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

Condition(s) targeted: Gastro-Intestinal Cancer

Intervention: 5-FU (Drug); Leucovorin (Drug); 5-FU (Drug); Irinotecan (Drug); Brivanib (Drug); Brivanib (Drug); Brivanib (Drug)

Phase: Phase 1

Status: Recruiting

Sponsored by: Bristol-Myers Squibb

Official(s) and/or principal investigator(s):
Bristol-Myers Squibb, Study Director, Affiliation: Bristol-Myers Squibb

Overall contact:
For participation information at a USA site use a phone number below. For site information outside the USA please email:, Email: Clinical.Trials@bms.com

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.

Official title: 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

Study design: Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Factorial Assignment, Masking: Open Label, Primary Purpose: Treatment

Primary outcome: 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

Secondary outcome:

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

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

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

Minimum age: 20 Years. Maximum age: 75 Years. Gender(s): Both.

Criteria:

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

For participation information at a USA site use a phone number below. For site information outside the USA please email:, Email: Clinical.Trials@bms.com

Local Institution, Villejuif Cedex 94800, France; Recruiting
Site 006

Local Institution, Edmonton, Alberta T6G 1Z2, Canada; Recruiting
Site 005

Usc/Norris Comprehensive Cancer Center, Los Angeles, California 90033, United States; Recruiting
Anthony El-Khoueiry, Site 002

Local Institution, Ottawa, Ontario K1H 8L6, Canada; Recruiting
Site 004

Texas Oncology, Dallas, Texas 75246, United States; Recruiting
Carlos H. Roberto Becerra, Site 001

Scott & White Memorial Hospital And Clinic, Temple, Texas 76508, United States; Recruiting
Lucas Wong, Site 003

BMS Clinical Trials Disclosure

Investigator Inquiry form

For FDA Safety Alerts and Recalls refer to the following link: http://www.fda.gov/MEDWATCH/safety.htm

Starting date: February 2010
Last updated: November 29, 2011