Belinostat in Treating Patients With Liver Cancer That Cannot Be Removed By Surgery
Adult Primary Hepatocellular Carcinoma
Advanced Adult Primary Liver Cancer
Localized Unresectable Adult Primary Liver Cancer
Recurrent Adult Primary Liver Cancer
|Study Design:||Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||A Phase I/II Study of PXD101 in Patients With Unresectable Hepatocellular Carcinoma With Pharmacokinetic and Pharmacodynamic Evaluation|
- Dose-limiting toxicities (DLT) and maximum tolerated dose (MTD) of belinostat in patients with inoperable HCC (Phase I) [ Time Frame: Course 1 ] [ Designated as safety issue: Yes ]DLT is defined as any grade 4 hematological toxicity and any grade 3 or 4 non hematological toxicity during cycle 1, excluding alopecia. Specifically, grade 3 nausea, vomiting, or diarrhea that does not respond to therapy is considered dose-limiting. Also, delays in treatment greater than 2 weeks are also dose-limiting. MTD is defined as the dose below which >= 2 of 3 or >= 2 of 6 patients experience DLT. Graded using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 3.0.
- Tumor response in patients with inoperable HCC using belinostat (Phase II) [ Time Frame: Every 2 courses (approximately 6 weeks) ] [ Designated as safety issue: No ]Evaluated in this study using the new international criteria proposed by the Response Evaluation Criteria in Solid Tumors (RECIST) Committee. The 95% confidence intervals should be provided.
|Study Start Date:||May 2006|
|Primary Completion Date:||August 2010 (Final data collection date for primary outcome measure)|
Experimental: Treatment (enzyme inhibitor therapy)
Patients receive belinostat IV over 30 minutes on days 1-5. Courses repeat every 3 weeks in the absence of disease progression or unacceptable toxicity.
Other Name: PXD101
I. Determine the dose-limiting toxicity (DLT) and establish the maximum tolerated dose (MTD) of PXD101 (belinostat) in patients with unresectable hepatocellular carcinoma (HCC). (Phase I) II. Assess the pharmacokinetic profiles of PXD101 in these patients. (Phase I) III. Assess tumor response in patients treated with this drug. (Phase II)
OUTLINE: This is a multicenter, dose-escalation phase I study followed by a phase II study.
PHASE I: Patients receive belinostat intravenously (IV) over 30 minutes on days 1-5. Courses repeat every 3 weeks in the absence of disease progression or unacceptable toxicity. Cohorts of 3-6 patients receive escalating doses of belinostat until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity.
PHASE II: Patients receive belinostat (as in phase I) at the MTD determined in phase I.
After completion of study therapy, patients are followed for up to 8 weeks.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00321594
|United States, Wisconsin|
|University of Wisconsin Hospital and Clinics|
|Madison, Wisconsin, United States, 53792|
|Cancer Therapeutics Research Group|
|Singapore, Singapore, 119074|
|Principal Investigator:||Winnie Yeo||Chinese University of Hong Kong-Prince of Wales Hospital|