Pharmacokinetic and Safety Study of Niraparib With Normal or Moderate Hepatic Impairment Patients

Inclusion Criteria

• •Diagnosis and Criteria for Inclusion:
• •All patients:
• •To be considered eligible to participate in this study, all of the following requirements must be met:
• •1. Patient, male or female, is at least 18 years of age.
• •2. Patient has a diagnosis of advanced solid malignancy that has failed standard therapy or for which standard therapy is not likely to provide meaningful benefit, or patient has refused standard therapy.
• •3. Patient has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1.
• •4. Patient is able to take oral medications.
• •5. Female patient, if of childbearing potential, has a negative serum pregnancy test within 72 hours prior to taking study drug and agrees to abstain from activities that could result in pregnancy from enrollment through 120 days after the last dose of study treatment, or be of non-childbearing potential. Non-childbearing potential is defined as (by other than medical reasons):
• •* ≥45 years of age and has not had menses for \> 1 year.
• •* Amenorrheic for \< 2 years without a hysterectomy Post hysterectomy, bilateral oophorectomy, or tubal ligation..
• •Note: Abstinence is acceptable if this is the established and preferred contraception for the patient.
• •6. Male patient agrees to use an adequate method of contraception starting with the first dose of study treatment through 120 days after the last dose of study treatment..
• •7. Patient is able to understand the study procedures and agrees to participate in the study by providing written informed consent.
• •Patients with normal hepatic function (Group 1):
• •Patients screened for the normal hepatic function group must meet the following additional criteria to be eligible for enrollment:
• •1. Patient has no history of hepatic impairment.
• •2. Patient has liver function test (LFT) results within normal range:
• •* Total bilirubin ≤ ULN
• •* Aspartate aminotransferase (AST) ≤ ULN.
• •* INR ≤1.5 X ULN unless the patient is receiving anticoagulant therapy and the INR is within therapeutic range of intended use of anticoagulants.
• •3. Patient has adequate hematologic and renal function as defined below:
• •* Absolute neutrophil count ≥1500/µL
• •* Platelets ≥100,000/µL
• •* Hemoglobin ≥9 g/dL
• •* Serum creatinine ≤1.5 × ULN or a calculated creatinine clearance ≥60 mL/min using the Cockcroft-Gault equation.
• •Patients with moderate hepatic impairment (Group 2):
• •Patients screened for the moderate hepatic impairment group must meet the following additional criteria to be eligible for enrollment:
• •1. Patient has stable, moderate hepatic impairment, defined as:
• •* BILI: \>1.5 × to 3 × ULN, for at least 2 weeks prior to Day 1
• •* AST: Any value
• •* INR less than 1.8 unless the patient is receiving anticoagulant therapy and the INR is within therapeutic range of intended use of anticoagulants.
• •2. Patient has hematologic and renal function as defined below:
• •* Absolute neutrophil count ≥1000/µL
• •* Platelets ≥75,000/µL
• •* Hemoglobin ≥8 g/dL
• •* Serum creatinine ≤1.5 × ULN or a calculated creatinine clearance ≥60 mL/min using the Cockcroft-Gault equation.
• •3. Patient's hepatic disease is deemed stable by the Investigator
• •Criteria for Exclusion:
• •Patients will not be eligible for study entry if any of the following criteria are met:
• •All patients:
• •1. Patient has undergone palliative radiotherapy within 1 week of study drug administration, encompassing \>20% of the bone marrow.
• •2. Patient is starting chemotherapy within 3 weeks of study drug administration.
• •3. Patient has a known hypersensitivity to the components of niraparib or excipients