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. (ARASEC)

Open-label Study of Androgen Receptor Inhibition With dArolutamide Plus Androgen Deprivation Therapy (ADT) Versus ADT in Men With Metastatic Hormone-Sensitive Prostate Cancer Using an External Control Arm

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.

Study Overview

• Status: Active, not recruiting
• Conditions: Metastatic Hormone-sensitive Prostate Cancer
• Intervention / Treatment: Drug: Darolutamide (BAY1841788, Nubeqa); Other: ADT

• Study Type: Interventional
• Enrollment (Actual): 223
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Alabama
    • Homewood, Alabama, United States, 35209
      • Urology Centers of Alabama, PC - Homewood
  • Arizona
    • Tucson, Arizona, United States, 85741
      • Arizona Urology Specialists - Tucson - W Orange Grove
  • California
    • Los Angeles, California, United States, 90048
      • Tower Urology
    • Orange, California, United States, 92868
      • UCI Health Center for Urological Care
    • San Diego, California, United States, 92037
      • UC San Diego Health - Moores Cancer Center
    • Santa Monica, California, United States, 90404
      • Providence Saint John's Cancer Institute
  • Georgia
    • Atlanta, Georgia, United States, 30318
      • Brigham and Women's Hospital (BWH) - Surgery Urology
    • Atlanta, Georgia, United States, 30318
      • Piedmont Cancer Institute - Atlanta
  • Illinois
    • Chicago, Illinois, United States, 60611
      • Northwestern University's Feinberg School of Medicine
    • Chicago, Illinois, United States, 60611
      • Northwestern Medicine - Urology
  • Maryland
    • Baltimore, Maryland, United States, 21201
      • UM Greenebaum Comprehensive Cancer Center
  • Michigan
    • Ann Arbor, Michigan, United States, 48105
      • Lieutenant Colonel Charles S. Kettles VA Medical Center - Oncology
    • Detroit, Michigan, United States, 48201
      • Barbara Ann Karmanos Cancer Institute - Detroit Headquarters
    • Troy, Michigan, United States, 48084
      • Michigan Institute of Urology - Troy - Town Center Building
  • Missouri
    • Kansas City, Missouri, United States, 64132
      • AMR - Kansas City
  • Nebraska
    • Omaha, Nebraska, United States, 68130
      • GU Research Network, LLC - Oncology radiology
    • Omaha, Nebraska, United States, 68130
      • XCancer Omaha
  • New Jersey
    • Clifton, New Jersey, United States, 07013
      • New Jersey Urology - Clifton
    • Voorhees Township, New Jersey, United States, 08043
      • New Jersey Urology - Voorhees
  • New Mexico
    • Albuquerque, New Mexico, United States, 87109
      • New Mexico Cancer Center - Albuquerque
  • New York
    • New York, New York, United States, 10029
      • Mount Sinai Faculty Practice Associates
    • New York, New York, United States, 10029
      • Mount Sinai Doctors - Faculty Practice
    • Syracuse, New York, United States, 13210
      • Associated Medical Professionals of NY Syracuse
  • Ohio
    • Cincinnati, Ohio, United States, 45212
      • The Urology Group - Norwood Surgery Center
    • Gahanna, Ohio, United States, 43230
      • Columbus Prostate Cancer Center / Radiation Oncology Clinic
  • Pennsylvania
    • Bala-Cynwyd, Pennsylvania, United States, 19004
      • MidLantic Urology - Bala Cynwyd
  • South Carolina
    • Myrtle Beach, South Carolina, United States, 29579
      • Carolina Urological Research Center
  • Tennessee
    • Nashville, Tennessee, United States, 37209
      • Urology Associates, PC - Nashville
  • Texas
    • Houston, Texas, United States, 77030
      • Houston Methodist Research Institute
  • Virginia
    • Fairfax, Virginia, United States, 22031
      • Inova Schar Cancer Institute (vendor)
  • Washington
    • Spokane, Washington, United States, 99202
      • Spokane Urology PS

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• 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.

Exclusion Criteria:

• 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
• Hypersensitivity to any of the study treatments, study treatment classes, or excipients in the formulation of the study treatments
• Inability to swallow oral medications

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Darolutamide+ADT; 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); 300 mg per tablet, oral administration with food; Other: ADT; LHRH agonist/antagonist or orchiectomy

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall survival (OS)	Time from the date of enrollment until death resulting from any cause or the date last known alive	Approximately 24 months after end of enrollment
Radiographic Progression-free survival (rPFS)	Time from enrollment to investigator-assessed 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 death, whichever occurs first	Approximately 24 months after end of enrollment
Time to castration-resistant prostate cancer (CRPC)	Time from enrollment until documented clinical or PSA progression with a testosterone level of less than 50 ng per deciliter or documented medical castration or surgical castration	Approximately 12 months after end of enrollment
Complete PSA response rate	PSA level of less than 0.2 ng per milliliter on two consecutive measurements at least 4 weeks apart	At 6 months after first administration
Number of participants with adverse events	Adverse Events will be assessed by National Cancer Institute-Common Terminology Criteria (NCI CTCAE) v. 5.0	From the signing of the informed consent form (ICF) until 30 (+7) days after last administration, approximately 12 months

Collaborators and Investigators

• Sponsor: Bayer

Publications and helpful links

General Publications

• 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.

Helpful Links

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

Study record dates

Study Major Dates

• Study Start (Actual): November 4, 2021
• Primary Completion (Actual): May 30, 2025
• Study Completion (Estimated): June 5, 2026

Study Registration Dates

• First Submitted: September 17, 2021
• First Submitted That Met QC Criteria: September 17, 2021
• First Posted (Actual): September 28, 2021

Study Record Updates

• Last Update Posted (Actual): May 1, 2026
• Last Update Submitted That Met QC Criteria: April 30, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Keywords: Prostate Cancer; Darolutamide; Metastatic hormone-sensitive prostate cancer (mHSPC); Nubeqa
• Additional Relevant MeSH Terms: Urogenital Diseases; Genital Diseases; Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Genital Diseases, Male; Prostatic Diseases; Male Urogenital Diseases; Prostatic Neoplasms; darolutamide
• Other Study ID Numbers: 21516

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

IPD Plan Description

Availability of this study's data will later be determined according to Bayer's commitment to the EFPIA/PhRMA "Principles for responsible clinical trial data sharing". This pertains to scope, timepoint and process of data access. As such, Bayer commits to sharing upon request from qualified researchers patient-level clinical trial data, study-level clinical trial data, and protocols from clinical trials in patients for medicines and indications approved in the US and EU as necessary for conducting legitimate research. This applies to data on new medicines and indications that have been approved by the EU and US regulatory agencies on or after January 01, 2014.

Interested researchers can use www.vivli.org to request access to anonymized patient-level data and supporting documents from clinical studies to conduct research. Information on the Bayer criteria for listing studies and other relevant information is provided in the member section of the portal.

Drug and device information, study documents

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