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A Study of Belinostat in Combination With Warfarin in Patients With Solid Tumors or Hematological Malignancies

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01317927
Recruitment Status : Completed
First Posted : March 17, 2011
Last Update Posted : September 23, 2015
Information provided by (Responsible Party):
Spectrum Pharmaceuticals, Inc

Brief Summary:

The purpose of this study is to evaluate the plasma concentration and pharmacodynamics effects of warfarin 5 mg, in the presence or absence of belinostat 1,000 mg/m².

Pharmacokinetic evaluation of belinostat 1,000 mg/m² and metabolites in the presence of warfarin 5 mg.

Condition or disease Intervention/treatment Phase
Solid Tumor Hematological Malignancy Drug: Belinostat, Warfarin Phase 1

Detailed Description:
This is an open-label, single center, pharmacokinetic and pharmacodynamic study in patients with solid tumor or hematological malignancies. Upon providing informed consent and satisfying screening procedures, eligible subjects will report to the clinic for Part I of the study 14 days before the first dose of belinostat (Day -14) for clinical laboratory tests, warfarin (5mg) single dose and a series PK collections. On days 1-5 of each 21-day cycle patients will receive belinostat 1000mg/m*2 and will have a series of subsequent PK samples collected. On day 3 of cycle 1 only, the patient will also receive warfarin 5mg single dose prior to belinostat infusion. PK samples, urine samples, electrocardiogram (ECG) and safety measurements will be collected from Day 1 through Day 10 of cycle one. If it is in the interest of the patient, belinostat can be continued during Part II- extension phase for 5 additional cycles of belinostat treatment on days 1-5 of each subsequent cycle, or until disease progression, patient withdraws consent or if unacceptable toxicity occurs. During the extension phase routine physical exams, laboratory tests and safety and efficacy assessments will be performed. Disease evaluations will be conducted per standard of care. Patients who discontinue for reasons other than disease progression will be followed until new anti-cancer treatment is initiated or death.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 27 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase I Study of Belinostat in Combination With Warfarin in Patients With Solid Tumors or Hematological Malignancies
Study Start Date : December 2010
Actual Primary Completion Date : June 2015
Actual Study Completion Date : June 2015

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Blood Thinners

Arm Intervention/treatment
Experimental: Warfarin, Belinostat
Warfarin 5 mg po will be given on Day -14 and Day 3. Belinostat 1000 mg/m² will be given as a 30 minute IV infusion on Days 1 - 5
Drug: Belinostat, Warfarin
1000 mg/m2 injection infusion given in a 30 min period plus Warfarin 5mg PO
Other Name: PXD101

Primary Outcome Measures :
  1. Plasma concentration and pharmacodynamic effects of warfarin [ Time Frame: 34 days ]
    Samples will be analyzed for S-warfarin and R-warfarin analytes in all evaluable subjects at the end of the trial

  2. Pharmacokinetic evaluation of belinostat [ Time Frame: 34 days ]
    Pharmacokinetic evaluation of belinostat 1,000 mg/m2 and metabolites in the presence of warfarin 5mg

Secondary Outcome Measures :
  1. Presence of PK analytes for all subjects. [ Time Frame: 34 days ]
    To measure the following analytes of all evaluable subjects at the end of the trial: Belinostat, belinostat glucuronide, methylated belinostat, Beliostat amide, belinostat acid and 3-ASBA.

  2. Safety profile of belinostat given concomitantly with warfarin [ Time Frame: 34 days ]
    To evaluate the safety profile of belinostat given concomitantly with warfarin 5mg. Safety and tolerability assessment include adverse events (AEs), physical examination, vital signs, clinical laboratory tests, and electrocardiograms (ECGs).

  3. Overall survival of patients [ Time Frame: 8 months ]
    To evaluate progress-free survival and to assess tumor measurement

Information from the National Library of Medicine

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

Inclusion Criteria:

  • Informed consent
  • Histological or cytological confirmed diagnosis of malignant disease
  • Age ≥18 years old
  • Adequate organ function
  • ECOG 0-2
  • Estimated life expectancy >3months
  • Negative pregnancy test for women of child bearing potential

Exclusion Criteria:

  • Low dose anticoagulation therapy within 2 week prior to study treatment
  • Anticancer therapy within 2 weeks prior to study treatment
  • Investigational therapy within 4 weeks of study treatment
  • Major surgery within 2 weeks of study treatment
  • Coexisting active infection or other medical condition likely to interfere with trial procedures
  • Significant cardiovascular disease (NYHA Class III or IV)
  • Baseline prolongation of QT/QTc
  • Clinically significant CNS disorder, altered mental status or psychiatric disorders precluding understanding of the informed consent process and/or completing trial procedures
  • Symptomatic or untreated CNS metastases
  • Pregnant or breast feeding women
  • Patients not willing to use effective contraception
  • Known infection with HIV, Hep B or Hep C

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 identifier (NCT number): NCT01317927

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United States, Utah
Huntsman Cancer Center, University of Utah
Salt Lake City, Utah, United States, 84112
Sponsors and Collaborators
Spectrum Pharmaceuticals, Inc
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Principal Investigator: Sunil Sharma, MD, FACP Huntsman Cancer Institute, University of Utah, 2000 Circle of Hope, UT 84112
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Responsible Party: Spectrum Pharmaceuticals, Inc Identifier: NCT01317927    
Other Study ID Numbers: PXD101-CLN-20
First Posted: March 17, 2011    Key Record Dates
Last Update Posted: September 23, 2015
Last Verified: September 2015
Keywords provided by Spectrum Pharmaceuticals, Inc:
hematological malignancy
solid tumors
PK/PD study
Additional relevant MeSH terms:
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Hematologic Neoplasms
Neoplasms by Site
Hematologic Diseases
Antineoplastic Agents
Histone Deacetylase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action