Study Of Sunitinib Malate Versus Sorafenib In Patients With Inoperable Liver Cancer

Study Overview
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Brief Summary
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The study will evaluate the efficacy and safety of sunitinib (Arm A), given at 37.5 mg orally once daily, compared to sorafenib (Arm B), given orally at 400 mg twice daily, in patients with inoperable liver cancer. A total number of 1200 patients will be enrolled, 600 on Arm A and 600 on Arm B. Study treatment may be adjusted based on patient tolerance. and will be given until disease progression, occurrence of unacceptable toxicity, or other withdrawal criteria are met. After discontinuation of study treatment, patients will be followed up in order to collect information on further antineoplastic therapy and survival.

Detailed Description
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This study was terminated on April 22th, 2010, based on a higher incidence of serious adverse events in the sunitinib arm compared to the sorafenib arm, and the fact that sunitinib did not meet the criteria to demonstrate that it was either superior or non-inferior to sorafenib in the survival of patients with advanced hepatocellular cancer. Patients on sunitinib who are judged by the investigator as receiving clinical benefit may chose to remain on study and continue treatment with sunitinib until clinical benefit as per the investigator's judgment.

Official Title
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A Multinational, Randomized, Open-Label, Phase 3 Study Of Sunitinib Malate Versus Sorafenib In Patients With Advanced Hepatocellular Carcinoma

Conditions
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Carcinoma, Hepatocellular

Intervention / Treatment
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* Drug: sunitinib malate
* Drug: sorafenib


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histologically-confirmed diagnosis of hepatocellular carcinoma presence of measurable disease by radiographic imaging Child-Pugh class A ECOG PS 0 or 1 adequate organ function. Exclusion Criteria: Prior treatment with any systemic treatment for hepatocellular carcinoma prior local treatment within 4 weeks from entry presence of clinically relevant ascites severe hemorrhage <4 weeks of starting study treatment known HIV or serious acute or chronic illness current treatment on another clinical trial pregnancy or breastfeeding

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: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arm A<br>sunitinib arm | Drug: sunitinib malate<br>* sunitinib capsules at starting dose of 37.5 mg PO daily, until disease progression, occurrence of unacceptable toxicity, or other withdrawal criteria are met. Sunitinib dosing interruptions and/or reductions are allowed based on patient tolerability.<br>* Other names: Sutent®;|
| Active Comparator: Arm B<br>sorafenib arm | Drug: sorafenib<br>* sorafenib tablets at starting dose of 400 mg PO twice daily, until disease progression, occurrence of unacceptable toxicity, or other withdrawal criteria are met. Sorafenib dosing interruptions and/or reductions are allowed based on patient tolerability.<br>* Other names: Nexavar®;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Survival (OS) | Overall survival is the duration from randomization to death. For participants who are alive, overall survival was censored at the last contact. | Baseline, every 4 weeks during treatment, every 8 weeks posttreatment up to Week 150 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression-Free Survival (PFS) | The period from randomization until disease progression or death. | Baseline, every 4 weeks during treatment, every 8 weeks posttreatment up to Week 150 | 
| Time to Tumor Progression (TTP) | Time in weeks from randomization to first documentation of objective tumor progression or death due to cancer, whichever comes first. Tumor progression was determined from oncologic assessment data (where data meet the criteria for progressive disease [PD]) | Baseline, every 4 weeks during treatment, every 8 weeks posttreatment up to Week 150 | 
| European Quality of Life (EQ-5D)- Health State Profile Utility Score | EQ-5D: participant rated questionnaire to assess health-related quality of life in terms of a single utility score. Health State Profile component assesses level of current health for 5 domains: mobility, self-care, usual activities, pain and discomfort, and anxiety and depression; 1 indicates better health state (no problems); 3 indicates worst health state (eg, confined to bed). Scoring formula assigns a utility value for each domain in the profile. Score is transformed and results in a score range -0.594 to 1.000; higher score indicates better health state. | Day 1 of each cycle | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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sunitinib, phase 3, randomized, hepatocellular, liver