Cetuximab With or Without Brivanib in Treating Patients With K-Ras Wild Type Tumours and Metastatic Colorectal Cancer
|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|
|Actual Primary Completion Date :||March 2011|
|Actual 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 ]
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00640471
Hide Study Locations
|Tom Baker Cancer Centre|
|Calgary, Alberta, Canada, T2N 4N2|
|Cross Cancer Institute|
|Edmonton, Alberta, Canada, T6G 1Z2|
|Canada, British Columbia|
|BCCA - Abbotsford Centre|
|Abbotsford, British Columbia, Canada, V2S 0C2|
|BCCA - Cancer Centre for the Southern Interior|
|Kelowna, British Columbia, Canada, V1Y 5L3|
|BCCA - Fraser Valley Cancer Centre|
|Surrey, British Columbia, Canada, V3V 1Z2|
|BCCA - Vancouver Cancer Centre|
|Vancouver, British Columbia, Canada, V5Z 4E6|
|Winnipeg, Manitoba, Canada, R3E 0V9|
|Canada, New Brunswick|
|The Moncton Hospital|
|Moncton, New Brunswick, Canada, E1C 6Z8|
|The Vitalite Health Network - Dr. Leon Richard|
|Moncton, New Brunswick, Canada, E1C 8X3|
|Atlantic Health Sciences Corporation|
|Saint John, New Brunswick, Canada, E2L 4L2|
|Canada, Newfoundland and Labrador|
|Dr. H. Bliss Murphy Cancer Centre|
|St. John's, Newfoundland and Labrador, Canada, AIB 3V6|
|The Royal Victoria Hospital|
|Barrie, Ontario, Canada, L4M 6M2|
|Juravinski Cancer Centre at Hamilton Health Sciences|
|Hamilton, Ontario, Canada, L8V 5C2|
|Cancer Centre of Southeastern Ontario at Kingston|
|Kingston, Ontario, Canada, K7L 5P9|
|London Regional Cancer Program|
|London, Ontario, Canada, N6A 4L6|
|Stronach Regional Health Centre at Southlake|
|Newmarket, Ontario, Canada, L3Y 2P9|
|Lakeridge Health Oshawa|
|Oshawa, Ontario, Canada, L1G 2B9|
|Ottawa Health Research Institute - General Division|
|Ottawa, Ontario, Canada, K1H 8L6|
|Algoma District Cancer Program|
|Sault Ste. Marie, Ontario, Canada, P6B 0A8|
|Niagara Health System|
|St. Catharines, Ontario, Canada, L2R 7C6|
|Thunder Bay Regional Health Science Centre|
|Thunder Bay, Ontario, Canada, P7B 6V4|
|Toronto East General Hospital|
|Toronto, Ontario, Canada, M4C 3E7|
|Odette Cancer Centre|
|Toronto, Ontario, Canada, M4N 3M5|
|St. Michael's Hospital|
|Toronto, Ontario, Canada, M5B 1W8|
|Univ. Health Network-Princess Margaret Hospital|
|Toronto, Ontario, Canada, M5G 2M9|
|Canada, Prince Edward Island|
|PEI Cancer Treatment Centre,Queen Elizabeth Hospital|
|Charlottetown, Prince Edward Island, Canada, C1A 8T5|
|Hopital Charles LeMoyne|
|Greenfield Park, Quebec, Canada, J4V 2H1|
|L'Hotel-Dieu de Levis|
|Levis, Quebec, Canada, G6V 3Z1|
|CHUM - Hopital Notre-Dame|
|Montreal, Quebec, Canada, H2L 4M1|
|McGill University - Dept. Oncology|
|Montreal, Quebec, Canada, H2W 1S6|
|Hopital du Sacre-Coeur de Montreal|
|Montreal, Quebec, Canada, H4J 1C5|
|CHUQ-Pavillon Hotel-Dieu de Quebec|
|Quebec City, Quebec, Canada, G1R 2J6|
|CHA-Hopital Du St-Sacrement|
|Quebec City, Quebec, Canada, G1S 4L8|
|Centre hospitalier universitaire de Sherbrooke|
|Sherbrooke, Quebec, Canada, J1H 5N4|
|Allan Blair Cancer Centre|
|Regina, Saskatchewan, Canada, S4T 7T1|
|Saskatoon Cancer Centre|
|Saskatoon, Saskatchewan, Canada, S7N 4H4|
|Study Chair:||Lillian L. Siu, MD, FRCPC||Princess Margaret Hospital, Canada|