Solid Tumor
Conditions
Keywords
rucaparib, CO-338, Clovis, Clovis Oncology, PARP inhibitor, Absorption, Metabolism, Excretion
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.
Interventions
DRUGRucaparib
200 & 300 mg tablet
DRUGC-14 labeled Rucaparib
Each dosage unit consists of a hard gelatin capsule filled with cold rucaparib camsylate and \[14C\]-rucaparib camsylate salt. Each capsule contains approximately 150 mg rucaparib (free base weight) and approximately 35 µCi of \[14C\]-rucaparib. Each patient will ingest four capsules in the fasted state for a total dose of 600 mg rucaparib (free base weight) with approximately 140 µCi of \[14C\]-rucaparib
Sponsors
pharmaand GmbH
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
OTHER
Masking
NONE
Masking description
Open Label
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Cumulative whole blood:plasma ratio calculated for AUCinf | Day 1-13 | AUC from time zero to infinity (AUCinf) |
| Cumulative whole blood:plasma ratio calculated for Cmax | Days 1-13 | peak concentration (Cmax) |
| Cumulative whole blood:plasma ratio calculated for AUC0-tlast | Day 1-13 | AUC from time zero to the last time point with concentration above the lower limit of quantitation (AUC0-last) |
| Pharmacokinetics of 14C-labeled rucaparib (radioactivity in whole blood and plasma): tmax | Days 1-13 | Time to peak concentration (tmax) |
| Pharmacokinetics of 14C-labeled rucaparib(Radioactivity in whole blood and plasma): Cmax | Days 1-13 | peak (maximum) concentration (Cmax) |
| Pharmacokinetics of 14C-labeled rucaparib(Radioactivity in whole blood and plasma): t1/2 | Days 1-13 | Elimination half-life (t1/2) |
| Pharmacokinetics of 14C-labeled rucaparib(Radioactivity in whole blood and plasma): AUC | Days 1-13 | Area under curve (AUC) |
| Pharmacokinetics of 14C-labeled rucaparib(Radioactivity in whole blood and plasma): CL/F | Days 1-13 | Oral clearance (CL/F) |
| Pharmacokinetics of 14C-labeled rucaparib(Radioactivity in whole blood and plasma): V/F | Days 1-13 | Apparent volume of distribution (V/F) |
| Excretion rate of 14C-labeled rucaparib(radioactivity in feces) | Days 1-13 | Percent of dose excreted in feces |
| Excretion rate of 14C-labeled rucaparib(radioactivity in urine) | Days 1-13 | Percent of dose excreted in urine |
| Pharmacokinetics of rucaparib (in urine): CLR | Days 1-13 | Renal clearance (CLR) |
| Excretion rate of 14C-labeled rucaparib(radioactivity in vomit, if applicable) | Days 1-13 | Percent of dose in vomit, if applicable |
| Metabolite identification of rucaparib in plasma, urine and feces | Days 1-13 | — |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Tolerability and safety of rucaparib assessed by incidence of Adverse Events (AEs), clinical laboratory abnormalities, and dose modifications | From cycle 1 Day 1 until radiologically confirmed disease progression, death, or initiation of subsequent treatment whichever comes first up to 52 weeks | Incidence of Adverse Events (AEs), clinical laboratory abnormalities, and dose modifications |
Other
| Measure | Time frame | Description |
|---|---|---|
| To evaluate the antitumor activity of rucaparib in BRCA mutated solid tumors based on Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 | Cycle 1 Day 1 until progression of disease, unacceptable toxicity, or discontinuation for other reasons | Response will be determined using Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 and tumor markers per applicable criteria for a given tumor type |
Countries
Hungary
Outcome results
None listed