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

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

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

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.

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.

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.

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.

Maximum serum concentration at steady state (Css,max). Estimation of the parameter was performed using non-compartmental methods.

Minimum serum concentration at steady state (Css, min). Estimation of the parameter was performed using non-compartmental methods.

Time of maximum serum concentration (tmax). Estimation of the parameter was performed using non-compartmental methods.

Volume of distribution at steady state (Vss). Estimation of the parameter was performed using non-compartmental methods.

Terminal half-life (t1/2) (apparent elimination half-life). Estimation of the parameter was performed using non-compartmental methods.

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.