Belinostat in Treating Patients With Liver Cancer That Cannot Be Removed By Surgery

Advanced Adult Primary Liver Cancer Clinical Trial

Official title:

A Phase I/II Study of PXD101 in Patients With Unresectable Hepatocellular Carcinoma With Pharmacokinetic and Pharmacodynamic Evaluation

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00321594
• Other study ID #: NCI-2009-00141
• Secondary ID: CTRG-HC06/21/05N
• Status: Completed
• Phase: Phase 1/Phase 2
• First received: May 2, 2006
• Last updated: October 3, 2017
• Start date: May 2006
• Est. completion date: October 2012

Study information

• Verified date: October 2017
• Source: National Cancer Institute (NCI)
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This phase I/II trial is studying the side effects and best dose of belinostat and to see how well it works in treating patients with liver cancer that cannot be removed by surgery. Belinostat may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth

Description:

PRIMARY OBJECTIVES:

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.

Other known NCT identifiers

• NCT01251445

Recruitment information / eligibility

• Status: Completed
• Enrollment: 54
• Est. completion date: October 2012
• Est. primary completion date: August 2010
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Histologically or cytologically confirmed hepatocellular carcinoma that is not amenable to curative resection

• Measurable disease, defined as = 1 lesion that can be accurately measured in = 1 dimension (longest diameter to be recorded) as = 20 mm with conventional techniques OR as = 10 mm with MRI or spiral CT scan

• No known brain metastases

• No clinical ascites or encephalopathy

• Life expectancy > 12 weeks

• ECOG performance status (PS) 0-2 or Karnofsky PS 60-100%

• WBC = 3,000/mm³

• Absolute neutrophil count = 1,500/mm³

• Platelet count = 100,000/mm³

• Bilirubin = 1.7 mg/dL

• Albumin = 2.8 mg/dL

• ALT = 5.0 times upper limit of normal (ULN)

• Alkaline phosphatase = 6 times ULN

• Prothrombin time = 4 sec above ULN

• Creatinine = 1.6 mg/dL

• Not pregnant or nursing

• Negative pregnancy test

• Fertile patients use effective contraception

• No Child's-Pugh's grading Class C hepatic impairment

• No history of allergic reaction attributed to compounds of similar chemical or biologic composition to PXD101

• No marked baseline prolongation of QT/QTc interval, including the following:

• Repeated demonstration of a QTc interval > 500 msec

• Long QT Syndrome

• No ongoing or active infection

• No significant cardiovascular disease, including any of the following:

• Unstable angina pectoris

• Uncontrolled hypertension

• Congestive heart failure related to primary cardiac disease

• Condition requiring anti-arrhythmic therapy

• Ischemic or severe valvular heart disease

• Myocardial infarction within the past 6 months

• No psychiatric illness or social situation that would preclude study compliance

• No other uncontrolled illness

• More than 4 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin C) and recovered

• More than 4 weeks since prior radiotherapy and recovered

• At least 2 weeks since prior valproic acid

• No concurrent combination antiretroviral therapy for HIV-positive patients

• No concurrent participation in another investigational study

• No other concurrent investigational agents

• No other concurrent anticancer therapy

• No concurrent use of any of the following:

• Disopyramide

• Dofetilide

• Ibutilide

• Procainamide

• Quinidine

• Sotalol

• Bepridil

• Amiodarone

• Arsenic trioxide

• Cisapride

• Calcium channel blockers (e.g., lidoflazine)

• Clarithromycin

• Erythromycin

• Halofantrine

• Pentamidine

• Sparfloxacin

• Domperidone

• Droperidol

• Chlorpromazine

• Haloperidol

• Mesoridazine

• Thioridazine

• Pimozide

• Methadone

Related Conditions & MeSH terms

• Adult Primary Hepatocellular Carcinoma
• Advanced Adult Primary Liver Cancer
• Carcinoma
• Carcinoma, Hepatocellular
• Liver Neoplasms
• Localized Unresectable Adult Primary Liver Cancer
• Recurrent Adult Primary Liver Cancer

Intervention

Drug:
• belinostat
Given IV

Locations

Country	Name	City	State
Singapore	Cancer Therapeutics Research Group	Singapore
United States	University of Wisconsin Hospital and Clinics	Madison	Wisconsin

Sponsors (1)

Lead Sponsor	Collaborator
National Cancer Institute (NCI)

Countries where clinical trial is conducted

United States,  Singapore, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	Course 1
Primary	Tumor Response in Patients With Inoperable HCC Using Belinostat (Phase II)	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.	Every 2 courses (approximately 6 weeks)