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

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.

Study Overview

• Status: Terminated
• Conditions: Metastatic Castration-Resistant Prostate Cancer
• Intervention / Treatment: Drug: Exicorilant; Drug: Enzalutamide; Drug: Placebo

Detailed Description

Exicorilant is a selective glucocorticoid receptor (GR) antagonist. In this study, exicorilant will be administered orally in combination with enzalutamide to patients with mCRPC to evaluate the safety, tolerability, PK, PD, and preliminary efficacy of the regimen. The study consists of 2 phases: a dose-determination phase and an expansion phase. The dose determination phase is designed to determine dose-limiting toxicities and the RD of exicorilant plus enzalutamide in patients with mCRPC. Once the recommended dosing regimen has been determined, the following expansion cohorts will be enrolled and treated with exicorilant plus enzalutamide at the RD level.

Abiraterone-Resistant Cohort: Patients who have progressed during treatment with abiraterone, and have received no other androgen receptor (AR)-blocking therapies.

AR Antagonist-Resistant Cohort: Patients who have progressed during treatment with enzalutamide or other second-generation AR inhibitors.

The effect of food on exicorilant PK will be assessed in a portion of the patients enrolled in the Expansion Phase. The 2 expansion cohorts will be enrolled in parallel.

In each phase of the study, routine assessments of safety and tolerability will be performed and samples will be collected to determine standard PK parameters for exicorilant, enzalutamide, and their major metabolites. PD, quality of life evaluations and preliminary evaluations of antitumor activity of exicorilant with enzalutamide will be performed throughout the study.

• Study Type: Interventional
• Enrollment (Actual): 39
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• United Kingdom
  • England
    • London, England, United Kingdom, W1T7HA
      • London
    • Southampton, England, United Kingdom, SO16 6YD
      • Southampton
  • Surrey
    • Sutton, Surrey, United Kingdom, SM2 5PT
      • Sutton
• United States
  • Arizona
    • Scottsdale, Arizona, United States, 85258
      • Scottsdale
  • Michigan
    • Detroit, Michigan, United States, 48201
      • Detroit
  • New Jersey
    • Basking Ridge, New Jersey, United States, 07920
      • Basking Ridge
  • New York
    • New York, New York, United States, 10065
      • New York
  • Oregon
    • Portland, Oregon, United States, 97239
      • Portland
  • Wisconsin
    • Madison, Wisconsin, United States, 53792
      • Madison

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Major Inclusion Criteria:

• 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:

  1. 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.
  2. 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.
  3. M0 disease is allowed

• Expansion Phase: Patients must have progressed while receiving an androgen-directed therapy as follows:

  1. Abiraterone-Resistant Cohort: Patients must have progressed during treatment with abiraterone
  2. 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)
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
• Adequate baseline organ function within 14 days prior to the first dose of study treatment (on-study enzalutamide and/or exicorilant, whichever is earliest)
• Patients receiving systemic corticosteroids greater than 2-weeks in duration within 3 months of study entry or with clinical evidence of adrenal insufficiency must have evidence of adequate adrenal function based upon morning plasma cortisol concentration or adrenocorticotrophic hormone (ACTH, cosyntropin) stimulation test
• If a patient engages in sexual intercourse with a woman of childbearing potential, a condom with spermicide and another form of birth control must be used during and for 100 days after the final dose of study treatment (exicorilant or enzalutamide, whichever is latest). A condom is required during and for 100 days after completing treatment with enzalutamide if a patient is engaged in sexual activity with a pregnant woman. Patients must also agree to avoid sperm donation during the study and for at least 100 days after the final treatment administration.

Major Exclusion Criteria:

• 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
• Received systemic glucocorticoids within 21 days prior to the first dose of exicorilant, or requirement for chronic or frequently used systemic or inhaled glucocorticoids for medical conditions (eg, rheumatoid arthritis, immunosuppression after organ transplantation). Short courses (≤5 days) for non-cancer related reasons are allowed if clinically required (such as prophylaxis for CT)
• Concurrent therapy with strong inhibitors or inducers of CYP3A4 or CYP2C8 or with sensitive substrates of CYP3A4, CYP2C9, or CYP2C19.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

10

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Dose Determination Segment 1 (Open-label) Cohort 1 - 360 mg Exicorilant; Patients 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.	Drug: Exicorilant; Exicorilant is supplied as capsules for oral dosing; Other Names: CORT125281; Drug: Enzalutamide; Enzalutamide will be taken orally; Other Names: Xtandi
Experimental: Dose Determination Segment 1 (Open-label) Cohort 2 - 280 mg Exicorilant; Patients 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.	Drug: Exicorilant; Exicorilant is supplied as capsules for oral dosing; Other Names: CORT125281; Drug: Enzalutamide; Enzalutamide will be taken orally; Other Names: Xtandi
Experimental: Dose Determination Segment 1 (Open-label) Cohort 3 - 280 mg Exicorilant; Patients 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.	Drug: Exicorilant; Exicorilant is supplied as capsules for oral dosing; Other Names: CORT125281; Drug: Enzalutamide; Enzalutamide will be taken orally; Other Names: Xtandi
Experimental: Dose Determination Segment 2: Arm A - Maximum Dose 240 mg Exicorilant; Patients 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.	Drug: Exicorilant; Exicorilant is supplied as capsules for oral dosing; Other Names: CORT125281; Drug: Enzalutamide; Enzalutamide will be taken orally; Other Names: Xtandi
Experimental: Dose Determination Segment 2: Arm A - Maximum Dose 280 mg Exicorilant; Patients 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.	Drug: Exicorilant; Exicorilant is supplied as capsules for oral dosing; Other Names: CORT125281; Drug: Enzalutamide; Enzalutamide will be taken orally; Other Names: Xtandi
Experimental: Dose Determination Segment 2: Arm A - Maximum Dose 320 mg Exicorilant; Patients 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.	Drug: Exicorilant; Exicorilant is supplied as capsules for oral dosing; Other Names: CORT125281; Drug: Enzalutamide; Enzalutamide will be taken orally; Other Names: Xtandi
Experimental: Dose Determination Segment 2: Arm B - 240 mg Exicorilant; Patients will receive combination treatment with once-daily exicorilant 240 mg, enzalutamide once daily, and placebo in 28-day dosing cycles.	Drug: Exicorilant; Exicorilant is supplied as capsules for oral dosing; Other Names: CORT125281; Drug: Enzalutamide; Enzalutamide will be taken orally; Other Names: Xtandi; Drug: Placebo; Placebo capsules to match the appearance of the exicorilant capsules
Experimental: Dose Expansion - Abi-Resistant Cohort (Open-label); Patients who have progressed during treatment with abiraterone and no other androgen receptor-blocking therapies will receive exicorilant and enzalutamide.	Drug: Exicorilant; Exicorilant is supplied as capsules for oral dosing; Other Names: CORT125281; Drug: Enzalutamide; Enzalutamide will be taken orally; Other Names: Xtandi
Experimental: Dose Expansion - Abi-Resistant Cohort Food Effect (Open-label); Subcohort (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.	Drug: Exicorilant; Exicorilant is supplied as capsules for oral dosing; Other Names: CORT125281; Drug: Enzalutamide; Enzalutamide will be taken orally; Other Names: Xtandi
Experimental: Dose Expansion - ARant-Resistant Cohort (Open-label); Patients who progressed during treatment with enzalutamide or second-generation androgen receptor-blocking (ARant) therapies will receive a daily dose of exicorilant and enzalutamide.	Drug: Exicorilant; Exicorilant is supplied as capsules for oral dosing; Other Names: CORT125281; Drug: Enzalutamide; Enzalutamide will be taken orally; Other Names: Xtandi

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Patients With One or More Treatment-Emergent Adverse Events	The safety of each treatment group will be assessed by evaluating the incidence of 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	AUC from time zero to 12 hours postdose (AUC0-12) calculated using linear up and log down method.	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	Maximum observed concentration over the dosing interval	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	AUC from time zero to 24 hours postdose (AUC0-24) calculated using linear up and log down method.	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	Maximum observed concentration over the dosing interval	Predose and at time intervals up to 24 hours postdose on Cycle 1 Day -1, Cycle 1 Day 1, and Cycle 2 Day 1
AUC of Plasma N-Desmethyl Enzalutamide: Segment 1	AUC0-24 calculated using linear up and log down method.	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 N-Desmethyl Enzalutamide: Segment 1	Maximum observed concentration over the dosing interval	Predose and at time intervals up to 24 hours postdose on Cycle 1 Day -1, Cycle 1 Day 1, and Cycle 2 Day 1
AUC of Plasma Enzalutamide Carboxylic Acid: Segment 1	AUC0-24 calculated using linear up and log down method.	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 Carboxylic Acid: Segment 1	Maximum observed concentration over the dosing interval	Predose and at time intervals up to 24 hours postdose on Cycle 1 Day -1, Cycle 1 Day 1, and Cycle 2 Day 1
AUC of Plasma Exicorilant: Segment 2	AUC from time zero to 6 hours postdose (AUC0-6) calculated using linear up and log down method. Patients in Arm B did not receive dose escalations, but they were sampled for pharmacokinetic analysis on the same time frame as the Arm A patients: Cycle 1 Day 15, Week 4, and Week 6.	Predose and at time intervals up to 6 hours on Cycle 1 Day 15 (before dose escalation), and at 2 weeks after each dose escalation (Week 4 for escalation from 240 mg to 280 mg exicorilant and Week 6 for escalation from 280 mg to 320 mg exicorilant).
Cmax of Plasma Exicorilant: Segment 2	Maximum observed concentration over the dosing interval. Patients in Arm B did not receive dose escalations, but they were sampled for pharmacokinetic analysis on the same time frame as the Arm A patients: Cycle 1 Day 15, Week 4, and Week 6.	Predose and at time intervals up to 6 hours on Cycle 1 Day 15 (before dose escalation), and at 2 weeks after each dose escalation (Week 4 for escalation from 240 mg to 280 mg exicorilant and Week 6 for escalation from 280 mg to 320 mg exicorilant).
AUC of Plasma Enzalutamide: Segment 2	AUC from time zero to 6 hours postdose (AUC0-6) calculated using linear up and log down method. Patients in Arm B did not receive dose escalations, but they were sampled for pharmacokinetic analysis on the same time frame as the Arm A patients: Cycle 1 Day 15, Week 4, and Week 6.	Predose and at time intervals up to 6 hours on Cycle 1 Day 15 (before dose escalation), and at 2 weeks after each dose escalation (Week 4 for escalation from 240 mg to 280 mg exicorilant and Week 6 for escalation from 280 mg to 320 mg exicorilant).
Cmax of Plasma Enzalutamide: Segment 2	Maximum observed concentration over the dosing interval. Patients in Arm B did not receive dose escalations, but they were sampled for pharmacokinetic analysis on the same time frame as the Arm A patients: Cycle 1 Day 15, Week 4, and Week 6.	Predose and at time intervals up to 6 hours on Cycle 1 Day 15 (before dose escalation), and at 2 weeks after each dose escalation (Week 4 for escalation from 240 mg to 280 mg exicorilant and Week 6 for escalation from 280 mg to 320 mg exicorilant).
AUC of Plasma N-Desmethyl Enzalutamide: Segment 2	AUC from time zero to 6 hours postdose (AUC0-6) calculated using linear up and log down method. Patients in Arm B did not receive dose escalations, but they were sampled for pharmacokinetic analysis on the same time frame as the Arm A patients: Cycle 1 Day 15, Week 4, and Week 6.	Predose and at time intervals up to 6 hours on Cycle 1 Day 15 (before dose escalation), and at 2 weeks after each dose escalation (Week 4 for escalation from 240 mg to 280 mg exicorilant and Week 6 for escalation from 280 mg to 320 mg exicorilant).
Cmax of Plasma N-Desmethyl Enzalutamide: Segment 2	Maximum observed concentration over the dosing interval. Patients in Arm B did not receive dose escalations, but they were sampled for pharmacokinetic analysis on the same time frame as the Arm A patients: Cycle 1 Day 15, Week 4, and Week 6.	Predose and at time intervals up to 6 hours on Cycle 1 Day 15 (before dose escalation), and at 2 weeks after each dose escalation (Week 4 for escalation from 240 mg to 280 mg exicorilant and Week 6 for escalation from 280 mg to 320 mg exicorilant).
AUC of Plasma Enzalutamide Carboxylic Acid: Segment 2	AUC from time zero to 6 hours postdose (AUC0-6) calculated using linear up and log down method. Patients in Arm B did not receive dose escalations, but they were sampled for pharmacokinetic analysis on the same time frame as the Arm A patients: Cycle 1 Day 15, Week 4, and Week 6.	Predose and at time intervals up to 6 hours on Cycle 1 Day 15 (before dose escalation), and at 2 weeks after each dose escalation (Week 4 for escalation from 240 mg to 280 mg exicorilant and Week 6 for escalation from 280 mg to 320 mg exicorilant).
Cmax of Plasma Enzalutamide Carboxylic Acid: Segment 2	Maximum observed concentration over the dosing interval. Patients in Arm B did not receive dose escalations, but they were sampled for pharmacokinetic analysis on the same time frame as the Arm A patients: Cycle 1 Day 15, Week 4, and Week 6.	Predose and at time intervals up to 6 hours on Cycle 1 Day 15 (before dose escalation), and at 2 weeks after each dose escalation (Week 4 for escalation from 240 mg to 280 mg exicorilant and Week 6 for escalation from 280 mg to 320 mg exicorilant).
Objective Response Rate (ORR)	Confirmed ORR is defined as the proportion of patients with measurable disease at Baseline who achieve a complete regression (CR) or partial regression (PR) by Prostate Cancer Clinical Trials Working Group 3 (PCWG3) / Modified Response Evaluation Criteria in Solid Tumors v1.1 (mRECIST) criteria, after confirmation.	Up to 22 months
Number of Patients With ≥50% Reduction in Prostate-Specific Antigen (PSA)		Up to 39 months
Time to PSA Progression	Assess the time to PSA progression defined as the first occurrence of 50% or greater increase in PSA levels. Kaplan-Meier estimates of time to PSA progression were calculated as (earliest date of PSA progression or censoring - date of first study treatment + 1)/30.4375.	Up to 39 months
Percentage of Patients Who Are Progression-Free by PSA Criteria at 4, 6, and 12 Months	Assess the percentage of patients who are progression-free by PSA criteria, or death. PSA progression was defined as the first occurrence of 50% or greater increase in PSA levels. Values are Kaplan-Meier estimates of the patients progression free at the time points specified.	4, 6, and 12 months
Time to First Symptomatic Skeletal Event (SSE)	Assess the time to first SSE defined as symptomatic fracture, radiation or surgery to bone, or spinal cord compression. Kaplan-Meier estimates of time to first SSE were calculated as (earliest date of SSE or censoring - date of first study treatment + 1)/30.4375.	Up to 39 months
Time to Progression by Radiographic Criteria	Assess radiographic progression free survival (PFS) defined as the time interval from first dose of study drug (exicorilant and/or enzalutamide) to the date when the first site of disease progression is found on computerized tomography (CT), magnetic resonance imaging (MRI), or radionucleotide bone scan per PCWG3/mRECIST v1.1, or death whichever occurs first. The data values are Kaplan-Meier estimates.	Up to 22 months
Percentage of Patients Who Are Progression-Free by Radiographic Criteria at 4, 6, and 12 Months	Assess the percentage of patients who are progression-free by radiographic criteria per PCWG3/RECIST v1.1, or death whichever occurs first. Values are Kaplan-Meier estimates of the patients progression free at the time points specified.	4, 6, and 12 months
Time to Progression by Clinical or Radiographic Criteria	Determine PFS by clinical or radiographic criteria, or death, whichever occurs first. Clinical progression was defined as treatment discontinuation due to disease progression by investigator assessment per PCWG3/mRECIST v1.1, or by PSA criteria. The data values are Kaplan-Meier estimates.	Up to 22 months
Percentage of Patients Who Are Progression-Free by Clinical or Radiographic Criteria at 4, 6, and 12 Months	Assess the percentage of patients who are progression-free by clinical or radiographic measures at 4, 6, and 12 months. Values are Kaplan-Meier estimates of the patients progression free at the time points specified.	4, 6, and 12 months
Time to Progression by Clinical or Biochemical Criteria	Determine PFS by clinical criteria or biochemical criteria (defined as treatment discontinuation due to clinical progression by investigator assessment, or by PSA criteria) PCWG3/mRECIST v1.1, or death whichever occurs first. The data values are Kaplan-Meier estimates.	Up to 33 months
Percentage of Patients Who Are Progression-Free by Clinical or Biochemical Criteria at 4, 6, and 12 Months	Assess the percentage of patients who are progression-free by clinical or biochemical criteria (defined as treatment discontinuation due to clinical progression by investigator assessment or by PSA criteria) PCWG3/mRECIST v1.1, or death whichever occurs first at 4, 6, and 12 months. Values are Kaplan-Meier estimates of the patients progression free at the time points specified.	4, 6, and 12 months
Duration of Response (DOR)	Determine the DOR as defined as the time from the first occurrence of a documented objective tumor response to the time of radiographic progression (per investigator using PCWG3/mRECIST v1.1 criteria) or death from any cause on study, whichever occurs first. DOR was calculated as (earliest date of progression, death, or censoring - date of first documented objective response +1)/30.4375. The data values are Kaplan-Meier estimates.	Up to 11 months
Overall Survival (OS)	Determine OS assessed as the time from the first dose of study drug (exicorilant and/or enzalutamide) to the date of death from any cause. The data values are Kaplan-Meier estimates.	Up to 52 months

Collaborators and Investigators

• Sponsor: Corcept Therapeutics
• Investigators: Study Director: Grace Mann, PhD, Corcept Therapeutics; Study Director: William Guyer, PharmD, Corcept Therapeutics

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start (Actual): February 20, 2018
• Primary Completion (Actual): October 13, 2021
• Study Completion (Actual): January 12, 2023

Study Registration Dates

• First Submitted: January 16, 2018
• First Submitted That Met QC Criteria: February 15, 2018
• First Posted (Actual): February 19, 2018

Study Record Updates

• Last Update Posted (Actual): May 15, 2026
• Last Update Submitted That Met QC Criteria: April 23, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Keywords: Prostate Cancer; enzalutamide; mCRPC; Antagonist; Castration-Resistant Prostate Cancer; androgen receptor; Glucocorticoid receptor
• Additional Relevant MeSH Terms: Urogenital Diseases; Genital Diseases; Central Nervous System Diseases; Nervous System Diseases; Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Genital Diseases, Male; Prostatic Diseases; Male Urogenital Diseases; Neuromuscular Diseases; Genetic Diseases, Inborn; Neurodegenerative Diseases; Heredodegenerative Disorders, Nervous System; Genetic Diseases, X-Linked; Spinal Cord Diseases; Motor Neuron Disease; Muscular Atrophy, Spinal; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Prostatic Neoplasms; Bulbo-Spinal Atrophy, X-Linked; enzalutamide
• Other Study ID Numbers: CORT125281-601; 2017-003287-12 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No