A Study of Avastin (Bevacizumab) in Combination Chemotherapy in Patients With Metastatic Cancer of the Colon or Rectum

Phase 2

Completed

• Conditions: Colorectal Cancer
• Interventions: Drug: Bevacizumab [Avastin]; Drug: Capecitabine; Drug: Irinotecan

• Registration Number: NCT01131078
• Lead Sponsor: Hoffmann-La Roche

Brief Summary

A study of Avastin (bevacizumab) in combination chemotherapy in patients with metastatic cancer of the colon or rectum. The anticipated time on study treatment is until disease progression.

Detailed Description

Not available

Basic Information
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Recruitment & Eligibility
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Study & Design

Study Timeline

• Study Start: 2005-06
• Study First Submitted: 2010-04-20
• Study First Submitted QC: 2010-05-25
• Study First Posted: 2010-05-26
• Primary Completion: 2012-11
• Study Completion: 2012-11
• Results First Submitted: 2014-12-19
• Results First Submitted QC: 2014-12-19
• Results First Posted: 2014-12-31
• Status Verified: 2015-06
• Last Update Submitted: 2015-06-02
• Last Update Posted: 2015-06-04

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 306

Inclusion Criteria

• adult patients >=18 years of age;
• colon or rectal cancer, with metastases;
• >=1 measurable lesion.

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Exclusion Criteria

• previous systemic treatment for advanced disease;
• radiotherapy to any site within 4 weeks before study;
• daily aspirin (>325 mg/day), anticoagulants, or other medications known to predispose to gastrointestinal ulceration;
• co-existing malignancies or malignancies diagnosed within last 5 years (except basal cell cancer or cervical cancer in situ).

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Bevacizumab + Capecitabine (1250 mg/m^2)	Bevacizumab [Avastin]	Bevacizumab was administered as a 7.5 mg/kg intravenous infusion over 30 to 90 minutes on Day 1 of each 3 week cycle in combination with capecitabine administered orally at 1250 mg/m\^2 twice daily (Day 1 to 14). Cycle length was 3 weeks with 2 weeks of capecitabine treatment followed by 1 week without treatment up to 6 cycles. After 6 cycles, participants with objective response or SD were treated with bevacizumab alone until unacceptable toxicity, PD, or participant withdrawal.
Bevacizumab + Irinotecan + Capecitabine (1000 mg/m^2)	Bevacizumab [Avastin]	Bevacizumab was administered as a 7.5 mg/kg intravenous infusion over 30 to 90 minutes on Day 1 of each 3 week cycle. Irinotecan was administered as a 240 mg/m\^2 intravenous infusion over 60 minutes (Day 1) every 3 weeks. Capecitabine was administered orally at a dose of 1000 mg/m\^2 twice daily (Day 2 to 15). Cycle length was 3 weeks consisting of 2 weeks of capecitabine treatment followed by 1 week without treatment up to 6 cycles. After 6 cycles, participants with objective response or SD were treated with bevacizumab alone until unacceptable toxicity, PD, or participant withdrawal.
Bevacizumab + Capecitabine (650 mg/m^2)	Bevacizumab [Avastin]	Bevacizumab was administered as a 7.5 mg/kg intravenous infusion over 30 to 90 minutes on Day 1 of each 3 Week cycle in combination with capecitabine administered orally at 650 mg/m\^2 twice daily (Day 1 to 21). Cycle length was 3 weeks with 3 weeks of capecitabine treatment without interruptions. Participants received the same regimen until unacceptable toxicity, PD, or participant withdrawal.
Bevacizumab + Irinotecan + Capecitabine (1000 mg/m^2)	Capecitabine	Bevacizumab was administered as a 7.5 mg/kg intravenous infusion over 30 to 90 minutes on Day 1 of each 3 week cycle. Irinotecan was administered as a 240 mg/m\^2 intravenous infusion over 60 minutes (Day 1) every 3 weeks. Capecitabine was administered orally at a dose of 1000 mg/m\^2 twice daily (Day 2 to 15). Cycle length was 3 weeks consisting of 2 weeks of capecitabine treatment followed by 1 week without treatment up to 6 cycles. After 6 cycles, participants with objective response or SD were treated with bevacizumab alone until unacceptable toxicity, PD, or participant withdrawal.
Bevacizumab + Irinotecan + Capecitabine (1000 mg/m^2)	Irinotecan	Bevacizumab was administered as a 7.5 mg/kg intravenous infusion over 30 to 90 minutes on Day 1 of each 3 week cycle. Irinotecan was administered as a 240 mg/m\^2 intravenous infusion over 60 minutes (Day 1) every 3 weeks. Capecitabine was administered orally at a dose of 1000 mg/m\^2 twice daily (Day 2 to 15). Cycle length was 3 weeks consisting of 2 weeks of capecitabine treatment followed by 1 week without treatment up to 6 cycles. After 6 cycles, participants with objective response or SD were treated with bevacizumab alone until unacceptable toxicity, PD, or participant withdrawal.
Bevacizumab + Capecitabine (650 mg/m^2)	Capecitabine	Bevacizumab was administered as a 7.5 mg/kg intravenous infusion over 30 to 90 minutes on Day 1 of each 3 Week cycle in combination with capecitabine administered orally at 650 mg/m\^2 twice daily (Day 1 to 21). Cycle length was 3 weeks with 3 weeks of capecitabine treatment without interruptions. Participants received the same regimen until unacceptable toxicity, PD, or participant withdrawal.
Bevacizumab + Capecitabine (1250 mg/m^2)	Capecitabine	Bevacizumab was administered as a 7.5 mg/kg intravenous infusion over 30 to 90 minutes on Day 1 of each 3 week cycle in combination with capecitabine administered orally at 1250 mg/m\^2 twice daily (Day 1 to 14). Cycle length was 3 weeks with 2 weeks of capecitabine treatment followed by 1 week without treatment up to 6 cycles. After 6 cycles, participants with objective response or SD were treated with bevacizumab alone until unacceptable toxicity, PD, or participant withdrawal.

Primary Outcome Measures

Name	Time	Method
Percentage of Participants With Disease Progression or Death	Randomization, Weeks 3, 6 and 9, and every 3 months up to 5 years or Death	Disease progression was defined according to National Cancer Institute (NCI) guidelines and best clinical practices.
Time to Progression (TTP)	Randomization, Weeks 3, 6 and 9, and every 3 months up to 5 years or Death	TTP is defined as the time from date of randomization until objective tumor progression or death due to any cause. It includes deaths and thus can be correlated to overall survival.

Secondary Outcome Measures

Name	Time	Method
Overall Survival	Randomization, Weeks 3, 6 and 9, and every 3 months up to 5 years or Death	Overall survival is defined as the time from date of randomization until death from any cause; Kaplan-Meier estimates were used for analysis.
Percentage of Participants With a Best Overall Response of CR or PR	Randomization, Weeks 3, 6 and 9, and every 3 months up to 5 years or Death	CR: Complete disappearance of all target lesions; PR: At least 30% decrease in the sum of the longest diameter of all target lesions taking as reference the baseline sum of all target lesions;
Time to Treatment Failure	Randomization, Weeks 3, 6 and 9, and every 3 months up to 5 years or Death	Time to treatment failure is defined as a composite endpoint measuring time from date of randomization to discontinuation of treatment for any reason, including disease progression, death, treatment toxicity, insufficient therapeutic response, failure to return, refusing treatment, being unwilling to cooperate and withdrawing consent. Analysis was performed using Kaplan-Meier estimates.
Percentage of Participants With Progression Excluding Deaths	Randomization, Weeks 3, 6 and 9, and every 3 months up to 5 years or Death	The failure event was defined as tumor progression excluding deaths due to any reason.
Percentage of Participants With Stable Disease	Randomization, Weeks 3, 6 and 9, and every 3 months up to 5 years or Death	Stable disease rate was the proportion of participants who achieved CR, PR, or SD.
Duration of Stable Disease (SD)	Randomization, Weeks 3, 6 and 9, and every 3 months up to 5 years or Death	Duration of SD was calculated as the number of months the participants remained in CR, PR or SD. Kaplan-Meier estimates were used for analysis.
Percentage of Participants Who Died	Randomization, Weeks 3, 6 and 9, and every 3 months up to 5 years or Death	Overall survival is defined as the time from date of randomization until death from any cause
Percentage of Participants With Treatment Failure	Randomization, Weeks 3, 6 and 9, and every 3 months up to 5 years or Death	Treatment failure is defined as discontinuation of treatment for any reason, including disease progression, death, treatment toxicity, insufficient therapeutic response, failure to return, refusing treatment, being unwilling to cooperate and withdrawing consent.
Time to Progression Excluding Deaths	Randomization, Weeks 3, 6 and 9, and every 3 months up to 5 years or Death	The failure event was defined as tumor progression excluding deaths due to any reason. Kaplan-Meier estimates were used for analysis.
Time to Progression Excluding Deaths Not Related to Underlying Cancer	Randomization, Weeks 3, 6 and 9, and every 3 months up to 5 years or Death	The failure event was defined as tumor progression excluding only deaths not related to underlying cancer. Kaplan-Meier estimates were used for analysis.
Percentage of Participants by Best Overall Response	Randomization, Weeks 3, 6 and 9, and every 3 months up to 5 years or Death	Best overall response is defined as the best response recorded from the date of randomization until disease progression or recurrence. Complete response (CR): at least 2 determinations of CR at least 4 weeks apart before progression; Partial response (PR): at least 2 determinations of PR at least 4 weeks apart before progression; Stable disease (SD): at least one SD assessment; Progressive Disease (PD): Disease progression or death due to underlying cancer. CR: Complete disappearance of all target lesions; PR: At least 30% decrease in the sum of the longest diameter of all target lesions taking as reference the baseline sum of all target lesions; PD: At least 20% decrease in the sum of the longest diameter of all target lesions taking as reference the baseline sum of longest diameter of all target lesions or the appearance of one or more new lesions; SD: Neither sufficient shrinkage to qualify for CR or PR or increase in lesions;
Percentage of Participants With Progressive Disease Within 12 Weeks From Start of Treatment	Randomization, Weeks 3, 6 and 9, and 12	Early progression was the proportion of participants with progressive disease within 12 weeks from the start of treatment.
Percentage of Participants With Progression Excluding Deaths Not Related to Underlying Cancer	Randomization, Weeks 3, 6 and 9, and every 3 months up to 5 years or Death	The failure event was defined as tumor progression excluding only deaths not related to underlying cancer.
Duration of Overall Response	Randomization, Weeks 3, 6 and 9, and every 3 months up to 5 years or Death	Duration of overall response included participants who achieved a CR or PR.
Duration of Overall Complete Response	Randomization, Weeks 3, 6 and 9, and every 3 months up to 5 years	Duration of complete response was calculated as the time in months from the date of randomization to the date of first documentation of CR. Kaplan-Meier estimates were used for analysis.