Cetuximab With or Without Brivanib in Treating Patients With K-Ras Wild Type Tumours and Metastatic Colorectal Cancer
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|ClinicalTrials.gov Identifier: NCT00640471|
Recruitment Status : Completed
First Posted : March 21, 2008
Last Update Posted : July 17, 2013
RATIONALE: Brivanib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth and by blocking blood flow to the tumor. Monoclonal antibodies, such as cetuximab, can block tumor growth in different ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and help kill them or carry tumor-killing substances to them. It is not yet known whether giving brivanib together with cetuximab is more effective than cetuximab alone in treating patients with metastatic colorectal cancer.
PURPOSE: This randomized phase III trial is studying cetuximab to see how well it works compared with cetuximab given together with brivanib in treating patients with metastatic colorectal cancer.
|Condition or disease||Intervention/treatment||Phase|
|Colorectal Cancer||Biological: cetuximab Drug: brivanib alaninate||Phase 3|
- To compare the overall survival of patients with previously treated K-Ras wild type metastatic colorectal carcinoma treated with brivanib alaninate in combination with cetuximab versus placebo in combination with cetuximab.
- 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, BRAF 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 associations with mRNA and/or protein expression and/or variations in genes associated with epidermal growth factor (EGF), vascular endothelial growth factor (VEGF), angiogenesis, and other related pathways 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 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 BRAF mutation status) and correlation with response.
After completion of study treatment, patients are followed at 4 weeks and then every 8 weeks thereafter.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||750 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||Triple (Participant, Investigator, Outcomes Assessor)|
|Official Title:||A Phase III Randomized Study of Brivanib Alaninate (BMS-582664) in Combination With Cetuximab (Erbitux®) Versus Placebo in Combination With Cetuximab (Erbitux®) in Patients With K-RAS Wild Type Tumors Previously Treated With Combination Chemotherapy for Metastatic Colorectal Carcinoma|
|Study Start Date :||May 2008|
|Primary Completion Date :||March 2011|
|Study Completion Date :||January 2013|
|Active Comparator: Brivanib||
cetuximab (Erbitux®) - Initial dose - Day 1 (Week 1): 400 mg/m2 IV over 120 minutes Maintenance Infusions (subsequent weeks): 250 mg/m2 IV over 60 minutesDrug: brivanib alaninate
brivanib (BMS-582664) 800 mg po, QD
|Active Comparator: Placebo||
cetuximab (Erbitux®) - Initial dose - Day 1 (Week 1): 400 mg/m2 IV over 120 minutes Maintenance Infusions (subsequent weeks): 250 mg/m2 IV over 60 minutes
- Overall survival [ Time Frame: 3 years ]
- Progression-free survival [ Time Frame: 3 years ]
- Objective response rate [ Time Frame: 3 years ]
- Duration of response [ Time Frame: 3 years ]
- Quality of life (using EORTC QLQ-C30 and Skindex-16 Dermatology Survey) [ Time Frame: 3 years ]
- Health utilities (using HUI3 Health Utilities Index) [ Time Frame: 3 years ]
- Economic evaluation [ Time Frame: 3 years ]
- Safety profile [ Time Frame: 3 years ]
- Molecular markers [ Time Frame: 3 years ]
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00640471
Show 36 Study Locations
|Study Chair:||Lillian L. Siu, MD, FRCPC||Princess Margaret Hospital, Canada|