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
Overview
- Phase
- Phase 3
- Intervention
- bevacizumab [Avastin]
- Conditions
- Colorectal Cancer
- Sponsor
- Hoffmann-La Roche
- Primary Endpoint
- Progression-free survival: native versus mutated K-RAS; tumour assessments according to RECIST criteria
- Status
- Withdrawn
- Last Updated
- 9 years ago
Overview
Brief Summary
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.
Investigators
Eligibility Criteria
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
Arms & Interventions
K-RAS mutated
Intervention: bevacizumab [Avastin]
K-RAS mutated
Intervention: mFOLFOX6
K-RAS native A
Intervention: bevacizumab [Avastin]
K-RAS native A
Intervention: mFOLFOX6
K-RAS native B
Intervention: cetuximab
K-RAS native B
Intervention: mFOLFOX6
Outcomes
Primary Outcomes
Progression-free survival: native versus mutated K-RAS; tumour assessments according to RECIST criteria
Time Frame: up to 4 years
Secondary Outcomes
- Objective response rate(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)
- Overall survival(up to 4 years)
- Progression-free survival: comparison of the two treatment regimens in the native K-RAS arms(up to 4 years)