A Phase I/II Study of PXD101 in Patients With Unresectable Hepatocellular Carcinoma With Pharmacokinetic and Pharmacodynamic Evaluation
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.
Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Dose-limiting toxicities (DLT) and maximum tolerated dose (MTD) of belinostat in patients with inoperable HCC (Phase I)
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.
Chinese University of Hong Kong-Prince of Wales Hospital
United States: Food and Drug Administration
|University of Wisconsin Hospital and Clinics||Madison, Wisconsin 53792-0001|