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

pharmaand GmbH3 个研究点分布在 1 个国家目标入组 17 人开始时间: 2016年4月最近更新: 2023年6月9日

适应症

干预措施

试验速览

阶段: 1 期
状态: 已完成
发起方: pharmaand GmbH
入组人数: 17
试验地点: 3
主要终点: PK parameters for caffeine, S-warfarin, omeprazole, midazolam, and digoxin with and without rucaparib treatment to be calculated from the plasma concentration-time data

研究概览研究设计入排标准研究组 & 干预措施结局指标研究者研究点记录与标识符相似试验

研究概览

简要总结

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.

详细描述

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.

研究设计

研究类型: Interventional
分配方式: Na
干预模型: Single Group
主要目的: Other
盲法: None

盲法说明

Open Label

入排标准

年龄范围: 18 Years 至 —（Adult, Older Adult）
性别: All
接受健康志愿者: 否

入选标准

•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

排除标准

•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.