NCT07476677

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

A Phase II Prospective, Open-Label Clinical Study of Darolutamide ± ADT as Neoadjuvant Therapy in High-Risk/Very High-Risk Localized Prostate Cancer

• Status: Not Yet Recruiting
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 60 (estimated)
• Sponsor: Cancer Institute and Hospital, Chinese Academy of Medical Sciences · Academic / Other
• Sex: Male
• Age: 18 Years – 80 Years
• Healthy volunteers: Not accepted

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.

Detailed description

Purpose Main research objectives: To explore the efficacy and safety of neoadjuvant Darolutamide monotherapy and Darolutamide combined with ADT followed by radical prostatectomy in two Parallel cohorts of High-risk/very high-risk localized-stage prostate cancer patients. Secondary study objectives: To explore the efficacy and safety of neoadjuvant Darolutamide monotherapy and Darolutamide combined with ADT followed by radical prostatectomy in two Parallel cohorts of High-risk/very high-risk localized-stage prostate cancer patients. Exploratory research objectives: The predictive effect of PSMA PET (SUVmax) and CTC (Circulating tumor cells) on curative effect and the value of monitoring recurrence after radical resection; Main Outcomes: The proportion of patients achieving MRD (minimal residual disease) in two parallel cohorts. Secondary Outcomes: Pathological downstaging rate, pCR rate (pathological complete remission), positive margin rate, proportion of undetectable PSA, bPFS (biochemical progression-free survival), MFS (metastasis-free survival), quality of life questionnaire Exploratory Outcomes: Biomarkers related to efficacy; Analysis of CTC status; exploration of the correlation between SUVmax measured by PSMA-PET and prognosis. Target treatment subject population: The target population of this study is patients diagnosed with high-risk/very high-risk localized-stage prostate cancer (Meet one of the following conditions): Clinical T stage ≥cT3; Gleason score 8-10 points; baseline PSA ≥20ng/ml; regional lymph node cN1; Planned duration of treatment: The duration of neoadjuvant therapy in this study will be 3 to 6 months, and the follow-up period will be 2 years. Eligible patients will receive: Parallel cohort 1: daily oral administration of Darolutamide 600 mg; Parallel cohort 2: daily oral administration of darolutamide 600 mg combined with ADT drugs (no restriction on drug categories, including LHRH agonists/LHRH antagonists, the specific dosage is determined according to the actual situation), for 3 to 6 months. The selection of the two parallel cohorts is determined by the clinician. Considering that ADT treatment can cause typical adverse reactions such as hot flashes, gynecomastia, fatigue, sexual dysfunction, etc., the clinician will decide the enrollment cohort based on the patient's specific clinical condition. Subjects will undergo robotic-assisted laparoscopic prostatectomy (RALP) ± standard lymph node dissection (LND), followed by a 2-year follow-up. Study drugs, dosage and administration route: The study drug is Darolutamide 600 mg, taken orally twice a day; ADT drug (the specific dosage is determined according to the actual instructions). Statistical methods: Primary endpoint: Proportion of patients achieving MRD (minimal residual disease) in two parallel cohorts. Secondary study endpoints: pCR rate (pathological complete remission), pathological downstaging rate, positive resection margin rate, proportion of PSA undetectable 8 weeks after surgery, biochemical progression-free survival (bPFS), metastasis-free survival (MFS), and quality of life questionnaire. Data will be summarized using appropriate descriptive statistics. Continuous variables will be summarized using number of observations (n), mean (or geometric mean, if appropriate), standard deviation (SD), median, quartiles (Q1 and Q3), minimum and maximum. Categorical variables will be summarized using frequencies and percentages for each category. 95% CIs will be provided where appropriate.

Conditions

• Prostate Cancer

Interventions

Type	Name	Description
DRUG	Darolutamide	daily oral administration of Darolutamide 600 mg
DRUG	Darolutamide combined with ADT	600 mg of Darolutamide orally daily combined with ADT

Timeline

• Start date: 2026-04-01
• Primary completion: 2027-12-31
• Completion: 2028-03-31
• First posted: 2026-03-17
• Last updated: 2026-03-17

Locations

1 site across 1 country: China