A Phase 1-2 Study of Onapristone in Patients With Advanced Castration-resistant Prostate Cancer
试验速览
- 阶段
- 1 期
- 发起方
- 入组人数
- 75
- 试验地点
- 1
- 主要终点
- Dose limiting toxicities related to onapristone or the combination of onapristone and abiraterone utilizing a day 57 safety cut off and based on CTCAE v4
研究概览
简要总结
This is an open-label, randomized, parallel group two-stage phase 1-2 study with an escalation and an expansion component. This study will evaluate an extended-release (ER) formulation of onapristone in patients with prostate cancer in which Progesterone Receptor (PR) may be contributing to tumor progression. A companion diagnostic to select patients whose prostate cancer expresses the activated form of the PR (APR) is under development and will be implemented in this study; it may be used to further enrich the selection of the population based upon ongoing review of the results. Patients will be treated until occurrence of an intolerable safety issue, treatment failure, if patient elects to withdraw, or for non-compliance with either protocol-specified evaluations or onapristone treatment. An additional cohort of patients will be included at the recommended phase 2 dose to gain additional understanding of the onapristone safety profile and potential anti-cancer activity.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- Male
- 接受健康志愿者
- 否
入选标准
- 未提供
排除标准
- 未提供
研究组 & 干预措施
onapristone 10 mg BID
onapristone 10 mg BID extended-release tablets
干预措施: onapristone (Drug)
onapristone 20 mg BID
onapristone 20 mg BID extended-release tablets
干预措施: onapristone (Drug)
onapristone 30 mg BID
onapristone 30 mg BID extended-release tablets
干预措施: onapristone (Drug)
onapristone 40 mg BID
onapristone 40 mg BID extended-release tablets
干预措施: onapristone (Drug)
onapristone 50 mg BID
onapristone 50 mg BID extended-release
干预措施: onapristone (Drug)
onapristone 30 mg BID + abiraterone 1000 mg
Expansion cohort: onapristone 30 mg BID + abiraterone 1000 mg
干预措施: onapristone (Drug)
onapristone 30 mg BID + abiraterone 1000 mg
Expansion cohort: onapristone 30 mg BID + abiraterone 1000 mg
干预措施: abiraterone (Drug)
onapristone 50 mg BID + abiraterone 1000 mg
Expansion cohort: onapristone 50 mg BID + abiraterone 1000 mg
干预措施: onapristone (Drug)
onapristone 50 mg BID + abiraterone 1000 mg
Expansion cohort: onapristone 50 mg BID + abiraterone 1000 mg
干预措施: abiraterone (Drug)
Expansion cohort: onapristone 50 mg BID
Expansion cohort: onapristone 50 mg BID
干预措施: onapristone (Drug)
结局指标
主要结局
Dose limiting toxicities related to onapristone or the combination of onapristone and abiraterone utilizing a day 57 safety cut off and based on CTCAE v4
时间窗: Baseline to 57 days post-first dose
Response to onapristone or the combination of onapristone and abiraterone
时间窗: Baseline to 30 Days after last dose
* Objective partial or complete response by RECIST 1.1, confirmed on a second CT scan at least 4 weeks apart and / or * PSA decline of ≥ 50% (according to the PCWG2).
次要结局
- Safety and tolerability of extended-release onapristone tablets BID(Baseline to 30 Days after last dose)
- PK of onapristone, mono-demethylated onapristone and other metabolites in plasma and urine(Baseline to 30 Days after last dose)