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

Bristol-Myers Squibb (BMS)

Status and phase: Completed; Phase 1

Conditions: Gastro-Intestinal Cancer

Treatments: Drug: Brivanib; Drug: 5-FU; Drug: Leucovorin; Drug: Irinotecan

Study type: Interventional

Funder types: Industry

Identifiers

NCT01046864

2009-016699-63 (EudraCT Number)

CA182-046

Details and patient eligibility

About

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.

Enrollment: 49 patients

Sex: All

Ages: 20 to 75 years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

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

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Factorial Assignment

Masking: None (Open label)

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49 participants in 3 patient groups

Arm 1

Experimental group

Treatment:

Drug: 5-FU

Drug: Brivanib

Drug: Brivanib

Drug: Leucovorin

Drug: 5-FU

Drug: Brivanib

Arm 2

Experimental group

Treatment:

Drug: 5-FU

Drug: Brivanib

Drug: Irinotecan

Drug: Brivanib

Drug: Leucovorin

Drug: 5-FU

Drug: Brivanib

Arm 3

Experimental group

Description:

Japanese Population

Treatment:

Drug: 5-FU

Drug: Brivanib

Drug: Irinotecan

Drug: Brivanib

Drug: Leucovorin

Drug: 5-FU

Drug: Brivanib