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

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

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

Study Overview

• Status: Completed
• Conditions: Solid Tumors; Hematological Malignancies
• Intervention / Treatment: Drug: Belinostat IV

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.

• Study Type: Interventional
• Enrollment (Actual): 17
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • California
    • Santa Monica, California, United States, 90404
      • John Wayne Cancer Institute @ Providence Saint John's Health Center
    • Whittier, California, United States, 90603
      • The Oncology Institute of Hope and Innovation
  • Ohio
    • Canton, Ohio, United States, 44718
      • Gabrail Cancer Center Research

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Wild Type UGT1A1; Cohort A: Open for Enrollment Wild Type UGT1A1, Belinostat IV	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.; Other Names: Beleodaq
Experimental: Heterozygous UGT1A1*28; Cohort B: Closed For Enrollment Heterozygous UGT1A1, Belinostat IV	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.; Other Names: Beleodaq
Experimental: Homozygous UGT1A1*28; Cohort C: Open For Enrollment Homozygous UGT1A1, Belinostat IV	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.; Other Names: Beleodaq

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
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

Collaborators and Investigators

• Sponsor: Acrotech Biopharma Inc.
• Collaborators: Axis Clinicals Limited
• Investigators: Study Director: Wasim Khan, MD, Acrotech Biopharma Inc.

Study record dates

Study Major Dates

• Study Start (Actual): April 27, 2016
• Primary Completion (Actual): July 21, 2020
• Study Completion (Actual): July 21, 2020

Study Registration Dates

• First Submitted: February 9, 2016
• First Submitted That Met QC Criteria: February 11, 2016
• First Posted (Estimate): February 12, 2016

Study Record Updates

• Last Update Posted (Actual): September 14, 2021
• Last Update Submitted That Met QC Criteria: September 10, 2021
• Last Verified: September 1, 2021

More Information

Terms related to this study

• Keywords: Belinostat; beleodaq; UGT1A1*28; wild type genotypes; heterozygous genotypes; homozygous genotypes
• Additional Relevant MeSH Terms: Neoplasms by Site; Hematologic Diseases; Neoplasms; Hematologic Neoplasms; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Histone Deacetylase Inhibitors; Belinostat
• Other Study ID Numbers: SPI-BEL-106

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO