Phase I/II Combination With Irinotecan- Erbitux

Study Overview
=================
Brief Summary
-----------------
Part 1: To define the recommended dose of brivanib that can be safely administered in combination with Erbitux (Cetuximab) and irinotecan to subjects with advanced metastatic colorectal cancer (MCRC) Part 2: To compare median duration of progression free survival (PFS)

Official Title
-----------------
A Blinded, Randomized, Phase 1/2 Study of Brivanib Alaninate vs Placebo in Combination With Erbitux and Irinotecan K-Ras Wildtype Subjects With Metastatic Colorectal Cancer

Conditions
-----------------
Metastatic Colorectal Cancer (MCRC)

Intervention / Treatment
-----------------
* Drug: Cetuximab
* Drug: Irinotecan
* Drug: Brivanib
* Drug: Brivanib
* Drug: Brivanib Placebo


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Biopsy proven MCRC Prior irinotecan allowed Prior Erbitux allowed Exclusion Criteria: No prior brivanib No prior combination of irinotecan with Erbitux No secondary malignancies No anti-coagulation therapy No prior history of blood clots requiring anti-coagulation

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Arm 1 - Phase 1<br>Cetuximab + Irinotecan + Brivanib OR Cetuximab + Irinotecan + Brivanib Placebo | Drug: Cetuximab<br>* IV solution, IV, QW, 400 mg/m2 X 1, followed by 250mg/m2, until progression<br>* Other names: BMS-564717;Drug: Irinotecan<br>* IV solution, IV, Q3W, 350 mg/m2, until progression<br>Drug: Brivanib<br>* Oral, Tablet, QD, (200 mg, 400 mg, 600 mg, 800 mg dose escalation) until progression<br>Drug: Brivanib Placebo<br>* Oral, tablet, QD, until progression<br>|
| Placebo Comparator: Arm 2 - Phase 2<br>Cetuximab + Irinotecan + Brivanib OR Cetuximab + Irinotecan + Brivanib Placebo | Drug: Cetuximab<br>* IV solution, IV, QW, 400 mg/m2 X 1, followed by 250mg/m2, until progression<br>* Other names: BMS-564717;Drug: Irinotecan<br>* IV solution, IV, Q3W, 350 mg/m2, until progression<br>Drug: Brivanib<br>* Oral, Tablet, QD, MTD determined in Arm 1, Phase 1, until progression<br>Drug: Brivanib Placebo<br>* Oral, tablet, QD, until progression<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pharmacokinetics and markers of exploratory coagulation pathways will be conducted during this trial |  | PK C1D1-C2-D3, biomarker throughout the study | 
| Safety and tolerability of interventions will be collected |  | throughout the study on Part II | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Efficacy on tumor progression and progression free survival will be collected on all enrolled subjects |  | throughout the study on Part II |