Clinical trial NCT02986100: Absorption, Metabolism, and Excretion Following a Single Oral Dose of [14C]-Rucaparib
Official title: An Open-Label, Non-Randomized, Phase I Study to Assess the Absorption, Metabolism, and Excretion Following a Single Oral Dose of [14C]-Rucaparib in Patients With Advanced Solid Tumors
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Solid Tumor
Keywords: rucaparib
CO-338
Clovis
Clovis Oncology
PARP inhibitor
Absorption
Metabolism
Excretion
Lead sponsor: pharmaand GmbH
Sponsor class: INDUSTRY
First posted: 2016-12-08
Enrollment: 6
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: OTHER

Brief summary: The purpose of this study is to characterize the mass balance, absorption, metabolism, and elimination pathways of orally administered \[14C\] rucaparib followed by cycle by cycle treatment with rucaparib continuing until disease progression or other reason for discontinuation

Detailed description: This is a Phase 1, open-label, non-randomized, mass balance study in patients with histologically or cytologically confirmed advanced solid tumors. Approximately 6 patients will be enrolled. The study will consist of 2 parts: a mass balance part (Part I) and a rucaparib treatment part (Part II).

Each patient will receive a single oral dose of 600 mg \[14C\] rucaparib (approximately 140 µCi) in the fasted state. Patients will be confined at the study site for the collection of blood samples and excreta for a maximum of 13 days, from Day -1. The patient can be discharged sooner than Day 13, if the discharge criteria are met. If the cumulative recovery of radioactivity exceeds 90% of the administered dose or if radioactivity in urine and feces is \< 1% of the administered dose over a 24 hour period on two consecutive days, as determined by quick counts.

In Part II, the treatment with rucaparib in 28-day cycles will continue until progression of disease, unacceptable toxicity, or other reason for discontinuation.

Eligibility criteria: Inclusion Criteria:

* Histologically or cytologically confirmed advanced solid tumor
* Part II only: Have a known deleterious BRCA1/2 mutation (germline or somatic) as determined by a local or central laboratory
* Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
* Adequate bone marrow, renal, and liver function

Exclusion Criteria:

* Prior treatment with chemotherapy, radiation, antibody therapy or other immunotherapy, gene therapy, vaccine therapy, or angiogenesis inhibitors within 14 days prior to Day 1
* Participation in a trial involving administration of \[14C\]-labeled compound(s) within the last 6 months prior to Day 1
* Arterial or venous thrombi (including cerebrovascular accident), myocardial infarction, admission for unstable angina, cardiac angioplasty, or stenting within the last 3 months prior to Screening
* Pre-existing duodenal stent, recent or existing bowel obstruction, and/or any gastrointestinal disorder or defect that would, in the opinion of the Investigator, interfere with absorption of rucaparib
* Untreated or symptomatic central nervous system (CNS) metastases
* Evidence or history of bleeding disorder
* Participation in another investigational drug trial within 14 days prior to Day 1 (or 5 times the half-life of the drug, whichever is longer) or exposure to more than three new investigational agents within 12 months prior to Day 1
* Acute illness (eg, nausea, vomiting, fever, diarrhea) within 14 days prior to Day 1, unless mild in severity and approved by the Investigator and Sponsor's/designated medical representative
* Active second malignancy

Primary outcomes:
measure: Pharmacokinetics of 14C-labeled rucaparib (radioactivity in whole blood and plasma): tmax
timeFrame: Days 1-13
measure: Pharmacokinetics of 14C-labeled rucaparib(Radioactivity in whole blood and plasma): Cmax
timeFrame: Days 1-13
measure: Pharmacokinetics of 14C-labeled rucaparib(Radioactivity in whole blood and plasma): t1/2
timeFrame: Days 1-13
measure: Pharmacokinetics of 14C-labeled rucaparib(Radioactivity in whole blood and plasma): AUC
timeFrame: Days 1-13
measure: Pharmacokinetics of 14C-labeled rucaparib(Radioactivity in whole blood and plasma): CL/F
timeFrame: Days 1-13
measure: Pharmacokinetics of 14C-labeled rucaparib(Radioactivity in whole blood and plasma): V/F
timeFrame: Days 1-13
measure: Excretion rate of 14C-labeled rucaparib(radioactivity in feces)
timeFrame: Days 1-13
measure: Excretion rate of 14C-labeled rucaparib(radioactivity in urine)
timeFrame: Days 1-13
measure: Pharmacokinetics of rucaparib (in urine): CLR
timeFrame: Days 1-13
measure: Excretion rate of 14C-labeled rucaparib(radioactivity in vomit, if applicable)
timeFrame: Days 1-13
measure: Metabolite identification of rucaparib in plasma, urine and feces
timeFrame: Days 1-13
measure: Cumulative whole blood:plasma ratio calculated for Cmax
timeFrame: Days 1-13
measure: Cumulative whole blood:plasma ratio calculated for AUC0-tlast
timeFrame: Day 1-13
measure: Cumulative whole blood:plasma ratio calculated for AUCinf
timeFrame: Day 1-13
Secondary outcomes:
measure: Tolerability and safety of rucaparib assessed by incidence of Adverse Events (AEs), clinical laboratory abnormalities, and dose modifications
timeFrame: From cycle 1 Day 1 until radiologically confirmed disease progression, death, or initiation of subsequent treatment whichever comes first up to 52 weeks
Other outcomes:
measure: To evaluate the antitumor activity of rucaparib in BRCA mutated solid tumors based on Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1
timeFrame: Cycle 1 Day 1 until progression of disease, unacceptable toxicity, or discontinuation for other reasons
Locations:
city: Budapest
country: Hungary
facility: PRA Magyarország Kft.
state: Rottenbiller Utca 13
Study officials:
References: