Clinical trial NCT00731445: Phase I/II Study of Z-208 in Advanced Hepatocellular Carcinoma (HCC)
Official title: Phase I/II Dose Escalation, Pharmacokinetic, Safety, and Efficacy Study of Oral Z-208 in Patients With Advanced Hepatocellular Carcinoma
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Advanced Hepatocellular Carcinoma
Keywords: Z-208
Lead sponsor: Zeria Pharmaceutical
Sponsor class: INDUSTRY
First posted: 2008-08-11
Enrollment: 43
Sex: ALL
Minimum age (years): 20
Maximum age (years): 79
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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

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.

Eligibility criteria: 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

Primary outcomes:
measure: Phase I: Determine the maximum tolerated dose (MTD) of Z-208 in patients with advanced hepatocellular carcinoma
timeFrame: 28 days
measure: Phase II : Assess the objective tumor response rate in patients according to Response Evaluation Criteria in Solid Tumors (RECIST) criteria
timeFrame: 28 days for 6 courses
Secondary outcomes:
measure: Phase I : Assess the objective tumor response rate in patients according to Response Evaluation Criteria in Solid Tumors (RECIST) criteria
timeFrame: 28 days for 6 courses
measure: Phase I : Determine the pharmacokinetics of this drug in these patients
timeFrame: 28 days for 6 courses
measure: Phase I : Determine the adverse effects profile of this drug in these patients
timeFrame: 28 days for 6 courses
measure: Phase II: Determine the PFS
timeFrame: 28 days for 6 courses
Other outcomes:
Locations:
city: Tokyo
country: Japan
facility: The University of Tokyo Hospital
Study officials:
affiliation: Tokyo University
name: Masao Omata, PhD, MD
role: STUDY_CHAIR
References: