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

Acrotech Biopharma

Status and phase: Terminated; Phase 1

Conditions: Relapsed/Refractory Solid Tumors/Hematological Malignancies

Treatments: Drug: Belinostat

Study type: Interventional

Funder types: Industry

Identifiers

NCT02679131

SPI-BEL-105

Details and patient eligibility

About

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.

Full 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.

Enrollment: 18 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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18 participants in 4 patient groups

Cohort A

Experimental group

Description:

Normal Renal function, Belinostat IV, Dose A

Treatment:

Drug: Belinostat

Cohort B

Experimental group

Description:

Mild Impairment, Belinostat IV, Dose A

Treatment:

Drug: Belinostat

Cohort C

Experimental group

Description:

Moderate Impairment, Belinostat IV, Dose B

Treatment:

Drug: Belinostat

Cohort D

Experimental group

Description:

Severe Impairment, Belinostat IV, Dose B

Treatment:

Drug: Belinostat