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

Study Overview
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Brief Summary
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This phase I/II is studying the side effect and best dose of Z-208 for patients with advanced hepatocellular carcinoma

Detailed Description
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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.

Official Title
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Phase I/II Dose Escalation, Pharmacokinetic, Safety, and Efficacy Study of Oral Z-208 in Patients With Advanced Hepatocellular Carcinoma

Conditions
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Advanced Hepatocellular Carcinoma

Intervention / Treatment
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* Drug: Z-208


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 20 Years
Maximum Age: 79 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Intervention/Treatment |
| --- |
|Drug: Z-208|Oral pills taken daily; 8mg, 12mg, 16mg, 4mg|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Phase I: Determine the maximum tolerated dose (MTD) of Z-208 in patients with advanced hepatocellular carcinoma |  | 28 days | 
| Phase II : Assess the objective tumor response rate in patients according to Response Evaluation Criteria in Solid Tumors (RECIST) criteria |  | 28 days for 6 courses | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Phase I : Assess the objective tumor response rate in patients according to Response Evaluation Criteria in Solid Tumors (RECIST) criteria |  | 28 days for 6 courses | 
| Phase I : Determine the pharmacokinetics of this drug in these patients |  | 28 days for 6 courses | 
| Phase I : Determine the adverse effects profile of this drug in these patients |  | 28 days for 6 courses | 
| Phase II: Determine the PFS |  | 28 days for 6 courses | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Z-208