AzTrials
AzTrials

Adult Primary Hepatocellular CarcinomaPhase 1/2NCT00321594

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

A Phase 1/2 study testing belinostat in people with Adult Primary Hepatocellular Carcinoma and Advanced Adult Primary Liver Cancer, run by National Cancer Institute (NCI) at 2 sites in 2 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

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 Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
belinostat
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
54 participants
Where
2 sitesin 2 countries
Study dates
May 2006to Oct 2012
Phase
Phase 1/2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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%
Show all 65Show fewer
  • 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

Who cannot join

None listed.

Trial locations and contacts

2 sites in 2 countries.

2 sites in 2 countries

United States1 site

  • University of Wisconsin Hospital and Clinics

    Madison, Wisconsin, 53792

Other trials in United States

Singapore1 site

  • Cancer Therapeutics Research Group

    Singapore, 119074

Other trials in Singapore

About this study

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

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

Read the detailed description

PRIMARY OBJECTIVES:

  1. 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.

Being tested
belinostat
Medical subject headings
Carcinoma, Hepatocellular

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • belinostatDrug

    Also called PXD101

    Given IV

Study groups in NCT00321594
Study groupRoleWhat they receive
Treatment (enzyme inhibitor therapy)ExperimentalPatients receive belinostat IV over 30 minutes on days 1-5. Courses repeat every 3 weeks in the absence of disease progression or unacceptable toxicity.
Receives: Drug: belinostat

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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.

    Measured: Course 1

  2. 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.

    Measured: Every 2 courses (approximately 6 weeks)

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted4 May 2006 (estimated)
  2. Study startMay 2006
  3. Primary completionAug 2010
  4. Study completionOct 2012

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1/2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
54 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00321594
Sponsor's protocol ID
NCI-2009-00141
Other IDs
CTRG-HC06/21/05, N01CM62205, CDR0000463519
Status last verified
Oct 2017
First submitted
2 May 2006
Last updated
6 Nov 2017
Data monitoring committee
Yes

Publications

  • 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.

    PubMed 25962426

  • 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.

    PubMed 23382909

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing belinostat in people with Adult Primary Hepatocellular Carcinoma and Advanced Adult Primary Liver Cancer, run by National Cancer Institute (NCI) at 2 sites in 2 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 65 inclusion and 0 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 6 Nov 2017. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 2 sites in United States, Singapore. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 26 Sep 2017). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Dose-limiting Toxicities (DLT) and Maximum Tolerated Dose (MTD) of Belinostat in Patients With Inoperable HCC (Phase I) (time frame: Course 1). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00321594, which also lists 2 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 6 Nov 2017.

AzTrials uses cookies for analytics and advertising. You can accept or reject them; the site works either way. Privacy Policy.

Free account

Log in to keep searching

You’ve used your 3 free searches. AzTrials is free: log in or create a free account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in