Clinical trial NCT01046864: Combination of Brivanib With 5-Fluorouracil/Leucovorin (5FU/LV) and 5-Fluorouracil/Leucovorin/Irinotecan (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 type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Gastro-Intestinal Cancer
Keywords: Gastro-Intestinal Cancer, NOS
Lead sponsor: Bristol-Myers Squibb
Sponsor class: INDUSTRY
First posted: 2010-01-12
Enrollment: 49
Sex: ALL
Minimum age (years): 20
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: FACTORIAL
Primary purpose: TREATMENT

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.


Eligibility 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

Primary outcomes:
measure: 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
timeFrame: Cycle 4, Day 1
Secondary outcomes:
measure: 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
timeFrame: Cycle 2, Day 2
measure: 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
timeFrame: Every 8 weeks
measure: 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
timeFrame: Cycle 1, Cycle 2, every other cycle
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: Usc/Norris Comprehensive Cancer Center
state: California
city: Dallas
country: United States
facility: Texas Oncology
state: Texas
city: Temple
country: United States
facility: Scott & White Memorial Hospital And Clinic
state: Texas
city: Edmonton
country: Canada
facility: Local Institution
state: Alberta
city: Ottawa
country: Canada
facility: Local Institution
state: Ontario
city: Villejuif Cedex
country: France
facility: Local Institution
Study officials:
affiliation: Bristol-Myers Squibb
name: Bristol-Myers Squibb
role: STUDY_DIRECTOR
References: