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

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
TopoTarget A/S
Information provided by (Responsible Party):
Spectrum Pharmaceuticals, Inc
ClinicalTrials.gov Identifier:
NCT01317927
First received: March 9, 2011
Last updated: February 11, 2014
Last verified: February 2014
  Purpose

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 Intervention Phase
Solid Tumor
Hematological Malignancy
Drug: Belinostat, Warfarin
Phase 1

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: 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

Resource links provided by NLM:


Further study details as provided by Spectrum Pharmaceuticals, Inc:

Primary Outcome Measures:
  • Plasma concentration and pharmacodynamic effects of warfarin [ Time Frame: 34 days ] [ Designated as safety issue: No ]
    Samples will be analyzed for S-warfarin and R-warfarin analytes in all evaluable subjects at the end of the trial

  • Pharmacokinetic evaluation of belinostat [ Time Frame: 34 days ] [ Designated as safety issue: No ]
    Pharmacokinetic evaluation of belinostat 1,000 mg/m2 and metabolites in the presence of warfarin 5mg


Secondary Outcome Measures:
  • Presence of PK analytes for all subjects. [ Time Frame: 34 days ] [ Designated as safety issue: No ]
    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.

  • Safety profile of belinostat given concomitantly with warfarin [ Time Frame: 34 days ] [ Designated as safety issue: Yes ]
    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).

  • Overall survival of patients [ Time Frame: 8 months ] [ Designated as safety issue: No ]
    To evaluate progress-free survival and to assess tumor measurement


Estimated Enrollment: 24
Study Start Date: December 2010
Estimated Study Completion Date: March 2014
Estimated Primary Completion Date: March 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01317927

Locations
United States, Utah
Huntsman Cancer Center, University of Utah
Salt Lake City, Utah, United States, 84112
Sponsors and Collaborators
Spectrum Pharmaceuticals, Inc
TopoTarget A/S
Investigators
Principal Investigator: Sunil Sharma, MD, FACP Huntsman Cancer Institute, University of Utah, 2000 Circle of Hope, UT 84112
  More Information

No publications provided

Responsible Party: Spectrum Pharmaceuticals, Inc
ClinicalTrials.gov Identifier: NCT01317927     History of Changes
Other Study ID Numbers: PXD101-CLN-20
Study First Received: March 9, 2011
Last Updated: February 11, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by Spectrum Pharmaceuticals, Inc:
belionstat
warfarin
hematological malignancy
solid tumors
PK/PD study

Additional relevant MeSH terms:
Neoplasms
Hematologic Neoplasms
Neoplasms by Site
Hematologic Diseases
Warfarin
Anticoagulants
Hematologic Agents
Therapeutic Uses
Pharmacologic Actions

ClinicalTrials.gov processed this record on April 22, 2014