Study of Axitinib in Patients With Unresectable Hepatocellular Carcinoma

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the potential role of Axitinib (AG-013736) in the treatment of unresectable/metastatic hepatocellular carcinoma (HCC)

Detailed Description
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This is a phase II study of an investigational drug, Axitinib following prior antiangiogenic therapy in patients with advanced hepatocellular carcinoma. Hepatocellular carcinoma (HCC) is a primary cancer of the liver. Angiogenesis is a physiological process involving the growth of new blood vessels from pre-existing vessels. A tyrosine kinase is an enzyme that can inhibit angiogenesis. In this study, patients with advanced HCC who have failed prior antiangiogenic therapy, will receive Axitinib in cycles of 4 weeks. Axitinib is an oral, potent and selective inhibitor of angiogenesis. This study will evaluate the response rate of HCC following treatment with Axitinib as well as safety, feasibility, overall survival of patients, progression-free survival, and quality of life in persons with unresectable HCC. The study also compares response determined by RECIST to response determined by Choi Criteria.

Official Title
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A Phase II Trial of Axitinib (AG-013736) After Prior Antiangiogenic Therapy in Advanced Hepatocellular Carcinoma

Conditions
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Hepatocellular Carcinoma

Intervention / Treatment
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* Drug: Axitinib (AG-013736)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Unresectable and/or metastatic Hepatocellular Carcinoma Previous treatment with tyrosine kinase inhibitors or antiangiogenic drugs Life expectancy of ≥12 weeks At least one tumor lesion At least 2 weeks since the end of prior systemic treatment No evidence of pre-existing uncontrolled hypertension ECOG 0 or 1 Adequate organ function Not appropriate for curative therapy Child A or B7 cirrhosis CLIP score ≤ 4 Exclusion Criteria: Received any other systemic therapy for Hepatocellular Carcinoma within 2 weeks prior to treatment Major surgery <4 weeks or radiation therapy <2 weeks of starting the study treatment Previous or concurrent cancer that is distinct in primary site or histology from Hepatocellular Carcinoma Severe acute or chronic medical or psychiatric condition Need for treatment with prohibited drugs Has received local therapy to all measurable lesions Stage B8 or higher liver cirrhosis Ascites refractory to diuretic therapy Clinically significant ECG abnormality

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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Axitinib<br>Oral Axitinib (5mg, twice daily) will be administered to all patients | Drug: Axitinib (AG-013736)<br>* 5mg, oral, twice daily, continuous dosing. A dosing cycle is defined as 4 weeks. Treatment may continue until disease progression/relapse<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Response rate |  | Response rate assessed by CT scan at 16 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Feasibility | The ability to administer one or more cycles of Axitinib to >70% of patients at a dose of 5mg po BID | Assessed at the end of stage 1 (10 patients accrued) and at the end of trial (Stage 2, 29 patients total) | 
| Overall survival |  | At the completion of trial, 1.5 years | 
| Response rate comparison |  | Comparison of outcomes with RECIST criteria to Choi criteria and changes to perfusion on DCE ultrasound will occur at the end of stage 1 (after accrual of 10 patients) and trial completion | 
| Progression-free survival |  | At trial completion, 1.5 years | 
| Quality of life | Assessed by FACT-Hep | At completion of trial, 1.5 years | 
| Number of Participants with Adverse Events as a Measure of Safety and Tolerability | Efficacy and Toxicity in Asian vs non-Asian patients will be assessed by comparing the adverse effects profile and rate of grade 3 and grade 4 toxicity in these populations | At completion of trial, 1.5 years | 
| Number of Participants with Adverse Events as a Measure of Safety | Adverse effects profile and rate of grade 3 and 4 toxicity will be assessed as a measure of safety | At completion of trial, 1.5 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Hepatocellular Carcinoma, Advanced Hepatocellular Carcinoma, Liver Cancer, Axitinib, AG-013736