Clinical trial NCT02679131: To Evaluate Safety and Pharmacokinetics of Belinostat in Patients Who Have Mild, Moderate and Severe Renal Impairment.
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 type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
Conditions: Relapsed/Refractory Solid Tumors/Hematological Malignancies
Keywords: relapsed/refractory solid tumors
beleodaq
renal impairment
belinostat
hematological malignancies
Lead sponsor: Acrotech Biopharma Inc.
Sponsor class: INDUSTRY
Collaborators: name: Axis Clinicals Limited
First posted: 2016-02-10
Enrollment: 18
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: 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.

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.

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 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.

Primary outcomes:
measure: 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
timeFrame: 26 weeks
measure: Establish pharmacokinetic (PK) profile of belinostat from Volume of Distribution (Vdss) parameters in patients based on renal impairments in cohorts A,B, C, & D
timeFrame: 26 weeks
measure: Establish pharmacokinetic (PK) profile of belinostat from Total Body Clearance (CLtot) parameters in patients based on renal impairments in cohorts A,B, C, & D
timeFrame: 26 weeks
measure: Establish pharmacokinetic (PK) profile of belinostat from Fraction Excreted (Fe) Unchanged parameters in patients based on renal impairments in cohorts A,B, C, & D
timeFrame: 26 weeks
measure: Establish pharmacokinetic (PK) profile of belinostat from Non Renal Clearance (CLnonren) parameters in patients based on renal impairments in cohorts A,B, C, & D
timeFrame: 26 weeks
measure: Establish pharmacokinetic (PK) profile of belinostat from peak concentration (Cmax) parameters in patients based on renal impairments in cohorts A,B, C, & D
timeFrame: 26 weeks
measure: Establish pharmacokinetic (PK) profile of belinostat half-life (t1/2) parameters in patients based on renal impairments in cohorts A,B, C, & D
timeFrame: 26 weeks
Secondary outcomes:
measure: Number and percentage of patients with any TEAEs by SOC (System Organ Class) and Preferred Term (PT)
timeFrame: First dose of study drug until 30 days after last dose
measure: Number and percentage of patients with any SAEs by SOC (System Organ Class) and Preferred Term (PT)
timeFrame: First dose of study drug until 30 days after last dose
measure: Number and percentage of patients with any TEAEs related to belinostat by SOC (System Organ Class) and Preferred Term (PT)
timeFrame: First dose of study drug until 30 days after last dose
measure: Number and percentage of patients with any TEAEs causing discontinuation of the study by SOC (System Organ Class ) and PT (Preferred Term)
timeFrame: First dose of study drug until 30 days after last dose
Other outcomes:
Locations:
city: Whittier
country: United States
facility: Innovative Clinical Research Institute
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: