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

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

NCT ID: NCT05726292

Condition: Prostate Cancer
Prostate Adenocarcinoma

Conditions: Official terms:
Prostatic Neoplasms
Androgens

Conditions: Keywords:
prostate cancer

Study type: Interventional

Study phase: Phase 2

Overall status: Recruiting

Study design:

Allocation: Randomized

Intervention model: Parallel Assignment

Primary purpose: Treatment

Masking: Double (Participant, Investigator)

Intervention:

Intervention type: Drug
Intervention name: Relacorilant
Description: 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.
Arm group label: Group 1: Participants Who Receive Study Drug (Relacorilant) with Hormone Therapy and Enzalutamide

Intervention type: Drug
Intervention name: Enzalutamide
Description: Enzalutamide, sold under the brand name Xtandi, is a nonsteroidal antiandrogen medication which is used in the treatment of prostate cancer.
Arm group label: Group 1: Participants Who Receive Placebo (no study drug) with Hormone Therapy and Enzalutamide
Arm group label: Group 1: Participants Who Receive Study Drug (Relacorilant) with Hormone Therapy and Enzalutamide

Other name: Xtandi

Intervention type: Other
Intervention name: Placebo (Sugar Pill)
Description: This would be a sugar pill consisting of 2 softgels. This is not an experimental drug or treatment.
Arm group label: Group 1: Participants Who Receive Placebo (no study drug) with Hormone Therapy and Enzalutamide

Intervention type: Other
Intervention name: Androgen Deprivation Therapy
Description: 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.
Arm group label: Group 1: Participants Who Receive Placebo (no study drug) with Hormone Therapy and Enzalutamide
Arm group label: Group 1: Participants Who Receive Study Drug (Relacorilant) with Hormone Therapy and Enzalutamide

Intervention type: Procedure
Intervention name: Radical Prostatectomy
Description: Radical prostatectomy is surgery to remove the entire prostate gland and surrounding lymph nodes to treat men with localized prostate cancer.
Arm group label: Group 1: Participants Who Receive Placebo (no study drug) with Hormone Therapy and Enzalutamide
Arm group label: Group 1: Participants Who Receive Study Drug (Relacorilant) with Hormone Therapy and Enzalutamide

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.

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).

Criteria for eligibility:
Criteria:
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.

Gender: Male

Gender based: Yes

Minimum age: 18 Years

Maximum age: N/A

Healthy volunteers: No

Locations:

Facility:
Name: University of Chicago Comprehensive Cancer Center

Address:
City: Chicago
Zip: 60453
Country: United States

Status: Recruiting

Contact:
Last name: Cancer Trials

Phone: 855-702-8222
Email: cancerclinicaltrials@bsd.uchicago.edu

Investigator:
Last name: Russell Szmulewitz, MD
Email: Principal Investigator

Facility:
Name: University of Texas Southwestern Medical Center

Address:
City: Dallas
Zip: 75390
Country: United States

Status: Recruiting

Contact:
Last name: Amy Rowell

Phone: 214-645-9688
Email: amy.rowell@utsouthwestern.edu

Investigator:
Last name: Kevin Courtney
Email: Principal Investigator

Start date: October 9, 2023

Completion date: April 1, 2029

Lead sponsor:
Agency: University of Chicago
Agency class: Other

Source: University of Chicago

Record processing date: ClinicalTrials.gov processed this data on November 12, 2024

Source: ClinicalTrials.gov page: https://clinicaltrials.gov/ct2/show/NCT05726292