A Study of Enzalutamide Plus the Glucocorticoid Receptor Antagonist Relacorilant Versus Placebo for Patients With High-risk Localized Prostate Cancer

NCT05726292 | Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: IRB22-1318
• Study Type: interventional
• Target: 90
• Locations: 1 country
• Sites: 2

Brief Summary

Researchers conducting this study hope to learn about the safety and effectiveness of combining two study drugs, relacorilant and enzalutamide, plus androgen deprivation therapy (ADT), also known as hormone therapy. This study is for individuals who have been diagnosed with advanced, high-risk prostate cancer and standard therapies available to treat your disease have not been effective. Participation in this research will last about 3 years and 9 months.

Conditions

Prostate Cancer; Prostate Adenocarcinoma

Keywords

prostate cancer

Outcome Measures

Primary Outcomes (1)

• Response Rate of Subjects Receiving Relacorilant with Enzalutamide and Hormone Therapy

  To determine if relacorilant (Rela) when added to androgen receptor signaling inhibition (ARSI) with enzalutamide (Enz) and androgen deprivation therapy (ADT) improves response rate compared to relacorilant with enzalutamide and ADT using both concurrent and historical controls. This outcome will be measured by assessing pathologic complete response rate (pCR) plus minimal residual disease (MRD) at radical prostatectomy (RP) after 24 weeks of neoadjuvant therapy.

  24 weeks

Secondary Outcomes (2)

• Radiographic Response Rate

  3 years and 9 months

• • To determine the 3-year biochemical recurrence-free survival (bRFS) and metastasis-free survival (MFS) rate with combination hormonal therapy with Rela + ARSI with Enz compared to ARSI with Enz alone

  3 years and 9 months

Study Arms (2)

Group 1: Participants Who Receive Study Drug (Relacorilant) with Hormone Therapy and Enzalutamide

EXPERIMENTAL

All participants in this group will have surgery up to 4 weeks after receiving enzalutamide/relacorilant with hormone therapy. A radical prostatectomy (removal of the prostate and any surrounding tissue that the surgeon thinks may be affected by the cancer).

Drug: Relacorilant; Drug: Enzalutamide; Other: Androgen Deprivation Therapy; Procedure: Radical Prostatectomy

Group 1: Participants Who Receive Placebo (no study drug) with Hormone Therapy and Enzalutamide

EXPERIMENTAL

All participants in this group will have surgery up to 4 weeks after receiving enzalutamide/placebo (sugar pill in the form of 2 softgel capsules) with hormone therapy. A radical prostatectomy (removal of the prostate and any surrounding tissue that the surgeon thinks may be affected by the cancer).

Drug: Enzalutamide; Other: Placebo (Sugar Pill); Other: Androgen Deprivation Therapy; Procedure: Radical Prostatectomy

Interventions

Relacorilant DRUG

Relacorilant is an antiglucocorticoid which is under development by Corcept Therapeutics for the treatment of Cushing's syndrome. It is being used in this study as an experimental drug combined with other treatments for prostate cancer.

Group 1: Participants Who Receive Study Drug (Relacorilant) with Hormone Therapy and Enzalutamide

Enzalutamide DRUG

Enzalutamide, sold under the brand name Xtandi, is a nonsteroidal antiandrogen medication which is used in the treatment of prostate cancer.

Also known as: Xtandi

Group 1: Participants Who Receive Placebo (no study drug) with Hormone Therapy and Enzalutamide; Group 1: Participants Who Receive Study Drug (Relacorilant) with Hormone Therapy and Enzalutamide

Placebo (Sugar Pill) OTHER

This would be a sugar pill consisting of 2 softgels. This is not an experimental drug or treatment.

Group 1: Participants Who Receive Placebo (no study drug) with Hormone Therapy and Enzalutamide

Androgen Deprivation Therapy OTHER

All participants in this study, who meet the requirements to participate, will get Androgen Deprivation Therapy (ADT; a form of hormone therapy) continuously before their radical prostatectomy surgery. As part of this study, ADT consists of one injection every 1-3 months. In this study, ADT is a gonadotropin releasing hormone (GnRH) agonists or antagonist; the choice of which brand of ADT to use is up to your treating physician. GnRH agonists and antagonists are drugs that lower the production of androgens (male hormones) in your body. Prostate cancer cells usually require androgens, such as testosterone, to grow. Androgen Deprivation Therapy (ADT) has been approved by United Stated Food and Drug Administration (US FDA) to treat patients with prostate cancer but is not approved to treat patients prior to prostatectomy.

Group 1: Participants Who Receive Placebo (no study drug) with Hormone Therapy and Enzalutamide; Group 1: Participants Who Receive Study Drug (Relacorilant) with Hormone Therapy and Enzalutamide

Radical Prostatectomy PROCEDURE

Radical prostatectomy is surgery to remove the entire prostate gland and surrounding lymph nodes to treat men with localized prostate cancer.

Group 1: Participants Who Receive Placebo (no study drug) with Hormone Therapy and Enzalutamide; Group 1: Participants Who Receive Study Drug (Relacorilant) with Hormone Therapy and Enzalutamide

Eligibility Criteria

• Age: 18 Years+
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Histologically or cytologically confirmed prostatic adenocarcinoma without primary small cell histology
• Localized disease:
• Surgical resectability must be documented prior to enrollment
• No evidence of distant metastatic disease on abdominopelvic imaging, bone imaging
• Enlarged lymph nodes below the iliac bifurcation (clinical stage N1) is allowed
• Either cross-sectional abdominopelvic imaging + technetium bone scan or PSMA PET imaging will be acceptable to rule out distant metastatic disease
• High or very high-risk disease (https://www.nccn.org/professionals/physician\_gls/pdf/prostate.pdf) as defined by having one or more of the following:
• Clinical T3a or higher
• Histologic Grade Group 4 or 5
• PSA \>20
• Eastern Cooperative Oncology Group performance status ≤ 1 (Appendix A)
• Total serum testosterone 100 ng/dL
• Patients must have normal hepatic function as defined below:
• Total bilirubin \<1.5 X the upper limit of normal (note that in subjects with Gilbert's syndrome, if total bilirubin is \>1.5 X ULN, measure direct and indirect bilirubin. If direct bilirubin is ≤1.5 X ULN, the subject may be eligible)
• AST(SGOT)/ALT(SGPT) \<2.5 X institutional upper limit of normal

You may not qualify if:

• Therapy with ANY hormonal therapy for prostate cancer (prior 5-alpha-reductase inhibitors for benign prostate disease is allowed but must be discontinued prior to study initiation).
• Inability to swallow capsules or known gastrointestinal malabsorption.
• History of other malignancies, with the exception of: adequately treated non-melanoma skin cancer, adequately treated superficial bladder cancer, stage 1 or 2 malignancies that are without evidence of disease, or other cancers curatively treated with no evidence of disease for \> 5 years from enrollment.
• Blood pressure that is not controlled despite \> 2 oral agents (SBP \>160 and DBP \>90 documented during the screening period with no subsequent blood pressure readings \>160/100).
• History of seizure disorder or active use of anticonvulsants. Medications used to treat neuropathic pain such as gabapentin or pregabalin are allowed.
• Serious inter-current infections or non-malignant medical illnesses that are uncontrolled.
• Active psychiatric illness/social situations that would limit compliance with protocol requirements.
• New York Heart Association (NYHA) class II, class III, or IV congestive heart failure (any symptomatic heart failure).
• Concurrent therapy with strong inhibitors of Cytochrome P450 3A4 or CYP2C8 due to concerning possible drug-drug interactions.
• Concurrent therapy with strong inducers of Cytochrome P450 3A4 due to concerning possible drug-drug interactions.
• Presence of concurrent medical conditions requiring systemic glucocorticoids for immunosuppression (e.g. autoimmune diseases, organ transplantation) that is active and has required glucocorticoids in the last 6 months.

Sponsors & Collaborators

• University of Chicago: lead

Study Sites (2)

University of Chicago Comprehensive Cancer Center

Chicago, Illinois, 60453, United States

RECRUITING

University of Texas Southwestern Medical Center

Dallas, Texas, 75390, United States

RECRUITING

MeSH Terms

Conditions

Prostatic Neoplasms

Interventions

relacorilant; enzalutamide; Sugars; Androgen Antagonists

Condition Hierarchy (Ancestors)

Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Genital Diseases, Male; Genital Diseases; Urogenital Diseases; Prostatic Diseases; Male Urogenital Diseases

Intervention Hierarchy (Ancestors)

Carbohydrates; Hormone Antagonists; Hormones, Hormone Substitutes, and Hormone Antagonists; Physiological Effects of Drugs; Pharmacologic Actions; Chemical Actions and Uses

Study Officials

• Russell Szmulewitz, MD

  University of Chicago

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Cancer Trials

CONTACT

1-855-702-8222; cancerclinicaltrials@bsd.uchicago.edu

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 2, 2023
• First Posted: February 13, 2023
• Study Start: January 6, 2025
• Primary Completion (Estimated): October 1, 2027
• Study Completion (Estimated): April 1, 2028
• Last Updated: March 4, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF

Locations

US (2)