Phase 1-2 Study of Onapristone in Patients With Advanced Castration-resistant Prostate Cancer

Phase 1

• Conditions: Prostate Cancer; Androgen-independent Prostate Cancer; Recurrent Prostate Cancer; Metastatic Prostate Cancer
• Interventions: Drug: onapristone; Drug: abiraterone

• Registration Number: NCT02049190
• Lead Sponsor: Arno Therapeutics

Brief Summary

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2014-01-28
• Study First Submitted QC: 2014-01-28
• Study First Posted: 2014-01-30
• Study Start: 2014-02
• Status Verified: 2015-06
• Last Update Submitted: 2015-06-22
• Last Update Posted: 2015-06-24
• Primary Completion: 2017-07
• Study Completion: 2017-12

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: Male
• Target Recruitment: 75

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
onapristone 20 mg BID	onapristone	onapristone 20 mg BID extended-release tablets
onapristone 30 mg BID	onapristone	onapristone 30 mg BID extended-release tablets
onapristone 40 mg BID	onapristone	onapristone 40 mg BID extended-release tablets
onapristone 30 mg BID + abiraterone 1000 mg	onapristone	Expansion cohort: onapristone 30 mg BID + abiraterone 1000 mg
onapristone 10 mg BID	onapristone	onapristone 10 mg BID extended-release tablets
onapristone 50 mg BID + abiraterone 1000 mg	abiraterone	Expansion cohort: onapristone 50 mg BID + abiraterone 1000 mg
onapristone 30 mg BID + abiraterone 1000 mg	abiraterone	Expansion cohort: onapristone 30 mg BID + abiraterone 1000 mg
onapristone 50 mg BID	onapristone	onapristone 50 mg BID extended-release
onapristone 50 mg BID + abiraterone 1000 mg	onapristone	Expansion cohort: onapristone 50 mg BID + abiraterone 1000 mg
Expansion cohort: onapristone 50 mg BID	onapristone	Expansion cohort: onapristone 50 mg BID

Primary Outcome Measures

Name	Time	Method
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	Baseline to 57 days post-first dose
Response to onapristone or the combination of onapristone and abiraterone	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).

Secondary Outcome Measures

Name	Time	Method
Safety and tolerability of extended-release onapristone tablets BID	Baseline to 30 Days after last dose	Safety will be assessed by physical exam, vital signs, monitoring of adverse events, changes in ECG, and changes in PSA and other clinical laboratory values.
PK of onapristone, mono-demethylated onapristone and other metabolites in plasma and urine	Baseline to 30 Days after last dose

Trial Locations

Locations (1)

Inst of Cancer Research & Royal Marsden NHS Foundation Trust; 🇬🇧 Sutton Surrey, United Kingdom