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

• ClinicalTrials.gov Identifier: NCT01317927
• Recruitment Status: Completed
• First Posted: March 17, 2011
• Last Update Posted: September 23, 2015
• Sponsor: Spectrum Pharmaceuticals, Inc
• Collaborator: Onxeo
• Information provided by (Responsible Party): Spectrum Pharmaceuticals, Inc

Study Description

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.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 27 participants
• 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

Arms and Interventions

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

Outcome Measures

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

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• 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

Locations

United States, Utah

Huntsman Cancer Center, University of Utah

Salt Lake City, Utah, United States, 84112

Sponsors and Collaborators

Spectrum Pharmaceuticals, Inc

Onxeo

Investigators

• Principal Investigator: Sunil Sharma, MD, FACP; Huntsman Cancer Institute, University of Utah, 2000 Circle of Hope, UT 84112

More Information

• Responsible Party: Spectrum Pharmaceuticals, Inc
• ClinicalTrials.gov Identifier: NCT01317927 History of Changes
• Other Study ID Numbers: PXD101-CLN-20
• First Posted: March 17, 2011
• Last Update Posted: September 23, 2015
• Last Verified: September 2015

Keywords provided by Spectrum Pharmaceuticals, Inc:

belionstat; warfarin; hematological malignancy; solid tumors; PK/PD study

Additional relevant MeSH terms:

Neoplasms; Belinostat; Warfarin; Anticoagulants; Antineoplastic Agents; Histone Deacetylase Inhibitors; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action