Neoplasms
Conditions
Keywords
rucaparib, CO-338, Clovis, Clovis Oncology, PARP Inhibitor, Drug-drug Interaction
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.
Interventions
DRUGRucaparib
Rucaparib 600 mg BID commencing on Day 5 until Day 23.
DRUGRosuvastatin
Single dose of 20mg oral rosuvastatin on Day 1 and Day 19 only.
Single dose of combined oral contraceptive (30 μg ethinylestradiol and 150 μg levonorgestrel) on Day 1 and Day 19 only.
Sponsors
pharmaand GmbH
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
OTHER
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| PK parameters for oral rosuvastatin, ethinylestradiol and levonorgestrel without and with rucaparib treatment. | Day 1 to Day 23 | Maximum plasma concentration (Cmax) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| PK parameters for oral rosuvastatin, ethinylestradiol and levonorgestrel without and with rucaparib treatment. | Day 1 to Day 23 | Terminal half-life (t1/2) |
| The following secondary PK parameter will be calculated for rucaparib. | Day 1 to Day 23 | Trough plasma concentration (Cmin) |
| Incidence of Adverse Events [Safety and Tolerability] | From Day 1 to last patient visit in Part II (approximately 2 years) | — |
| Incidence of clinical laboratory abnormalities [Safety and Tolerability] | From Day 1 to last patient visit in Part II (approximately 2 years) | — |
| Incidence of dose modifications [Safety and Tolerability] | From Day 1 to last patient visit in Part II (approximately 2 years) | — |
Countries
Hungary, Poland, Slovakia
Outcome results
None listed