Efficacy and Safety of Darolutamide Combined With Docetaxel and ADT as Neoadjuvant Therapy for Locally Advanced Prostate Cancer.

Efficacy and Safety of Darolutamide Combined With Docetaxel and ADT as Neoadjuvant Therapy for Locally Advanced Prostate Cancer: A Multicenter, Prospective, Randomized Controlled Study

The goal of this study is to evaluate the efficacy and safety of darolutamide combined with docetaxel and ADT compared to docetaxel combined with ADT in treating locally advanced prostate cancer patients scheduled for radical prostatectomy. The participant population includes adult males with locally advanced prostate cancer (cT3b-cT4, N0, M0 or any cT, N1, M0). The main questions it aims to answer are:

Does the combination of darolutamide, docetaxel, and ADT improve treatment outcomes compared to docetaxel combined with ADT? What are the safety profiles and adverse effects associated with each treatment group? Researchers will compare the control group (docetaxel combined with ADT) to the experimental group (darolutamide combined with docetaxel and ADT) to see if the experimental treatment is more effective.

Participants will:

Receive either docetaxel combined with ADT or darolutamide combined with docetaxel and ADT for 4 cycles (16 weeks) as neoadjuvant treatment.

Undergo radical prostatectomy after completing the neoadjuvant treatment. Be followed up for 36 months post-surgery to assess treatment efficacy and safety.

Study Overview

• Status: Not yet recruiting
• Conditions: Prostate Cancer; Prostate; Prostate Cancer Patients
• Intervention / Treatment: Drug: Darolutamide; Drug: docetaxel; Drug: ADT

• Study Type: Interventional
• Enrollment (Estimated): 200
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Xiaoguang Shao; Phone Number: +(86)021-1234567; Email: shaoxgg@163.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Male, age >= 18 years and <= 75 years at the time of signing the informed consent form;
2. Confirmed as prostate cancer by histological or cytological examination, and planned for radical prostatectomy;
3. Clinical stage conforms to the definition of locally advanced prostate cancer: cT3b-cT4, N0, M0 or any cT, N1, M0 (based on PSMA-PET/CT examination);
4. Eastern Cooperative Oncology Group (ECOG) performance status score is 0-1;
5. Expected lifespan >= 10 years;
6. Important laboratory indicators meet the following requirements: a. Hemoglobin >= 90 g/L b. Serum total bilirubin <= 1.5 times the upper limit of normal value, transaminase (AST/ALT) <= 2.5 times the upper limit of normal value c. Serum albumin >= 30 g/L d. Serum creatinine <= 1.5 times the upper limit of normal value e. Absolute neutrophil count >= 1.5 x 10^9/L, platelet count >= 100 x 10^9/L;
7. No difficulty in swallowing (can take the medicine in whole), chronic diarrhea, intestinal obstruction or other factors affecting drug administration and absorption;
8. No use of opioid analgesics (including codeine, oxycodone, etc.) to relieve cancer pain;
9. If the spouse is a fertile female, the subject consents to take effective contraceptive measures during the treatment period and for 4 months after the surgery;
10. The subject voluntarily participates in this trial, signs the informed consent form, and is willing to comply with the requirements of the research protocol throughout the study period.

Exclusion Criteria:

1. Pathological diagnosis of neuroendocrine prostate cancer, including small cell carcinoma;
2. Prior local or systemic treatment for prostate cancer, including but not limited to radiotherapy, chemotherapy, or endocrine therapy;
3. Confirmed bone metastasis, hepatic metastasis, brain metastasis, or other visceral metastases on imaging;
4. Known hypersensitivity to the study drugs (active ingredients or excipients) or drugs of the same class;
5. Contraindications to prednisone acetate or docetaxel, such as active infection, allergy, or other conditions;
6. Chronic disease requiring prednisone acetate at doses exceeding those specified in the protocol (5 mg orally twice daily, starting 14 days before docetaxel chemotherapy and stopping 3 weeks after the last chemotherapy cycle);
7. Poorly controlled hypertension despite medication (systolic blood pressure >=160 mmHg or diastolic blood pressure >=95 mmHg);
8. Active or symptomatic viral hepatitis or other chronic liver disease; known human immunodeficiency virus (HIV) infection;
9. History of pituitary or adrenal dysfunction;
10. Active autoimmune disease requiring hormonal therapy;
11. Major cardiovascular or cerebrovascular disease within 6 months prior to the start of study treatment, including: severe/unstable angina, myocardial infarction, congestive heart failure [New York Heart Association (NYHA) class III or above], cerebrovascular accident, or arrhythmia requiring pharmacological treatment;
12. History of allogeneic organ transplantation or allogeneic hematopoietic stem cell transplantation;
13. Grade ≥2 peripheral sensory or motor neuropathy;
14. Other malignancies occurring within the past 2 years or currently concurrent malignancies;
15. Major surgery requiring general anesthesia within 28 days before the first dose;
16. Treatment with strong CYP3A4 inhibitors (e.g., itraconazole, clarithromycin, ketoconazole) or strong CYP3A4 inducers (e.g., carbamazepine, phenytoin, phenobarbital, St. John's wort) that cannot be discontinued, and have not been stopped for at least 7 days before randomization;
17. History of epilepsy;
18. Alcohol or drug abuse or dependence;
19. Participation in another therapeutic clinical study within 1 month before the start of study treatment;
20. Any other condition that the investigator considers unsuitable for participation in this study;

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Darolutamide + docetaxel + ADT; Adopting the triple neoadjuvant treatment regimen of Darolutamide + docetaxel + ADT	Drug: Darolutamide; Darolutamide: oral administration, 600 mg per dose, twice daily, taken with food.; Drug: docetaxel; Docetaxel: intravenous injection, 75 mg/m², once every 3 weeks, for a total of 4 doses/cycles. (Oral prednisone acetate should be started 14 days before docetaxel chemotherapy at 5 mg twice daily and discontinued 3 weeks after the last chemotherapy cycle.); Drug: ADT; ADT: leuprorelin, goserelin, or triptorelin, selected by the investigator according to the patient's condition, administered by subcutaneous or intramuscular injection, using a once-monthly formulation uniformly.
Active Comparator: Docetaxel + ADT; Adopting the dual neoadjuvant treatment regimen of docetaxel + ADT	Drug: docetaxel; Docetaxel: intravenous injection, 75 mg/m², once every 3 weeks, for a total of 4 doses/cycles. (Oral prednisone acetate should be started 14 days before docetaxel chemotherapy at 5 mg twice daily and discontinued 3 weeks after the last chemotherapy cycle.); Drug: ADT; ADT: leuprorelin, goserelin, or triptorelin, selected by the investigator according to the patient's condition, administered by subcutaneous or intramuscular injection, using a once-monthly formulation uniformly.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
3-year biochemical progression-free survival (bPFS)	Every 3 months (±14 days) up to 36 months after surgery

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
3-year biochemical progression-free survival (bPFS)		Every 3 months (±14 days) up to 36 months after surgery
Pathological Downstaging Rate after Radical Prostatectomy		On Surgery day
Incidence of Treatment-Related Adverse Events		From screening visit to 30 days after the last neoadjuvant dose or start of new anticancer therapy
Time to Castration-Resistant Prostate Cancer (CRPC) at 3 Years		every 3 months PSA tests and every 6 months imaging assessments up to 36 months after surgery
Objective Response Rate (ORR)		2-4 weeks after completion of neoadjuvant therapy
3-year Radiographic Progression-Free Survival (rPFS)		Every 6 months (±1 month) post-surgery until 36 months post-surgery (months 6, 12, 18, 24, 30, 36)
Undetectable PSA Rate post-Radical Prostatectomy		6 weeks post-surgery (±7 days)
Subject Quality of Life as assessed by FACT-P( Functional Assessment of Cancer Therapy - Prostate) scale	The FACT-P(Functional Assessment of Cancer Therapy - Prostate) scale will be used to assess the quality of life of subjects. The total score is calculated from the general functional and prostate cancer-specific subscale scores, with a total score range of 0 to 156, where higher scores indicate better functional status. Changes in the total score and individual domain scores will be analyzed.	Baseline (V0), post-neoadjuvant/pre-surgery (V5), and at 6, 12, 24, 36 months post-surgery (±14 days)
Perioperative Complications		From surgery date through 90 days post-surgery
Positive Surgical Margin Rate after Radical Prostatectomy		On surgery day
Time to Castration-Resistant Prostate Cancer (CRPC) at 3 Years		PSA tests every 3 months and imaging assessments every 6 months up to 36 months post-surgery
Pathological Complete Response (pCR) or Minimal Residual Disease (MRD) Rate		On surgery day
3-year Overall Survival (OS)		Every 3 months (+/-1 month) post-surgery until 36 months post-surgery

Collaborators and Investigators

• Sponsor: RenJi Hospital
• Collaborators: Bayer

Study record dates

Study Major Dates

• Study Start (Estimated): August 1, 2026
• Primary Completion (Estimated): December 31, 2031
• Study Completion (Estimated): December 31, 2031

Study Registration Dates

• First Submitted: July 7, 2026
• First Submitted That Met QC Criteria: July 22, 2026
• First Posted (Actual): July 28, 2026

Study Record Updates

• Last Update Posted (Actual): July 28, 2026
• Last Update Submitted That Met QC Criteria: July 22, 2026
• Last Verified: July 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Urogenital Diseases; Genital Diseases; Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Genital Diseases, Male; Prostatic Diseases; Male Urogenital Diseases; Prostatic Neoplasms; Organic Chemicals; Hydrocarbons; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Terpenes; Taxoids; Cyclodecanes; Diterpenes; Docetaxel; darolutamide
• Other Study ID Numbers: 23233

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No