Pharmacokinetic Drug-Drug Interaction Study of Rucaparib

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.

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.