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

NCT01046864 | Completed Phase 1

• 2 other identifiers: CA182-0462009-016699-63
• Study Type: interventional
• Target: 49
• Locations: 3 countries
• Sites: 6

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

Keywords

Gastro-Intestinal Cancer, NOS

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (3)

• 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

Study Arms (3)

Arm 1

EXPERIMENTAL

Drug: 5-FU; Drug: Leucovorin; Drug: Brivanib

Arm 2

EXPERIMENTAL

Drug: 5-FU; Drug: Leucovorin; Drug: Irinotecan; Drug: Brivanib

Arm 3

EXPERIMENTAL

Japanese Population

Drug: 5-FU; Drug: Leucovorin; Drug: Irinotecan; Drug: Brivanib

Interventions

5-FU DRUG

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

Also known as: Fluorouracil

Arm 1; Arm 2; Arm 3

Leucovorin DRUG

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

Also known as: Folinic acid

Arm 1; Arm 2; Arm 3

Irinotecan DRUG

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

Also known as: Camptosar

Arm 2; Arm 3

Brivanib DRUG

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

Arm 1

Eligibility Criteria

• Age: 20 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Bristol-Myers Squibb: lead

Study Sites (6)

Usc/Norris Comprehensive Cancer Center

Los Angeles, California, 90033, United States

Location

Texas Oncology

Dallas, Texas, 75246, United States

Location

Scott & White Memorial Hospital And Clinic

Temple, Texas, 76508, United States

Location

Local Institution

Edmonton, Alberta, T6G 1Z2, Canada

Location

Local Institution

Ottawa, Ontario, K1H 8L6, Canada

Location

Local Institution

Villejuif, 94800, France

Location

Related Links

• BMS clinical trial educational resource
• Investigator Inquiry form

MeSH Terms

Conditions

Pyloric Stenosis, Hypertrophic

Interventions

Fluorouracil; Leucovorin; Irinotecan; brivanib

Condition Hierarchy (Ancestors)

Pyloric Stenosis; Gastric Outlet Obstruction; Stomach Diseases; Gastrointestinal Diseases; Digestive System Diseases

Intervention Hierarchy (Ancestors)

Uracil; Pyrimidinones; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Formyltetrahydrofolates; Tetrahydrofolates; Folic Acid; Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Coenzymes; Enzymes and Coenzymes; Camptothecin; Alkaloids

Study Officials

• Bristol-Myers Squibb

  Bristol-Myers Squibb

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: FACTORIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 11, 2010
• First Posted: January 12, 2010
• Study Start: February 1, 2010
• Primary Completion: June 1, 2014
• Study Completion: June 1, 2014
• Last Updated: September 16, 2014

Record last verified: 2014-09

Locations

FR (1); US (3); CA (2)