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

Sponsor

Spectrum Pharmaceuticals, Inc (Industry)

Overall Status

Completed

CT.gov ID

NCT01317927

Collaborator

Onxeo (Industry)

Enrollment

Location

Arm

Duration (Months)

0.5

Patients Per Site Per Month

Study Details

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

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 :

Dec 1, 2010

Actual Primary Completion Date :

Jun 1, 2015

Actual Study Completion Date :

Jun 1, 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 Names: PXD101

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

Outcome Measures

Primary Outcome Measures

Plasma concentration and pharmacodynamic effects of warfarin [34 days]
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 [34 days]
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. [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.
Safety profile of belinostat given concomitantly with warfarin [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).
Overall survival of patients [8 months]
To evaluate progress-free survival and to assess tumor measurement

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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