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

NCT ID: NCT01046864

Last Updated: 2014-09-16

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 49 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2010-02-28
• Study Completion Date: 2014-06-30

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.

Conditions

Gastro-Intestinal Cancer

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: FACTORIAL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Arm 1

Group Type: EXPERIMENTAL

5-FU

Intervention Type: DRUG

IV solution, IV bolus over 2-4 minutes, 400 mg/m², Every 14 days, Until disease progression/toxicity

Leucovorin

Intervention Type: DRUG

IV solution, IV over 2 hours, 400 mg/m², Every 14 days, Until disease progression/toxicity

5-FU

Intervention Type: DRUG

IV solution, IV infusion over 46 hours, 2400 mg/m², Every 14 days, Until disease progression/toxicity

Brivanib

Intervention Type: DRUG

Tablets, Oral, 400 - 800 mg, once daily, Until disease progression/toxicity

Arm 2

Group Type: EXPERIMENTAL

5-FU

Intervention Type: DRUG

IV solution, IV bolus over 2-4 minutes, 400 mg/m², Every 14 days, Until disease progression/toxicity

Leucovorin

Intervention Type: DRUG

IV solution, IV over 2 hours, 400 mg/m², Every 14 days, Until disease progression/toxicity

5-FU

Intervention Type: DRUG

IV solution, IV infusion over 46 hours, 2400 mg/m², Every 14 days, Until disease progression/toxicity

Irinotecan

Intervention Type: DRUG

IV solution, IV over 90 minutes, 180 mg/m², Every 14 days, Until disease progression/toxicity

Brivanib

Intervention Type: DRUG

Tablets, Oral, 600 - 800 mg, once daily, Until disease progression/toxicity

Arm 3

Japanese Population

Group Type: EXPERIMENTAL

5-FU

Intervention Type: DRUG

IV solution, IV bolus over 2-4 minutes, 400 mg/m², Every 14 days, Until disease progression/toxicity

Leucovorin

Intervention Type: DRUG

IV solution, IV over 2 hours, 400 mg/m², Every 14 days, Until disease progression/toxicity

5-FU

Intervention Type: DRUG

IV solution, IV infusion over 46 hours, 2400 mg/m², Every 14 days, Until disease progression/toxicity

Irinotecan

Intervention Type: DRUG

IV solution, IV over 90 minutes, 180 mg/m², Every 14 days, Until disease progression/toxicity

Brivanib

Intervention Type: DRUG

Tablets, Oral, 800 mg, once daily, Until disease progression/toxicity

Interventions

5-FU

IV solution, IV bolus over 2-4 minutes, 400 mg/m², Every 14 days, Until disease progression/toxicity

Intervention Type: DRUG

Leucovorin

IV solution, IV over 2 hours, 400 mg/m², Every 14 days, Until disease progression/toxicity

Intervention Type: DRUG

5-FU

IV solution, IV infusion over 46 hours, 2400 mg/m², Every 14 days, Until disease progression/toxicity

Intervention Type: DRUG

Irinotecan

IV solution, IV over 90 minutes, 180 mg/m², Every 14 days, Until disease progression/toxicity

Intervention Type: DRUG

Brivanib

Tablets, Oral, 400 - 800 mg, once daily, Until disease progression/toxicity

Intervention Type: DRUG

Brivanib

Tablets, Oral, 600 - 800 mg, once daily, Until disease progression/toxicity

Intervention Type: DRUG

Brivanib

Tablets, Oral, 800 mg, once daily, Until disease progression/toxicity

Intervention Type: DRUG

Other Intervention Names

Fluorouracil; Folinic acid; Fluorouracil; Camptosar; BMS-582664; BMS-582664

Eligibility 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

• Minimum Eligible Age: 20 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Bristol-Myers Squibb

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Bristol-Myers Squibb

Role: STUDY_DIRECTOR

Bristol-Myers Squibb

Locations

Usc/Norris Comprehensive Cancer Center

Los Angeles, California, United States

Texas Oncology

Dallas, Texas, United States

Scott & White Memorial Hospital And Clinic

Temple, Texas, United States

Local Institution

Edmonton, Alberta, Canada

Local Institution

Ottawa, Ontario, Canada

Local Institution

Villejuif, , France

Countries

United States; Canada; France

Related Links

http://www.bms.com/studyconnect/Pages/home.aspx

BMS clinical trial educational resource

http://www.bms.com/clinical_trials/Pages/Investigator_Inquiry_form.aspx

Investigator Inquiry form

Other Identifiers

2009-016699-63

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

CA182-046

Identifier Type: -

Identifier Source: org_study_id