Ph 1 Trial of ADI PEG 20 Plus Sorafenib to Treat Patients With Liver Cancer

Inclusion criteria

• Prior diagnosis of HCC confirmed histologically.
• HCC tissue either from an archived specimen or from a new biopsy of sufficient amount and quality should be available for IHC determination of ASS status, and other biomarkers, to be performed retrospectively. Subjects with no tissue available would require a biopsy.
• No prior treatment with systemic chemotherapy (except as noted in exclusion criteria # 10).
• Measurable disease using RECIST 1.1 criteria (Appendix A). At least 1 measurable lesion must be present. Subjects who have received local-regional therapy such as (but not limited to) chemoembolization, embolization, cryoablation, hepatic artery therapy, percutaneous ethanol injection, radiation therapy, radiofrequency ablation or surgery are eligible, provided that they have either a target lesion which has not been treated with local therapy and/or the target lesion(s) within the field of the local regional therapy has shown an increase of ≥ 20% in size. Local-regional therapy must be completed at least 4 weeks prior to the baseline CT scan. Local therapies including chemoembolization do not count as prior systemic therapy.
• Cirrhotic status of Child-Pugh grade A. Child-Pugh status should be determined based on clinical findings and laboratory data during the screening period (Appendix B). Subjects on anti-coagulants are to receive 1 point for their INR status, as they are presumed to have a <1.7 baseline PT/INR.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0-1 (Appendix C).
• Expected survival of at least 3 months.
• Age ≥ 18 years.

Exclusion criteria

• Candidate for potential curative therapies (i.e., resection or transplantation).
• Prior allograft transplantation including liver transplantation.
• Serious infection requiring treatment with systemically administered antibiotics at the time of study entrance, or an infection requiring systemic antibiotic therapy within 7 days prior to the first dose of study treatment.
• Pregnancy or lactation.
• Expected non-compliance.
• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure (New York Heart Association Class III or IV; Appendix D), unstable angina pectoris, cardiac arrhythmia, or psychiatric illness or social situations that would limit compliance with study requirements.
• Subjects who have not fully recovered from toxicities associated with previous HCC loco-regional 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.