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

Primary Purpose

Adult Primary Hepatocellular Carcinoma, Advanced Adult Primary Liver Cancer, Localized Unresectable Adult Primary Liver Cancer

Status
Completed
Phase
Phase 1
Locations
International
Study Type
Interventional
Intervention
belinostat
Sponsored by
National Cancer Institute (NCI)
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Adult Primary Hepatocellular Carcinoma

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • University of Wisconsin Hospital and Clinics
  • Cancer Therapeutics Research Group

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Treatment (enzyme inhibitor therapy)

Arm Description

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.

Outcomes

Primary Outcome Measures

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.
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.

Secondary Outcome Measures

Full Information

First Posted
May 2, 2006
Last Updated
October 3, 2017
Sponsor
National Cancer Institute (NCI)
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1. Study Identification

Unique Protocol Identification Number
NCT00321594
Brief Title
Belinostat in Treating Patients With Liver Cancer That Cannot Be Removed By Surgery
Official Title
A Phase I/II Study of PXD101 in Patients With Unresectable Hepatocellular Carcinoma With Pharmacokinetic and Pharmacodynamic Evaluation
Study Type
Interventional

2. Study Status

Record Verification Date
October 2017
Overall Recruitment Status
Completed
Study Start Date
May 2006 (undefined)
Primary Completion Date
August 2010 (Actual)
Study Completion Date
October 2012 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
National Cancer Institute (NCI)

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

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
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Adult Primary Hepatocellular Carcinoma, Advanced Adult Primary Liver Cancer, Localized Unresectable Adult Primary Liver Cancer, Recurrent Adult Primary Liver Cancer

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
54 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Treatment (enzyme inhibitor therapy)
Arm Type
Experimental
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
belinostat
Other Intervention Name(s)
PXD101
Intervention Description
Given IV
Primary Outcome Measure Information:
Title
Dose-limiting Toxicities (DLT) and Maximum Tolerated Dose (MTD) of Belinostat in Patients With Inoperable HCC (Phase I)
Description
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.
Time Frame
Course 1
Title
Tumor Response in Patients With Inoperable HCC Using Belinostat (Phase II)
Description
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.
Time Frame
Every 2 courses (approximately 6 weeks)

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Winnie Yeo
Organizational Affiliation
Chinese University of Hong Kong-Prince of Wales Hospital
Official's Role
Principal Investigator
Facility Information:
Facility Name
University of Wisconsin Hospital and Clinics
City
Madison
State/Province
Wisconsin
ZIP/Postal Code
53792
Country
United States
Facility Name
Cancer Therapeutics Research Group
City
Singapore
ZIP/Postal Code
119074
Country
Singapore

12. IPD Sharing Statement

Citations:
PubMed Identifier
25962426
Citation
Yeo W, Chan SL, Mo FK, Chu CM, Hui JW, Tong JH, Chan AW, Koh J, Hui EP, Loong H, Lee K, Li L, Ma B, To KF, Yu SC. Phase I/II study of temsirolimus for patients with unresectable Hepatocellular Carcinoma (HCC)- a correlative study to explore potential biomarkers for response. BMC Cancer. 2015 May 12;15:395. doi: 10.1186/s12885-015-1334-6.
Results Reference
derived
PubMed Identifier
23382909
Citation
Wang LZ, Ramirez J, Yeo W, Chan MY, Thuya WL, Lau JY, Wan SC, Wong AL, Zee YK, Lim R, Lee SC, Ho PC, Lee HS, Chan A, Ansher S, Ratain MJ, Goh BC. Glucuronidation by UGT1A1 is the dominant pathway of the metabolic disposition of belinostat in liver cancer patients. PLoS One. 2013;8(1):e54522. doi: 10.1371/journal.pone.0054522. Epub 2013 Jan 30. Erratum In: PLoS One. 2014;9(1). doi:10.1371/annotation/df796504-a2ea-4807-a412-85985bb2550b.
Results Reference
derived

Learn more about this trial

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

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