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

A Randomized Phase II Trial of Neoadjuvant Enzalutamide Plus the Glucocorticoid Receptor Antagonist Relacorilant Versus Placebo for Patients With High-risk Localized Prostate Cancer

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.

Study Overview

• Status: Recruiting
• Conditions: Prostate Cancer; Prostate Adenocarcinoma
• Intervention / Treatment: Drug: Relacorilant; Drug: Enzalutamide; Other: Androgen Deprivation Therapy; Procedure: Radical Prostatectomy; Other: Placebo (Sugar Pill)

Detailed Description

The purpose of this research is to gather information on the safety and effectiveness of combining two study drugs (relacorilant and enzalutamide) with hormone therapy. Doctors leading this study hope to learn if combining these study drugs with hormone therapy is safe and could improve the results of surgery and delay the time to when prostate cancer tumors spread to other parts of the body in individuals with advanced, high-risk prostate cancer who plan to receive a radical prostatectomy (surgical removal of the whole prostate and surrounding tissue).

Prostate cancer cells usually need hormones (called androgens) to grow. One of these hormones is testosterone, which is mostly produced in the testicles. The usual approach for treating prostate cancer after it progresses involves taking medications to decrease or block the development of hormones (including testosterone) so that prostate cancer cells can't continue to grow. This approach is called androgen deprivation therapy (hormone therapy). Enzalutamide is a hormone-blocking medication, which is a standard of care for prostate cancer when it spreads (metastasizes).

• Study Type: Interventional
• Enrollment (Estimated): 90
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Cancer Trials; Phone Number: 1-855-702-8222; Email: cancerclinicaltrials@bsd.uchicago.edu

Study Locations

• United States
  • Illinois
    • Chicago, Illinois, United States, 60453
      • Recruiting
      • University of Chicago Comprehensive Cancer Center
      • Principal Investigator: Russell Szmulewitz, MD
      • Contact: Cancer Trials; Phone Number: 855-702-8222; Email: cancerclinicaltrials@bsd.uchicago.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Histologically or cytologically confirmed prostatic adenocarcinoma without primary small cell histology

2. 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

3. 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
4. Eastern Cooperative Oncology Group performance status ≤ 1 (Appendix A)
5. Total serum testosterone 100 ng/dL

6. 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
   • Albumin 3.0 g/dL

7. Patients must have normal bone marrow function as defined below:

   • Platelet count (plt) 100,000 /L
   • Hemoglobin (Hgb) 10 g/dL
   • Absolute neutrophil count (ANC) 1500

8. Patients must have adequate renal function as defined below:

   • glomerular filtration rate (GFR) 30 mL/min

9. Ability to understand and the willingness to sign a written informed consent document.
10. Patients with active diabetes mellitus on glucose lowering medications are eligible provided they agree to and are able to self-monitor daily blood glucose levels due to potential risk of lowering glucose levels on relacorilant.

11. Male patient and his female partner who is of childbearing potential must use 2 acceptable methods of birth control (one of which must include a condom as a barrier method of contraception) starting at screening and continuing throughout the study period and for 3 months after final study drug administration. Two acceptable methods of birth control thus include the following:

    • Condom (barrier method of contraception) AND

    • One of the following is required:

      1. Established use of oral, injected or implanted hormonal method of contraception by the female partner;
      2. Placement of an intrauterine device (IUD) or intrauterine system (IUS) by the female partner;
      3. Additional barrier method: Occlusive cap (diaphragm or cervical/vault caps) with spermicidal foam/gel/film/cream/suppository by the female partner;
      4. Tubal ligation in the female partner;
      5. Vasectomy or other procedure resulting in infertility (e.g., bilateral orchiectomy), for more than 6 months.

3.2 Exclusion Criteria

1. 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).
2. Inability to swallow capsules or known gastrointestinal malabsorption.
3. 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.
4. 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).
5. History of seizure disorder or active use of anticonvulsants. Medications used to treat neuropathic pain such as gabapentin or pregabalin are allowed.
6. Serious inter-current infections or non-malignant medical illnesses that are uncontrolled.
7. Active psychiatric illness/social situations that would limit compliance with protocol requirements.
8. New York Heart Association (NYHA) class II, class III, or IV congestive heart failure (any symptomatic heart failure).
9. Concurrent therapy with strong inhibitors of Cytochrome P450 3A4 or CYP2C8 due to concerning possible drug-drug interactions.
10. Concurrent therapy with strong inducers of Cytochrome P450 3A4 due to concerning possible drug-drug interactions.
11. 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.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Group 1: Participants Who Receive Study Drug (Relacorilant) with Hormone Therapy and Enzalutamide; 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; 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.; Drug: Enzalutamide; Enzalutamide, sold under the brand name Xtandi, is a nonsteroidal antiandrogen medication which is used in the treatment of prostate cancer.; Other Names: Xtandi; Other: Androgen Deprivation Therapy; 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.; Procedure: Radical Prostatectomy; Radical prostatectomy is surgery to remove the entire prostate gland and surrounding lymph nodes to treat men with localized prostate cancer.
Experimental: Group 1: Participants Who Receive Placebo (no study drug) with Hormone Therapy and Enzalutamide; 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; Enzalutamide, sold under the brand name Xtandi, is a nonsteroidal antiandrogen medication which is used in the treatment of prostate cancer.; Other Names: Xtandi; Other: Androgen Deprivation Therapy; 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.; Procedure: Radical Prostatectomy; Radical prostatectomy is surgery to remove the entire prostate gland and surrounding lymph nodes to treat men with localized prostate cancer.; Other: Placebo (Sugar Pill); This would be a sugar pill consisting of 2 softgels. This is not an experimental drug or treatment.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
Radiographic Response Rate	To determine if relacorliant when added to androgen receptor signaling inhibition (ARSI) improves radiographic and prostate-specific antigen (PSA) response rate compared to ARSI alone.	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	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

Collaborators and Investigators

• Sponsor: University of Chicago
• Investigators: Principal Investigator: Russell Szmulewitz, MD, University of Chicago

Study record dates

Study Major Dates

• Study Start (Actual): October 9, 2023
• Primary Completion (Estimated): October 1, 2025
• Study Completion (Estimated): April 1, 2029

Study Registration Dates

• First Submitted: February 2, 2023
• First Submitted That Met QC Criteria: February 2, 2023
• First Posted (Actual): February 13, 2023

Study Record Updates

• Last Update Posted (Actual): April 10, 2024
• Last Update Submitted That Met QC Criteria: April 8, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Keywords: prostate cancer
• Additional Relevant MeSH Terms: Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Genital Neoplasms, Male; Prostatic Diseases; Urogenital Diseases; Male Urogenital Diseases; Genital Diseases, Male; Genital Diseases; Prostatic Neoplasms; Physiological Effects of Drugs; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Androgens
• Other Study ID Numbers: IRB22-1318

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF

Drug and device information, study documents

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