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

NCT02679131 | Terminated Phase 1

• 1 other identifier: SPI-BEL-105
• Study Type: interventional
• Target: 18
• Locations: 1 country
• Sites: 2

Brief Summary

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.

Conditions

Relapsed/Refractory Solid Tumors/Hematological Malignancies

Keywords

relapsed/refractory solid tumors; beleodaq; renal impairment; belinostat; hematological malignancies

Outcome Measures

Primary Outcomes (7)

• 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 Outcomes (4)

• Number and percentage of patients with any TEAEs by SOC (System Organ Class) and Preferred Term (PT)

  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)

  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)

  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)

  First dose of study drug until 30 days after last dose

Study Arms (4)

Cohort A

EXPERIMENTAL

Normal Renal function, Belinostat IV, Dose A

Drug: Belinostat

Cohort B

EXPERIMENTAL

Mild Impairment, Belinostat IV, Dose A

Drug: Belinostat

Cohort C

EXPERIMENTAL

Moderate Impairment, Belinostat IV, Dose B

Drug: Belinostat

Cohort D

EXPERIMENTAL

Severe Impairment, Belinostat IV, Dose B

Drug: Belinostat

Interventions

Belinostat DRUG

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.

Also known as: Beleodaq

Cohort A; Cohort B; Cohort C; Cohort D

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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 therapy for the current malignancy and has recovered from any toxicity of the prior therapy at screening.
• Patient has either normal or impaired renal functions.
• Patient has adequate hematological and hepatic functions.

You may not qualify if:

• 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.
• Patient has acute HBV or HCV
• Patient has known human immunodeficiency virus (HIV) positive diagnosis.
• Patient has had previous exposure to belinostat.

Sponsors & Collaborators

• Acrotech Biopharma Inc.: lead
• Axis Clinicals Limited: collaborator

Study Sites (2)

Innovative Clinical Research Institute

Whittier, California, 90603, United States

Location

Gabrail Cancer Center Research

Canton, Ohio, 44718, United States

Location

MeSH Terms

Conditions

Recurrence; Renal Insufficiency; Hematologic Neoplasms

Interventions

belinostat

Condition Hierarchy (Ancestors)

Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Neoplasms by Site; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases

Study Officials

• Wasim Khan, MD

  Acrotech Biopharma Inc.

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 27, 2016
• First Posted: February 10, 2016
• Study Start: March 1, 2016
• Primary Completion: June 1, 2017
• Study Completion: June 1, 2017
• Last Updated: November 20, 2019

Record last verified: 2019-11

Data Sharing

• IPD Sharing: Will not share

Locations

US (2)