Combination of Brivanib With 5-Fluorouracil/Leucovorin (5FU/LV) and 5-Fluorouracil/Leucovorin/Irinotecan (FOLFIRI)
Information source: Bristol-Myers Squibb
ClinicalTrials.gov processed this data on August 20, 2015 Link to the current ClinicalTrials.gov record.
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: Completed
Sponsored by: Bristol-Myers Squibb Official(s) and/or principal investigator(s): Bristol-Myers Squibb, Study Director, Affiliation: Bristol-Myers Squibb
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.
Clinical Details
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 BrivanibEfficacy-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
Eligibility
Minimum age: 20 Years.
Maximum age: 75 Years.
Gender(s): Both.
Criteria:
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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
Locations and Contacts
Local Institution, Villejuif Cedex 94800, France
Local Institution, Edmonton, Alberta T6G 1Z2, Canada
Usc/Norris Comprehensive Cancer Center, Los Angeles, California 90033, United States
Local Institution, Ottawa, Ontario K1H 8L6, Canada
Texas Oncology, Dallas, Texas 75246, United States
Scott & White Memorial Hospital And Clinic, Temple, Texas 76508, United States
Additional Information
BMS Clinical Trial Information BMS clinical trial educational resource Investigator Inquiry form FDA Safety Alerts and Recalls
Starting date: February 2010
Last updated: September 15, 2014
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