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Comeback From Long coursE Androgen Deprivation Therapy (ADT) With RElugolix and Darolutamide (CLEARED) | Clinical Trials | Clareo Health

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Comeback From Long coursE Androgen Deprivation Therapy (ADT) With RElugolix and Darolutamide (CLEARED)

Comeback From Long coursE ADT With RElugolix and Darolutamide in Hormone-sensitive Prostate Cancer (CLEARED)

NCT06463457•Atish Choudhury, MD

View on ClinicalTrials.gov

Summary

This research study is being done to determine the rate of testosterone recovery after completing two years of treatment with the combination of relugolix and darolutamide as well as to assess the safety of the drugs when administered in combination. The names of the drugs in this study are: * Relugolix (a type of gonadotropin-releasing hormone receptor antagonist) * Darolutamide (a type of androgen receptor antagonist)

Detailed Description

The aim of this single-arm phase 2 study is to assess testosterone recovery after completion of two years of combination treatment with relugolix and darolutamide and to describe safety, tolerability and pharmacokinetics of relugolix and darolutamide when administered in combination. Participants will select enrollment into one of two groups (Group 1 or Group 2). The purpose of Group 1 is to determine the amount of each drug in the bloodstream after 2 hours, 4 hours, and 8 hours of treatment, whereas the purpose of Group 2 is to determine the amount of each drug in the bloodstream after 1 day, 7 days, and 28 days of treatment. The US Food and Drug Administration (FDA) has approved relugolix for the treatment of advanced prostate cancer. The FDA has approved the combination of darolutamide with docetaxel for initial treatment of metastatic prostate cancer, that is, cancer that has spread to other parts of the body. The FDA has also approved darolutamide alone for treatment of non-metastatic castration-resistant prostate cancer, that is, cancer that has become resistant to testosterone lowering medications without evidence of spread of the cancer to other parts of the body that can be detected on Computerized Tomography (CT) or bone scans. While darolutamide and relugolix can be prescribed together based on the FDA-approved indications of the individual drugs, this combination has not been approved by the FDA or formally tested in clinical trials. The research study procedures include screening for eligibility, study treatment visits, questionnaires, and blood tests. Electrocardiograms (EKGs) will be performed if felt to be clinically indicated by the treating physician. Imaging using a Computerized Tomography (CT) scan, Magnetic Resonance Imaging (MRI) scan, bone scan, and/or Prostate-Specific Membrane Antigen Positron Emission Tomography (PSMA-PET) scan is required before starting study treatment, and will be performed after starting study treatment when felt to be clinically indicated by the treating physician. Participants will receive study treatment of relugolix and darolutamide for 2 years and will be followed for 18 months after the treatment period. It is expected that about 33 participants will take part in this research study. Bayer AG, Pfizer, and Sumitomo Pharma America (SMPA), Inc. are funding this research study. Bayer and SMPA are providing the study drugs darolutamide and relugolix, respectively.

Eligibility

Age

18 - No limit years

Sex

MALE

Healthy Volunteers

Inclusion Criteria

•Participants must have histologically or cytologically confirmed prostate cancer.
•Hormone-sensitive prostate cancer (with detectable prostate-specific antigen \[PSA\] \> 0.02 ng/ml, testosterone ≥ lower limit of normal \[LLN\] per institutional assay) planned for two years of intensified androgen deprivation therapy per investigator discretion. This includes the following indications:
•* Treatment-naïve high risk lymph node-negative (N0) disease planned for primary radiation therapy
•* Treatment-naïve clinically pelvic lymph node positive (cN+) disease planned for primary radiation therapy
•* Pathologically pelvic lymph node positive (pN+) disease after prostatectomy planned for salvage radiation therapy
•* Regional nodal recurrence after prior local therapy (often in the context of radiation to lymph nodes)
•* Synchronous or metachronous low volume metastatic hormone sensitive prostate cancer (mHSPC) by Chemohormonal Therapy Versus Androgen Ablation Randomized Trial for Extensive Disease (CHAARTED) criteria planned for treatment interruption after 2 years (often in the context of radiation to sites of disease).
•* N.B: While CHAARTED criteria were established based on conventional imaging, patients who had PSMA PET imaging that would meet criteria for high volume disease (visceral metastases or ≥ 4 definitive bone metastases with at least one outside the axial skeleton) are excluded from this study.
•Prior hormonal therapy is permitted in the context of neoadjuvant/concurrent/adjuvant treatment with prior local therapy or biochemical recurrence by conventional imaging (for patients enrolling for recurrent rather than treatment-naïve disease), but patients must have had testosterone recovery to ≥ LLN at time of enrollment to this trial.
•Age ≥18 years. Children under 18 are excluded from this study as prostate cancer is a disease of adults.
+14 more criteria

Exclusion Criteria

•Participants who received prior systemic therapy for the disease state (high risk localized, lymph node positive, or low volume mHSPC) for which they are enrolling on this trial. Prior hormonal therapy is permitted for patients with recurrent disease after prior therapy.
•Participants who previously experienced any rise in PSA with castrate level testosterone (\< 50 ng/dl).
•Participants who are receiving any other investigational agents for this condition.
•Participants with brain metastases, leptomeningeal disease, or metastases involving other visceral organs since these patients would be considered to have "high volume" metastatic disease by CHAARTED criteria.
•History of allergic reactions attributed to compounds of similar chemical or biologic composition to relugolix or darolutamide.
•Participants with predicted significant drug-drug interaction with darolutamide and/or relugolix are ineligible or must be monitored carefully as detailed below:
•* Participants receiving combined P-glycoprotein (P-gp) and strong CYP3A inducers (e.g. apalutamide, carbamazepine, fosphenytoin, phenobarbital, phenytoin, primidone, rifampin, rifapentine, and St. John's wort) or combined P-gp and moderate CYP3A4 inducers (e.g. efavirenz, rifabutin) are ineligible.
•* Participants receiving combined P-gp and strong CYP3A4 inhibitors (e.g. ketoconazole, itraconazole, posaconazole, clarithromycin, cobicistat, cyclosporine, tacrolimus, nelfinavir, ritonavir, lopinavir, saquinivir, tipranavir) are ineligible to enroll.
•* Participants receiving Breast cancer resistance protein (BCRP) substrates (e.g. glyburide, cimetidine, nitrofurantoin, dipyridamole, sulfasalazine, and rosuvastatin) are not excluded but participants should be monitored more frequently for adverse reactions to the BCRP substrate drug, and dose reduction of the BCRP substrate drug should be considered.
•* Participants receiving P-gp inhibitors are not excluded but participants must be able to dose the P-gp inhibitor at least 6 hours after relugolix dose during the conduct of the study. Participants unable to dose the P-gp inhibitor at least 6 hours after relugolix dose, or requiring twice daily or more frequent dosing of a P-gp inhibitor are ineligible.
+5 more criteria

Locations (3)

Beth Israel Deaconess Medical Center

Boston, Massachusetts, United States

Brigham and Women's Hospital

Boston, Massachusetts, United States

Dana-Farber Cancer Institute

Boston, Massachusetts, United States

Key Dates

Start Date

December 13, 2024

Primary Completion Date

November 30, 2028

Completion Date

November 30, 2028

Last Updated

March 9, 2026

Enrollment

ESTIMATED participants

Conditions

Prostate CancerAdvanced Prostate CancerHormone Sensitive Prostate Cancer

Interventions

Darolutamide

DRUG

Relugolix

DRUG

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Data Source & Attribution

This clinical trial information is sourced from ClinicalTrials.gov, a service of the U.S. National Institutes of Health.

ClinicalTrials.gov last update: March 9, 2026Data synced to Clareo: March 29, 2026

Modifications: This data has been reformatted for display purposes. Eligibility criteria have been parsed into inclusion/exclusion sections. Location data has been geocoded to enable distance-based search. For the authoritative and most current information, please visit ClinicalTrials.gov.

Neither the United States Government nor Clareo Health make any warranties regarding the data. Check ClinicalTrials.gov frequently for updates.

View ClinicalTrials.gov Terms and Conditions

Comeback From Long coursE Androgen Deprivation Therapy (ADT) With RElugolix and Darolutamide (CLEARED)

Inclusion Criteria

Exclusion Criteria

A Study of FG-3246 in Participants With Metastatic Castration-Resistant Prostate Cancer (mCRPC)

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