A Study of Avastin (Bevacizumab) and Xeloda (Capecitabine) as Maintenance Treatment in Patients With Metastatic Colorectal Cancer

Study Overview
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Brief Summary
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This 2 arm study assessed the efficacy and safety of maintenance treatment with Avastin (bevacizumab) + Xeloda (capecitabine), after initial treatment with Xeloda + oxaliplatin + Avastin, in patients with metastatic colorectal cancer. Patients were randomized into one of 2 groups to receive 1) Xeloda + oxaliplatin + Avastin until disease progression or 2) Xeloda + oxaliplatin + Avastin for 6 3-week cycles, followed by Xeloda + Avastin until disease progression. Xeloda was administered at a dose of 1000 mg/m^2 orally twice a day on days 1-14 of each cycle, oxaliplatin at a dose of 130 mg/m^2 intravenously (iv) on day 1 of each cycle, and Avastin at a dose of 7.5 mg/kg iv on day 1 of each cycle.

Official Title
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A Randomized, Multicenter Phase III Trial to Assess the Efficacy and Safety of Bevacizumab and Capecitabine as Maintenance Treatment, After Initial Combination Treatment With Capecitabine, Oxaliplatin and Bevacizumab in Patients With Metastatic Colorectal Adenocarcinoma

Conditions
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Colorectal Cancer

Intervention / Treatment
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* Drug: Bevacizumab
* Drug: Capecitabine
* Drug: Oxaliplatin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Adult patients, ≥ 18 years of age. Histologically confirmed colon or rectal cancer, with unresectable metastatic disease. At least 1 measurable lesion. Outpatient, with Eastern Cooperative Oncology Group (ECOG) Performance Status = 0-1. Exclusion Criteria: Previous treatment with Avastin. Previous systemic treatment for advanced or metastatic disease. clinically significant cardiovascular disease. Daily chronic treatment with high doses of aspirin (> 325 mg/day) or non-steroidal anti-inflammatory drugs.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Bevacizumab+capecitabine+oxaliplatin<br>Participants received bevacizumab 7.5 mg/kg intravenously (IV) on Day 1 of each 3-week cycle + oxaliplatin 130 mg/m^2 IV on Day 1 of each 3-week cycle + capecitabine 1000 mg/m^2 orally twice a day on Days 1-14 of each 3-week cycle until disease progression. | Drug: Bevacizumab<br>* Bevacizumab was supplied as a solution in single-use vials.<br>* Other names: Avastin;Drug: Capecitabine<br>* Capecitabine was supplied as film-coated tablets.<br>* Other names: Xeloda;Drug: Oxaliplatin<br>* Oxaliplatin was supplied as a lyophilized powder in vials.<br>* Other names: Eloxatin;|
| Experimental: Bevacizumab(B)+capecitabine(C)+oxaliplatin followed by B+C<br>Participants received bevacizumab 7.5 mg/kg intravenously (IV) on Day 1 of each 3-week cycle + oxaliplatin 130 mg/m^2 IV on Day 1 of each 3-week cycle + capecitabine 1000 mg/m^2 orally twice a day on Days 1-14 of each 3-week cycle for 6 cycles followed by bevacizumab 7.5 mg/kg intravenously (IV) on Day 1 of each 3-week cycle + capecitabine 1000 mg/m^2 orally twice a day on Days 1-14 of each 3-week cycle until disease progression. | Drug: Bevacizumab<br>* Bevacizumab was supplied as a solution in single-use vials.<br>* Other names: Avastin;Drug: Capecitabine<br>* Capecitabine was supplied as film-coated tablets.<br>* Other names: Xeloda;Drug: Oxaliplatin<br>* Oxaliplatin was supplied as a lyophilized powder in vials.<br>* Other names: Eloxatin;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression-free Survival | Progression-free survival was defined as the time from the first administration of study drug to the first documented disease progression or death, whichever occurs first. Progressive disease was defined as at least a 20% increase in the sum of the longest diameter of target lesions, taking as reference the smallest sum longest diameter recorded since treatment started or the unequivocal progression of existing non-target lesions. All measurable lesions up to a maximum of 5 lesions per organ and 10 lesions in total, representative of all involved organs, should be identified as target lesions at Baseline. Target lesions should be selected on the basis of their size (lesions with the longest diameter) and their suitability for accurate repeated measurements (either by imaging techniques or clinically). A sum of the longest diameter for all target lesions will be calculated and reported as the Baseline sum longest diameter. | Baseline to the end of the study (up to 4 years, 2 months) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Survival | Overall survival was defined as the time from the first administration of study drug to death. | Baseline to the end of the study (up to 4 years, 2 months) | 
| Percentage of Participants With a Complete Response or a Partial Response | A complete response was defined as the disappearance of all target lesions. A partial response was defined as at least a 30% decrease in the sum of the longest diameter of target lesions taking as reference the Baseline sum longest diameter. All measurable lesions up to a maximum of 5 lesions per organ and 10 lesions in total, representative of all involved organs, should be identified as target lesions at Baseline. All other lesions (or sites of disease) should be identified as non-target lesions. Target lesions should be selected on the basis of their size (lesions with the longest diameter) and their suitability for accurate repeated measurements (either by imaging techniques or clinically). A sum of the longest diameter for all target lesions will be calculated and reported as the Baseline sum longest diameter. | Baseline to the end of the study (up to 4 years, 2 months) | 
| Time Until a Complete Response or a Partial Response | Time until a complete response or a partial response was defined as the time from the first administration of study drug until the first complete response or partial response. | Baseline to Month 13 | 
| Duration of Response | Duration of response was defined as the time from the first complete response or partial response until disease progression or death. Progressive disease was defined as at least a 20% increase in the sum of the longest diameter of target lesions, taking as reference the smallest sum longest diameter recorded since treatment started or the unequivocal progression of existing non-target lesions. All measurable lesions up to a maximum of 5 lesions per organ and 10 lesions in total, representative of all involved organs, should be identified as target lesions at Baseline. Target lesions should be selected on the basis of their size (lesions with the longest diameter) and their suitability for accurate repeated measurements (either by imaging techniques or clinically). A sum of the longest diameter for all target lesions will be calculated and reported as the Baseline sum longest diameter. | Baseline to the end of the study (up to 4 years, 2 months) | 
| Percentage of Participants With Metastatic Lesions Previously Considered Inoperable Who Became Operable and Underwent Surgery |  | Baseline to the end of the study (up to 4 years, 2 months) | 
| Percentage of Participants With a R0 Resection | An R0 resection indicates a microscopically margin-negative resection, in which no gross or microscopic tumor remains in the primary tumor bed. | Baseline to the end of the study (up to 4 years, 2 months) |