Clinical trial NCT01317927: A Study of Belinostat in Combination With Warfarin in Patients With Solid Tumors or Hematological Malignancies
Official title: A Phase I Study of Belinostat in Combination With Warfarin in Patients With Solid Tumors or Hematological Malignancies
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Solid Tumor
Hematological Malignancy
Keywords: belionstat
warfarin
hematological malignancy
solid tumors
PK/PD study
Lead sponsor: Spectrum Pharmaceuticals, Inc
Sponsor class: INDUSTRY
Collaborators: name: Valerio Therapeutics
First posted: 2011-03-17
Enrollment: 27
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Eligibility 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

Primary outcomes:
measure: Plasma concentration and pharmacodynamic effects of warfarin
timeFrame: 34 days
measure: Pharmacokinetic evaluation of belinostat
timeFrame: 34 days
Secondary outcomes:
measure: Presence of PK analytes for all subjects.
timeFrame: 34 days
measure: Safety profile of belinostat given concomitantly with warfarin
timeFrame: 34 days
measure: Overall survival of patients
timeFrame: 8 months
Other outcomes:
Locations:
city: Salt Lake City
country: United States
facility: Huntsman Cancer Center, University of Utah
state: Utah
Study officials:
affiliation: Huntsman Cancer Institute, University of Utah, 2000 Circle of Hope, UT 84112
name: Sunil Sharma, MD, FACP
role: PRINCIPAL_INVESTIGATOR
References: