Back to resultsEstablish the PK of Belinostat in Patients With Wild-type, Heterozygous, and Homozygous UGT1A1*28 Genotypes
Primary Purpose
Solid Tumors, Hematological Malignancies
Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
Belinostat IV
Sponsored by
About this trial
This is an interventional treatment trial for Solid Tumors focused on measuring UGT1A1*28, Belinostat, beleodaq, wild type genotypes, heterozygous genotypes, homozygous genotypes
Eligibility Criteria
Inclusion Criteria:
- 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.
Exclusion Criteria:
- 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.
Sites / Locations
- John Wayne Cancer Institute @ Providence Saint John's Health Center
- The Oncology Institute of Hope and Innovation
- Gabrail Cancer Center Research
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm Type
Experimental
Experimental
Experimental
Arm Label
Wild Type UGT1A1
Heterozygous UGT1A1*28
Homozygous UGT1A1*28
Arm Description
Cohort A: Open for Enrollment Wild Type UGT1A1, Belinostat IV
Cohort B: Closed For Enrollment Heterozygous UGT1A1, Belinostat IV
Cohort C: Open For Enrollment Homozygous UGT1A1, Belinostat IV
Outcomes
Primary Outcome Measures
Plasma and urine concentrations of belinostat will be measured
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
Assess overall incidence of treatment emergent adverse events (TEAEs) using CTCAE version 4.03
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
Assess Safety of belinostat in patients with wild type, heterozygous, and homozygousUGT1A1*28 genotypes
Full Information
NCT ID
NCT02680795
First Posted
February 9, 2016
Last Updated
September 10, 2021
Sponsor
Acrotech Biopharma Inc.
Collaborators
Axis Clinicals Limited
1. Study Identification
Unique Protocol Identification Number
NCT02680795
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
Study Type
Interventional
2. Study Status
Record Verification Date
September 2021
Overall Recruitment Status
Completed
Study Start Date
April 27, 2016 (Actual)
Primary Completion Date
July 21, 2020 (Actual)
Study Completion Date
July 21, 2020 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Acrotech Biopharma Inc.
Collaborators
Axis Clinicals Limited
4. Oversight
Data Monitoring Committee
No
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Solid Tumors, Hematological Malignancies
Keywords
UGT1A1*28, Belinostat, beleodaq, wild type genotypes, heterozygous genotypes, homozygous genotypes
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
17 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Wild Type UGT1A1
Arm Type
Experimental
Arm Description
Cohort A: Open for Enrollment Wild Type UGT1A1, Belinostat IV
Arm Title
Heterozygous UGT1A1*28
Arm Type
Experimental
Arm Description
Cohort B: Closed For Enrollment Heterozygous UGT1A1, Belinostat IV
Arm Title
Homozygous UGT1A1*28
Arm Type
Experimental
Arm Description
Cohort C: Open For Enrollment Homozygous UGT1A1, Belinostat IV
Intervention Type
Drug
Intervention Name(s)
Belinostat IV
Other Intervention Name(s)
Beleodaq
Intervention Description
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.
Primary Outcome Measure Information:
Title
Plasma and urine concentrations of belinostat will be measured
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)
Time Frame
26 Weeks
Secondary Outcome Measure Information:
Title
Assess overall incidence of treatment emergent adverse events (TEAEs) using CTCAE version 4.03
Description
Assess Safety of belinostat in patients with wild type, heterozygous, and homozygousUGT1A1*28 genotypes
Time Frame
26 Weeks
Title
Assess any adverse events (AEs) (changes in physical exam or laboratory findings related to study medication dosing
Description
Assess Safety of belinostat in patients with wild type, heterozygous, and homozygousUGT1A1*28 genotypes
Time Frame
26 Weeks
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
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.
Exclusion Criteria:
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Wasim Khan, MD
Organizational Affiliation
Acrotech Biopharma Inc.
Official's Role
Study Director
Facility Information:
Facility Name
John Wayne Cancer Institute @ Providence Saint John's Health Center
City
Santa Monica
State/Province
California
ZIP/Postal Code
90404
Country
United States
Facility Name
The Oncology Institute of Hope and Innovation
City
Whittier
State/Province
California
ZIP/Postal Code
90603
Country
United States
Facility Name
Gabrail Cancer Center Research
City
Canton
State/Province
Ohio
ZIP/Postal Code
44718
Country
United States
12. IPD Sharing Statement
Plan to Share IPD
No
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Establish the PK of Belinostat in Patients With Wild-type, Heterozygous, and Homozygous UGT1A1*28 Genotypes
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