Clinical trial NCT03954366: Drug-Drug Interaction Study of Rucaparib, Rosuvastatin and Oral Contraceptives
Official title: A Phase 1, Open-label, Drug-drug-interaction Study to Determine the Effect of Rucaparib on the Pharmacokinetics of Oral Rosuvastatin (Arm A) and Oral Contraceptives (Ethinylestradiol and Levonorgestrel) (Arm B) 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: 2019-05-17
Enrollment: 36
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: OTHER

Brief summary: This study will investigate the drug-drug interactions (DDIs) between rucaparib and oral rosuvastatin (Arm A), and between rucaparib and oral ethinylestradiol and levonorgestrel (Arm B), with rucaparib as a perpetrator.

Detailed description: This is a Phase 1, open-label, drug-drug-interaction (DDI) study in patients with advanced solid tumor. In Part I, the effects of rucaparib (600 mg twice daily \[BID\]) on the PK of oral rosuvastatin (Arm A) and the combined oral contraceptives (ethinylestradiol and levonorgestrel; Arm B) will be assessed.

Part I: patients will receive single oral doses of rosuvastatin or oral contraceptives (according to assigned arm) on Day 1 and Day 19. Continuous treatment with rucaparib at 600 mg BID will commence on Day 5 and continue until the end of Part I (Day 23).

Part II (optional): treatment with rucaparib in 28-day cycles may continue (at the discretion of the Investigator) until progression of disease, unacceptable toxicity, or other reason for discontinuation.

Eligibility criteria: Inclusion Criteria (All patients):

* Willing to sign the ICF and to comply with the study restrictions
* Body mass index (BMI) 18.0 to 35.0 kg/m2
* Histologically or cytologically confirmed advanced solid tumor
* Patients who, in the opinion of the Investigator, could potentially benefit from treatment with rucaparib
* ECOG performance status less than or equal to 1
* Adequate organ function

Inclusion Criteria (Arm A):

- Male or female patients ≥ 18 years of age

Inclusion Criteria (Arm B):

- Female patients ≥ 18 years of age

Exclusion Criteria (All patients):

* Specific cancer treatments within 14 days prior to Day 1
* Arterial or venous thrombi (including cerebrovascular accident), myocardial infarction, admission for unstable angina, acute coronary syndrome, cardiac angioplasty, stenting, or poorly controlled hypertension within the last 3 months prior to screening
* Pre-existing duodenal stent, recent or existing bowel obstruction
* Untreated or symptomatic central nervous system (CNS) metastases. Patients with treated asymptomatic CNS metastases are eligible
* Known HIV or AIDS-related illness, acute or history of chronic hepatitis B or C
* Female patients who are pregnant or breastfeeding
* Participation in another investigational drug trial within 30 days prior to Day 1 or exposure to more than 3 new investigational agents within 12 months prior to Day 1
* Presence of active infection requiring antibiotics
* Active second malignancy
* History of drug abuse (including alcohol)

Exclusion Criteria (Arm A):

* Current use of rosuvastatin or any other statin
* History of hypersensitivity to rosuvastatin
* Current, or history of, clinically significant myopathy

Exclusion Criteria (Arm B):

* Current use of any 1 of the contraceptive drugs or previous contraceptive implants or depot injections, which may still be clinically effective
* History of hypersensitivity to ethinylestradiol or levonorgestrel

Primary outcomes:
measure: PK parameters for oral rosuvastatin, ethinylestradiol and levonorgestrel without and with rucaparib treatment.
timeFrame: Day 1 to Day 23
measure: PK parameters for oral rosuvastatin, ethinylestradiol and levonorgestrel without and with rucaparib treatment.
timeFrame: Day 1 to Day 23
measure: PK parameters for oral rosuvastatin, ethinylestradiol and levonorgestrel without and with rucaparib treatment.
timeFrame: Day 1 to Day 23
Secondary outcomes:
measure: PK parameters for oral rosuvastatin, ethinylestradiol and levonorgestrel without and with rucaparib treatment.
timeFrame: Day 1 to Day 23
measure: PK parameters for oral rosuvastatin, ethinylestradiol and levonorgestrel without and with rucaparib treatment.
timeFrame: Day 1 to Day 23
measure: PK parameters for oral rosuvastatin, ethinylestradiol and levonorgestrel without and with rucaparib treatment.
timeFrame: Day 1 to Day 23
measure: PK parameters for oral rosuvastatin, ethinylestradiol and levonorgestrel without and with rucaparib treatment.
timeFrame: Day 1 to Day 23
measure: The following secondary PK parameter will be calculated for rucaparib.
timeFrame: Day 1 to Day 23
measure: Incidence of Adverse Events [Safety and Tolerability]
timeFrame: From Day 1 to last patient visit in Part II (approximately 2 years)
measure: Incidence of clinical laboratory abnormalities [Safety and Tolerability]
timeFrame: From Day 1 to last patient visit in Part II (approximately 2 years)
measure: Incidence of dose modifications [Safety and Tolerability]
timeFrame: From Day 1 to last patient visit in Part II (approximately 2 years)
Other outcomes:
Locations:
city: Budapest
country: Hungary
facility: PRA Magyarország Fázis I-es Klinikai Farmakológiai Vizsgálóhely FMC Dialízis Központ, II. em.
city: Biała Podlaska
country: Poland
facility: Wojewódzki Szpital Specjalistyczny w Białej Podlaskiej
city: Józefów
country: Poland
facility: BioVirtus Centrum Medyczne
city: Kraków
country: Poland
facility: Ujastek Sp. z o.o. Centrum medyczne
city: Poznań
country: Poland
facility: Med Polonia Sp. z o.o.
city: Warszawa
country: Poland
facility: Zdrowie Kobiety Centrum Leczniczo-Rehabilitacyjne i Medycyny Pracy ATTIS Sp. z o.o., Zakład Onkologii Kobiecej
city: Bratislava
country: Slovakia
facility: Summit Clinical Research s.r.o.
Study officials:
References:
citation: Liao M, Jeziorski KG, Tomaszewska-Kiecana M, Lang I, Jasiowka M, Skarbova V, Centkowski P, Ramlau R, Gornas M, Lee J, Edwards S, Habeck J, Nash E, Grechko N, Xiao JJ. A phase 1, open-label, drug-drug interaction study of rucaparib with rosuvastatin and oral contraceptives in patients with advanced solid tumors. Cancer Chemother Pharmacol. 2021 Nov;88(5):887-897. doi: 10.1007/s00280-021-04338-7. Epub 2021 Aug 9.