A Study of Avastin (Bevacizumab) in Combination With XELOX or FOLFOX-4 in Patients With Metastatic Colorectal Cancer.

Study Overview
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Brief Summary
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This 2 arm study will compare the pharmacokinetics and safety of Avastin at steady state under 2 different dosing regimens, in combination with XELOX (oxaliplatin + Xeloda) or FOLFOX-4 (oxaliplatin, leucovorin and 5-fluorouracil). Patients randomized to the XELOX arm will receive Avastin (7.5mg/kg iv) on Day 1 of each 3 week cycle; patients randomized to the FOLFOX-4 arm will receive Avastin (5mg/kg iv) on Day 1 of each 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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A Randomized, Open Label Trial to Assess the Steady State Pharmacokinetics of Avastin Given With Either XELOX or FOLFOX-4 in Patients With Metastatic Colorectal Cancer

Conditions
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Colorectal Cancer

Intervention / Treatment
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* Drug: bevacizumab [Avastin]
* Drug: XELOX
* Drug: bevacizumab [Avastin]
* Drug: FOLFOX-4


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: adult patients, >=18 years of age; adenocarcinoma of the colon or rectum, with metastatic or locally advanced disease; >=1 target lesion. Exclusion Criteria: patients who have previously received systemic treatment for advanced or metastatic disease; patients who have received adjuvant treatment for non-metastatic disease in past 3 months; previous therapy with oxaliplatin or Avastin.

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: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1<br> | Drug: bevacizumab [Avastin]<br>* 7.5mg/kg iv on day 1 of each 3 week cycle<br>Drug: XELOX<br>* As prescribed<br>|
| Experimental: 2<br> | Drug: bevacizumab [Avastin]<br>* 5mg/kg iv on day 1 of each 2 week cycle<br>Drug: FOLFOX-4<br>* As prescribed<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Weekly Steady-state Exposure of Bevacizumab | Area under the serum concentration-time curve per week, at steady state (AUCss per week). Estimation of the parameter was performed using non-compartmental methods. | Up to 48 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time Zero to Last Measurable Plasma Concentration of Bevacizumab | Area under the serum concentration-time curve from time zero to the time of the last measurable plasma concentration (AUC 0-last). Estimation of the parameter was performed using non-compartmental methods. | Up to 48 weeks | 
| Steady-state Exposure of Bevacizumab From Time Zero to Tau | Area under the serum concentration-time curve from time zero to tau, at steady state (AUCss 0-tau), where tau was the length of the cycle, i.e., tau = 3 weeks for XELOX+BV and tau = 2 weeks for FOLFOX-4+BEV. Estimation of the parameter was performed using non-compartmental methods. | Up to 48 weeks | 
| Maximum Serum Concentration of Bevacizumab at Steady State | Maximum serum concentration at steady state (Css,max). Estimation of the parameter was performed using non-compartmental methods. | Up to 48 weeks | 
| Minimum Serum Concentration of Bevacizumab at Steady State | Minimum serum concentration at steady state (Css, min). Estimation of the parameter was performed using non-compartmental methods. | Up to 48 weeks | 
| Serum Clearance of Bevacizumab | Serum clearance (CL). Estimation of the parameter was performed using non-compartmental methods. | Up to 48 weeks | 
| Time of Maximum Serum Concentration of Bevacizumab | Time of maximum serum concentration (tmax). Estimation of the parameter was performed using non-compartmental methods. | Up to 48 weeks | 
| Volume of Distribution of Bevacizumab at Steady State | Volume of distribution at steady state (Vss). Estimation of the parameter was performed using non-compartmental methods. | Up to 48 weeks | 
| Terminal Half-life of Bevacizumab | Terminal half-life (t1/2) (apparent elimination half-life). Estimation of the parameter was performed using non-compartmental methods. | Up to 48 weeks |