Clinical Trials /

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

NCT02680795

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

Related Conditions:
  • Hematopoietic and Lymphoid Malignancy
  • Malignant Solid Tumor
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

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

DrugSynonymsArms
Belinostat IVBeleodaqWild Type UGT1A1

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

NameTypeDescriptionInterventions
Wild Type UGT1A1ExperimentalCohort A: Open for Enrollment Wild Type UGT1A1, Belinostat IV
  • Belinostat IV
Heterozygous UGT1A1*28ExperimentalCohort B: Closed For Enrollment Heterozygous UGT1A1, Belinostat IV
  • Belinostat IV
Homozygous UGT1A1*28ExperimentalCohort C: Open For Enrollment Homozygous UGT1A1, Belinostat IV
  • 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 18, 2019