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

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

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

Study Overview

• Status: Completed
• Conditions: Advanced Hepatocellular Carcinoma
• Intervention / Treatment: Drug: Z-208

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Anticipated): 43
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• Japan
  • Tokyo, Japan
    • The University of Tokyo Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years to 79 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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	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

Collaborators and Investigators

• Sponsor: Zeria Pharmaceutical
• Investigators: Study Chair: Masao Omata, PhD, MD, Tokyo University

Study record dates

Study Major Dates

• Study Start: July 1, 2008
• Primary Completion (Actual): January 1, 2012
• Study Completion (Actual): June 1, 2012

Study Registration Dates

• First Submitted: August 8, 2008
• First Submitted That Met QC Criteria: August 8, 2008
• First Posted (Estimate): August 11, 2008

Study Record Updates

• Last Update Posted (Estimate): July 3, 2012
• Last Update Submitted That Met QC Criteria: June 29, 2012
• Last Verified: June 1, 2012

More Information

Terms related to this study

• Keywords: Z-208
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Adenocarcinoma; Neoplasms, Glandular and Epithelial; Digestive System Neoplasms; Liver Diseases; Liver Neoplasms; Carcinoma; Carcinoma, Hepatocellular
• Other Study ID Numbers: 07010101