Hematological Malignancies, Solid Tumors
Conditions
Keywords
UGT1A1*28, Belinostat, beleodaq, wild type genotypes, heterozygous genotypes, homozygous genotypes
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.
Interventions
DRUGBelinostat IV
Cohort A: Belinostat 1000mg will be administered once daily on days 1 through 5 of one 21-day cycle via 30-minute IV infusion. Cohort B: Belinostat 1000mg will be administered once daily on days 1 through 5 of one 21-day cycle via 30-minute IV infusion. Cohort C: Belinostat 750mg will be administered once daily on days 1 through 5 of one 21-day cycle via 30-minute IV infusion.
Sponsors
Axis Clinicals Limited
Axis Clinical Trials
Acrotech Biopharma Inc.
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Patient is diagnosed with advanced solid tumors or advanced hematological malignancy that is relapsed/refractory, for which no standard salvage therapy exists. 2. 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. 3. Patient has adequate hematological and hepatic functions.
Exclusion criteria
1. Patient is taking UGT1A1 inhibitors (eg, atazanavir, gemfibrozil, indinavir, ketoconazole, sorafenib) at screening. 2. Patient has HBV or HCV 3. Patient has a known HIV positive diagnosis. 4. Patient has congestive heart failure Class III/IV 5. Patient has had previous exposure to belinostat.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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 |
Countries
United States
Outcome results
None listed