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

Gastro-Intestinal Cancer Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01046864
• Other study ID #: CA182-046
• Secondary ID: 2009-016699-63
• Status: Completed
• Phase: Phase 1
• First received: January 11, 2010
• Last updated: September 15, 2014
• Start date: February 2010
• Est. completion date: June 2014

Study information

• Verified date: September 2014
• Source: Bristol-Myers Squibb
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug AdministrationCanada: Health CanadaFrance: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)Japan: Ministry of Health, Labor and WelfareJapan: Pharmaceuticals and Medical Devices Agency
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 49
• Est. completion date: June 2014
• Est. primary completion date: June 2014
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 20 Years to 75 Years

Eligibility

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 Design

Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Factorial Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Gastro-Intestinal Cancer
• Gastrointestinal Neoplasms
• Intestinal Neoplasms

Intervention

Drug:
• 5-FU
IV solution, IV bolus over 2-4 minutes, 400 mg/m², Every 14 days, Until disease progression/toxicity
• Leucovorin
IV solution, IV over 2 hours, 400 mg/m², Every 14 days, Until disease progression/toxicity
• 5-FU
IV solution, IV infusion over 46 hours, 2400 mg/m², Every 14 days, Until disease progression/toxicity
• Irinotecan
IV solution, IV over 90 minutes, 180 mg/m², Every 14 days, Until disease progression/toxicity
• Brivanib
Tablets, Oral, 400 - 800 mg, once daily, Until disease progression/toxicity
• Brivanib
Tablets, Oral, 600 - 800 mg, once daily, Until disease progression/toxicity
• Brivanib
Tablets, Oral, 800 mg, once daily, Until disease progression/toxicity

Locations

Country	Name	City	State
Canada	Local Institution	Edmonton	Alberta
Canada	Local Institution	Ottawa	Ontario
France	Local Institution	Villejuif Cedex
United States	Texas Oncology	Dallas	Texas
United States	Usc/Norris Comprehensive Cancer Center	Los Angeles	California
United States	Scott & White Memorial Hospital And Clinic	Temple	Texas

Sponsors (1)

Lead Sponsor	Collaborator
Bristol-Myers Squibb

Countries where clinical trial is conducted

United States,  Canada,  France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Yes
Secondary	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	No
Secondary	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	No
Secondary	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	No

External Links

•   BMS clinical trial educational resource
•   BMS Clinical Trial Information
•   FDA Safety Alerts and Recalls
•   Investigator Inquiry form