A Study to Learn How Well Darolutamide Administered Together With Androgen Deprivation Therapy (ADT) Works in Men With Metastatic Hormone-sensitive Prostate Cancer. Results Will be Compared With ADT Alone From a Previously Conducted Study.

NCT05059236 | Active Not Recruiting Phase 2 FDA Drug

• 1 other identifier: 21516
• Study Type: interventional
• Target: 223
• Locations: 1 country
• Sites: 31

Brief Summary

The purpose of the study is to assess if the addition of darolutamide to ADT compared with ADT alone would result in superior clinical efficacy in participants with metastatic hormone-sensitive prostate cancer (mHSPC) by progression-free survival. The researchers want to learn how long it takes for the cancer to get worse (also known as "progression-free survival") by either increasing symptoms, new metastases, PSA rise or death. All participants will be on treatment and take darolutamide with ADT until their cancer spreads, they have a medical problem, or they leave the study. The results will then be compared with patients' results from another study who received ADT alone (CHAARTED). This study will also assess safety by gathering adverse event information throughout the duration of the study. An adverse event is any medical problem, related or not to study treatment that a participant has during a study. The study drug, darolutamide, is already available for doctors to prescribe to patients with prostate cancer that has not yet spread to other parts of the body. It works by blocking a protein called a receptor from attaching to a hormone called androgen that is found in men. This protein can also be found in prostate cancer cells. ADT is a treatment that doctors are currently able to prescribe to patients with mHSPC. ADT is used to lower the amount of the androgen hormone.

Conditions

Metastatic Hormone-sensitive Prostate Cancer

Keywords

Metastatic hormone-sensitive prostate cancer (mHSPC); Prostate Cancer; Darolutamide; Nubeqa

Outcome Measures

Primary Outcomes (1)

• Progression-free survival (PFS)

  Time interval from enrollment to PSA progression, clinical progression or death, whichever occurs first. PSA progression is defined as when the PSA demonstrates an increase that is more than 50% of nadir, taking as reference the lowest recorded PSA level since starting androgen deprivation therapy (ADT). Clinical progression is defined as increasing symptomatic bone metastases, radiographic progression per Response Evaluation Criteria In Solid Tumors (RECIST) criteria (v. 1.1) for soft tissue metastases and PCWG3 criteria for bone metastases, or clinical deterioration due to cancer per investigator's opinion.

  Approximately 12 months after end of enrollment

Secondary Outcomes (5)

• Overall survival (OS)

  Approximately 24 months after end of enrollment

• Radiographic Progression-free survival (rPFS)

  Approximately 24 months after end of enrollment

• Time to castration-resistant prostate cancer (CRPC)

  Approximately 12 months after end of enrollment

• Complete PSA response rate

  At 6 months after first administration

• Number of participants with adverse events

  From the signing of the informed consent form (ICF) until 30 (+7) days after last administration, approximately 12 months

Study Arms (1)

Darolutamide+ADT

EXPERIMENTAL

Participants will receive darolutamide plus ADT in the ARASEC treatment arm. The control arm for the study will be derived from the participants treated with ADT alone in the CHAARTED trial using a matching approach

Drug: Darolutamide (BAY1841788, Nubeqa); Other: ADT

Interventions

ADT OTHER

LHRH agonist/antagonist or orchiectomy

Darolutamide+ADT

Darolutamide (BAY1841788, Nubeqa) DRUG

300 mg per tablet, oral administration with food

Darolutamide+ADT

Eligibility Criteria

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

You may qualify if:

• Histologically or cytologically confirmed adenocarcinoma of prostate. Participants may have begun androgen-deprivation therapy (up to 120 days prior to enrollment). Note: Relugolix is not permitted as ADT in this study.
• Metastatic disease and will be stratified by presence of high volume or low volume disease.
• Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) of 0, 1 or 2
• Adequate bone marrow, liver and renal function within 4 weeks of enrollment
• At least 4 weeks since prior major surgery and recovered from all toxicity from such surgery prior to enrollment
• Prior adjuvant or neoadjuvant hormonal therapy allowed provided the following criteria are met:
• Therapy was discontinued ≥ 12 months ago AND there was a clinical state without evidence of disease at least 12 months after completing adjuvant or neoadjuvant hormonal therapy, as defined by 1 of the following:
• PSA \< 0.1 ng/mL after prostatectomy plus hormonal therapy
• PSA \< 0.5 ng/mL and has not doubled above nadir after radiotherapy plus hormonal therapy
• Therapy lasted no more than 24 months
• Prior palliative radiotherapy allowed for participants, if commenced within 30 days before starting androgen deprivation.
• Bicalutamide, nilutamide or flutamide are allowed as single-agent therapy ≤ 28 days before medical castration to prevent flare.

You may not qualify if:

• PSA met criteria for PSA progression
• History of malignancy in the past 5 years, with the exception of basal cell and squamous cell carcinoma of the skin.
• Had any of the following within 6 months before randomization: myocardial infarction, severe/unstable angina pectoris, congestive heart failure, hospitalization for any cardiac event, including conduction abnormalities
• Pathological finding consistent with small cell, or neuroendocrine carcinoma of the prostate
• Known brain/ leptomeningeal metastases
• An active viral hepatitis (defined as Hepatitis B surface antigen \[HBsAg\] reactive or detectable \[qualitative\] HBV DNA defined as HCV Ribonucleic Acid \[RNA\] \[qualitative\] is detected), known human immunodeficiency virus infection with detectable viral load, or chronic liver disease with a need of treatment
• Uncontrolled hypertension as indicated by a resting systolic BP ≥ 160 mmHg or diastolic BP ≥ 100 mmHg despite medical management
• A gastrointestinal (GI) disorder or procedure which is expected to interfere significantly with absorption of study drug
• Any other serious or unstable illness, or medical, social, or psychological condition, that could jeopardize the safety of the participant and/or his compliance with study procedures or may interfere with the participant's participation in the study or evaluation of the study results.
• Prior hormone therapy in the metastatic setting
• Prior chemotherapy in the adjuvant or neoadjuvant setting
• Concurrent use or previous exposure of 5-alpha reductase inhibitors (within 28 days before the start of darolutamide or 5 half-lives of the drug, whichever is longer)
• Any Prior treatment with second-generation androgen receptor (AR) inhibitors such as enzalutamide, apalutamide, darolutamide, or other investigational AR inhibitors, Cytochrome P17 enzyme inhibitor such as abiraterone acetate or other investigational CYP 17 as antineoplastic treatment for prostate cancer
• Previous (within 28 days before the start of darolutamide or 5 half-lives of the investigational treatment of the previous study, whichever is longer) or concomitant participation in another clinical study with investigational medicinal product(s).
• Contraindication to both CT and MRI contrast agent

Sponsors & Collaborators

• Bayer: lead

Study Sites (31)

Urology Centers of Alabama, PC - Homewood

Homewood, Alabama, 35209, United States

Location

Arizona Urology Specialists - Tucson - W Orange Grove

Tucson, Arizona, 85741, United States

Location

Tower Urology

Los Angeles, California, 90048, United States

Location

UCI Health Center for Urological Care

Orange, California, 92868, United States

Location

UC San Diego Health - Moores Cancer Center

San Diego, California, 92037, United States

Location

Providence Saint John's Cancer Institute

Santa Monica, California, 90404, United States

Location

Brigham and Women's Hospital (BWH) - Surgery Urology

Atlanta, Georgia, 30318, United States

Location

Piedmont Cancer Institute - Atlanta

Atlanta, Georgia, 30318, United States

Location

Northwestern Medicine - Urology

Chicago, Illinois, 60611, United States

Location

Northwestern University's Feinberg School of Medicine

Chicago, Illinois, 60611, United States

Location

UM Greenebaum Comprehensive Cancer Center

Baltimore, Maryland, 21201, United States

Location

Lieutenant Colonel Charles S. Kettles VA Medical Center - Oncology

Ann Arbor, Michigan, 48105, United States

Location

Barbara Ann Karmanos Cancer Institute - Detroit Headquarters

Detroit, Michigan, 48201, United States

Location

Michigan Institute of Urology - Troy - Town Center Building

Troy, Michigan, 48084, United States

Location

AMR - Kansas City

Kansas City, Missouri, 64132, United States

Location

GU Research Network, LLC - Oncology radiology

Omaha, Nebraska, 68130, United States

Location

XCancer Omaha

Omaha, Nebraska, 68130, United States

Location

New Jersey Urology - Clifton

Clifton, New Jersey, 07013, United States

Location

New Jersey Urology - Voorhees

Voorhees Township, New Jersey, 08043, United States

Location

New Mexico Cancer Center - Albuquerque

Albuquerque, New Mexico, 87109, United States

Location

Mount Sinai Doctors - Faculty Practice

New York, New York, 10029, United States

Location

Mount Sinai Faculty Practice Associates

New York, New York, 10029, United States

Location

Associated Medical Professionals of NY Syracuse

Syracuse, New York, 13210, United States

Location

The Urology Group - Norwood Surgery Center

Cincinnati, Ohio, 45212, United States

Location

Columbus Prostate Cancer Center / Radiation Oncology Clinic

Gahanna, Ohio, 43230, United States

Location

MidLantic Urology - Bala Cynwyd

Bala-Cynwyd, Pennsylvania, 19004, United States

Location

Carolina Urological Research Center

Myrtle Beach, South Carolina, 29579, United States

Location

Urology Associates, PC - Nashville

Nashville, Tennessee, 37209, United States

Location

Houston Methodist Research Institute

Houston, Texas, 77030, United States

Location

Inova Schar Cancer Institute (vendor)

Fairfax, Virginia, 22031, United States

Location

Spokane Urology PS

Spokane, Washington, 99202, United States

Location

Related Publications (1)

• McKay RR, Ross AE, Preston MA, Gregg JR, Salami SS, Littleton N, Constantinovici N, Srinivasan S, Verholen F, Shore ND. Darolutamide plus androgen-deprivation therapy: propensity score matching of ARASEC and historic clinical trial patients. Future Oncol. 2025 May;21(11):1365-1375. doi: 10.1080/14796694.2025.2482360. Epub 2025 Apr 1.

  PMID: 40165634 DERIVED

Related Links

• Click here to find further information and, after study completion, the study results according to Bayer's transparency standards.

MeSH Terms

Conditions

Prostatic Neoplasms

Interventions

darolutamide

Condition Hierarchy (Ancestors)

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

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 17, 2021
• First Posted: September 28, 2021
• Study Start: November 4, 2021
• Primary Completion: May 30, 2025
• Study Completion (Estimated): June 5, 2026
• Last Updated: May 1, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (31)