Primary Outcome Measures:
- Phase I: Determine the maximum tolerated dose (MTD) of Z-208 in patients with advanced hepatocellular carcinoma [ Time Frame: 28 days ] [ Designated as safety issue: Yes ]
- Phase II : Assess the objective tumor response rate in patients according to Response Evaluation Criteria in Solid Tumors (RECIST) criteria [ Time Frame: 28 days for 6 courses ] [ Designated as safety issue: No ]
Secondary Outcome Measures:
- Phase I : Assess the objective tumor response rate in patients according to Response Evaluation Criteria in Solid Tumors (RECIST) criteria [ Time Frame: 28 days for 6 courses ] [ Designated as safety issue: No ]
- Phase I : Determine the pharmacokinetics of this drug in these patients [ Time Frame: 28 days for 6 courses ] [ Designated as safety issue: Yes ]
- Phase I : Determine the adverse effects profile of this drug in these patients [ Time Frame: 28 days for 6 courses ] [ Designated as safety issue: Yes ]
- Phase II: Determine the PFS [ Time Frame: 28 days for 6 courses ] [ Designated as safety issue: Yes ]
Intervention Details:
Drug: Z-208
Oral pills taken daily; 8mg, 12mg, 16mg, 4mg
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.