Hematological Malignancy, Solid Tumor
Conditions
Keywords
belionstat, warfarin, hematological malignancy, solid tumors, PK/PD study
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.
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.
Interventions
DRUGBelinostat, Warfarin
1000 mg/m2 injection infusion given in a 30 min period plus Warfarin 5mg PO
Sponsors
Valerio Therapeutics
Spectrum Pharmaceuticals, Inc
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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 |
Countries
United States
Outcome results
None listed