Clinical Trials/NCT01046864

NCT01046864

Completed

Phase 1

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

Bristol-Myers Squibb4 sites in 2 countries49 target enrollmentFebruary 2010

ConditionsGastro-Intestinal Cancer

Interventions5-FU Leucovorin Brivanib Irinotecan

Drugs5-FU Leucovorin Irinotecan Brivanib

Overview

Phase: Phase 1
Intervention: 5-FU
Conditions: Gastro-Intestinal Cancer
Sponsor: Bristol-Myers Squibb
Enrollment: 49
Locations: 4
Primary Endpoint: 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
Status: Completed
Last Updated: 11 years ago

Overview Investigators Eligibility Criteria Arms & Interventions Outcomes Sites Similar Trials

Overview

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.

Registry

clinicaltrials.gov

Start Date

February 2010

End Date

June 2014

Last Updated

11 years ago

Study Type

Interventional

Study Design

Factorial

Sex

All

Investigators

Sponsor

Bristol-Myers Squibb

Responsible Party

Sponsor

Eligibility Criteria

Inclusion Criteria

•Histological/cytological confirmed diagnosis of Gastrointestinal malignancy, except pancreatic cancer
•Eligible for 5FU/LV or FOLFIRI chemotherapy
•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

Arms & Interventions

Arm 1

Intervention: 5-FU

Arm 1

Intervention: Leucovorin

Arm 1

Intervention: Brivanib

Arm 2

Intervention: 5-FU

Arm 2

Intervention: Leucovorin

Arm 2

Intervention: Irinotecan

Arm 2

Intervention: Brivanib

Arm 3

Japanese Population

Intervention: 5-FU

Arm 3

Japanese Population

Intervention: Leucovorin

Arm 3

Japanese Population

Intervention: Irinotecan

Arm 3

Japanese Population

Intervention: Brivanib

Outcomes

Primary Outcomes

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

Time Frame: Cycle 4, Day 1

Secondary Outcomes

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)