Now Available for Public Comment: Notice of Proposed Rulemaking (NPRM) for FDAAA 801 and NIH Draft Reporting Policy for NIH-Funded Trials

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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Bristol-Myers Squibb
ClinicalTrials.gov Identifier:
NCT01046864
First received: January 11, 2010
Last updated: September 15, 2014
Last verified: September 2014
  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:


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 ]

Enrollment: 49
Study Start Date: February 2010
Study Completion Date: June 2014
Primary Completion Date: June 2014 (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

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

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: September 15, 2014
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:
Gastrointestinal Neoplasms
Intestinal Neoplasms
Digestive System Diseases
Digestive System Neoplasms
Gastrointestinal Diseases
Intestinal Diseases
Neoplasms
Neoplasms by Site
Fluorouracil
Irinotecan
Antimetabolites
Antimetabolites, Antineoplastic
Antineoplastic Agents
Antineoplastic Agents, Phytogenic
Enzyme Inhibitors
Immunologic Factors
Immunosuppressive Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Physiological Effects of Drugs
Radiation-Sensitizing Agents
Therapeutic Uses
Topoisomerase I Inhibitors
Topoisomerase Inhibitors

ClinicalTrials.gov processed this record on November 20, 2014