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

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ClinicalTrials.gov Identifier: NCT00321594
Recruitment Status : Completed
First Posted : May 4, 2006
Results First Posted : September 26, 2017
Last Update Posted : November 6, 2017
Information provided by (Responsible Party):
National Cancer Institute (NCI)

Brief 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

Condition or disease Intervention/treatment Phase
Adult Primary Hepatocellular Carcinoma Advanced Adult Primary Liver Cancer Localized Unresectable Adult Primary Liver Cancer Recurrent Adult Primary Liver Cancer Drug: belinostat Phase 1 Phase 2

Detailed Description:


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.

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 54 participants
Intervention Model: Single Group Assignment
Masking: None (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
Study Start Date : May 2006
Primary Completion Date : August 2010
Study Completion Date : October 2012

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Liver Cancer
Drug Information available for: Belinostat
U.S. FDA Resources

Arm Intervention/treatment
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.
Drug: belinostat
Given IV
Other Name: PXD101

Primary Outcome Measures :
  1. Dose-limiting Toxicities (DLT) and Maximum Tolerated Dose (MTD) of Belinostat in Patients With Inoperable HCC (Phase I) [ Time Frame: Course 1 ]
    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.

  2. Tumor Response in Patients With Inoperable HCC Using Belinostat (Phase II) [ Time Frame: Every 2 courses (approximately 6 weeks) ]
    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.

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00321594

United States, Wisconsin
University of Wisconsin Hospital and Clinics
Madison, Wisconsin, United States, 53792
Cancer Therapeutics Research Group
Singapore, Singapore, 119074
Sponsors and Collaborators
National Cancer Institute (NCI)
Principal Investigator: Winnie Yeo Chinese University of Hong Kong-Prince of Wales Hospital

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00321594     History of Changes
Obsolete Identifiers: NCT01251445
Other Study ID Numbers: NCI-2009-00141
N01CM62205 ( U.S. NIH Grant/Contract )
CDR0000463519 ( Registry Identifier: PDQ (Physician Data Query) )
First Posted: May 4, 2006    Key Record Dates
Results First Posted: September 26, 2017
Last Update Posted: November 6, 2017
Last Verified: October 2017

Additional relevant MeSH terms:
Liver Neoplasms
Carcinoma, Hepatocellular
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Digestive System Neoplasms
Neoplasms by Site
Digestive System Diseases
Liver Diseases
Antineoplastic Agents
Histone Deacetylase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action