Study of Pegylated Human Recombinant Arginase for Liver Cancer (BCT-100-002)

Recombinant Human Arginase I (rhArgI) for Patients With Advanced Hepatocellular Carcinoma (HCC)

The purpose of this study is to determine whether recombinant human arginase (PEG-BCT-100) is safe and effective in the treatment of advanced hepatocellular carcinoma (HCC).

The primary objectives of this study are:

• To evaluate any objective tumor responses to PEG-BCT-100 in HCC patients receiving weekly doses of PEG-BCT-100 alone.
• To perform PK and PD analysis
• To measure Quality of Life of the patients

Secondary objectives of this study are:

• To define any toxicity associated with the metabolic and cellular alterations of ADD relative to dose and PK of PEG-BCT-100 (rhArgIpeg5000).
• To confirm the safety and anti-tumor activity of PEG-BCT-100 at the preferred dose (1600U/kg) in 50 patients (at least 18 evaluable subjects) with advanced HCC.
• To measure duration of response including Overall Survival and Time to Progression analysis

Inclusion Criteria:

• Confirmed diagnosis of HCC according to the European Association for the Study of the Liver criteria
• Known underlying HCC etiology specified by hepatitis B, hepatitis C, post alcoholic cirrhosis, or other
• HCC lesion(s) which are not resectable and which are measurable by C-T scan
• Progression of or non-response of HCC lesions after treatments which are considered best standard of care - surgical resection, radiofrequency ablation, chemoembolization
• No cancer treatment or surgery within the prior 4 weeks, either chemotherapy, targeted biologic or enzymes, either approved or investigational;
• Males or females from 18 to 75 years-old, inclusive;
• Ability and willingness to provide written informed consent;
• Karnofsky performance status of 80% or above and expected survival of more than 12 weeks; and,
• Negative urine pregnancy test, if female, and willingness to use an effective method of contraception during the entire study period
• No cognitive impairment
• Ability to understand and read Chinese

Exclusion Criteria:

• Advancing liver failure indicated by uncontrolled ascites, pleural effusions, encephalopathy, or a Child-Pugh score of C
• Significant hepatic, renal or bone marrow dysfunction indicated by total bilirubin >40 µmol/L, evidence of bile duct obstruction, serum albumin <30 g/L, serum SGOT >5 x upper limit of normal, ANC <1.0 x 10^9/L, platelets <100 x 10^9/L, or INR >2.0
• Significant cardiac or pulmonary disease defined by New York Heart Association (NYHA) Class III or IV, VEF <50% by echo or MUGA, or a history of myocardial infarction within the past 6 months, significant unstable arrhythmia or evidence of ischemia on ECG
• Pregnant or nursing women. NOTE: Women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control or abstinence) prior to study entry and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately.
• Significant active infection including HIV requiring oral or parenteral anti-infective therapies;
• Use of investigational drug(s) within 4 weeks of enrollment; or,
• Prior treatment with arginine depleting agent.