Combination of Brivanib With 5-Fluorouracil/Leucovorin (5FU/LV) and 5-Fluorouracil/Leucovorin/Irinotecan (FOLFIRI)
This study is ongoing, but not recruiting participants.
Sponsor:
Bristol-Myers Squibb
Information provided by (Responsible Party):
Bristol-Myers Squibb
ClinicalTrials.gov Identifier:
NCT01046864
First received: January 11, 2010
Last updated: June 18, 2012
Last verified: February 2012
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Purpose
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.
| Condition | Intervention | Phase |
|---|---|---|
|
Gastro-Intestinal Cancer |
Drug: 5-FU Drug: Leucovorin Drug: Irinotecan Drug: Brivanib |
Phase 1 |
| Study Type: | Interventional |
| Study Design: | Allocation: Non-Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Factorial Assignment Masking: Open Label Primary Purpose: Treatment |
| 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 |
Resource links provided by NLM:
MedlinePlus related topics:
Cancer
Drug Information available for:
Fluorouracil
Folic acid
Leucovorin calcium
Levoleucovorin
Irinotecan
Irinotecan hydrochloride
U.S. FDA Resources
Further study details as provided by Bristol-Myers Squibb:
Primary Outcome Measures:
- 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 ] [ Designated as safety issue: Yes ]
Secondary Outcome Measures:
- 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 [ Time Frame: Cycle 2, Day 2 ] [ Designated as safety issue: No ]
- 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 [ Time Frame: Every 8 weeks ] [ Designated as safety issue: No ]
- 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 [ Time Frame: Cycle 1, Cycle 2, every other cycle ] [ Designated as safety issue: No ]
| Estimated Enrollment: | 72 |
| Study Start Date: | February 2009 |
| Estimated Study Completion Date: | July 2012 |
| Estimated Primary Completion Date: | July 2012 (Final data collection date for primary outcome measure) |
| Arms | Assigned Interventions |
|---|---|
| Experimental: Arm 1 |
Drug: 5-FU
IV solution, IV bolus over 2-4 minutes, 400 mg/m², Every 14 days, Until disease progression/toxicity
Other Name: Fluorouracil
Drug: Leucovorin
IV solution, IV over 2 hours, 400 mg/m², Every 14 days, Until disease progression/toxicity
Other Name: Folinic acid
Drug: 5-FU
IV solution, IV infusion over 46 hours, 2400 mg/m², Every 14 days, Until disease progression/toxicity
Other Name: Fluorouracil
Drug: Brivanib
Tablets, Oral, 400 - 800 mg, once daily, Until disease progression/toxicity
|
| Experimental: Arm 2 |
Drug: 5-FU
IV solution, IV bolus over 2-4 minutes, 400 mg/m², Every 14 days, Until disease progression/toxicity
Other Name: Fluorouracil
Drug: Leucovorin
IV solution, IV over 2 hours, 400 mg/m², Every 14 days, Until disease progression/toxicity
Other Name: Folinic acid
Drug: 5-FU
IV solution, IV infusion over 46 hours, 2400 mg/m², Every 14 days, Until disease progression/toxicity
Other Name: Fluorouracil
Drug: Irinotecan
IV solution, IV over 90 minutes, 180 mg/m², Every 14 days, Until disease progression/toxicity
Other Name: Camptosar
Drug: Brivanib
Tablets, Oral, 600 - 800 mg, once daily, Until disease progression/toxicity
Other Name: BMS-582664
|
|
Experimental: Arm 3
Japanese Population
|
Drug: 5-FU
IV solution, IV bolus over 2-4 minutes, 400 mg/m², Every 14 days, Until disease progression/toxicity
Other Name: Fluorouracil
Drug: Leucovorin
IV solution, IV over 2 hours, 400 mg/m², Every 14 days, Until disease progression/toxicity
Other Name: Folinic acid
Drug: 5-FU
IV solution, IV infusion over 46 hours, 2400 mg/m², Every 14 days, Until disease progression/toxicity
Other Name: Fluorouracil
Drug: Irinotecan
IV solution, IV over 90 minutes, 180 mg/m², Every 14 days, Until disease progression/toxicity
Other Name: Camptosar
Drug: Brivanib
Tablets, Oral, 800 mg, once daily, Until disease progression/toxicity
Other Name: BMS-582664
|
Eligibility| Ages Eligible for Study: | 20 Years to 75 Years |
| Genders Eligible for Study: | Both |
| Accepts Healthy Volunteers: | No |
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
Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01046864
Locations
| United States, California | |
| Usc/Norris Comprehensive Cancer Center | |
| Los Angeles, California, United States, 90033 | |
| United States, Texas | |
| Texas Oncology | |
| Dallas, Texas, United States, 75246 | |
| Scott & White Memorial Hospital And Clinic | |
| Temple, Texas, United States, 76508 | |
| Canada, Alberta | |
| Local Institution | |
| Edmonton, Alberta, Canada, T6G 1Z2 | |
| Canada, Ontario | |
| Local Institution | |
| Ottawa, Ontario, Canada, K1H 8L6 | |
| France | |
| Local Institution | |
| Villejuif Cedex, France, 94800 | |
Sponsors and Collaborators
Bristol-Myers Squibb
Investigators
| Study Director: | Bristol-Myers Squibb | Bristol-Myers Squibb |
More Information
Additional Information:
No publications provided
| Responsible Party: | Bristol-Myers Squibb |
| ClinicalTrials.gov Identifier: | NCT01046864 History of Changes |
| Other Study ID Numbers: | CA182-046, 2009-016699-63 |
| Study First Received: | January 11, 2010 |
| Last Updated: | June 18, 2012 |
| Health Authority: | United States: Food and Drug Administration Canada: Health Canada France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis) Japan: Ministry of Health, Labor and Welfare Japan: Pharmaceuticals and Medical Devices Agency |
Keywords provided by Bristol-Myers Squibb:
|
Gastro-Intestinal Cancer, NOS |
Additional relevant MeSH terms:
|
Intestinal Neoplasms Gastrointestinal Neoplasms Digestive System Neoplasms Neoplasms by Site Neoplasms Digestive System Diseases Gastrointestinal Diseases Intestinal Diseases Fluorouracil Irinotecan Leucovorin Levoleucovorin Antimetabolites Molecular Mechanisms of Pharmacological Action Pharmacologic Actions |
Antimetabolites, Antineoplastic Antineoplastic Agents Therapeutic Uses Immunosuppressive Agents Immunologic Factors Physiological Effects of Drugs Vitamin B Complex Vitamins Micronutrients Growth Substances Antidotes Protective Agents Antineoplastic Agents, Phytogenic Radiation-Sensitizing Agents Topoisomerase I Inhibitors |
ClinicalTrials.gov processed this record on May 16, 2013