A Study of Avastin (Bevacizumab) in Combination With XELOX in Patients With Metastatic Colorectal Cancer

Study Overview
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Brief Summary
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This single arm study will assess the resection rate of liver metastasis, time to disease progression, and safety of neoadjuvant treatment with Avastin in combination with oxaliplatin and capecitabine (XELOX) in patients with metastatic colorectal cancer with unresectable liver metastasis. Patients will receive Avastin 5mg/kg iv on day 1 of every 2 week cycle, oxaliplatin 85mg/m2 iv on day 1 of every 2 week cycle, and capecitabine 1000mg/m2 on days 1-5 and 8-12 of every 2 week cycle. The anticipated time on study treatment is 3-12 months, and the target sample size is <100 individuals.

Official Title
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An Open Label Study to Assess the Resection Rate of Liver Metastases Following Neoadjuvant Therapy With Avastin in Combination With Oxaliplatin and Capecitabine (XELOX) in Patients With Metastatic Colorectal Cancer With Unresectable Liver Metastasis

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, <=75 years of age; chemotherapy-naive for stage IV colorectal cancer with unresectable liver metastasis; >=1 measurable lesion; ECOG status 0-2. Exclusion Criteria: prior exposure to Avastin; clinical or radiological evidence of CNS metastases; uncontrolled hypertension, or clinically significant cardiovascular disease; ongoing treatment with aspirin (>325mg/day) or other medications known to predispose to gastrointestinal ulceration.

Ages Eligible for Study
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Maximum Age: 75 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>* 5mg/kg iv on day 1 of each 2 week cycle.<br>Drug: capecitabine [Xeloda]<br>* 1000mg/m2 iv on days 1-5 and 8-12 of each 2 week cycle<br>Drug: oxaliplatin<br>* 85mg/m2 iv on day 1 of each 2 week cycle<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With Conversion From Unresectable to Resectable Liver Metastases | Participants were assessed via microscopic and macroscopic examination for tumor resectability after completion of 5 cycles of neoadjuvant treatment. Unresectable participants exhibited any of the following criteria: greater than or equal to (≥) 4 liver metastases; location and/or distribution of metastatic disease within the liver considered unsuitable for resection with clear margins; liver involvement precluding resection, in the setting of adequate parenchymal volume for otherwise viable liver function in the immediate postoperative period; and inability to maintain adequate circulation for viable liver function. Participants who had not met any of the above criteria at the end of 5 cycles underwent surgical resection. The percentage of participants with conversion from initially unresectable to resectable liver metastases was calculated as [number of participants eligible for surgical resection divided by the number analyzed] multiplied by 100. | After 5 cycles of neoadjuvant treatment (10 weeks) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With Disease Progression | Objective tumor response was assessed using RECIST version 1.1. Disease progression was defined as a ≥20 percent (%) increase in the sum of longest diameters of target lesions, taking as reference the smallest sum obtained at previous tumor assessment, or the appearance of any new lesions. The percentage of participants with disease progression was calculated as [number of participants meeting the above criteria divided by the number analyzed] multiplied by 100. | Up to approximately 3 years (at Baseline, end of Cycle 5, time of surgery, and within 4 weeks of end of treatment [EOT]) | 
| Time to Disease Progression | Objective tumor response was assessed using RECIST version 1.1. Disease progression was defined as a ≥20% increase in the sum of longest diameters of target lesions, taking as reference the smallest sum obtained at previous tumor assessment, or the appearance of any new lesions. Time to disease progression was defined as the time from first dose to time of disease progression. Participants without progression were censored at the time of last tumor assessment. Time to disease progression was estimated using Kaplan-Meier analysis and expressed in months. | Up to approximately 3 years (at Baseline, end of Cycle 5, time of surgery, and within 4 weeks of EOT) | 
| Percentage of Participants With a Best Overall Tumor Response of Complete Response (CR) or PR According to RECIST Version 1.1 | Objective tumor response was assessed using RECIST version 1.1. CR was defined as the disappearance of all target lesions, and PR was defined as a ≥30% decrease in the sum of longest diameters compared to Baseline. Response was confirmed at a minimum of 4 weeks after the first documented response. The percentage of participants with confirmed CR or PR was calculated as [number of participants meeting the respective criteria divided by the number analyzed] multiplied by 100. | Up to approximately 3 years (at Baseline, end of Cycle 5, time of surgery, within 4 weeks of EOT, and at least 4 weeks after initial response) | 
| Percentage of Participants by Best Overall Tumor Response According to RECIST Version 1.1 | Objective tumor response was assessed using RECIST version 1.1. CR was defined as the disappearance of all target lesions, and PR was defined as a ≥30% decrease in the sum of longest diameters compared to Baseline. Response was to be confirmed at a minimum of 4 weeks after the first documented response. Stable disease (SD) was defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, as well as no new target lesions. Disease progression or PD was defined as a ≥20% increase in the sum of longest diameters of target lesions, taking as reference the smallest sum obtained at previous tumor assessment, or the appearance of any new lesions. Non-evaluability for tumor assessment was also documented when applicable. The percentage of participants with each level of response was calculated as [number of participants meeting the respective criteria divided by the number analyzed] multiplied by 100. | Up to approximately 3 years (at Baseline, end of Cycle 5, time of surgery, within 4 weeks of EOT, and at least 4 weeks after initial response) |