Darolutamide ± ADT as Neoadjuvant Therapy in High-Risk/Very High-Risk Localized Prostate Cancer

NCT07476677 | Not Yet Recruiting Phase 2 DMC

• 1 other identifier: 24/605-4885
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 1

Brief Summary

This is a two-Parallel cohort, prospective study, aimed to explore Efficacy and safety of neoadjuvant Darolutamide with or without ADT in high-risk/very high-risk localized-stage prostate cancer. Two parallel cohorts will enroll 30 patients with high-risk/very high-risk localized-stage prostate cancer according to the criteria, respectively. Eligible patients in cohort 1 will receive 600 mg of Darolutamide orally daily, and patients in cohort 2 will receive 600 mg of Darolutamide orally daily combined with ADT. The selection of the two parallel cohorts will be determined by the clinician. Considering that ADT treatment will bring typical adverse-reactions such as hot flashes, gynecomastia, fatigue, and sexual dysfunction, the clinician will decide the enrollment cohort based on the patient's specific clinical condition. After both cohorts receive 3-6 months of neoadjuvant treatment, these patients will receive robotic-assisted laparoscopic prostatectomy (RALP) ± standard lymph node dissection (LND), and the specific surgical plan will be formulated by the clinician. Patients will receive postoperative adjuvant therapy as same as the original prescription according to different conditions (the application of postoperative adjuvant radiotherapy is determined by the clinician). Follow-up: (1) PSA and testosterone levels: Monitor monthly for the first 6 months. Monitor every 3 months within 2 years. Monitor every 6 months thereafter. (2) Radiological evaluation: Monitor every 6 minutes within 2 years after surgery, and every 12 minutes thereafter.

Conditions

Prostate Cancer

Keywords

localized-stage prostate cancer; Darolutamide; neoadjuvant

Outcome Measures

Primary Outcomes (1)

• Main Outcome

  Number of Participants Achieving Minimal Residual Disease (MRD) Positivity

  6 months

Secondary Outcomes (6)

• Pathological complete response (pCR) rate

  6 months

• Positive surgical margin rate

  6 months

• Proportion of participants with undetectable PSA

  6 months

• Biochemical progression-free survival (bPFS)

  1 year

• Metastasis-free survival (MFS)

  1 year

Other Outcomes (3)

• Biomarkers Related to Treatment Efficacy

  1 year

• Circulating Tumor Cell (CTC) Status

  1 year

• Correlation Between PSMA-PET SUVmax and Prognosis

  1 year

Study Arms (2)

Darolutamide

ACTIVE COMPARATOR

A Group treated with Darolutamide 600 mg

Drug: Darolutamide

Darolutamide combined with ADT

EXPERIMENTAL

A Group treated with Darolutamide combined with ADT

Drug: Darolutamide combined with ADT

Interventions

Darolutamide DRUG

daily oral administration of Darolutamide 600 mg

Darolutamide

Darolutamide combined with ADT DRUG

600 mg of Darolutamide orally daily combined with ADT

Darolutamide combined with ADT

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: male
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Informed consent was provided before the initiation of either study procedure
• Age between 18 and 80 years of age (including 18 and 80 years of age)
• ECOG performance status of 0-1 points, without severe cardiovascular and psychiatric disorders
• Histologically confirmed adenocarcinoma of the prostate
• Any one of the following conditions:
• \) Clinical T stage ≥cT3; 2) Gleason score 8-10; 3) baseline PSA ≥20ng/ml; 4) presence of regional lymph node cN1; 6. No previous topical therapy and chemotherapy, ARi2nd 7. Patients previously treated with conventional ADT for ≤6 months (±ARi1st) 8. Subjects meet the criteria for resectability.The resectability criteria were defined as: clear lateral border of prostate and clear and non-invasive bladder neck on rectal digital examination
• a, and no urethral or external sphincter invasion of the prostate apex 9. The subject has not received local treatment of the primary lesion of prostate cancer in the past and has no contraindications to radical prostatectomy 10. Male subjects have undergone surgical sterilization or used acceptable contraceptive methods (defined as barrier contraception containing spermicide) during the duration of the study and 3 months after the last study drug administration to prevent their partner from getting pregnant 11. Blood donor subjects are not allowed to donate blood during the study period and during the 3 months after the last study drug administration 12. During the duration of the study (including treatment and planned visits and examinations), subjects voluntarily and able to comply with the protocol

You may not qualify if:

• Staff members involved in planning and/or conducting this study (research center staff).
• Previously participated in the current study.
• Participated in another clinical study involving an investigational product (IP) in the past month.
• Previously underwent surgical castration or chemotherapy.
• Previously received PARP inhibitor treatment.
• Subjects with known hypersensitivity to ADT drugs/darolutamide or any excipient in the product.
• Subjects with psychiatric or physical conditions that, in the investigator's judgment, would prevent them from safely receiving treatment.
• Subjects with any laboratory test abnormalities that, in the investigator's judgment, would put them at risk if they participated in the study.
• Subjects with persistent toxicity from prior cancer treatment (\> CTCAE Grade 2), except for alopecia.
• Patients with known active hepatitis (i.e., hepatitis B or hepatitis C) due to the risk of bloodborne or other bodily fluid transmission.
• Immunocompromised subjects, such as those known to be HIV seropositive.
• Unwilling or unable to comply with protocol requirements and scheduled visits.

Sponsors & Collaborators

• Cancer Institute and Hospital, Chinese Academy of Medical Sciences: lead

Study Sites (1)

Cancer Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College

Beijing, Beijing Municipality, 101205, China

Location

MeSH Terms

Conditions

Prostatic Neoplasms

Interventions

darolutamide; Androgen Antagonists

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Hormone Antagonists; Hormones, Hormone Substitutes, and Hormone Antagonists; Physiological Effects of Drugs; Pharmacologic Actions; Chemical Actions and Uses

Study Design

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

Study Record Dates

• First Submitted: September 24, 2025
• First Posted: March 17, 2026
• Study Start: April 1, 2026
• Primary Completion (Estimated): December 31, 2027
• Study Completion (Estimated): March 31, 2028
• Last Updated: March 17, 2026

Record last verified: 2025-03

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)