Ph 3 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 diseaseafter 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) orloco-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 thatwould limit compliance with study requirements.

• Subjects who have had any anticancer treatment within 2 weeks prior to entering thestudy.

• Subjects who have not fully recovered from toxicities associated with previous HCCloco-regional or systemic therapies.

• Subjects with history of another primary cancer, with the exception of: a) curativelyresected 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 ofthe investigator will not affect patient outcome in the setting of current HCCdiagnosis.

• Allergy to pegylated products.

• Bleeding esophageal or gastric varices within the prior three months, except if bandedor 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 daysprior to screening laboratories or after screening laboratories have been obtaineduntil first dose of study drug or placebo.

• Use of traditional medicines approved by local authorities, including but not limitedto Chinese herbs within 14 days of first dose of study drug or placebo.

• ECOG performance status > 2.

• Prior allograft,including liver transplant.