Establish the PK of Belinostat in Patients With Wild-type, Heterozygous, and Homozygous UGT1A1*28 Genotypes
- Registration Number
- NCT02680795
- Lead Sponsor
- Acrotech Biopharma Inc.
- Brief Summary
This is a Phase 1, open-label, nonrandomized study to determine the PK profiles of belinostat in patients with relapsed/refractory solid tumors or hematological malignancies who have heterozygous and homozygous UGT1A1\*28 genotypes and wild-type UGT1A1 gene. Enrolled patients will be assigned to 1 of 3 cohorts (A, B, or C) based on their UGT1A1 genotype
- Detailed Description
This is a Phase 1, open-label, nonrandomized study to determine the PK profiles of belinostat in patients with relapsed/refractory solid tumors or hematological malignancies who have heterozygous and homozygous UGT1A1\*28 genotypes and wild-type UGT1A1 gene. Enrolled patients will be assigned to 1 of 3 cohorts (A, B, or C) based on their UGT1A1 genotype
Enrollment into all cohorts will occur simultaneously rather than sequentially. Belinostat will be administered via a 30-minute infusion once daily from Day 1 to Day 5 of one 21-day cycle. Clinical safety will be monitored in each patient. Blood samples for PK analysis will be collected from Day 1 to Day 3, and urine samples for PK analysis will be collected from Day 1 to Day 4.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 17
- Patient is diagnosed with advanced solid tumors or advanced hematological malignancy that is relapsed/refractory, for which no standard salvage therapy exists.
- Patient must have received at least 1 prior systemic therapy for the current malignancy and has recovered from any toxicity of the prior therapy at screening.
- Patient has adequate hematological and hepatic functions.
- Patient is taking UGT1A1 inhibitors (eg, atazanavir, gemfibrozil, indinavir, ketoconazole, sorafenib) at screening.
- Patient has HBV or HCV
- Patient has a known HIV positive diagnosis.
- Patient has congestive heart failure Class III/IV
- Patient has had previous exposure to belinostat.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Wild Type UGT1A1 Belinostat IV Cohort A: Open for Enrollment Wild Type UGT1A1, Belinostat IV Heterozygous UGT1A1*28 Belinostat IV Cohort B: Closed For Enrollment Heterozygous UGT1A1, Belinostat IV Homozygous UGT1A1*28 Belinostat IV Cohort C: Open For Enrollment Homozygous UGT1A1, Belinostat IV
- Primary Outcome Measures
Name Time Method Plasma and urine concentrations of belinostat will be measured 26 Weeks PK will be measured for area under the time-concentration curve (AUC), steady state volume of distribution (Vdss),PK will be measured for total body clearance (CLtot),PK will be measured for fraction excreted unchanged (fe), PK will be measured for renal clearance (CLren), PK will be measured for non-renal clearance (CLnonren), PK will be measured for peak concentration (Cmax),and half-life (t1/2)
- Secondary Outcome Measures
Name Time Method Assess overall incidence of treatment emergent adverse events (TEAEs) using CTCAE version 4.03 26 Weeks Assess Safety of belinostat in patients with wild type, heterozygous, and homozygousUGT1A1\*28 genotypes
Assess any adverse events (AEs) (changes in physical exam or laboratory findings related to study medication dosing 26 Weeks Assess Safety of belinostat in patients with wild type, heterozygous, and homozygousUGT1A1\*28 genotypes
Trial Locations
- Locations (3)
Gabrail Cancer Center Research
🇺🇸Canton, Ohio, United States
John Wayne Cancer Institute @ Providence Saint John's Health Center
🇺🇸Santa Monica, California, United States
The Oncology Institute of Hope and Innovation
🇺🇸Whittier, California, United States