A 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.
Drug: Belinostat, Warfarin
|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|
- 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
- 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
|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)|
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
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.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01317927
|United States, Utah|
|Huntsman Cancer Center, University of Utah|
|Salt Lake City, Utah, United States, 84112|
|Principal Investigator:||Sunil Sharma, MD, FACP||Huntsman Cancer Institute, University of Utah, 2000 Circle of Hope, UT 84112|