Establish the PK of Belinostat in Patients With Wild-type, Heterozygous, and Homozygous UGT1A1*28 Genotypes

Solid Tumors Clinical Trial

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 Details — Status: Completed

Administrative data

• NCT number: NCT02680795
• Other study ID #: SPI-BEL-106
• Status: Completed
• Phase: Phase 1
• Start date: April 27, 2016
• Est. completion date: July 21, 2020

Study information

• Verified date: September 2021
• Source: Acrotech Biopharma LLC
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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

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 information / eligibility

• Status: Completed
• Enrollment: 17
• Est. completion date: July 21, 2020
• Est. primary completion date: July 21, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Hematologic Neoplasms
• Hematological Malignancies
• Neoplasms
• Solid Tumors

Intervention

Drug:
• Belinostat 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.

Locations

Country	Name	City	State
United States	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

Sponsors (2)

Lead Sponsor	Collaborator
Acrotech Biopharma LLC	Axis Clinicals Limited

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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)	26 Weeks
Secondary	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	26 Weeks
Secondary	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	26 Weeks