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Trial record 1 of 12 for:    Pharmacokinetics of Belinostat
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To Evaluate Safety and Pharmacokinetics of Belinostat in Patients Who Have Mild, Moderate and Severe Renal Impairment.

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ClinicalTrials.gov Identifier: NCT02679131
Recruitment Status : Terminated (Close out study w/o Cohort D; Severe Impairment (eGFR=15 to <30mL/min/1.73m²))
First Posted : February 10, 2016
Last Update Posted : November 20, 2019
Sponsor:
Collaborator:
Axis Clinicals Limited
Information provided by (Responsible Party):
Acrotech Biopharma LLC

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.

Condition or disease Intervention/treatment Phase
Relapsed/Refractory Solid Tumors/Hematological Malignancies Drug: Belinostat Phase 1

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.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 18 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: 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
Study Start Date : March 2016
Actual Primary Completion Date : June 2017
Actual Study Completion Date : June 2017

Resource links provided by the National Library of Medicine

Drug Information available for: Belinostat

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 Name: 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 Name: 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 Name: 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 Name: Beleodaq




Primary Outcome Measures :
  1. 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 [ Time Frame: 26 weeks ]
    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

  2. Establish pharmacokinetic (PK) profile of belinostat from Volume of Distribution (Vdss) parameters in patients based on renal impairments in cohorts A,B, C, & D [ Time Frame: 26 weeks ]
    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

  3. Establish pharmacokinetic (PK) profile of belinostat from Total Body Clearance (CLtot) parameters in patients based on renal impairments in cohorts A,B, C, & D [ Time Frame: 26 weeks ]
    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.

  4. Establish pharmacokinetic (PK) profile of belinostat from Fraction Excreted (Fe) Unchanged parameters in patients based on renal impairments in cohorts A,B, C, & D [ Time Frame: 26 weeks ]
    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.

  5. Establish pharmacokinetic (PK) profile of belinostat from Non Renal Clearance (CLnonren) parameters in patients based on renal impairments in cohorts A,B, C, & D [ Time Frame: 26 weeks ]
    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

  6. Establish pharmacokinetic (PK) profile of belinostat from peak concentration (Cmax) parameters in patients based on renal impairments in cohorts A,B, C, & D [ Time Frame: 26 weeks ]
    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

  7. Establish pharmacokinetic (PK) profile of belinostat half-life (t1/2) parameters in patients based on renal impairments in cohorts A,B, C, & D [ Time Frame: 26 weeks ]
    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


Secondary Outcome Measures :
  1. Number and percentage of patients with any TEAEs by SOC (System Organ Class) and Preferred Term (PT) [ Time Frame: First dose of study drug until 30 days after last dose ]
    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

  2. Number and percentage of patients with any SAEs by SOC (System Organ Class) and Preferred Term (PT) [ Time Frame: First dose of study drug until 30 days after last dose ]
    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

  3. Number and percentage of patients with any TEAEs related to belinostat by SOC (System Organ Class) and Preferred Term (PT) [ Time Frame: First dose of study drug until 30 days after last dose ]
    safety analysis of patients with new onset of treatment emergent adverse event related to study drug based on pyrexia, thrombocytopenia and blood creatinine increase

  4. Number and percentage of patients with any TEAEs causing discontinuation of the study by SOC (System Organ Class ) and PT (Preferred Term) [ Time Frame: First dose of study drug until 30 days after last dose ]
    safety analysis of patients who discontinued treatment based on anemia, fatigue, febrile neutropenia, pneumonia, & multi-organ failure



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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 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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02679131


Locations
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United States, California
Innovative Clinical Research Institute
Whittier, California, United States, 90603
United States, Ohio
Gabrail Cancer Center Research
Canton, Ohio, United States, 44718
Sponsors and Collaborators
Acrotech Biopharma LLC
Axis Clinicals Limited
Investigators
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Study Director: Wasim Khan, MD Acrotech Biopharma LLC
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Responsible Party: Acrotech Biopharma LLC
ClinicalTrials.gov Identifier: NCT02679131    
Other Study ID Numbers: SPI-BEL-105
First Posted: February 10, 2016    Key Record Dates
Last Update Posted: November 20, 2019
Last Verified: November 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No
Keywords provided by Acrotech Biopharma LLC:
relapsed/refractory solid tumors
beleodaq
renal impairment
belinostat
hematological malignancies
Additional relevant MeSH terms:
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Belinostat
Hematologic Neoplasms
Renal Insufficiency
Neoplasms
Kidney Diseases
Urologic Diseases
Neoplasms by Site
Hematologic Diseases
Antineoplastic Agents
Histone Deacetylase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action