A Study of Avastin (Bevacizumab) in Combination With mFOLFOX6 in Treatment-Naïve Patients With Metastatic Colorectal Cancer With or Without K-RAS Mutations, and Comparison to Cetuximab

This randomized, open-label study will evaluate the safety and efficacy of Avastin (Bevacizumab) added to standard mFOLFOX6 chemotherapy in treatment-naïve patients with Stage IV metastatic colorectal cancer. According to K-RAS gene mutation status, patients will be assigned or randomized to receive either Avastin 5 mg/kg intravenously (iv) on Day 1 of each 2-week cycle or cetuximab 400 mg/m2 iv on Day 1 followed by 250 mg/m2 iv every week, in addition to mFOLFOX6 every 2 weeks. Anticipated time on study treatment is until disease progression or unacceptable toxicity occurs.

Study Overview

• Status: Withdrawn
• Conditions: Colorectal Cancer
• Intervention / Treatment: Drug: bevacizumab [Avastin]; Drug: mFOLFOX6; Drug: cetuximab

• Study Type: Interventional
• Phase: Phase 3

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
• Histologically confirmed adenocarcinoma of the colon or rectum
• Stage IV metastatic disease with at least one measurable metastatic lesion according to RECIST criteria
• Tumour tissue sample available for assessment of K-RAS and BRAF genes
• Prior radiotherapy must have been completed 4 weeks before randomization
• Adequate bone marrow, kidney and liver function
• Eastern Cooperative Oncology Group (ECOG) performance status 0-1

Exclusion Criteria:

• Previous chemotherapy for metastatic disease
• Completion of adjuvant treatment for colorectal cancer (Stage I, II and III) in the 12 months preceding randomization
• Prior treatment with bevacizumab, cetuximab or other EGFR inhibitors
• Clinical or radiographic evidence of brain metastases
• Clinically significant cardiovascular disease or disorder
• History of neoplastic disease other than colorectal cancer in the 3 years prior to start of study treatment, except for successfully treated non-invasive carcinomas such as cervical cancer in situ, basal cell carcinoma of the skin or superficial bladder tumours
• HIV, hepatitis B or C infection

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

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: K-RAS mutated	Drug: bevacizumab [Avastin]; 5 mg/kg iv on Day 1 of each 2-week cycle until disease progression, unacceptable toxicity or withdrawal of consent; Drug: mFOLFOX6; Standard mFOLFOX6 chemotherapy, 2-week cycles until disease progression, unacceptable toxicity or withdrawal of consent
Experimental: K-RAS native A	Drug: bevacizumab [Avastin]; 5 mg/kg iv on Day 1 of each 2-week cycle until disease progression, unacceptable toxicity or withdrawal of consent; Drug: mFOLFOX6; Standard mFOLFOX6 chemotherapy, 2-week cycles until disease progression, unacceptable toxicity or withdrawal of consent
Active Comparator: K-RAS native B	Drug: mFOLFOX6; Standard mFOLFOX6 chemotherapy, 2-week cycles until disease progression, unacceptable toxicity or withdrawal of consent; Drug: cetuximab; 400 mg /m2 iv on Day 1, followed by 250 mg/m2 every week until disease progression, unacceptable toxicity or withdrawal of consent

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Progression-free survival: native versus mutated K-RAS; tumour assessments according to RECIST criteria	up to 4 years

Secondary Outcome Measures

Outcome Measure	Time Frame
Objective response rate	4 years
Overall survival	up to 4 years
Safety: Incidence of adverse events	4 years
Quality of Life: European Organisation for Research and Treatment of Cancer Quality of Life questionnaire (EORTC QLQ-C30)	up to 4 years
Progression-free survival: comparison of the two treatment regimens in the native K-RAS arms	up to 4 years

Collaborators and Investigators

• Sponsor: Hoffmann-La Roche

Study record dates

Study Major Dates

• Study Start: June 1, 2011
• Primary Completion (Anticipated): May 1, 2015
• Study Completion (Anticipated): May 1, 2015

Study Registration Dates

• First Submitted: April 18, 2011
• First Submitted That Met QC Criteria: April 18, 2011
• First Posted (Estimate): April 19, 2011

Study Record Updates

• Last Update Posted (Estimate): November 2, 2016
• Last Update Submitted That Met QC Criteria: November 1, 2016
• Last Verified: November 1, 2016

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; Cetuximab
• Other Study ID Numbers: ML25686