Colorectal Cancer
Conditions
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.
Interventions
DRUGbevacizumab [Avastin]
5 mg/kg iv on Day 1 of each 2-week cycle until disease progression, unacceptable toxicity or withdrawal of consent
DRUGcetuximab
400 mg /m2 iv on Day 1, followed by 250 mg/m2 every week until disease progression, unacceptable toxicity or withdrawal of consent
DRUGmFOLFOX6
Standard mFOLFOX6 chemotherapy, 2-week cycles until disease progression, unacceptable toxicity or withdrawal of consent
Sponsors
Hoffmann-La Roche
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Progression-free survival: native versus mutated K-RAS; tumour assessments according to RECIST criteria | up to 4 years |
Secondary
| Measure | Time frame |
|---|---|
| Overall survival | up to 4 years |
| 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 |
| Progression-free survival: comparison of the two treatment regimens in the native K-RAS arms | up to 4 years |
Outcome results
None listed