To Evaluate Safety and Pharmacokinetics of Belinostat in Patients Who Have Mild, Moderate and Severe Renal Impairment.

An Open-label, Nonrandomized, Phase 1 Study to Evaluate the Safety and Pharmacokinetics of Belinostat in Patients With Relapsed/Refractory Solid Tumors or Hematological Malignancies Who Have Mild, Moderate, and Severe Renal Impairment

A phase I, open-label, nonrandomized study to determine the PK profile of belinostat in patients with relapsed/refractory solid tumors or hematological malignancies in patients with renal impairment. Eligible patients will be assigned to 1 of 4 cohorts (A, B, C or D) based on their level of renal function (normal, mild, moderate, or severe renal impairment) and receive belinostat dose A for normal or mild renal impairment, and dose B for moderate or severe renal impairment.

Study Overview

• Status: Terminated
• Conditions: Relapsed/Refractory Solid Tumors/Hematological Malignancies
• Intervention / Treatment: Drug: Belinostat

Detailed Description

Study Design:

A phase I, open-label, nonrandomized study to determine safety and pharmacokinetics of belinostat in patients with relapsed/refractory solid tumors or hematological malignancies and to determine the PK profiles in patients with renal impairment. Eligible patients will be assigned to 1 of 4 cohorts (A, B, C or D) based on their level of renal function (normal, mild, moderate, or severe renal impairment) and receive belinostat dose A for normal or mild renal impairment, and dose B for moderate or severe renal impairment.

Enrollment into all cohorts will occur simultaneously rather than sequentially except in the following instance: Before any patient is enrolled in Cohort D, safety will be assessed for at least 1 patient in Cohort C through the end of Cycle 6. If the patient in Cohort C experiences a toxicity that is at least Grade 3 in severity, Cohort D will proceed at a reduced starting dose.

Belinostat will be administered via a 30-minute intravenous (IV) infusion once daily on Days 1 to 5 of a 21-day cycle (for up to 6 cycles). Clinical safety will be monitored in each patient, and up to two dose reductions from the starting dose (not less than 250mg/m^2) is allowed based on pre-defined criteria.

If a patient cannot tolerate the reduced dose due to Grade 3 or 4 toxicity, belinostat administration must be discontinued. Dose escalation is not allowed. 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): 18
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • California
    • Whittier, California, United States, 90603
      • Innovative Clinical Research Institute
  • 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 therapy for the current malignancy and has recovered from any toxicity of the prior therapy at screening.
3. Patient has either normal or impaired renal functions.
4. Patient has adequate hematological and hepatic functions.

Exclusion Criteria:

1. Patient has acute or progressive renal impairment related to disease or any other cause (eg, toxicity, obstructive uropathy due to retroperitoneal disease, proteinuria, nephrotic syndrome), or requires dialysis.
2. Patient has acute HBV or HCV
3. Patient has known human immunodeficiency virus (HIV) positive diagnosis.
4. 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

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Cohort A; Normal Renal function, Belinostat IV, Dose A	Drug: Belinostat; Belinostat will be administered once daily on days 1 to 5 of a 21-day cycle (up to 6 cycles) via 30-min. IV infusion.; Other Names: Beleodaq
Experimental: Cohort B; Mild Impairment, Belinostat IV, Dose A	Drug: Belinostat; Belinostat will be administered once daily on days 1 to 5 of a 21-day cycle (up to 6 cycles) via 30-min. IV infusion.; Other Names: Beleodaq
Experimental: Cohort C; Moderate Impairment, Belinostat IV, Dose B	Drug: Belinostat; Belinostat will be administered once daily on days 1 to 5 of a 21-day cycle (up to 6 cycles) via 30-min. IV infusion.; Other Names: Beleodaq
Experimental: Cohort D; Severe Impairment, Belinostat IV, Dose B	Drug: Belinostat; Belinostat will be administered once daily on days 1 to 5 of a 21-day cycle (up to 6 cycles) via 30-min. IV infusion.; Other Names: Beleodaq

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Establish pharmacokinetic (PK) profile of belinostat from Area under the Curve (AUC) parameters in patients based on renal impairments in cohorts A,B, C, & D	Area under the plasma drug concentration vs. time curve (AUC) at time 0 to tn will be determined based on specified time points of plasma sample collection from Day 1 to Day 3 of belinostat administration	26 weeks
Establish pharmacokinetic (PK) profile of belinostat from Volume of Distribution (Vdss) parameters in patients based on renal impairments in cohorts A,B, C, & D	Volume of Distribution (Vdss) proportionality of drug confined to the plasma vs proportion distributed to other tissues will be determined based on total dose of the drug over specified time points of plasma sample collection from Day 1 to Day 3 of belinostat administration	26 weeks
Establish pharmacokinetic (PK) profile of belinostat from Total Body Clearance (CLtot) parameters in patients based on renal impairments in cohorts A,B, C, & D	Total Body Clearance (CLtot) of the drug will be determined by the specified time points of in the Urine PK sample collection from Day 1 to Day 4 of belinostat administration.	26 weeks
Establish pharmacokinetic (PK) profile of belinostat from Fraction Excreted (Fe) Unchanged parameters in patients based on renal impairments in cohorts A,B, C, & D	Fraction of the drug that is excreted unchanged (Fe) in the urine will be determined by dividing renal clearance over the total renal clearance based on Urine PK samples collection from specified time points in Day 1 to Day 4 of belinostat administration.	26 weeks
Establish pharmacokinetic (PK) profile of belinostat from Non Renal Clearance (CLnonren) parameters in patients based on renal impairments in cohorts A,B, C, & D	Non renal clearance (CLnonren) of the drug will be determined by total clearance minus renal clearance based on Urine PK sample collections from specified time points in Day 1 to Day 4 of belinostat administration	26 weeks
Establish pharmacokinetic (PK) profile of belinostat from peak concentration (Cmax) parameters in patients based on renal impairments in cohorts A,B, C, & D	Peak Concentration (Cmax) rate of absorption will be determined as the highest observed concentration in a concentration-time profile of Plasma PK sample collection from Day 1 to Day 3 of belinostat administration	26 weeks
Establish pharmacokinetic (PK) profile of belinostat half-life (t1/2) parameters in patients based on renal impairments in cohorts A,B, C, & D	Half-life (t1/2 ) of the drug will be determined by by volume of distribution (Vdss) over clearance (Cl) based on specified time points of plasma sample collection from Day 1 to Day 3 of belinostat administration	26 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number and percentage of patients with any TEAEs by SOC (System Organ Class) and Preferred Term (PT)	safety analysis of patients with onset of treatment emergent related events from Grade 1-5 of the most common TEAE: nausea, fatigue,pyrexia, anemia, vomiting, thrombocytopenia, dypsnea, neutropenia and hypokalemia	First dose of study drug until 30 days after last dose
Number and percentage of patients with any SAEs by SOC (System Organ Class) and Preferred Term (PT)	safety analysis of patients with serious adverse events includes pneumonia, pyrexia, infection,anemia, deep vein thrombosis, blood creatinine increase, multi-organ failure, and pulmonary embolism	First dose of study drug until 30 days after last dose
Number and percentage of patients with any TEAEs related to belinostat by SOC (System Organ Class) and Preferred Term (PT)	safety analysis of patients with new onset of treatment emergent adverse event related to study drug based on pyrexia, thrombocytopenia and blood creatinine increase	First dose of study drug until 30 days after last dose
Number and percentage of patients with any TEAEs causing discontinuation of the study by SOC (System Organ Class ) and PT (Preferred Term)	safety analysis of patients who discontinued treatment based on anemia, fatigue, febrile neutropenia, pneumonia, & multi-organ failure	First dose of study drug until 30 days after last dose

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: March 1, 2016
• Primary Completion (Actual): June 1, 2017
• Study Completion (Actual): June 1, 2017

Study Registration Dates

• First Submitted: January 27, 2016
• First Submitted That Met QC Criteria: February 5, 2016
• First Posted (Estimate): February 10, 2016

Study Record Updates

• Last Update Posted (Actual): November 20, 2019
• Last Update Submitted That Met QC Criteria: November 18, 2019
• Last Verified: November 1, 2019

More Information

Terms related to this study

• Keywords: renal impairment; hematological malignancies; beleodaq; belinostat; relapsed/refractory solid tumors
• Additional Relevant MeSH Terms: Neoplasms by Site; Kidney Diseases; Urologic Diseases; Hematologic Diseases; Neoplasms; Hematologic Neoplasms; Renal Insufficiency; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Histone Deacetylase Inhibitors; Belinostat
• Other Study ID Numbers: SPI-BEL-105

Plan for Individual participant data (IPD)

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