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

Acrotech Biopharma Inc.17 enrolled

Overview

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

Allocation

NON_RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Solid Tumors Hematological Malignancies

Interventions

Belinostat IVDRUG

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.

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

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.

Locations (3)

John Wayne Cancer Institute @ Providence Saint John's Health Center

Santa Monica, California, United States

The Oncology Institute of Hope and Innovation

Whittier, California, United States

Gabrail Cancer Center Research

Canton, Ohio, United States

Outcomes

Primary Outcomes

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)

Time frame: 26 Weeks

Secondary Outcomes

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

Time frame: 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

Time frame: 26 Weeks

Data from ClinicalTrials.gov

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