Combination of Brivanib With 5-Fluorouracil/Leucovorin (5FU/LV) and 5-Fluorouracil/Leucovorin/Irinotecan (FOLFIRI)

A Phase Ib Multiple Ascending Dose Study to Evaluate the Safety of Brivanib in Combination With 5-Fluorouracil/Leucovorin (5FU/LV) and Brivanib in Combination With 5-Fluorouracil/Leucovorin/Irinotecan (FOLFIRI) in Subjects With Advanced or Metastatic Gastrointestinal Malignancies

The purpose of this study is to determine a safe and maximum tolerable dose of Brivanib when combined with standard dose 5FU/LV and FOLFIRI.

For more information regarding BMS clinical trial participation, please visit www.BMSStudyConnect.com

Inclusion Criteria:

• Histological/cytological confirmed diagnosis of Gastrointestinal malignancy, except pancreatic cancer
• Eligible for 5FU/LV or FOLFIRI chemotherapy
• ECOG 0-1
• Able to swallow and tolerate tablets
• Life expectancy of 3 months

Exclusion Criteria:

• Unwilling to use acceptable method to avoid pregnancy of partner/self for the entire study period and up to 4 weeks after last dose
• Women who are pregnant or breastfeeding
• Pancreatic cancer
• Known brain metastasis, evidence of leptomeningeal disease
• History of thrombo-embolic disease
• Hemorrhage/bleeding events
• Uncontrolled or significant cardiovascular disease
• Any 3 or more of the following risk factors: arterial thrombosis , smoking, hypercholesterolemia, hypertension, obesity (BMS>30) and diabetes
• Pre-existing thyroid abnormality, not maintained with medication
• QTC (Fridericia) >450 msec on two consecutive ECG's
• Subjects with concomitant second malignancies ( except adequately treated non-melanoma skin, in situ carcinoma of bladder, cervix or breast, early prostate cancer)
• Any major surgery within 4 weeks of study drug administration
• Increased levels of both D-Dimer and Prothrombin fragment 1 +2
• Arm B and C only-positive UGT1A1 genotype of TA7/TA7
• History of allergy of brivanib or drug class
• History of severe reactions to fluoropyrimidine therapy or irinotecan
• Prior therapy with brivanib