Belinostat in Treating Patients With Liver Cancer That Cannot Be Removed By Surgery
This study has been completed.
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00321594
First received: May 2, 2006
Last updated: January 30, 2013
Last verified: December 2012
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Purpose
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 | Intervention | 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 |
| Study Type: | Interventional |
| 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 |
Resource links provided by NLM:
Further study details as provided by National Cancer Institute (NCI):
Primary Outcome Measures:
- 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.
| Enrollment: | 61 |
| Study Start Date: | May 2006 |
| Primary Completion Date: | August 2010 (Final data collection date for primary outcome measure) |
| Arms | Assigned Interventions |
|---|---|
|
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
|
Detailed 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.
Eligibility| Ages Eligible for Study: | 18 Years and older |
| Genders Eligible for Study: | Both |
| Accepts Healthy Volunteers: | No |
Criteria
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
Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00321594
Locations
| United States, Wisconsin | |
| University of Wisconsin Hospital and Clinics | |
| Madison, Wisconsin, United States, 53792 | |
| Singapore | |
| Cancer Therapeutics Research Group | |
| Singapore, Singapore, 119074 | |
Sponsors and Collaborators
Investigators
| Principal Investigator: | Winnie Yeo | Chinese University of Hong Kong-Prince of Wales Hospital |
More Information
No publications provided by National Cancer Institute (NCI)
Additional 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, CTRG-HC06/21/05, N01CM62205, CDR0000463519 |
| Study First Received: | May 2, 2006 |
| Last Updated: | January 30, 2013 |
| Health Authority: | United States: Food and Drug Administration |
Additional relevant MeSH terms:
|
Carcinoma Liver Neoplasms Carcinoma, Hepatocellular Neoplasms, Glandular and Epithelial Neoplasms by Histologic Type Neoplasms |
Digestive System Neoplasms Neoplasms by Site Digestive System Diseases Liver Diseases Adenocarcinoma |
ClinicalTrials.gov processed this record on May 22, 2013