Clinical trial NCT02476552: Absorption, Metabolism, Excretion, and the Determination of Absolute Bioavailability of Niraparib in Subjects With Cancer
Official title: Absorption, Metabolism, Excretion, and the Determination of Absolute Bioavailability of Niraparib in Subjects With Cancer
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Cancer
Lead sponsor: Tesaro, Inc.
Sponsor class: INDUSTRY
First posted: 2015-06-19
Enrollment: 12
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: This is an open-label study with 2 parts, plus an extension study following completion of Parts 1 or 2, that is being conducted in approximately 12 subjects (6 subjects in Part 1; 6 subjects in Part 2) with cancer to examine the absorption, metabolism, excretion, and absolute bioavailability of niraparib.

Detailed description: Part 1: After an overnight fast of at least 10 hours, subjects will receive a single, oral dose of niraparib (unlabeled active pharmaceutical ingredient) on Day 1. Two hours after the oral dose, subjects will receive a 15-minute IV infusion of niraparib (labeled pharmaceutical ingredient).

Part 2: After an overnight fast of at least 10 hours, subjects will receive a single, oral dose of niraparib, labeled active pharmaceutical ingredient.

Eligibility criteria: Inclusion Criteria:

* Subject, male or female, is at least 18 years of age.
* 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.
* The subject has adequate organ function:
* Subject must have an ECOG performance status of 0 to 2.
* Female subjects of childbearing potential must have a negative serum pregnancy test (beta human chorionic gonadotropin \[hCG\]) within 72 hours prior to receiving the first dose of study drug.

Exclusion Criteria:

* Subject has undergone palliative radiotherapy within 1 week of study drug administration, encompassing \>20% of the bone marrow.
* Subject has persistent \>Grade 2 toxicity from prior cancer therapy.
* Subject has known hypersensitivity to the components of niraparib.
* Subject has had major surgery within 3 weeks of study drug administration or has not recovered from all effects of any major surgery.
* 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.
* Subject has participated in a radioactive clinical study and has received an investigational radiolabeled drug within 6 months prior to study drug administration (for subjects participating in Part 2)

Primary outcomes:
measure: Oral bioavailability (F) will be derived using F=AUCoral / AUCiv as a %
timeFrame: 0 - 22 days
Secondary outcomes:
measure: AUC0-last
timeFrame: 0 - 22 days
measure: Cmax
timeFrame: 0 - 22 days
Other outcomes:
Locations:
city: Amsterdam
country: Netherlands
facility: The Netherlands Cancer Institute
Study officials:
affiliation: Tesaro, Inc.
name: Shefali Agarwal, MD
role: STUDY_DIRECTOR
References: