Comparison of Brivanib and Best Supportive Care to Placebo for Treatment of Liver Cancer for Those Subjects Who Have Failed Sorafenib Treatment

Study Overview
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Brief Summary
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The purpose of this study is to determine if Brivanib is an effective treatment for liver cancer in patients who have failed or could not take Sorafenib

Official Title
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A Randomized, Double-blind, Multi-center Phase III Study of Brivanib Plus Best Supportive Care (BSC) Versus Placebo Plus BSC in Subjects With Advanced Hepatocellular Carcinoma (HCC) Who Have Failed or Are Intolerant to Sorafenib: The BRISK PS Study (Brivanib Study in HCC Patients at Risk Post Sorafenib)

Conditions
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Liver Cancer

Intervention / Treatment
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* Drug: Brivanib
* Other: Placebo
* Procedure: Best Supportive Care


Participation Criteria
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Eligibility Criteria
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For more information regarding BMS clinical trial participation, please visit www.BMSStudyConnect.com. Inclusion Criteria: Histologic or cytologic confirmed diagnosis of HCC Advanced disease defined as (i) disease not eligible for surgical or loco-regional therapy or (ii) disease progressive after surgical or loco-regional therapy Patient has failed ≥ 14 days of Sorafenib treatment Cirrhotic status of Child-Pugh Class A or B with a score of 7 Eastern Cooperative Oncology Group (ECOG) performance status 0, 1, 2 Subjects who have a life expectancy of at least 8 weeks Adequate hematologic, hepatic, and renal function Exclusion Criteria: women of childbearing potential (WOCBP) who are unwilling or unable to use an acceptable method to avoid pregnancy Previous or concurrent cancer that is distinct in primary site History of active cardiac disease Thrombotic or embolic events within the past 6 months Any other hemorrhage/bleeding event > Common Terminology Criteria for Adverse Events (CTCAE) Grade 3 within 4 weeks Inability to swallow tablets or untreated malabsorption syndrome History of human immunodeficiency virus (HIV) infection Prior use of systemic investigational agents for HCC (except for Sorafenib)

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Brivanib<br> | Drug: Brivanib<br>* Tablets, Oral, 800 mg, once daily, until disease progression or toxicity<br>* Other names: BMS-582664;Procedure: Best Supportive Care<br>* Trans-Arterial Chemo-Embolization (TACE) Therapy<br>|
| Placebo Comparator: Placebo<br> | Other: Placebo<br>* Tablets, Oral, 0 mg, once daily, until disease progression or toxicity<br>Procedure: Best Supportive Care<br>* Trans-Arterial Chemo-Embolization (TACE) Therapy<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To compare overall survival of subjects with advanced HCC who have progressed on/after or are intolerant to Sorafenib and receive Brivanib plus best supportive care (BSC) to those receiving placebo plus BSC |  | computerized tomography (CT)/ magnetic resonance imaging (MRI) every six weeks until progression or death | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To compare time to progression (TTP) (Investigator assessed using modified Response Evaluation Criteria In Solid Tumors (RECIST) for HCC criteria) |  | 35 months | 
| To compare the Independent Radiological Review Committee (IRRC) assessed objective response rate (ORR) and disease control rate (DCR) using modified RECIST for HCC criteria |  | 35 months | 
| To assess duration of response, duration of disease control and time to response |  | 6 weeks | 
| To assess safety profile of brivanib. Safety will be assessed by the number of adverse events (AEs), serious adverse events (SAEs), periodic data monitoring committee (DMC) review |  | 35 months |