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

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

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.

Study Overview

• Status: Completed
• Conditions: Solid Tumor; Hematological Malignancy
• Intervention / Treatment: Drug: Belinostat, Warfarin

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.

• Study Type: Interventional
• Enrollment (Actual): 27
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Utah
    • Salt Lake City, Utah, United States, 84112
      • Huntsman Cancer Center, University of Utah

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / 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 Names: PXD101

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Plasma concentration and pharmacodynamic effects of warfarin	Samples will be analyzed for S-warfarin and R-warfarin analytes in all evaluable subjects at the end of the trial	34 days
Pharmacokinetic evaluation of belinostat	Pharmacokinetic evaluation of belinostat 1,000 mg/m2 and metabolites in the presence of warfarin 5mg	34 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Presence of PK analytes for all subjects.	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.	34 days
Safety profile of belinostat given concomitantly with warfarin	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).	34 days
Overall survival of patients	To evaluate progress-free survival and to assess tumor measurement	8 months

Collaborators and Investigators

• Sponsor: Spectrum Pharmaceuticals, Inc
• Collaborators: Onxeo
• Investigators: Principal Investigator: Sunil Sharma, MD, FACP, Huntsman Cancer Institute, University of Utah, 2000 Circle of Hope, UT 84112

Study record dates

Study Major Dates

• Study Start: December 1, 2010
• Primary Completion (Actual): June 1, 2015
• Study Completion (Actual): June 1, 2015

Study Registration Dates

• First Submitted: March 9, 2011
• First Submitted That Met QC Criteria: March 16, 2011
• First Posted (Estimate): March 17, 2011

Study Record Updates

• Last Update Posted (Estimate): September 23, 2015
• Last Update Submitted That Met QC Criteria: September 21, 2015
• Last Verified: September 1, 2015

More Information

Terms related to this study

• Keywords: solid tumors; warfarin; belionstat; hematological malignancy; PK/PD study
• Additional Relevant MeSH Terms: Neoplasms by Site; Hematologic Diseases; Neoplasms; Hematologic Neoplasms; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Anticoagulants; Histone Deacetylase Inhibitors; Warfarin; Belinostat
• Other Study ID Numbers: PXD101-CLN-20