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

Advanced Hepatocellular Carcinoma Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00731445
• Other study ID #: 07010101
• Status: Completed
• Phase: Phase 1/Phase 2
• First received: August 8, 2008
• Last updated: June 29, 2012
• Start date: July 2008
• Est. completion date: June 2012

Study information

• Verified date: June 2012
• Source: Zeria Pharmaceutical
• Contact: n/a
• Is FDA regulated: No
• Health authority: Japan: Pharmaceuticals and Medical Devices Agency
• Study type: Interventional

Clinical Trial Summary

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

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 43
• Est. completion date: June 2012
• Est. primary completion date: January 2012
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 20 Years to 79 Years

Eligibility

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 Design

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Advanced Hepatocellular Carcinoma
• Carcinoma
• Carcinoma, Hepatocellular

Intervention

Drug:
• Z-208
Oral pills taken daily; 8mg, 12mg, 16mg, 4mg

Locations

Country	Name	City	State
Japan	The University of Tokyo Hospital	Tokyo

Sponsors (1)

Lead Sponsor	Collaborator
Zeria Pharmaceutical

Country where clinical trial is conducted

Japan, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Phase I: Determine the maximum tolerated dose (MTD) of Z-208 in patients with advanced hepatocellular carcinoma		28 days	Yes
Primary	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	No
Secondary	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	No
Secondary	Phase I : Determine the pharmacokinetics of this drug in these patients		28 days for 6 courses	Yes
Secondary	Phase I : Determine the adverse effects profile of this drug in these patients		28 days for 6 courses	Yes
Secondary	Phase II: Determine the PFS		28 days for 6 courses	Yes