITT population, only participants who achieved a best overall response of CR, PR, or SD during first line treatment were included in the analysis.
Arm/Group Title Bevucizamab+Oxaliplatin+Capecitabine/Bevacizumab
Hide Arm/Group Description:

Cycles 1-8 (3-week cycles): Participants received bevacizumab 7.5 mg/kg IV and oxaliplatin 130 mg/m^2 IV on Day 1 and capecitabine 1000 mg/m^2 tablets, orally, every 12 hours starting the evening of Day 1 for 14 days continuously; cycle was repeated until disease progression or for a maximum of 8 cycles.

Cycle 9 and beyond (3-week cycles): If the first 8 cycles were tolerated with no disease progression participants received bevacizumab 7.5 mg/kg IV on Day 1; the cycle was repeated until disease progression.

Overall Number of Participants Analyzed 152
Median (95% Confidence Interval)
Unit of Measure: months
10.39
(9.02 to 11.44)
10.Secondary Outcome
Title Percentage of Participants With Treatment Failure
Hide Description Treatment-failure was defined as discontinuation of treatment for any reason, including the following qualifying events: death due to any cause, adverse event, insufficient therapeutic response (progression of disease), failure to return (lost to follow-up), refusing treatment (participant non-compliance), being unwilling to cooperate and withdrawing consent (participant withdrew consent).
Time Frame Baseline, every 3 weeks (every cycle) to disease progression or death up to 5 years
Hide Outcome Measure Data
Hide Analysis Population Description
ITT population.
Arm/Group Title Bevucizamab+Oxaliplatin+Capecitabine/Bevacizumab
Hide Arm/Group Description:

Cycles 1-8 (3-week cycles): Participants received bevacizumab 7.5 mg/kg IV and oxaliplatin 130 mg/m^2 IV on Day 1 and capecitabine 1000 mg/m^2 tablets, orally, every 12 hours starting the evening of Day 1 for 14 days continuously; cycle was repeated until disease progression or for a maximum of 8 cycles.

Cycle 9 and beyond (3-week cycles): If the first 8 cycles were tolerated with no disease progression participants received bevacizumab 7.5 mg/kg IV on Day 1; the cycle was repeated until disease progression.

Overall Number of Participants Analyzed 197
Measure Type: Number
Unit of Measure: percentage of participants
82.74
11.Secondary Outcome
Title Time to Treatment Failure
Hide Description Time to treatment-failure was defined as the time from the first day of treatment to discontinuation of treatment for any reason, including: death due to any cause, adverse event, insufficient therapeutic response (progression of disease), failure to return (lost to follow-up), refusing treatment (participant non-compliance), being unwilling to cooperate and withdrawing consent (participant withdrew consent). For participants who did not experience a qualifying event, their data were censored at the earlier of either the date of last tumour assessment or the date of the last intake of study medication. Median time to treatment-failure was estimated using the Kaplan-Meier method.
Time Frame Baseline, every 3 weeks (every cycle) to disease progression or death up to 5 years
Hide Outcome Measure Data
Hide Analysis Population Description
ITT population.
Arm/Group Title Bevucizamab+Oxaliplatin+Capecitabine/Bevacizumab
Hide Arm/Group Description:

Cycles 1-8 (3-week cycles): Participants received bevacizumab 7.5 mg/kg IV and oxaliplatin 130 mg/m^2 IV on Day 1 and capecitabine 1000 mg/m^2 tablets, orally, every 12 hours starting the evening of Day 1 for 14 days continuously; cycle was repeated until disease progression or for a maximum of 8 cycles.

Cycle 9 and beyond (3-week cycles): If the first 8 cycles were tolerated with no disease progression participants received bevacizumab 7.5 mg/kg IV on Day 1; the cycle was repeated until disease progression.

Overall Number of Participants Analyzed 197
Median (95% Confidence Interval)
Unit of Measure: months
6.69
(5.97 to 7.74)
12.Secondary Outcome
Title Overall Survival: Percentage of Participants That Died Due to Any Cause
Hide Description Overall survival was defined as the time from the date of the first day of treatment until the date of death from any cause. If a participant was not known to have died, survival was censored at the last date the participant was known to be alive.
Time Frame Baseline, Day 1 of every cycle to end-of-treatment, every 3 months during longer-term follow-up, or to death due to any cause up to 5 years
Hide Outcome Measure Data
Hide Analysis Population Description
ITT population.
Arm/Group Title Bevucizamab+Oxaliplatin+Capecitabine/Bevacizumab
Hide Arm/Group Description:

Cycles 1-8 (3-week cycles): Participants received bevacizumab 7.5 mg/kg IV and oxaliplatin 130 mg/m^2 IV on Day 1 and capecitabine 1000 mg/m^2 tablets, orally, every 12 hours starting the evening of Day 1 for 14 days continuously; cycle was repeated until disease progression or for a maximum of 8 cycles.

Cycle 9 and beyond (3-week cycles): If the first 8 cycles were tolerated with no disease progression participants received bevacizumab 7.5 mg/kg IV on Day 1; the cycle was repeated until disease progression.

Overall Number of Participants Analyzed 197
Measure Type: Number
Unit of Measure: percentage of participants
50.76
13.Secondary Outcome
Title Overall Survival: Time to Event
Hide Description Overall survival was defined as the time from the date of the first day of treatment until the date of death from any cause. If a participant was not known to have died, survival was censored at the last date the participant was known to be alive. Median overall survival was estimated using the Kaplan-Meier method.
Time Frame Baseline, Day 1 of every cycle to end-of-treatment, every 3 months during longer-term follow-up, or to death due to any cause up to 5 years
Hide Outcome Measure Data
Hide Analysis Population Description
ITT population.
Arm/Group Title Bevucizamab+Oxaliplatin+Capecitabine/Bevacizumab
Hide Arm/Group Description:

Cycles 1-8 (3-week cycles): Participants received bevacizumab 7.5 mg/kg IV and oxaliplatin 130 mg/m^2 IV on Day 1 and capecitabine 1000 mg/m^2 tablets, orally, every 12 hours starting the evening of Day 1 for 14 days continuously; cycle was repeated until disease progression or for a maximum of 8 cycles.

Cycle 9 and beyond (3-week cycles): If the first 8 cycles were tolerated with no disease progression participants received bevacizumab 7.5 mg/kg IV on Day 1; the cycle was repeated until disease progression.

Overall Number of Participants Analyzed 197
Median (95% Confidence Interval)
Unit of Measure: months
23.15
(20.07 to 27.15)
14.Secondary Outcome
Title Percentage of Participants Undergoing Surgical Intervention With Residual Disease Status Post-surgery
Hide Description The percentage of participants who underwent surgery during the study period with an evaluation of their disease status after surgery. The surgery during the study period was described by reason: curative, palliative, biopsy, other, or unknown. Residual disease status after surgery was described as: no residual disease due to radical surgery, presence of residual disease, unknown or not applicable.
Time Frame At surgery, at least 6 to 8 weeks after last dose of bevacizumab up to 5 years
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Hide Analysis Population Description
The 52 participant subpopulation of the ITT population who underwent surgery during the time period of the study.
Arm/Group Title Bevucizamab+Oxaliplatin+Capecitabine/Bevacizumab
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Cycles 1-8 (3-week cycles): Participants received bevacizumab 7.5 mg/kg IV and oxaliplatin 130 mg/m^2 IV on Day 1 and capecitabine 1000 mg/m^2 tablets, orally, every 12 hours starting the evening of Day 1 for 14 days continuously; cycle was repeated until disease progression or for a maximum of 8 cycles.

Cycle 9 and beyond (3-week cycles): If the first 8 cycles were tolerated with no disease progression participants received bevacizumab 7.5 mg/kg IV on Day 1; the cycle was repeated until disease progression.

Overall Number of Participants Analyzed 52
Measure Type: Number
Unit of Measure: percentage of participants
Curative, no residual disease 55.77
Curative, residual disease 13.46
Curative, unknown 3.85
Curative, not applicable 7.69
Palliative, no residual disease 3.85
Palliative, residual disease 7.69
Palliative, unknown 3.85
Palliative, not applicable 1.92
Biopsy, residual disease 1.92
Biopsy, not applicable 1.92
Unknown, unknown 1.92
Unknown, not applicable 3.85
Other, residual disease 1.92
Other, not applicable 3.85
15.Secondary Outcome
Title Percentage of Participants With Best Overall Response of CR or PR by Kirsten Rat Sarcoma Viral Oncogene Homolog (K-Ras)/V-Raf Murine Sarcoma Viral Oncogene Homolog B (B-Raf) Mutation Status
Hide Description

The percentage of participants with a best overall response of CR or PR according to RECIST. CR was defined as complete disappearance of all target lesions and non-target disease, with the exception of nodal disease. All nodes, both target and non-target, must have decreased to normal (short axis <10 mm). No new lesions. PR was defined as ≥30% decrease under baseline of the sum of diameters of all target lesions. The short axis was used in the sum for target nodes, while the longest diameter was used in the sum for all other target lesions. No unequivocal progression of non-target disease. No new lesions.

The K-Ras and/or the B-Raf gene mutation status of participants was evaluated by the central laboratory using tumor samples. Wild-type participants did not have a mutation in either gene.

Time Frame Baseline, every 9 weeks (every 3 cycles) until end of treatment, disease progression, or withdrawal up to 5 years
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Hide Analysis Population Description
ITT population; only participants with a known K-Ras and/or B-Raf gene mutation status and at least 1 post-baseline tumor assessment. Number (n) equals (=) number of participants with either wild-type or K-Ras/B-Raf gene mutation.
Arm/Group Title Bevucizamab+Oxaliplatin+Capecitabine/Bevacizumab
Hide Arm/Group Description:

Cycles 1-8 (3-week cycles): Participants received bevacizumab 7.5 mg/kg IV and oxaliplatin 130 mg/m^2 IV on Day 1 and capecitabine 1000 mg/m^2 tablets, orally, every 12 hours starting the evening of Day 1 for 14 days continuously; cycle was repeated until disease progression or for a maximum of 8 cycles.

Cycle 9 and beyond (3-week cycles): If the first 8 cycles were tolerated with no disease progression participants received bevacizumab 7.5 mg/kg IV on Day 1; the cycle was repeated until disease progression.

Overall Number of Participants Analyzed 33
Measure Type: Number
Unit of Measure: percentage of participants
Wild-type (n=18) 88.89
Gene mutation (n=15) 66.67
16.Secondary Outcome
Title European Quality of Life 5 Dimension (EQ-5D) Raw-Index Score
Hide Description Quality of life (QoL) assessments were used to derive pre-specified QoL scores according to the QoL manual “EQ-5D-3 Level (3L)" user guide for instrument version 4.0. The EQ-5D is a participant rated questionnaire to assess health-related quality of life in terms of a single index value. The visual analog scale (VAS) component rates current health state on a scale from 0 (worst imaginable health state) to 100 (best imaginable health state); higher scores indicate a better health state. The overall health score absolute changes were calculated for each participant as follows: (score at the end of treatment minus score at baseline). EQ-5D health states were converted into EQ-5D-3L raw index value by applying the scoring algorithm based on the European EQ-net VAS set. The raw index was chosen instead of rescaled index, since the questionnaire was used in order to obtain a quality of life assessment. The raw index scores ranged from 0 (worst health state) to 100 (best health state).
Time Frame Baseline, every 9 weeks (every 3 cycles), at end-of-treatment up to 5 years
Hide Outcome Measure Data
Hide Analysis Population Description
ITT population, only participants who had EQ-5D-3L scores for both baseline and last visit were included in the analysis.
Arm/Group Title Bevucizamab+Oxaliplatin+Capecitabine/Bevacizumab
Hide Arm/Group Description:

Cycles 1-8 (3-week cycles): Participants received bevacizumab 7.5 mg/kg IV and oxaliplatin 130 mg/m^2 IV on Day 1 and capecitabine 1000 mg/m^2 tablets, orally, every 12 hours starting the evening of Day 1 for 14 days continuously; cycle was repeated until disease progression or for a maximum of 8 cycles.

Cycle 9 and beyond (3-week cycles): If the first 8 cycles were tolerated with no disease progression participants received bevacizumab 7.5 mg/kg IV on Day 1; the cycle was repeated until disease progression.

Overall Number of Participants Analyzed 114
Mean (Standard Deviation)
Unit of Measure: units on a scale
Baseline 80.24  (14.32)
Last visit 74.94  (19.08)
Absolute change from baseline -5.30  (19.13)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Bevucizamab+Oxaliplatin+Capecitabine/Bevacizumab
Comments Change from baseline to last visit
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0076
Comments [Not Specified]
Method Signed-rank test
Comments [Not Specified]
Time Frame Adverse events (AE) were collected from the date of first administration of study treatment until 28 days after the last dose of study treatment up to 5 years
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Bevacizumab+Oxaliplatin+Capecitabine/Bevacizumab
Hide Arm/Group Description

Cycles 1-8 (3-week cycles): Participants received bevacizumab 7.5 mg/kg IV) and oxaliplatin 130 mg mg/m^2 IV on Day 1 and capecitabine 1000 mg/m^2 tablets, orally, every 12 hours starting the evening of Day 1 for 14 days continuously; cycle was repeated until disease progression or for a maximum of 8 cycles.

Cycle 9 and beyond (3-week cycles): If the first 8 cycles were tolerated with no disease progression, participants received bevacizumab 7.5 mg/kg IV on Day 1; the cycle was repeated until disease progression.

All-Cause Mortality
Bevacizumab+Oxaliplatin+Capecitabine/Bevacizumab
Affected / at Risk (%)
Total   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
Bevacizumab+Oxaliplatin+Capecitabine/Bevacizumab
Affected / at Risk (%)
Total   56/197 (28.43%) 
Blood and lymphatic system disorders   
Anaemia * 1  1/197 (0.51%) 
Cardiac disorders   
Cardiac arrest * 1  1/197 (0.51%) 
Cardio-respiratory arrest * 1  1/197 (0.51%) 
Cardiovascular disorder * 1  1/197 (0.51%) 
Coronary artery disease * 1  1/197 (0.51%) 
Myocardial infarction * 1  1/197 (0.51%) 
Gastrointestinal disorders   
Diarrhoea * 1  4/197 (2.03%) 
Intestinal obstruction * 1  2/197 (1.02%) 
Intestinal perforation * 1  2/197 (1.02%) 
Subileus * 1  4/197 (2.03%) 
Abdominal pain * 1  1/197 (0.51%) 
Abdominal strangulated hernia * 1  1/197 (0.51%) 
Anal fistula * 1  1/197 (0.51%) 
Constipation * 1  1/197 (0.51%) 
Gastrointestinal disorder * 1  1/197 (0.51%) 
Gastrointestinal inflammation * 1  1/197 (0.51%) 
Gastrointestinal obstruction * 1  1/197 (0.51%) 
Ileus paralytic * 1  1/197 (0.51%) 
Nausea * 1  1/197 (0.51%) 
Peritonitis * 1  1/197 (0.51%) 
Vomiting * 1  1/197 (0.51%) 
General disorders   
Asthenia * 1  2/197 (1.02%) 
Chest pain * 1  1/197 (0.51%) 
Death * 1  1/197 (0.51%) 
Fatigue * 1  1/197 (0.51%) 
Ill-defined disorder * 1  1/197 (0.51%) 
Pyrexia * 1  1/197 (0.51%) 
Hepatobiliary disorders   
Hepatic failure * 1  1/197 (0.51%) 
Immune system disorders   
Hypersensitivity * 1  3/197 (1.52%) 
Anaphylactic shock * 1  1/197 (0.51%) 
Drug hypersensitivity * 1  1/197 (0.51%) 
Infections and infestations   
Pneumonia * 1  3/197 (1.52%) 
Abscess * 1  1/197 (0.51%) 
Bronchitis * 1  1/197 (0.51%) 
Psoas abscess * 1  1/197 (0.51%) 
Renal abscess * 1  1/197 (0.51%) 
Sepsis * 1  1/197 (0.51%) 
Tuberculosis * 1  1/197 (0.51%) 
Injury, poisoning and procedural complications   
Rib fracture * 1  1/197 (0.51%) 
Metabolism and nutrition disorders   
Cachexia * 1  2/197 (1.02%) 
Hyperglycaemia * 1  1/197 (0.51%) 
Musculoskeletal and connective tissue disorders   
Pain in extremity * 1  1/197 (0.51%) 
Nervous system disorders   
Hemiparesis * 1  1/197 (0.51%) 
Neuropathy peripheral * 1  1/197 (0.51%) 
Neurotoxicity * 1  1/197 (0.51%) 
Syncope * 1  1/197 (0.51%) 
Transient ischaemic attack * 1  1/197 (0.51%) 
Renal and urinary disorders   
Hydronephrosis * 1  1/197 (0.51%) 
Renal failure * 1  1/197 (0.51%) 
Renal failure acute * 1  1/197 (0.51%) 
Renal vein thrombosis * 1  1/197 (0.51%) 
Reproductive system and breast disorders   
Genital haemorrhage * 1  1/197 (0.51%) 
Respiratory, thoracic and mediastinal disorders   
Pulmonary embolism * 1  7/197 (3.55%) 
Dyspnoea * 1  1/197 (0.51%) 
Laryngeal obstruction * 1  1/197 (0.51%) 
Surgical and medical procedures   
Vertebroplasty * 1  1/197 (0.51%) 
Vascular disorders   
Deep vein thrombosis * 1  2/197 (1.02%) 
Hypertensive crisis * 1  3/197 (1.52%) 
Hypertension * 1  1/197 (0.51%) 
*
Indicates events were collected by non-systematic assessment
1
Term from vocabulary, MedDRA (11.1)
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 0%
Bevacizumab+Oxaliplatin+Capecitabine/Bevacizumab
Affected / at Risk (%)
Total   179/197 (90.86%) 
Blood and lymphatic system disorders   
Anaemia * 1  11/197 (5.58%) 
Leukopenia * 1  13/197 (6.60%) 
Neutropenia * 1  32/197 (16.24%) 
Thrombocytopenia * 1  26/197 (13.20%) 
Cardiac disorders   
Atrial fibrillation * 1  1/197 (0.51%) 
Cardiac ventricular disorder * 1  1/197 (0.51%) 
Palpitations * 1  2/197 (1.02%) 
Tachycardia * 1  2/197 (1.02%) 
Congenital, familial and genetic disorders   
Dihydropyrimidine dehydrogenase deficiency * 1  1/197 (0.51%) 
Ear and labyrinth disorders   
Deafness * 1  1/197 (0.51%) 
Ear pain * 1  1/197 (0.51%) 
Hypoacusis * 1  1/197 (0.51%) 
Tinnitus * 1  1/197 (0.51%) 
Vertigo * 1  8/197 (4.06%) 
Eye disorders   
Conjunctivitis * 1  3/197 (1.52%) 
Diplopia * 1  1/197 (0.51%) 
Eye irritation * 1  1/197 (0.51%) 
Eye pain * 1  1/197 (0.51%) 
Lacrimation increased * 1  1/197 (0.51%) 
Scleral haemorrhage * 1  1/197 (0.51%) 
Gastrointestinal disorders   
Abdominal pain * 1  29/197 (14.72%) 
Abdominal pain upper * 1  12/197 (6.09%) 
Constipation * 1  27/197 (13.71%) 
Diarrhoea * 1  73/197 (37.06%) 
Nausea * 1  84/197 (42.64%) 
Stomatitis * 1  10/197 (5.08%) 
Vomiting * 1  48/197 (24.37%) 
Abdominal distension * 1  2/197 (1.02%) 
Abdominal hernia * 1  1/197 (0.51%) 
Anal haemorrhage * 1  1/197 (0.51%) 
Anal inflammation * 1  1/197 (0.51%) 
Anorectal discomfort * 1  2/197 (1.02%) 
Dental discomfort * 1  1/197 (0.51%) 
Dry mouth * 1  1/197 (0.51%) 
Dyspepsia * 1  4/197 (2.03%) 
Dysphagia * 1  1/197 (0.51%) 
Enteritis * 1  1/197 (0.51%) 
Enterocolitis haemorrhage * 1  1/197 (0.51%) 
Flatulence * 1  2/197 (1.02%) 
Gastritis * 1  1/197 (0.51%) 
Gastrointestinal pain * 1  1/197 (0.51%) 
Gastrointestinal toxicity * 1  1/197 (0.51%) 
Gingival bleeding * 1  3/197 (1.52%) 
Gingivitis * 1  1/197 (0.51%) 
Haematochezia * 1  1/197 (0.51%) 
Haemorrhoidal haemorrhage * 1  1/197 (0.51%) 
Haemorrhoids * 1  4/197 (2.03%) 
Inguinal hernia * 1  1/197 (0.51%) 
Mouth haemorrhage * 1  1/197 (0.51%) 
Proctalgia * 1  3/197 (1.52%) 
Rectal haemorrhage * 1  7/197 (3.55%) 
Rectal tenesmus * 1  1/197 (0.51%) 
Subileus * 1  1/197 (0.51%) 
Tooth disorder * 1  1/197 (0.51%) 
General disorders   
Asthenia * 1  60/197 (30.46%) 
Fatigue * 1  29/197 (14.72%) 
Mucosal inflammation * 1  21/197 (10.66%) 
Pyrexia * 1  40/197 (20.30%) 
Chest pain * 1  5/197 (2.54%) 
Discomfort * 1  1/197 (0.51%) 
Facial pain * 1  1/197 (0.51%) 
Hyperpyrexia * 1  2/197 (1.02%) 
Infusion site extravasation * 1  1/197 (0.51%) 
Infusion site pain * 1  2/197 (1.02%) 
Injection site haematoma * 1  1/197 (0.51%) 
Oedema * 1  1/197 (0.51%) 
Oedema peripheral * 1  7/197 (3.55%) 
Pain * 1  2/197 (1.02%) 
Performance status decreased * 1  1/197 (0.51%) 
Hepatobiliary disorders   
Hepatomegaly * 1  2/197 (1.02%) 
Hepatotoxicity * 1  1/197 (0.51%) 
Hyperbilirubinaemia * 1  6/197 (3.05%) 
Hypertransaminasaemia * 1  2/197 (1.02%) 
Immune system disorders   
Drug hypersensitivity * 1  4/197 (2.03%) 
Hypersensitivity * 1  4/197 (2.03%) 
Infections and infestations   
Bronchitis * 1  2/197 (1.02%) 
Cystitis * 1  2/197 (1.02%) 
Ear infection * 1  1/197 (0.51%) 
Folliculitis * 1  1/197 (0.51%) 
Fungal infection * 1  2/197 (1.02%) 
Herpes virus infection * 1  1/197 (0.51%) 
Infection * 1  1/197 (0.51%) 
Influenza * 1  4/197 (2.03%) 
Labyrinthitis * 1  1/197 (0.51%) 
Pharyngitis * 1  1/197 (0.51%) 
Pneumonia * 1  1/197 (0.51%) 
Psoas abscess * 1  1/197 (0.51%) 
Rhinitis * 1  5/197 (2.54%) 
Tooth abscess * 1  2/197 (1.02%) 
Urinary tract infection * 1  5/197 (2.54%) 
Injury, poisoning and procedural complications   
Fall * 1  1/197 (0.51%) 
Foot fracture * 1  1/197 (0.51%) 
Gastrointestinal stoma complications * 1  1/197 (0.51%) 
Wrist fracture * 1  1/197 (0.51%) 
Investigations   
Alanine aminotransferase increased * 1  5/197 (2.54%) 
Aspartate aminotransferase increased * 1  7/197 (3.55%) 
Blood alkaline phosphatase increased * 1  3/197 (1.52%) 
Blood bilirubin increased * 1  2/197 (1.02%) 
Blood creatinine increased * 1  1/197 (0.51%) 
Blood iron decreased * 1  1/197 (0.51%) 
Blood lactate dehydrogenase increased * 1  4/197 (2.03%) 
Blood uric acid increased * 1  1/197 (0.51%) 
Haemoglobin decreased * 1  4/197 (2.03%) 
Weight decreased * 1  8/197 (4.06%) 
Weight increased * 1  1/197 (0.51%) 
Metabolism and nutrition disorders   
Anorexia * 1  18/197 (9.14%) 
Cachexia * 1  1/197 (0.51%) 
Decreased appetite * 1  1/197 (0.51%) 
Dehydration * 1  1/197 (0.51%) 
Gout * 1  1/197 (0.51%) 
Hypercalcaemia * 1  1/197 (0.51%) 
Hypercholesterolaemia * 1  1/197 (0.51%) 
Hyperglycaemia * 1  3/197 (1.52%) 
Hyperkalaemia * 1  1/197 (0.51%) 
Hypertriglyceridaemia * 1  1/197 (0.51%) 
Hypocalcaemia * 1  2/197 (1.02%) 
Hypokalaemia * 1  8/197 (4.06%) 
Hypophosphataemia * 1  1/197 (0.51%) 
Musculoskeletal and connective tissue disorders   
Musculoskeletal pain * 1  10/197 (5.08%) 
Pain in extremity * 1  16/197 (8.12%) 
Arthralgia * 1  6/197 (3.05%) 
Back pain * 1  6/197 (3.05%) 
Bone pain * 1  7/197 (3.55%) 
Groin pain * 1  2/197 (1.02%) 
Musculoskeletal discomfort * 1  2/197 (1.02%) 
Musculoskeletal stiffness * 1  1/197 (0.51%) 
Myalgia * 1  4/197 (2.03%) 
Neck pain * 1  3/197 (1.52%) 
Torticollis * 1  1/197 (0.51%) 
Nervous system disorders   
Headache * 1  10/197 (5.08%) 
Neuropathy peripheral * 1  38/197 (19.29%) 
Neurotoxicity * 1  11/197 (5.58%) 
Paraesthesia * 1  59/197 (29.95%) 
Dizziness * 1  2/197 (1.02%) 
Dysaesthesia * 1  2/197 (1.02%) 
Dysgeusia * 1  9/197 (4.57%) 
Migraine * 1  2/197 (1.02%) 
Neuralgia * 1  1/197 (0.51%) 
Peripheral sensory neuropathy * 1  5/197 (2.54%) 
Presyncope * 1  1/197 (0.51%) 
Sciatica * 1  1/197 (0.51%) 
Syncope * 1  4/197 (2.03%) 
Syncope vasovagal * 1  1/197 (0.51%) 
Tremor * 1  1/197 (0.51%) 
Psychiatric disorders   
Anxiety * 1  6/197 (3.05%) 
Depression * 1  3/197 (1.52%) 
Insomnia * 1  6/197 (3.05%) 
Mood altered * 1  2/197 (1.02%) 
Renal and urinary disorders   
Proteinuria * 1  17/197 (8.63%) 
Dysuria * 1  4/197 (2.03%) 
Haematuria * 1  4/197 (2.03%) 
Nocturia * 1  1/197 (0.51%) 
Pollakiuria * 1  1/197 (0.51%) 
Strangury * 1  2/197 (1.02%) 
Reproductive system and breast disorders   
Balanitis * 1  1/197 (0.51%) 
Genital haemorrhage * 1  1/197 (0.51%) 
Orchitis noninfective * 1  1/197 (0.51%) 
Testicular disorder * 1  1/197 (0.51%) 
Respiratory, thoracic and mediastinal disorders   
Dyspnoea * 1  12/197 (6.09%) 
Epistaxis * 1  14/197 (7.11%) 
Bronchospasm * 1  2/197 (1.02%) 
Bronchostenosis * 1  1/197 (0.51%) 
Cough * 1  7/197 (3.55%) 
Dysaesthesia pharynx * 1  4/197 (2.03%) 
Dysphonia * 1  3/197 (1.52%) 
Hiccups * 1  1/197 (0.51%) 
Laryngeal disorder * 1  3/197 (1.52%) 
Laryngospasm * 1  1/197 (0.51%) 
Larynx irritation * 1  2/197 (1.02%) 
Oropharyngeal pain * 1  1/197 (0.51%) 
Oropharyngeal spasm * 1  1/197 (0.51%) 
Pharyngeal inflammation * 1  1/197 (0.51%) 
Pleural effusion * 1  1/197 (0.51%) 
Pulmonary embolism * 1  1/197 (0.51%) 
Skin and subcutaneous tissue disorders   
Palmar-plantar erythrodysaesthesia syndrome * 1  18/197 (9.14%) 
Alopecia * 1  1/197 (0.51%) 
Dermatitis * 1  1/197 (0.51%) 
Dermatitis exfoliative * 1  2/197 (1.02%) 
Dry skin * 1  1/197 (0.51%) 
Erythema * 1  3/197 (1.52%) 
Hyperhidrosis * 1  1/197 (0.51%) 
Nail disorder * 1  1/197 (0.51%) 
Petechiae * 1  1/197 (0.51%) 
Pruritus * 1  4/197 (2.03%) 
Rash * 1  5/197 (2.54%) 
Skin disorder * 1  1/197 (0.51%) 
Skin exfoliation * 1  2/197 (1.02%) 
Skin lesion * 1  2/197 (1.02%) 
Urticaria * 1  3/197 (1.52%) 
Surgical and medical procedures   
Cyst drainage * 1  1/197 (0.51%) 
Vascular disorders   
Hypertension * 1  45/197 (22.84%) 
Aortic thrombosis * 1  1/197 (0.51%) 
Axillary vein thrombosis * 1  1/197 (0.51%) 
Blood pressure fluctuation * 1  1/197 (0.51%) 
Deep vein thrombosis * 1  5/197 (2.54%) 
Hot flush * 1  1/197 (0.51%) 
Hypertensive crisis * 1  1/197 (0.51%) 
Hypotension * 1  5/197 (2.54%) 
Lymphoedema * 1  1/197 (0.51%) 
Orthostatic hypotension * 1  1/197 (0.51%) 
Phlebitis * 1  4/197 (2.03%) 
Thrombophlebitis * 1  1/197 (0.51%) 
Thrombophlebitis superficial * 1  1/197 (0.51%) 
Thrombosis * 1  2/197 (1.02%) 
Vena cava thrombosis * 1  1/197 (0.51%) 
*
Indicates events were collected by non-systematic assessment
1
Term from vocabulary, MedDRA (11.1)
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
The Study being conducted under this agreement is part of the Overall Study. Investigator is free to publish in reputable journals or to present at professional conferences the results of the Study, but only after the first publication or presentation that involves the Overall Study. The Sponsor may request the Confidential Information be deleted and/or the publication be postponed in order to protect the Sponsor's intellectual property rights.
Results Point of Contact
Name/Title: Medical Communications
Organization: Hoffmann-LaRoche
Phone: 800-821-8590
Responsible Party: Hoffmann-La Roche
ClinicalTrials.gov Identifier: NCT00577031     History of Changes
Other Study ID Numbers: ML21380
First Submitted: December 18, 2007
First Posted: December 19, 2007
Results First Submitted: July 15, 2014
Results First Posted: August 18, 2015
Last Update Posted: August 18, 2015