A Study of Avastin (Bevacizumab) and Oxaliplatin Plus Xeloda (Capecitabine) in Patients With Advanced Colorectal Cancer.

Study Overview
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Brief Summary
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This study will assess the efficacy and safety of treatment with the combination Avastin (bevacizumab) 5mg/kg iv every 2 weeks, Xeloda (capecitabine) 1000 mg po b.i.d. on Days 1-14 of every 28-day cycle and oxaliplatin 40mg/m2 iv weekly in patients with inoperable locally advanced or metastatic colorectal cancer. The anticipated time on study treatment is until disease progression.

Official Title
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Phase II Study of the Combination of Bevacizumab (rhuMab VEGF) and Oxaliplatin Plus Capecitabine (XELOX) in Patients With Advanced Colorectal Cancer

Conditions
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Colorectal Cancer

Intervention / Treatment
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* Drug: bevacizumab [Avastin]
* Drug: capecitabine [Xeloda]
* Drug: oxaliplatin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Adult patients >=18 years of age Locally advanced or metastatic colorectal cancer No previous treatment with chemotherapy for metastatic disease Measurable and/or evaluable lesions Exclusion Criteria: Radiotherapy within 4 weeks before study Untreated brain metastases or primary brain tumors Chronic, daily treatment with high-dose aspirin (>325mg/day) Co-existing malignancies, or malignancies diagnosed within the last 5 years, with the exception of basal and squamous cell cancer, or cervical cancer in situ

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 intravenously every 14 days<br>Drug: capecitabine [Xeloda]<br>* 1000 mg/m2 orally b.i.d. , Days 1 - 14 of every 28-day cycle<br>Drug: oxaliplatin<br>* 40 mg/m2 iv weekly<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With Objective Response (OR) | Percentage of participants with OR was defined as the percentage of participants who achieved complete response (CR) or partial response (PR) according to Response Evaluation Criteria in Solid Tumors (RECIST). CR was 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) diameters of all target lesions. No unequivocal progression of non-target disease. No new lesions. Complete and partial responses must have been confirmed no less than 4 weeks after the criteria for response were first met. | Baseline, every 3 months to progression of disease or end of study (up to 24 months) | 
| Percentage of Participants by Best Overall Response | Best response recorded from the start of treatment until disease progression. Based on assessment of CR, PR, stable disease (SD), or progressive disease (PD), according to RECIST. CR: disappearance of all target lesions, non-target lesions, and normalization of tumor marker level. PR: ≥30% decrease under baseline of the sum of the LD diameters of all target lesions. CR and PR persist on repeat imaging study at least 4 weeks after initial documentation. SD: neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD. Reference is the smallest sum LD. PD: at least a 20% increase in the sum of the LD of target lesions, taking as reference the smallest sum longest diameter recorded or the appearance of one or more new lesions. | Baseline, every 3 months to progression of disease or end of study (up to 24 months) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Duration of Response - Percentage of Participants With an Event by 24 Months | Duration of overall response (CR or PR) was calculated only for participants of the ITT population whose best overall response was CR or PR based on RECIST criteria. Duration of overall response was defined as the time from the date of the first assessment of CR or PR status until the date of progression or death. Data for participants who were alive without any objectively documented disease progression at the end of the study were censored as of the date of last contact. | Baseline, every 3 months to progression of disease or end of study (up to 24 months) | 
| Duration of Response | Duration of overall response (CR or PR) was calculated for participants of the ITT population whose best overall response was CR or PR based on RECIST criteria. Duration of overall response was defined as the time from the date of the first assessment of CR or PR status until the date of progression or death. Data for participants who were alive without any objectively documented disease progression at the end of the study were censored as of the date of last contact. Mean time to event was estimated using the Kaplan-Meier method. | Baseline, every 3 months to progression of disease or end of study (up to 24 months) | 
| Duration of Stable Disease - Percentage of Participants With an Event by 24 Months | Duration of stable response (CR, PR, or stable disease [SD]) was calculated only for participants of the ITT population whose best overall response was CR, PR, or SD based on RECIST criteria. Duration of overall response was defined as the time from the date of the first assessment of CR, PR, or SD status until the date of progression or death. Data for participants who were alive without any objectively documented disease progression at the end of the study were censored as of the date of last contact. | Baseline, every 3 months to progression of disease or end of study (up to 24 months) | 
| Duration of Stable Disease | Duration of stable response (CR, PR, or SD) was calculated only for participants of the ITT population whose best overall response was CR, PR, or SD based on RECIST criteria. Duration of overall response was defined as the time from the date of the first assessment of CR, PR, or SD status until the date of progression or death. Data for participants who were alive without any objectively documented disease progression at the end of the study were censored as of the date of last contact. Mean time to event was estimated using the Kaplan-Meier method. | Baseline, every 3 months to progression of disease or end of study (up to 24 months) | 
| Time to Treatment Failure (TTF) - Percentage of Participants With an Event by 24 Months | TTF was defined as the time in months from Day 1 until discontinuation of treatment for any reasons. These reasons included: death due to any cause, treatment toxicity (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). | Baseline, every month to end of treatment (up to 24 months) | 
| Time to Treatment Failure | TTF was defined as the time in months from Day 1 until discontinuation of treatment for any reasons. These reasons included: death due to any cause, treatment toxicity (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). Mean TTF was estimated using the Kaplan-Meier method. | Baseline, monthly to end of study (up to 24 months) | 
| Time to Progression (TTP) - Percentage of Participants With an Event by 24 Months | TTP was defined as the time time in months from Day 1 until the date of first documented progressive disease, or death due to any cause. Data for participants who were alive without disease progression at the end of study, or who were non-responder participants (without tumor assessment after baseline) were censored at Day 1. | Baseline, monthly to end of study (up to 24 months) | 
| Time to Progression | TTP was defined as the time in months from Day 1 until the date of first documented progressive disease, or death due to any cause. Data for participants who were alive without disease progression at the end of study, or who were non-responder participants (without tumor assessment after baseline) were censored at Day 1. Mean TTP was estimated using the Kaplan-Meier method. | Baseline, monthly to end of study (up to 24 months) | 
| Overall Survival (OS) - Percentage of Participants With an Event by 24 Months | OS was defined as the time in months from Day 1 until the date of death due to any cause. Data for participants who were alive at the end of the study were censored at the date of the last available follow-up visit. | Baseline, monthly to end of study (up to 24 months) | 
| Overall Survival | OS was defined as the time in months from Day 1 until the date of death due to any cause. Data for participants who were alive at the end of the study were censored at the date of the last available follow-up visit. Mean OS was estimated using the Kaplan-Meier method. | Baseline, monthly to end of study (up to 24 months) |