Clinical trial NCT02680795: 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
Overall status: COMPLETED
Phase: PHASE1
Conditions: Solid Tumors
Hematological Malignancies
Keywords: UGT1A1*28
Belinostat
beleodaq
wild type genotypes
heterozygous genotypes
homozygous genotypes
Lead sponsor: Acrotech Biopharma Inc.
Sponsor class: INDUSTRY
Collaborators: name: Axis Clinicals Limited
First posted: 2016-02-12
Enrollment: 17
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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.

Primary outcomes:
measure: Plasma and urine concentrations of belinostat will be measured
timeFrame: 26 Weeks
Secondary outcomes:
measure: Assess overall incidence of treatment emergent adverse events (TEAEs) using CTCAE version 4.03
timeFrame: 26 Weeks
measure: Assess any adverse events (AEs) (changes in physical exam or laboratory findings related to study medication dosing
timeFrame: 26 Weeks
Other outcomes:
Locations:
city: Santa Monica
country: United States
facility: John Wayne Cancer Institute @ Providence Saint John's Health Center
state: California
city: Whittier
country: United States
facility: The Oncology Institute of Hope and Innovation
state: California
city: Canton
country: United States
facility: Gabrail Cancer Center Research
state: Ohio
Study officials:
affiliation: Acrotech Biopharma Inc.
name: Wasim Khan, MD
role: STUDY_DIRECTOR
References: