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

Phase 1

Completed

• Conditions: Gastro-Intestinal Cancer
• Interventions: Drug: 5-FU; Drug: Leucovorin; Drug: Irinotecan; Drug: Brivanib

• Registration Number: NCT01046864
• Lead Sponsor: Bristol-Myers Squibb

Brief Summary

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2010-01-11
• Study First Submitted QC: 2010-01-11
• Study First Posted: 2010-01-12
• Study Start: 2010-02
• Primary Completion: 2014-06
• Study Completion: 2014-06
• Status Verified: 2014-09
• Last Update Submitted: 2014-09-15
• Last Update Posted: 2014-09-16

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 49

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: FACTORIAL

Arm && Interventions

Group	Intervention	Description
Arm 2	Brivanib	-
Arm 1	5-FU	-
Arm 1	Leucovorin	-
Arm 1	Brivanib	-
Arm 2	5-FU	-
Arm 2	Leucovorin	-
Arm 2	Irinotecan	-
Arm 3	5-FU	Japanese Population
Arm 3	Irinotecan	Japanese Population
Arm 3	Leucovorin	Japanese Population
Arm 3	Brivanib	Japanese Population

Primary Outcome Measures

Name	Time	Method
Safety-Toxicity, evaluated according to NCI Common Terminology Criteria for Adverse Events v3.0. Assessments based on medical review of adverse events, results of vital signs, ECGs, echocardiography, physical examinations, and clinical laboratory tests	Cycle 4, Day 1

Secondary Outcome Measures

Name	Time	Method
Exploratory Measures (Biomarkers for Predictive Analysis): Potential predictive markers, including activity of FGF, VEGF and related pathways as well as K-RAS mutation status, will be evaluated based on blood or tumor samples	Cycle 1, Cycle 2, every other cycle
Pharmacokinetics (Cmax, Tmax, AUC (TAU), T-HALF) plasma concentration vs time for brivanib given alone and in combination with FOLFIRI. Individual concentrations (C) of 5FU will be calculated from samples on Day 2 in the presence and absence of Brivanib	Cycle 2, Day 2
Efficacy-Tumor BOR determined for treated subjects by radiological responses assessed by CT scan or MRI, by RECIST criteria (v1.1). Radiological tumor assessments to evaluate response & progression will be done every 8 wks or more frequently if indicated	Every 8 weeks

Trial Locations

Locations (4)

Usc/Norris Comprehensive Cancer Center; 🇺🇸 Los Angeles, California, United States

Texas Oncology; 🇺🇸 Dallas, Texas, United States

Scott & White Memorial Hospital And Clinic; 🇺🇸 Temple, Texas, United States

Local Institution; 🇫🇷 Villejuif Cedex, France