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.

Study Overview

• Status: Completed
• Conditions: Colorectal Cancer
• Intervention / Treatment: Drug: bevacizumab [Avastin]; Drug: bevacizumab [Avastin]; Drug: XELOX; Drug: FOLFOX-4

• Study Type: Interventional
• Enrollment (Actual): 64
• Phase: Phase 3

Contacts and Locations

Study Locations

• Australia
  • Box Hill, Australia, 3128
  • Fitzroy, Australia, 3065
  • Sydney, Australia, 2031
• Canada
  • Ontario
    • Brampton, Ontario, Canada, L6R 3J7
    • Hamilton, Ontario, Canada, L8V 5C2
    • Toronto, Ontario, Canada, M5G 2M9
• New Zealand
  • Christchurch, New Zealand

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Hoffmann-La Roche

Study record dates

Study Major Dates

• Study Start: August 1, 2006
• Primary Completion (Actual): November 1, 2008
• Study Completion (Actual): November 1, 2008

Study Registration Dates

• First Submitted: July 6, 2006
• First Submitted That Met QC Criteria: July 6, 2006
• First Posted (Estimate): July 7, 2006

Study Record Updates

• Last Update Posted (Estimate): September 18, 2012
• Last Update Submitted That Met QC Criteria: September 12, 2012
• Last Verified: September 1, 2012

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Intestinal Neoplasms; Rectal Diseases; Colorectal Neoplasms; Physiological Effects of Drugs; Antineoplastic Agents; Antineoplastic Agents, Immunological; Angiogenesis Inhibitors; Angiogenesis Modulating Agents; Growth Substances; Growth Inhibitors; Bevacizumab
• Other Study ID Numbers: NO20254