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.

Metastatic Hormone-sensitive Prostate Cancer Clinical Trial

— ARASEC  

Official title:

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT05059236
• Other study ID #: 21516
• Status: Active, not recruiting
• Phase: Phase 2
• Start date: November 4, 2021
• Est. completion date: June 22, 2026

Study information

• Verified date: June 2024
• Source: Bayer
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 223
• Est. completion date: June 22, 2026
• Est. primary completion date: April 15, 2025
• Accepts healthy volunteers: No
• Gender: Male
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Hypersensitivity
• Metastatic Hormone-sensitive Prostate Cancer
• Prostatic Neoplasms

Intervention

Drug:
• Darolutamide (BAY1841788, Nubeqa)
300 mg per tablet, oral administration with food

Other:
• ADT
LHRH agonist/antagonist or orchiectomy

Locations

Country	Name	City	State
United States	University of New Mexico Cancer Center	Albuquerque	New Mexico
United States	VA Ann Arbor Healthcare System	Ann Arbor	Michigan
United States	Brigham and Women's Hospital (BWH) - Surgery Urology	Atlanta	Georgia
United States	Piedmont Atlanta Hospital	Atlanta	Georgia
United States	MidLantic Urology	Bala-Cynwyd	Pennsylvania
United States	University of Maryland	Baltimore	Maryland
United States	Northwestern University Feinberg School of Medicine	Chicago	Illinois
United States	Northwestern University's Feinberg School of Medicine	Chicago	Illinois
United States	The Urology Group	Cincinnati	Ohio
United States	New Jersey Urology - Clifton	Clifton	New Jersey
United States	Barbara Ann Karmanos Cancer Institute - Detroit	Detroit	Michigan
United States	Inova Schar Cancer Institute	Fairfax	Virginia
United States	Central Ohio Urology	Gahanna	Ohio
United States	Urology Centers of Alabama, PC	Homewood	Alabama
United States	Houston Methodist Research Institute	Houston	Texas
United States	Alliance for Multispecialty Research LLC - Kansas City	Kansas City	Missouri
United States	University of Cal. San Diego Moores Cancer Ctr.	La Jolla	California
United States	Tower Urology	Los Angeles	California
United States	Carolina Urological Research Center	Myrtle Beach	South Carolina
United States	Urology Associates, PC	Nashville	Tennessee
United States	Mount Sinai Faculty Practice Associates	New York	New York
United States	GU Research Network, LLC - Oncology radiology	Omaha	Nebraska
United States	UC Irvine Health	Orange	California
United States	John Wayne Cancer Institute	Santa Monica	California
United States	Spokane Urology PS	Spokane	Washington
United States	Associated Medical Professionals of NY, PLLC	Syracuse	New York
United States	Michigan Institute of Urology, PC	Troy	Michigan
United States	Arizona Urology Specialists	Tucson	Arizona
United States	New Jersey Urology, LLC	Voorhees	New Jersey
United States	GU Research Network, LLC	Wichita	Kansas

Sponsors (1)

Lead Sponsor	Collaborator
Bayer

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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

External Links

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