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
Title
- Brief Title: Establish the PK of Belinostat in Patients With Wild-type, Heterozygous, and Homozygous UGT1A1*28 Genotypes
- Official Title: Open-label, Nonrandomized, Phase 1 Study Evaluating Safety and Pharmacokinetics of Belinostat in Patients With Relapsed/Refractory Solid Tumors or Hematological Malignancies in Wild-Type, Heterozygous, and Homozygous UGT1A1*28 Genotypes
Clinical Trial IDs
- ORG STUDY ID:
SPI-BEL-106
- NCT ID:
NCT02680795
Conditions
- Solid Tumors
- Hematological Malignancies
Interventions
| Drug | Synonyms | Arms |
|---|
| Belinostat IV | Beleodaq | Heterozygous UGT1A1*28 |
Purpose
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.
Trial Arms
| Name | Type | Description | Interventions |
|---|
| Wild Type UGT1A1 | Experimental | Cohort A: Open for Enrollment Wild Type UGT1A1, Belinostat IV | |
| Heterozygous UGT1A1*28 | Experimental | Cohort B: Closed For Enrollment Heterozygous UGT1A1, Belinostat IV | |
| Homozygous UGT1A1*28 | Experimental | Cohort C: Open For Enrollment Homozygous UGT1A1, Belinostat IV | |
Eligibility Criteria
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.
| Maximum Eligible Age: | N/A |
| Minimum Eligible Age: | 18 Years |
| Eligible Gender: | All |
| Healthy Volunteers: | No |
Primary Outcome Measures
| Measure: | Plasma and urine concentrations of belinostat will be measured |
| Time Frame: | 26 Weeks |
| Safety Issue: | |
| Description: | 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
| Measure: | Assess overall incidence of treatment emergent adverse events (TEAEs) using CTCAE version 4.03 |
| Time Frame: | 26 Weeks |
| Safety Issue: | |
| Description: | Assess Safety of belinostat in patients with wild type, heterozygous, and homozygousUGT1A1*28 genotypes |
| Measure: | Assess any adverse events (AEs) (changes in physical exam or laboratory findings related to study medication dosing |
| Time Frame: | 26 Weeks |
| Safety Issue: | |
| Description: | Assess Safety of belinostat in patients with wild type, heterozygous, and homozygousUGT1A1*28 genotypes |
Details
| Phase: | Phase 1 |
| Primary Purpose: | Interventional |
| Overall Status: | Recruiting |
| Lead Sponsor: | Acrotech Biopharma LLC |
Trial Keywords
- UGT1A1*28
- Belinostat
- beleodaq
- wild type genotypes
- heterozygous genotypes
- homozygous genotypes
Last Updated
November 20, 2019
