Primary Outcome Measures:
- Overall survival [ Designated as safety issue: No ]
Secondary Outcome Measures:
- Progression-free survival [ Designated as safety issue: No ]
- Objective response rate [ Designated as safety issue: No ]
- Duration of response [ Designated as safety issue: No ]
- Quality of life (using EORTC QLQ-C30 and Skindex-16 Dermatology Survey) [ Designated as safety issue: No ]
- Health utilities (using HUI3 Health Utilities Index) [ Designated as safety issue: No ]
- Economic evaluation [ Designated as safety issue: No ]
- Safety profile [ Designated as safety issue: Yes ]
- Molecular markers [ Designated as safety issue: No ]
OBJECTIVES:
Primary
- To compare the overall survival of patients with previously treated metastatic colorectal carcinoma treated with brivanib alaninate in combination with cetuximab versus placebo in combination with cetuximab.
Secondary
- To compare the progression-free survival of these patients.
- To compare the objective response rate and duration of response in these patients.
- To compare the quality of life of these patients.
- To compare the health utilities of these patients.
- To conduct a comparative economic evaluation of these patients.
- To evaluate the safety profile of this regimen in these patients.
- To explore an association between FGF-2, K-RAS mutations, amphiregulin (AREG) and epiregulin (EREG) as determined from paraffin embedded tumor specimens and the potential for clinical benefit from the addition of brivanib alaninate or placebo to cetuximab in terms of overall survival, progression-free survival and objective response rate compared to cetuximab alone.
- To explore an association with changes of Collagen IV in the blood and the potential for clinical benefit from the addition of brivanib alaninate to cetuximab in terms of overall survival, progression-free survival and objective response rate compared to cetuximab alone.
- To establish a comprehensive tumor bank linked to a clinical database for the further study of molecular markers in colorectal cancer.
OUTLINE: This is a multicenter study. Patients are stratified according to participating center and ECOG performance status (0-1 vs 2). Patients are randomized to 1 of 2 arms.
- Arm I: Patients receive oral brivanib alaninate once daily and cetuximab IV over 60-120 minutes once weekly.
- Arm II: Patients receive oral placebo once daily and cetuximab IV over 60-120 minutes once weekly.
In both arms, treatment continues in the absence of disease progression or unacceptable toxicity.
Tumor tissue and blood samples are collected for correlative studies. Samples are analyzed for biomarker levels (Collagen IV, FGF-2, and epiregulin, amphiregulin, and K-ras mutations status) and correlation with response.
After completion of study treatment, patients are followed at 4 weeks and then every 8 weeks thereafter.