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

September 15, 2014 updated by: Bristol-Myers Squibb

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

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

49

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Canada
    • Alberta
      • Edmonton, Alberta, Canada, T6G 1Z2
        • Local Institution
    • Ontario
      • Ottawa, Ontario, Canada, K1H 8L6
        • Local Institution
  • France
      • Villejuif Cedex, France, 94800
        • Local Institution
  • United States
    • California
      • Los Angeles, California, United States, 90033
        • USC/Norris Comprehensive Cancer Center
    • Texas
      • Dallas, Texas, United States, 75246
        • Texas Oncology
      • Temple, Texas, United States, 76508
        • Scott & White Memorial Hospital and Clinic

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

20 years to 75 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Factorial Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
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 Names:
  • Fluorouracil
Drug: Leucovorin
IV solution, IV over 2 hours, 400 mg/m², Every 14 days, Until disease progression/toxicity
Other Names:
  • Folinic acid
Drug: 5-FU
IV solution, IV infusion over 46 hours, 2400 mg/m², Every 14 days, Until disease progression/toxicity
Other Names:
  • Fluorouracil
Drug: Brivanib
Tablets, Oral, 400 - 800 mg, once daily, Until disease progression/toxicity
Drug: Brivanib
Tablets, Oral, 600 - 800 mg, once daily, Until disease progression/toxicity
Other Names:
  • BMS-582664
Drug: Brivanib
Tablets, Oral, 800 mg, once daily, Until disease progression/toxicity
Other Names:
  • BMS-582664
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 Names:
  • Fluorouracil
Drug: Leucovorin
IV solution, IV over 2 hours, 400 mg/m², Every 14 days, Until disease progression/toxicity
Other Names:
  • Folinic acid
Drug: 5-FU
IV solution, IV infusion over 46 hours, 2400 mg/m², Every 14 days, Until disease progression/toxicity
Other Names:
  • Fluorouracil
Drug: Brivanib
Tablets, Oral, 400 - 800 mg, once daily, Until disease progression/toxicity
Drug: Brivanib
Tablets, Oral, 600 - 800 mg, once daily, Until disease progression/toxicity
Other Names:
  • BMS-582664
Drug: Brivanib
Tablets, Oral, 800 mg, once daily, Until disease progression/toxicity
Other Names:
  • BMS-582664
Drug: Irinotecan
IV solution, IV over 90 minutes, 180 mg/m², Every 14 days, Until disease progression/toxicity
Other Names:
  • Camptosar
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 Names:
  • Fluorouracil
Drug: Leucovorin
IV solution, IV over 2 hours, 400 mg/m², Every 14 days, Until disease progression/toxicity
Other Names:
  • Folinic acid
Drug: 5-FU
IV solution, IV infusion over 46 hours, 2400 mg/m², Every 14 days, Until disease progression/toxicity
Other Names:
  • Fluorouracil
Drug: Brivanib
Tablets, Oral, 400 - 800 mg, once daily, Until disease progression/toxicity
Drug: Brivanib
Tablets, Oral, 600 - 800 mg, once daily, Until disease progression/toxicity
Other Names:
  • BMS-582664
Drug: Brivanib
Tablets, Oral, 800 mg, once daily, Until disease progression/toxicity
Other Names:
  • BMS-582664
Drug: Irinotecan
IV solution, IV over 90 minutes, 180 mg/m², Every 14 days, Until disease progression/toxicity
Other Names:
  • Camptosar

What is the study measuring?

Primary Outcome Measures

Outcome 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
Time Frame: Cycle 4, Day 1
Cycle 4, Day 1

Secondary Outcome Measures

Outcome 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
Time Frame: Cycle 2, Day 2
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
Time Frame: Every 8 weeks
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
Time Frame: Cycle 1, Cycle 2, every other cycle
Cycle 1, Cycle 2, every other cycle

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Bristol-Myers Squibb

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

February 1, 2010

Primary Completion (Actual)

June 1, 2014

Study Completion (Actual)

June 1, 2014

Study Registration Dates

First Submitted

January 11, 2010

First Submitted That Met QC Criteria

January 11, 2010

First Posted (Estimate)

January 12, 2010

Study Record Updates

Last Update Posted (Estimate)

September 16, 2014

Last Update Submitted That Met QC Criteria

September 15, 2014

Last Verified

September 1, 2014

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • CA182-046
  • 2009-016699-63 (EudraCT Number)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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