Gastro-Intestinal Cancer
Conditions
Keywords
Gastro-Intestinal Cancer, NOS
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.
Interventions
DRUG5-FU
IV solution, IV bolus over 2-4 minutes, 400 mg/m², Every 14 days, Until disease progression/toxicity
DRUGLeucovorin
IV solution, IV over 2 hours, 400 mg/m², Every 14 days, Until disease progression/toxicity
DRUGIrinotecan
IV solution, IV over 90 minutes, 180 mg/m², Every 14 days, Until disease progression/toxicity
DRUGBrivanib
Tablets, Oral, 400 - 800 mg, once daily, Until disease progression/toxicity
Sponsors
Bristol-Myers Squibb
Study design
Allocation
NON_RANDOMIZED
Intervention model
FACTORIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
20 Years to 75 Years
Healthy volunteers
No
Inclusion 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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| 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
| Measure | Time frame |
|---|---|
| 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 |
| 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 |
Countries
Canada, France, United States
Outcome results
None listed