ARASEC: 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.

Sponsor

Bayer (Industry)

Overall Status

Recruiting

CT.gov ID

NCT05059236

Collaborator

(none)

200

Enrollment

Locations

Arm

54.7

Anticipated Duration (Months)

16.7

Patients Per Site

0.3

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Metastatic Hormone-sensitive Prostate Cancer	Drug: Darolutamide (BAY1841788, Nubeqa) Other: ADT	Phase 2

Study Design

Study Type:

Interventional

Anticipated Enrollment :

200 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

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

Actual Study Start Date :

Nov 29, 2021

Anticipated Primary Completion Date :

Jun 22, 2024

Anticipated Study Completion Date :

Jun 22, 2026

Arms and Interventions

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

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

Outcome Measures

Primary Outcome Measures

Progression-free survival (PFS) [Approximately 12 months after end of enrollment]
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.

Secondary Outcome Measures

Overall survival (OS) [Approximately 24 months after end of enrollment]
Time from the date of enrollment until death resulting from any cause or the date last known alive
Radiographic Progression-free survival (rPFS) [Approximately 24 months after end of enrollment]
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
Time to castration-resistant prostate cancer (CRPC) [Approximately 12 months after end of enrollment]
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
Complete PSA response rate [At 6 months after first administration]
PSA level of less than 0.2 ng per milliliter on two consecutive measurements at least 4 weeks apart
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]
Adverse Events will be assessed by National Cancer Institute-Common Terminology Criteria (NCI CTCAE) v. 5.0

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

Male

Accepts Healthy Volunteers:

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Urology Centers of Alabama PC	Homewood	Alabama	United States	35209
2	Tower Urology	Los Angeles	California	United States	90048
3	Brigham and Women's Hospital (BWH) - Surgery Urology	Atlanta	Georgia	United States	30318
4	Piedmont Healthcare	Atlanta	Georgia	United States	30318
5	Meridian Clinical Research - Urology	Savannah	Georgia	United States	31405
6	Northwestern University's Feinberg School of Medicine	Chicago	Illinois	United States	60611
7	University Of Maryland	Baltimore	Maryland	United States	21201
8	GU Research Network, LLC - Oncology radiology	Omaha	Nebraska	United States	68130
9	Mount Sinai Faculty Practice Associates	New York	New York	United States	10029
10	MidLantic Urology	Bala-Cynwyd	Pennsylvania	United States	19004
11	Carolina Urological Research Center	Myrtle Beach	South Carolina	United States	29572
12	Carolina Urological Research Center	Myrtle Beach	South Carolina	United States	29579