ADI-PEG 20 Versus Placebo in Subjects With Advanced Hepatocellular Carcinoma Who Have Failed Prior Systemic Therapy

Inclusion Criteria:

• Prior diagnosis of HCC confirmed histologically.
• Prior treatment with at least 1 systemic agent, with documented progressive disease after systemic agent(s), or adverse event(s)associated with prior systemic agent(s) that resulted in discontinuance of that agent(s).
• Cirrhotic status of Child-Pugh grade B7.
• Expected survival of at least 3 months.
• Adequate hematologic, hepatic, and renal function.

Exclusion Criteria:

• Candidate for potential curative therapies (i.e., resection or transplantation) or loco-regional approaches (i.e., ablation, embolization).
• Significant cardiac disease.
• Serious infection requiring treatment with systemically administered antibiotics.
• Pregnancy or lactation.
• Expected non-compliance.
• Uncontrolled intercurrent illness, or psychiatric illness or social situations that would limit compliance with study requirements.
• Subjects who have had any anticancer treatment within 2 weeks prior to entering the study.
• Subjects who have not fully recovered from toxicities associated with previous HCC loco-regional or systemic therapies.
• Subjects with history of another primary cancer, with the exception of: a) curatively resected non-melanoma skin cancer; b) curatively treated cervical carcinoma in situ; or c) other primary solid tumor with no known active disease present in the opinion of the investigator will not affect patient outcome in the setting of current HCC diagnosis.
• Allergy to pegylated products.
• Bleeding esophageal or gastric varices within the prior three months, except if banded or treated.
• Subjects known to be HIV positive.
• Uncontrolled ascites (defined as not easily controlled with diuretic treatment).
• Having received any blood transfusion, blood component preparation, erythropoietin, albumin preparation, or granulocyte colony stimulating factors (G-CSF) within 7 days prior to screening laboratories or after screening laboratories have been obtained until first dose of study drug or placebo.
• Use of traditional medicines approved by local authorities, including but not limited to Chinese herbs within 14 days of first dose of study drug or placebo.
• ECOG performance status > 2.
• Prior allograft,including liver transplant.