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

Study Overview
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Brief Summary
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This study will assess the efficacy and safety of intravenous Avastin in combination with chemotherapy regimens as second-line treatment of metastatic cancer of the colon or rectum. The anticipated time of study treatment is until disease progression.

Official Title
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An Open-label Study of Avastin in Combination With Chemotherapy Regimens as Second-line Treatment in Patients With Metastatic Colon or Rectal Cancer

Conditions
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Colorectal Cancer

Intervention / Treatment
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* Drug: bevacizumab [Avastin]


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients with metastatic colon or rectal cancer, progressing or relapsing after first-line treatment; Women of childbearing potential must use adequate contraception up to at least 6 months after the last dose of bevacizumab. Exclusion Criteria: Patients with metastatic colon or rectal cancer scheduled for a first-line systemic treatment; Untreated brain metastases, spinal cord compression or primary brain tumours; Pregnant or lactating women; Major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to study start; Treatment with any investigational drug, or participation in another investigational study, within 30 days prior to enrollment.

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: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1<br> | Drug: bevacizumab [Avastin]<br>* 5 mg/kg every 2 weeks or 7.5 mg/kg every 3 weeks according to the chemotherapy regimen<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants Achieving Overall Disease Control (ODC) | ODC was defined as the percentage of participants with measurable disease at baseline who on assessment achieved complete response (CR), partial response (PR), or stable disease (SD) according to Response Evaluation Criteria in Solid Tumors (RECIST). CR defined as disappearance of all target lesions, non-target lesions, and normalization of tumor marker level. PR was defined as greater than or equal to (≥) 30 percent (%) decrease under baseline of the sum of the longest diameter (LD) of all target lesions. SD defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease, taking as reference the smallest sum LD since start of treatment. CR and PR were confirmed no less than 4 weeks after the criteria for response were met. | Baseline, after every other cycle to disease progression or death (Maximum of 52.5 months follow-up) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants Achieving a Best Overall Response of CR or PR | Percentage of participants achieving CR or PR as defined by RECIST criteria. CR defined as disappearance of all target lesions, non-target lesions, and normalization of tumor marker level. PR was defined as ≥30% decrease under baseline of the sum of the LD of all target lesions. CR and PR were confirmed no less than 4 weeks after the criteria for response were met. | Baseline, every cycle to progression or death (Maximum of 52.5 months follow-up) | 
| Progression-Free Survival (PFS) - Percentage of Participants With an Event | PFS was defined as the time from start of study treatment to investigator assessed disease progression, or death due to any cause, whichever comes first. Progression was based on tumor assessments made by the investigators according to RECIST. | Baseline, every cycle to progression or death (Maximum of 52.5 months follow-up) | 
| PFS - Time to Event | PFS was defined as the time from start of study treatment to investigator assessed disease progression, or death due to any cause, whichever comes first. Progression was based on tumor assessments made by the investigators according to RECIST. Median PFS was estimed using the Kaplan-Meier method. | Baseline, every cycle to progression or death (Maximum of 52.5 months follow-up) | 
| Duration of Response | Duration of response was defined as the time in months from the day of CR or PR was first noted to the day of progression of disease, death or last follow-up. Median duraiton of response is estimated sing the Kaplan-Meier method. | Baseline, every cycle until progression or death (Maximum of 52.5 months follow-up) | 
| Duration of Overall Disease Control | ODC duration was defined as the time in months, from when measurement criteria were first met for CR, PR, or SD (whichever status was recorded first) until the first date when progressive disease or the death from any cause was documented. Data were censored for participants who were lost to follow-up, discontinued prematurely without progression/death, or who reached the end of study without progression. Median ODC was estimated using the Kaplan-Meier method. | Baseline, every cycle until progression or death. (Maximum of 52.5 months follow-up) | 
| Overall Survival (OS) - Percentage of Participants With an Event | Overall survival was defined as the time from start of study treatment to death from any cause. | Baseline, every cycle to progression or death (Maximum of 52.5 months follow-up) | 
| OS - Time to Event | OS was defined as the time from start of study treatment to death from any cause. Median OS was estimated using the Kaplan-Meier method. | Baseline, every cycle to progression or death. (Maximum of 52.5 months follow-up) |