and that may benefit from treatment with a PARP inhibitor cancer
Conditions
Interventions
This is an open-label study with 2 parts, plus an extension study following
completion of Part 1 or 2, to be conducted in subjects with cancer at a single
study center in conformance with Good Clini
Sponsors
TESARO, Inc
Eligibility
Age
18 Years to 99 Years
Inclusion criteria
Inclusion criteria: To be considered eligible to participate in this study, all of the following requirements must be met: 1. Subject is capable of understanding the written informed consent, provides signed and witnessed written informed consent, and agrees to comply with protocol requirements. 2. Subject, male or female, is at least 18 years of age. 3. Subject has histologically or cytologically confirmed diagnosis of metastatic or locally advanced solid tumors that have failed to respond to standard therapy, have progressed despite standard therapy, refuse standard therapy, or for which no standard therapy exists, and that may benefit from treatment with a poly (adenosine diphosphate [ADP]-ribose) polymerase (PARP) inhibitor. The diagnosis must be confirmed with a previous computed tomography (CT) scan. 4. The subject has adequate organ function: a. Absolute neutrophil count >=1500/µL b. Platelets >=150,000/µL c. Hemoglobin >=9 g/dL (5.6 mM) d. Serum creatinine =60 mL/min using the Cockcroft-Gault equation e. Total bilirubin
Exclusion criteria
Exclusion criteria: Subjects will not be eligible for study entry if any of the following criteria are met: 1. Subject has undergone palliative radiotherapy within 1 week of study drug administration, encompassing >20% of the bone marrow. 2. Subject has persistent >Grade 2 toxicity from prior cancer therapy. 3. Subject has any known, persistent (>4 weeks) >=Grade 3 hematological toxicity or fatigue from prior cancer therapy. 4. Subject has symptomatic uncontrolled brain or leptomeningeal metastases. To be considered *controlled,* the subject must have undergone treatment (eg, radiation or chemotherapy at least 1 month prior to study entry) for the central nervous system (CNS) disease. The subject must have no new or progressive signs or symptoms related to the CNS disease and must be taking a stable dose of steroids or no steroids. A scan to confirm the absence of brain metastases is not required. Subjects with spinal cord compression may be considered if they have received definitive treatment and there is evidence of the disease being clinically stable for 28 days. 5. Subject has known hypersensitivity to the components of niraparib. 6. Subject has had major surgery within 3 weeks of study drug administration or has not recovered from all effects of any major surgery. 7. Subject is considered a medical risk due to a serious, uncontrolled medical disorder; nonmalignant systemic disease; or active, uncontrolled infection. Examples include, but are not limited to, uncontrolled ventricular arrhythmia, recent (within 90 days of the Screening Visit) myocardial infarction, uncontrolled major seizure disorder, unstable spinal cord compression, superior vena cava syndrome, or any psychiatric disorder that prohibits obtaining informed consent. 8. Subject received (or is anticipated to receive) a platelet transfusion within 4 weeks of study drug administration. 9. Subject has a history or current evidence of any condition, therapy, or laboratory abnormality (including active or uncontrolled myelosuppresion [ie, anemia, leukopenia, neutropenia, thrombocytopenia]) that might confound the results of the study, interfere with the subject*s participation for the full duration of the study treatment, or suggests it is not in the best interest of the subject to participate. 10. Subject has any known history of myelodysplastic syndrome (MDS) or a pre-treatment cytogenetic testing result at risk for a diagnosis of MDS/acute myeloid leukemia (AML). 11. Subject is pregnant, breastfeeding, or expecting to conceive children within the projected duration of the study treatment. 12. Subject is immunocompromised with an active event and is being treated with medications. 13. Subject has confirmed or suspected hepatitis B virus (HBV), hepatitis C virus (HCV), or human immunodeficiency virus (HIV). 14. Subject has a corrected QT interval (QTc) prolongation of >470 msec at the Screening Visit. 15. Subject is receiving concomitant medication(s) that prolong QTc and is unable to discontinue use for the duration of the study. 16. Subject is starting chemotherapy within 3 weeks of study drug administration. 17. Subject is taking proton pump inhibitors, antacids, or H2 blockers within 48 hours prior to study drug administration, and/or within 6 hours after study drug administration. 18. Subject has a history of illicit drug use. 19. Subject has a past or current history of chronic alcohol use (3 or
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| The absolute bioavailability of niraparib in subjects with cancer (part 1). Plasma niraparib concentrations will be used to determine the following PK parameters: maximum observed plasma concentration (Cmax); time to reach Cmax (Tmax); and area under the plasma concentration-time curve (AUC) from time 0 to the last quantifiable concentration (AUC0-last); and if the data allow: AUC from time 0 to infinity (AUC0-inf); apparent oral volume of distribution (Vd/F); apparent oral clearance (CL/F); and half-life (t*). Absolute bioavailability of niraparib will be calculated as the ratio of dose normalized oral to IV niraparib exposure. | — |
Secondary
| Measure | Time frame |
|---|---|
| Pharmacokinetics, safety and tolerability of niraparib in subjects with cancer (part 2 and extension study). Whole blood and plasma total radioactivity and niraparib concentration-time data will be used to determine the following PK parameters: Cmax, Tmax, and AUC0-last. The plasma niraparib concentration will be used to determine the following PK parameters: Cmax, Tmax, and AUC0-last, and if the data allow: AUC0-inf, Vd/F, CL/F, and t*. Additionally, the following PK parameters will be determined: amount of drug excreted in the urine in a 24-hour period, Ae (day), and total amount of drug excreted in the urine, Ae (total). Urine and fecal elimination of radioactivity will be determined, and total recovery of radioactivity over the collection period will be calculated. Data interpolation will be used to project recovery estimates. Other PK parameters, such as the extent of absorption (f), could be estimated, if appropriate. Selected plasma, urine, and fecal samples will also be subjected to metabolic profiling. Extension study: Plasma niraparib concentrations will be used to determine the following PK parameters: Cmax, Tmax, AUC0-last, AUC0-inf, and t*. Safety: Safety will be assessed based on adverse events (AEs), physical examinations, vital signs, electrocardiograms (ECGs), and clinical laboratory results. | — |
Countries
Netherlands
Outcome results
None listed