Phase I/II Study of Z-208 in Advanced Hepatocellular Carcinoma (HCC)

This is an open-label, dose-escalation study PhaseI Treatments repeats for 28 days for 1 course in the unacceptable toxicity

Cohort of 3 patients receive escalating doses of Z-208 until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 1 of 3 patients experience dose-limiting toxicity.

PhaseII Treatments repeats for 28 days for 6 courses until absence of disease progression or unacceptable toxicity.

Inclusion criteria

• Histologically or cytologically confirmed hepatocellular carcinoma
• At least one measurable site of disease according to RECIST criteria that has not been irradiated.
• Child-Pugh classification A & B
• ECOG performance status of 0-1
• Life expectancy is more than 90 days
• Adequate organ function as defined by the following criteria, Hemoglobin ≥ 8.0 g/dL WBC ≥ 3,000/mm^3 <12,000/mm^3 Absolute neutrophil count ≥ 1,500/mm^3 Platelet count ≥ 50,000/mm^3 AST and ALT ≤ 5 times upper limit of normal (ULN) Albumin ≥ 2.8 g/dL Bilirubin ≤ 2.0 mg/dL Creatinine ≤ 1.5 times ULN
• Must provide written informed consent prior to the implementation of any study assessment or procedures

Exclusion criteria

• Patients received treatment with any of the following within the specified timeframe;Any surgical procedure, radiofrequency ablation, intraarterial chemotherapy within 30 days prior to signing the ICF, any treatment with transfusion, albumin preparation, G-CSF within 15 days prior to signing the ICF
• CNS involvement must have completed appropriate treatment
• Prior deep vein thrombosis
• Has ascites, pleural effusions or pericardial fluid refractory
• Active clinically serious infection excluding chronic hepatitis
• Any history of deep vein thrombosis, pulmonary embolism, myocardial infraction, cerebrovascular accident
• Allergy or hypersensitivity to Vitamin A
• Women who are pregnant or breast feeding