Clinical trial NCT02740712: Pharmacokinetic Drug-Drug Interaction Study of Rucaparib
Official title: A Phase 1, Open-label, Multiple-probe Drug-drug Interaction Study to Determine the Effect of Rucaparib on Pharmacokinetics of Caffeine, S-Warfarin, Omeprazole, Midazolam, and Digoxin in Patients With Advanced Solid Tumors
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Neoplasms
Keywords: rucaparib
CO-338
Clovis
Clovis Oncology
PARP Inhibitor
Drug-Drug Interaction
Lead sponsor: pharmaand GmbH
Sponsor class: INDUSTRY
First posted: 2016-04-15
Enrollment: 17
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 assess pharmacokinetic concentrations of multiple probes alone followed by assessment of the same drug pharmacokinetic concentrations when the patient has steady-state exposure to 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, sequential, drug-drug-interaction (DDI) study in patients with advanced solid tumors. The study will consist of 2 parts: a DDI part (Part I) and a rucaparib treatment part (Part II).

In Part I, the PK of cytochrome P450 (CYP) cocktail probes: caffeine, S-warfarin, omeprazole, and midazolam and a P-glycoprotein probe (digoxin) will be assessed with and without rucaparib treatment. Patients will receive single doses of CYP drug cocktail (caffeine, warfarin, omeprazole, and midazolam) on Day 1 and Day 12, and single doses of digoxin on Day 2 and Day 13. Continuous treatment with 600 mg rucaparib twice daily (BID) will start on Day 5 and will last until at least Day 16 of Part I.

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
* Have evidence of measurable disease as defined by RECIST Version 1.1
* 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, angiogenesis inhibitors, or experimental drugs within 14 days prior to Day 1
* Prior treatment with any poly adenosine diphosphate ribose polymerase inhibitor (PARPi)
* Arterial or venous thrombi (including cerebrovascular accident), myocardial infarction, admission for unstable angina, cardiac angioplasty, stenting or poorly controlled hypertension 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 study drugs
* Current use of therapeutic anticoagulation (low molecular weight heparin, oral anticoagulant agents including acetylsalicylic acid),
* Current use of one of the probe drugs;
* Untreated or symptomatic central nervous system (CNS) metastases.
* Evidence or history of bleeding disorder
* Participation in another investigational drug trial within 30 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 within 14 days prior to Day 1 unless mild in severity and approved by the Investigator and Sponsor's medical representative
* Active second malignancy, i.e., patient known to have potentially fatal cancer present for which they may be (but not necessarily) currently receiving treatment.

Primary outcomes:
measure: PK parameters for caffeine, S-warfarin, omeprazole, midazolam, and digoxin with and without rucaparib treatment to be calculated from the plasma concentration-time data
timeFrame: Days 1-5 and Days 12-16
measure: PK parameters for caffeine, S-warfarin, omeprazole, midazolam, and digoxin with and without rucaparib treatment to be calculated from the plasma concentration-time data
timeFrame: Days 1-5 and Days 12-16
Secondary outcomes:
measure: PK parameters for caffeine, S-warfarin, omeprazole, midazolam, and digoxin with and without rucaparib treatment to be calculated from the plasma concentration-time data
timeFrame: Days 1-5 and Days 12-16
measure: Tolerability and safety of rucaparib with and without co-administration of the probe drugs assessed by incidence of Adverse Events (AEs), clinical laboratory abnormalities, and dose modifications"
timeFrame: Days 1-16
measure: PK parameters will be calculated for rucaparib at steady-state
timeFrame: Day 7-12
measure: PK parameters will be calculated for rucaparib at steady-state
timeFrame: Day 7-12
measure: PK parameters will be calculated for rucaparib at steady-state
timeFrame: Day 7-12
measure: PK parameters will be calculated for rucaparib at steady-state
timeFrame: Day 7-12
measure: PK parameters for caffeine, S-warfarin, omeprazole, midazolam, and digoxin with and without rucaparib treatment to be calculated from the plasma concentration-time data
timeFrame: Days 1-5 and Days 12-16
measure: PK parameters for caffeine, S-warfarin, omeprazole, midazolam, and digoxin with and without rucaparib treatment to be calculated from the plasma concentration-time data
timeFrame: Days 1-5 and Days 12-16
measure: PK parameters for caffeine, S-warfarin, omeprazole, midazolam, and digoxin with and without rucaparib treatment to be calculated from the plasma concentration-time data
timeFrame: Days 1-5 and Days 12-16
measure: PK parameters for caffeine, S-warfarin, omeprazole, midazolam, and digoxin with and without rucaparib treatment to be calculated from the plasma concentration-time data
timeFrame: Days 1-5 and Days 12-16
Other outcomes:
measure: 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
timeFrame: From cycle 1 Day 1until radiologically confirmed disease progression, death, or initiation of subsequent treatment whichever comes first up to 52 weeks
Locations:
city: Kajetany
country: Poland
facility: BioVirtus Research Site
state: Mokra 7
city: Poznan
country: Poland
facility: Med Polonia
city: Szczecin
country: Poland
facility: Zachodniopomorskie Centrum Onkologii Centrum Innowacji
Study officials:
References:
citation: Xiao JJ, Nowak D, Ramlau R, Tomaszewska-Kiecana M, Wysocki PJ, Isaacson J, Beltman J, Nash E, Kaczanowski R, Arold G, Watkins S. Evaluation of Drug-Drug Interactions of Rucaparib and CYP1A2, CYP2C9, CYP2C19, CYP3A, and P-gp Substrates in Patients With an Advanced Solid Tumor. Clin Transl Sci. 2019 Jan;12(1):58-65. doi: 10.1111/cts.12600. Epub 2018 Dec 20.