A Study to Learn How Well a Combination of Darolutamide and Androgen Deprivation Therapy (ADT) Works as a Treatment Before Surgery for Men Who Have High-risk Localized Prostate Cancer.

NCT07450599 | Recruiting Phase 2

• 1 other identifier: 22982
• Study Type: interventional
• Target: 250
• Locations: 1 country
• Sites: 23

Brief Summary

Researchers are looking for a better way to treat men who have high-risk localized prostate cancer, which refers to a type of prostate cancer that is still confined to the prostate gland but has certain characteristics that make it more likely to grow and spread. The study treatment darolutamide plus androgen deprivation therapy (ADT) is under development as treatment before surgery for men who have high-risk localized prostate cancer. Darolutamide works by blocking the attachment of androgen hormones to androgen receptors in cancer cells, thereby blocking cancer progression and growth. ADT is an established treatment that is used to lower the amount of androgen hormones (e.g., testosterone) in the body. The main purpose of this study is to learn how the cancer responds to the two different treatment durations (12 weeks or 24 weeks) of darolutamide combined with ADT used before the men undergo surgery to remove the prostate. For this, the researchers will compare the percentage of participants who either achieve complete response to the treatment (where no cancer cells are found) or with condition of minimal residual disease after the treatment (where only a small amount of cancer cells remains). The study participants will be randomly (by chance) assigned to one of two treatment groups. Depending on the group, they will receive darolutamide tablets by mouth plus ADT administered under the skin for either 12 weeks or 24 weeks. No more than 30 days after the end of the treatments, study participants will be performed with surgery to remove the prostate. Each participant will be in the study for approximately 29 to 32 months, including a screening phase of up to 28 days, 12 weeks or 24 weeks of treatment depending on the treatment groups, followed by the surgery no more than 30 days after the treatment, and a follow up phase of up to 2 years after the surgery. 2 visits to the study site are planned during the screening phase, followed by 3 to 6 visits (every 28 days) during treatment. The treatment period ends with a visit within 7 days after the last dose of treatment. During the study, the doctors and their study team will:

• take blood and urine samples
• check the participants' health parameters
• do physical examinations
• check if the participants' cancer has grown and/or spread using CT (computed tomography) or MRI (magnetic resonance imaging) and, if needed, bone scan
• take tumor samples
• ask the participants questions about how they are feeling and what adverse events they are having. An adverse event is any medical problem that a participant has during a study. Doctors keep track of all adverse events, irrespective if they think it is related or not to the study treatments. About 30 days after the last dose of treatment, 5 weeks after the surgery and every 12 weeks thereafter, the study doctors and their team will check the participants' health and any changes in cancer. This follow-up period ends 2 years after the surgery.

Conditions

High-Risk Localized Prostate Cancer

Outcome Measures

Primary Outcomes (1)

• The proportion of participants achieving pathologic response rate (pRR: pathologic complete response [pCR] or minimal residual disease [MRD])

  pRR is defined as the proportion of participants with either condition of pCR or MRD at week 12 or 24 in corresponding arm. Proportion of participants with pCR is defined as the proportion of participants with no residual tumor detected in radical prostatectomy (RP) specimens following 12 or 24 weeks of neoadjuvant treatment of darolutamide and ADT per randomization. Proportion of participants with MRD is defined as the proportion of participants that have residual cancer burden (RCB) ≤0.25 cm\^3 in the RP specimens.

  Completion of Follow-up 1, 30 days after last dose of study drug

Secondary Outcomes (6)

• Proportion of participants with pathologic complete response (pCR)

  Completion of Follow-up 1, 30 days after last dose of study drug

• Percentage of participants with tumor downstaging (e.g. clinical T3 to pathologic T2)

  At baseline and immediately after radical prostatectomy

• Percentage of participants with positive surgical margin (PSM)

  Immediately after radical prostatectomy

• Biochemical complete response (CR) rate prior to radical prostatectomy (RP) and at landmark timepoints post-RP

  At pre-RP, at 5 weeks, 12 weeks post-RP, and every 3 months after that until Year 2 after RP or end of follow up

• Biochemical recurrent free survival since radical prostatectomy (RP) among participants with prostate-specific antigen (PSA) <0.1 ng/mL after RP

  From RP to biochemical recurrence or death whichever occurs first, up to 2.5 years

Study Arms (2)

Darolutamide + ADT (12 weeks)

EXPERIMENTAL

Participants will receive darolutamide and androgen deprivation therapy (ADT) as neoadjuvant treatment for 12 weeks, followed by radical prostatectomy (RP).

Drug: Darolutamide; Drug: ADT

Darolutamide + ADT (24 weeks)

EXPERIMENTAL

Participants will receive darolutamide and androgen deprivation therapy (ADT) as neoadjuvant treatment for 24 weeks, followed by radical prostatectomy (RP).

Drug: Darolutamide; Drug: ADT

Interventions

ADT DRUG

Goserelin acetate implant (ZOLADEX), at a dose of 10.8 mg, will be administered subcutaneously every 12 weeks into the anterior abdominal wall below the navel line.

Darolutamide + ADT (12 weeks); Darolutamide + ADT (24 weeks)

Darolutamide DRUG

Oral tablets of 600 mg twice daily (BID).

Darolutamide + ADT (12 weeks); Darolutamide + ADT (24 weeks)

Eligibility Criteria

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

You may qualify if:

• Participants must be 18 years or older at the time of signing the informed consent.
• Darolutamide-naïve participants who are with localized prostate adenocarcinoma who plan to receive radical prostatectomy (RP) and defined as high risk with National Comprehensive Cancer Network (NCCN) criteria (version 1.2025).
• No evidence of distant metastasis based on computed tomography (CT), magnetic resonance imaging (MRI), and whole body bone scan (WBBS) within 42 days prior to start of study treatment.
• Candidate for RP with pelvic lymph node dissection (PLND) or extended PLND (ePLND) as per the investigator.
• Participants must have at least one of the following features according to NCCN definition of high-risk:
• Biopsy Gleason score ≥8, and/or
• Prostate-specific antigen (PSA) \>20 ng/mL measured during Screening and prior to randomization, or
• Clinical stage ≥ T3a.
• Participants with pelvic lymph node involvement (N1) can be included.
• Eastern Cooperative Oncology Group (ECOG) performance status score of 0 or 1.

You may not qualify if:

• Prostate cancer with known neuroendocrine (NE) differentiation or small cell features.
• Intolerant to darolutamide or androgen deprivation therapy (ADT) treatment.
• History of
• Loss of consciousness or transient ischemic attack or stroke within 6 months prior to randomization, or
• Significant cardiovascular disease within 6 months prior to randomization.
• Any contraindications for RP.
• Uncontrolled or treatment-resistant hypertension.
• History of another malignancy within 5 years prior to randomization.

Sponsors & Collaborators

• Bayer: lead

Study Sites (23)

The Second Affiliated Hospital of Anhui Medical University

Hefei, Anhui, 230601, China

NOT YET RECRUITING

Cancer Hospital, Chinese Academy of Medical Sciences

Beijing, Beijing Municipality, 100000, China

RECRUITING

Peking University First Hospital - Oncology Department

Beijing, Beijing Municipality, 100034, China

NOT YET RECRUITING

Fujian Medical University - The First Affiliated Hospital

Fuzhou, Fujian, 350005, China

NOT YET RECRUITING

Lanzhou University - The Second Hospital (The Second Clinical Medical College of Lanzhou University)

Lanzhou, Gansu, 730030, China

NOT YET RECRUITING

The first Affiliated Hospital of Guangzhou Medical University

Guangzhou, Guangdong, 510230, China

NOT YET RECRUITING

Nanfang Hospital, Southern Medical University

Guangzhou, Guangdong, 510515, China

NOT YET RECRUITING

The 2nd Hospital of Hebei Medical University

Shijiazhuang, Hebei, 050000, China

NOT YET RECRUITING

2nd affiliated Hos. Harbin Medical University

Harbin, Heilongjiang, 150086, China

NOT YET RECRUITING

Zhengzhou University - First Affiliated Hospital (Henan Medical University - First Affiliated Hospital)

Zhengzhou, Henan, 450052, China

NOT YET RECRUITING

Huazhong University of Science and Technology - Tongji Medical College - Wuhan Union Hospital

Wuhan, Hubei, 430022, China

NOT YET RECRUITING

Wuhan University - Renmin Hospital (Wuhan University People's Hospital/Hubei Provincial People's Hospital)

Wuhan, Hubei, 430060, China

NOT YET RECRUITING

NJ Drum Tower Hospital, the Affil Hos of NJ Univ Med School

Nanjing, Jiangsu, 210008, China

RECRUITING

Nanchang University - The First Affiliated Hospital

Nanchang, Jiangxi, 330006, China

NOT YET RECRUITING

China Medical University (CMU) - First Affiliated Hospital

Shenyang, Liaoning, 110001, China

NOT YET RECRUITING

Qilu Hosp., Shandong Univ.

Jinan, Shandong, 250012, China

NOT YET RECRUITING

Shanghai General Hospital

Shanghai, Shanghai Municipality, 200080, China

NOT YET RECRUITING

Shanghai Jiao Tong University School of Medicine (SJTUSM) - XinHua Hospital

Shanghai, Shanghai Municipality, 200092, China

NOT YET RECRUITING

Sichuan Cancer Hospital-Urology Department

Chengdu, Sichuan, 610041, China

NOT YET RECRUITING

The Second Hospital of Tianjin Medical University

Tianjin, Tianjin Municipality, 300211, China

NOT YET RECRUITING

Kunming Medical University (KMU) - Second Affiliated Hospital

Kunming, Yunnan, 650101, China

NOT YET RECRUITING

Jinhua Municipal Central Hospital-Oncology Department

Jinhua, Zhejiang, 321000, China

NOT YET RECRUITING

Dongyang People's Hospital

Jinhua, Zhejiang, 322199, China

NOT YET RECRUITING

MeSH Terms

Interventions

darolutamide

Central Study Contacts

Bayer Clinical Trials Contact

CONTACT

(+)1-888-84 22937; clinical-trials-contact@bayer.com

Study Design

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

Study Record Dates

• First Submitted: February 12, 2026
• First Posted: March 4, 2026
• Study Start: April 27, 2026
• Primary Completion (Estimated): June 15, 2028
• Study Completion (Estimated): October 15, 2030
• Last Updated: June 24, 2026

Record last verified: 2026-06

Data Sharing

• IPD Sharing: Will not share

Locations

CN (23)