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

Sponsor

Acrotech Biopharma LLC (Industry)

Overall Status

Completed

CT.gov ID

NCT02680795

Collaborator

Axis Clinicals Limited (Industry)

Enrollment

Locations

Arms

50.8

Actual Duration (Months)

5.7

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

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

Condition or Disease	Intervention/Treatment	Phase
Solid Tumors Hematological Malignancies	Drug: Belinostat IV	Phase 1

Detailed Description

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 Design

Study Type:

Interventional

Actual Enrollment :

17 participants

Allocation:

Non-Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

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

Actual Study Start Date :

Apr 27, 2016

Actual Primary Completion Date :

Jul 21, 2020

Actual Study Completion Date :

Jul 21, 2020

Arms and Interventions

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

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

Other Names:

Beleodaq

Experimental: Homozygous UGT1A1*28

Cohort C: Open For Enrollment Homozygous UGT1A1, Belinostat IV

Drug: Belinostat IV

Other Names:

Beleodaq

Outcome Measures

Primary Outcome Measures

Plasma and urine concentrations of belinostat will be measured [26 Weeks]
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

Assess overall incidence of treatment emergent adverse events (TEAEs) using CTCAE version 4.03 [26 Weeks]
Assess Safety of belinostat in patients with wild type, heterozygous, and homozygousUGT1A1*28 genotypes
Assess any adverse events (AEs) (changes in physical exam or laboratory findings related to study medication dosing [26 Weeks]
Assess Safety of belinostat in patients with wild type, heterozygous, and homozygousUGT1A1*28 genotypes

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Patient is diagnosed with advanced solid tumors or advanced hematological malignancy that is relapsed/refractory, for which no standard salvage therapy exists.
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.
Patient has adequate hematological and hepatic functions.

Exclusion Criteria:

Patient is taking UGT1A1 inhibitors (eg, atazanavir, gemfibrozil, indinavir, ketoconazole, sorafenib) at screening.
Patient has HBV or HCV
Patient has a known HIV positive diagnosis.
Patient has congestive heart failure Class III/IV
Patient has had previous exposure to belinostat.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	John Wayne Cancer Institute @ Providence Saint John's Health Center	Santa Monica	California	United States	90404
2	The Oncology Institute of Hope and Innovation	Whittier	California	United States	90603
3	Gabrail Cancer Center Research	Canton	Ohio	United States	44718