Absorption, Metabolism, and Excretion Following a Single Oral Dose of [14C]-Rucaparib (AME)

pharmaand

Status and phase: Completed; Phase 1

Conditions: Solid Tumor

Treatments: Drug: C-14 labeled Rucaparib; Drug: Rucaparib

Study type: Interventional

Funder types: Industry

Identifiers

NCT02986100

2015-004394-32 (EudraCT Number)

CO-338-045 (Other Identifier)

Details and patient eligibility

About

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

Full 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.

Enrollment: 6 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Other

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

---

6 participants in 1 patient group

C-14 labeled rucaparib

Experimental group

Description:

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. After completion of Part I, patients with a deleterious BRCA mutation will have the option to participate in Part II by receiving 600 mg BID rucaparib tablets orally in 28 day cycles until disease progression, unacceptable toxicity, death, or discontinuation for other reasons

Treatment:

Drug: Rucaparib

Drug: C-14 labeled Rucaparib