Study Stopped
The level of benefit observed did not justify enrolling patients in the Dose Expansion phase of the study.
Study to Evaluate Exicorilant (CORT125281) in Combination With Enzalutamide in Patients With Metastatic Castration-Resistant Prostate Cancer
Phase 1/2a Dose-Escalation and Expansion Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of CORT125281 With Enzalutamide in Patients With Metastatic Castration-Resistant Prostate Cancer
2 other identifiers
interventional
39
2 countries
9
Brief Summary
This study consists of a dose escalation study with an expansion phase to evaluate the safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD), and preliminary efficacy of exicorilant (CORT125281) in combination with enzalutamide in patients with metastatic castration-resistant prostate cancer (mCRPC) to identify a recommended dose (RD) for Phase 2 studies.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P50-P75 for phase_1
Started Feb 2018
Longer than P75 for phase_1
9 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
January 16, 2018
CompletedFirst Posted
Study publicly available on registry
February 19, 2018
CompletedStudy Start
First participant enrolled
February 20, 2018
CompletedPrimary Completion
Last participant's last visit for primary outcome
October 13, 2021
CompletedStudy Completion
Last participant's last visit for all outcomes
January 12, 2023
CompletedResults Posted
Study results publicly available
May 15, 2026
CompletedMay 15, 2026
April 1, 2026
3.6 years
January 16, 2018
September 11, 2024
April 23, 2026
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
Number of Patients With One or More Dose-Limiting Toxicity (DLT)
Assess the maximum tolerated dose (MTD) and/or biologically active doses of exicorilant in combination with enzalutamide to identify the recommended dose (RD) for Phase 2 studies based on the number of patients who experienced a DLT while receiving exicorilant in combination with enzalutamide. DLTs were defined as any of the protocol-specified toxicities that the Investigator considered possibly or probably related to study drug that occurred during the DLT-evaluation period. The MTD is defined as the highest dose at which the DLT rate was \<33%.
From first dose of exicorilant through completion of Cycle 1 (up to 28 days) for Segment 1 and from first dose of exicorilant through completion of Cycle 3 (up to 84 days) for Segment 2
Secondary Outcomes (30)
Number of Patients With One or More Treatment-Emergent Adverse Events
Up to 27 months for Segment 1 and up to 19 months for Segment 2
Area Under the Concentration Versus Time Curve (AUC) of Plasma Exicorilant: Segment 1
Predose and at time intervals up to 12 hours postdose on Cycle 1 Day 1 and Cycle 2 Day 1
Maximum Observed Concentration (Cmax) of Plasma Exicorilant: Segment 1
Predose and at time intervals up to 12 hours postdose on Cycle 1 Day 1 and Cycle 2 Day 1
AUC of Plasma Enzalutamide: Segment 1
Predose and at time intervals up to 24 hours postdose on Cycle 1 Day -1, Cycle 1 Day 1, and Cycle 2 Day 1
Cmax of Plasma Enzalutamide: Segment 1
Predose and at time intervals up to 24 hours postdose on Cycle 1 Day -1, Cycle 1 Day 1, and Cycle 2 Day 1
- +25 more secondary outcomes
Study Arms (10)
Dose Determination Segment 1 (Open-label) Cohort 1 - 360 mg Exicorilant
EXPERIMENTALPatients will receive lead-in enzalutamide monotherapy once daily for 28 days. Patients will then receive combination treatment with twice-daily exicorilant 180 mg (total daily dose 360 mg) and enzalutamide once daily in 28-day dosing cycles.
Dose Determination Segment 1 (Open-label) Cohort 2 - 280 mg Exicorilant
EXPERIMENTALPatients will receive lead-in enzalutamide monotherapy once daily for 28 days. Patients will then receive combination treatment with twice-daily exicorilant 140 mg (total daily dose 280 mg) and enzalutamide once daily in 28-day dosing cycles.
Dose Determination Segment 1 (Open-label) Cohort 3 - 280 mg Exicorilant
EXPERIMENTALPatients will not receive lead-in enzalutamide monotherapy. Patients will receive combination treatment with twice-daily exicorilant 140 mg (total daily dose 280 mg) and enzalutamide once daily in 28-day dosing cycles.
Dose Determination Segment 2: Arm A - Maximum Dose 240 mg Exicorilant
EXPERIMENTALPatients will receive treatment with once-daily exicorilant starting at 240 mg and titrating to 280 mg and then to 320 mg at 2-week intervals, as tolerated, in combination with enzalutamide once daily in 28-day dosing cycles. Patients in this arm are reported at the highest titrated dose of exicorilant achieved: 240 mg exicorilant.
Dose Determination Segment 2: Arm A - Maximum Dose 280 mg Exicorilant
EXPERIMENTALPatients will receive treatment with once-daily exicorilant starting at 240 mg and titrating to 280 mg and then to 320 mg at 2-week intervals, as tolerated, in combination with enzalutamide once daily in 28-day dosing cycles. Patients in this arm are reported at the highest titrated dose of exicorilant achieved: 280 mg exicorilant.
Dose Determination Segment 2: Arm A - Maximum Dose 320 mg Exicorilant
EXPERIMENTALPatients will receive treatment with once-daily exicorilant starting at 240 mg and titrating to 280 mg and then to 320 mg at 2-week intervals, as tolerated, in combination with enzalutamide once daily in 28-day dosing cycles. Patients in this arm are reported at the highest titrated dose of exicorilant achieved: 320 mg exicorilant.
Dose Determination Segment 2: Arm B - 240 mg Exicorilant
EXPERIMENTALPatients will receive combination treatment with once-daily exicorilant 240 mg, enzalutamide once daily, and placebo in 28-day dosing cycles.
Dose Expansion - Abi-Resistant Cohort (Open-label)
EXPERIMENTALPatients who have progressed during treatment with abiraterone and no other androgen receptor-blocking therapies will receive exicorilant and enzalutamide.
Dose Expansion - Abi-Resistant Cohort Food Effect (Open-label)
EXPERIMENTALSubcohort (first 10 patients enrolled into Cohort A). Patients enrolled into this subcohort will receive a single dose of exicorilant at Cycle 1 Day -7 and a single dose of exicorilant at Cycle 1 Day 1 30 minutes after a standard breakfast to assess the effect of food on pharmacokinetic (PK)parameters. Patients will then begin exicorilant in combination with enzalutamide on Cycle 1 Day 2 and continue in 28-day dosing cycles.
Dose Expansion - ARant-Resistant Cohort (Open-label)
EXPERIMENTALPatients who progressed during treatment with enzalutamide or second-generation androgen receptor-blocking (ARant) therapies will receive a daily dose of exicorilant and enzalutamide.
Interventions
Placebo capsules to match the appearance of the exicorilant capsules
Exicorilant is supplied as capsules for oral dosing
Enzalutamide will be taken orally
Eligibility Criteria
You may qualify if:
- Able to understand the purpose and risks of the study; willing and able to adhere to scheduled visits, treatment plans, laboratory tests, and other study evaluations and procedures, and provide written informed consent
- Males ≥18 years of age at the time of signing consent
- Histologically confirmed adenocarcinoma of the prostate with metastatic disease
- Dose-Determination Phase Segment 1 and Expansion Phase: Progressive disease as defined by prostate-specific antigen (PSA) or imaging after most recent prior therapy. PSA ≥1 ng/mL, if a confirmed rise in PSA is the only indication of progression. Progression by PSA requires rising PSA over a previous reference value by at least 2 measurements obtained ≥1 week apart. PSA measurements can be collected during or after the most recent prior therapy.
- Dose-Determination Phase Segment 2: Currently receiving enzalutamide with a rising PSA as follows:
- Rising PSA: 25% increase over nadir and an absolute value of \>1 ng/mL by at least 2 measurements obtained ≥1 week apart. PSA measurements can be collected during or after the most recent prior therapy.
- Patients must have received enzalutamide for a minimum of 12 weeks and have been on stable doses of enzalutamide ≥80 mg once daily for at least 4 weeks prior to Cycle 1 Day 1. Patients will continue enzalutamide without interruption during the Screening Period (no wash-out period). This will be the enzalutamide starting dose for combination with exicorilant beginning on Cycle 1 Day 1.
- M0 disease is allowed
- Expansion Phase: Patients must have progressed while receiving an androgen-directed therapy as follows:
- Abiraterone-Resistant Cohort: Patients must have progressed during treatment with abiraterone
- Androgen Receptor Antagonist-Resistant Cohort: Patients must have progressed during treatment with enzalutamide or second-generation AR-blocking therapies. Patients progressing on enzalutamide immediately prior to enrolling in this study must be on stable doses of enzalutamide. These patients will continue enzalutamide without interruption during the Screening Period (no wash-out period required).
- Baseline tumor assessment performed within 28 days prior to the first dose of study treatment (exicorilant and/or on-study enzalutamide, whichever is earliest).
- Prior surgical or chemical castration with serum testosterone \<1.7 nmol/L (50 ng/dL). If the method of castration is use of a luteinizing hormone-releasing hormone (LHRH) analogue, there must be a plan to maintain effective LHRH analogue treatment for the duration of the trial.
- Consent to have all protocol-required pharmacodynamic biomarker samples, including the pretreatment and on treatment paired tumor biopsies (mandatory for a subset of patients)
- Consent to provide mandatory pharmacogenomic blood sample (Dose-Determination Segment 1 only)
- +4 more criteria
You may not qualify if:
- Received chemotherapy, non-palliative radiotherapy, immunotherapy, or any investigational cancer therapies within 21 days prior to the first dose of exicorilant, or treatment with such therapies is planned during protocol treatment. Concomitant anticancer therapy is not permitted during the enzalutamide Lead-In Period during Dose-Determination Phase Segment 1.
- More than 2 prior cytotoxic chemotherapy regimens for the treatment of mCRPC
- Dose Determination Phase and Expansion Phases will exclude patients for the following:
- Dose-Determination Phase (Segment 1 only):
- Progressed during treatment with enzalutamide prior to Cycle 1 Day -28 (only applies to patients receiving enzalutamide Lead-In) or
- Received prior second-generation anti-androgen and require urgent disease response or stabilization
- Expansion Phase Abi-Resistant Cohort:
- Received prior treatment with enzalutamide, or
- Received prior second-generation anti-androgen and require urgent disease response or stabilization
- Expansion Phase ARant-Resistant Cohort: Require urgent disease response or stabilization
- Ongoing or anticipated therapy with hormone therapy (other than LHRH analogue), including any dose of megestrol acetate (Megace), finasteride (Proscar), dutasteride (Avodart) or received abiraterone within 28 days prior to the first dose of exicorilant
- Contraindication or precaution for enzalutamide
- Parenchymal brain metastases
- Any clinically significant uncontrolled condition that may increase the risk to the study patient or that the Investigator considers places the patient at unacceptable risk
- Received herbal products or alternative therapies that may decrease PSA levels or that may have hormonal anti-prostate cancer activity within 21 days of study treatment initiation or plans to initiate treatment with these products/alternative therapies during the entire duration of the study
- +2 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (9)
Scottsdale
Scottsdale, Arizona, 85258, United States
Detroit
Detroit, Michigan, 48201, United States
Basking Ridge
Basking Ridge, New Jersey, 07920, United States
New York
New York, New York, 10065, United States
Portland
Portland, Oregon, 97239, United States
Madison
Madison, Wisconsin, 53792, United States
London
London, England, W1T7HA, United Kingdom
Southampton
Southampton, England, SO16 6YD, United Kingdom
Sutton
Sutton, Surrey, SM2 5PT, United Kingdom
Related Publications (1)
Serritella AV, Shevrin D, Heath EI, Wade JL, Martinez E, Anderson A, Schonhoft J, Chu YL, Karrison T, Stadler WM, Szmulewitz RZ. Phase I/II Trial of Enzalutamide and Mifepristone, a Glucocorticoid Receptor Antagonist, for Metastatic Castration-Resistant Prostate Cancer. Clin Cancer Res. 2022 Apr 14;28(8):1549-1559. doi: 10.1158/1078-0432.CCR-21-4049.
PMID: 35110415DERIVED
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Results Point of Contact
- Title
- Medical Director
- Organization
- Corcept Therapeutics
Study Officials
- STUDY DIRECTOR
William Guyer, PharmD
Corcept Therapeutics
- STUDY DIRECTOR
Grace Mann, PhD
Corcept Therapeutics
Publication Agreements
- PI is Sponsor Employee
- No
- Restriction Type
- OTHER
- Restrictive Agreement
- Yes
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- RANDOMIZED
- Masking
- QUADRUPLE
- Who Masked
- PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
January 16, 2018
First Posted
February 19, 2018
Study Start
February 20, 2018
Primary Completion
October 13, 2021
Study Completion
January 12, 2023
Last Updated
May 15, 2026
Results First Posted
May 15, 2026
Record last verified: 2026-04
Data Sharing
- IPD Sharing
- Will not share