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

Phase 3
Completed
Conditions
Colorectal Cancer
Interventions
Registration Number
NCT00623805
Lead Sponsor
Hoffmann-La Roche
Brief Summary

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.

Detailed Description

Not available

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
123
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.

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Bevacizumab+capecitabine+oxaliplatinBevacizumabParticipants 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.
Bevacizumab+capecitabine+oxaliplatinCapecitabineParticipants 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.
Bevacizumab(B)+capecitabine(C)+oxaliplatin followed by B+CBevacizumabParticipants 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.
Bevacizumab+capecitabine+oxaliplatinOxaliplatinParticipants 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.
Bevacizumab(B)+capecitabine(C)+oxaliplatin followed by B+CCapecitabineParticipants 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.
Bevacizumab(B)+capecitabine(C)+oxaliplatin followed by B+COxaliplatinParticipants 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.
Primary Outcome Measures
NameTimeMethod
Progression-free SurvivalBaseline to the end of the study (up to 4 years, 2 months)

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.

Secondary Outcome Measures
NameTimeMethod
Overall SurvivalBaseline to the end of the study (up to 4 years, 2 months)

Overall survival was defined as the time from the first administration of study drug to death.

Percentage of Participants With a Complete Response or a Partial ResponseBaseline to the end of the study (up to 4 years, 2 months)

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.

Time Until a Complete Response or a Partial ResponseBaseline to Month 13

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.

Duration of ResponseBaseline to the end of the study (up to 4 years, 2 months)

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.

Percentage of Participants With Metastatic Lesions Previously Considered Inoperable Who Became Operable and Underwent SurgeryBaseline to the end of the study (up to 4 years, 2 months)
Percentage of Participants With a R0 ResectionBaseline to the end of the study (up to 4 years, 2 months)

An R0 resection indicates a microscopically margin-negative resection, in which no gross or microscopic tumor remains in the primary tumor bed.

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