177Lu-PSMA-617 Combined With Darolutamide in Neoadjuvant Treatment of High-risk Localized Prostate Cancer: a Prospective, Single-arm, Multi-center Clinical Trial

NCT07677566 | Not Yet Recruiting Phase 4

• 1 other identifier: 23232
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

Brief Summary

The goal of this clinical trial is to explore the efficacy and safety of darolutamide combined with 177Lu-PSMA-617 in treating high-risk localized prostate cancer patients who are scheduled to undergo radical prostatectomy. The main questions it aims to answer are: Does this combination treatment improve the pathological complete response rate (pCR)? What is the minimal residual disease (MRD) rate in these patients? What are the safety profiles and any adverse effects associated with this treatment? Researchers will compare the combination of darolutamide and 177Lu-PSMA-617 to a placebo to see if the combination is effective in treating high-risk localized prostate cancer. Participants will: Receive either darolutamide combined with 177Lu-PSMA-617 or a placebo every day for 12 weeks. Visit the clinic every 6 weeks for checkups and tests. Keep a diary of their symptoms and any side effects experienced during the treatment. Undergo imaging tests, including prostate MRI and PSMA PET/CT, before surgery and during follow-up.

Conditions

Prostate Cancer; Prostate Cancer Patients

Outcome Measures

Primary Outcomes (1)

• pCR + MRD

  pCR + MRD (pCR: Pathological Complete Response; Minimal Residual Disease (MRD) rate: defined as the proportion of patients achieving MRD among all patients; MRD is defined as postoperative pathology indicating that the longest diameter of the tumor is ≤ 5 mm)

  Screening, End of Neoadjuvant Treatment( 12 weeks after baseline)

Secondary Outcomes (7)

• Patient Sexual Function

  Day 1 of Cycle 1&2 ( each cycle is 6 weeks), 1 month after treatment, 3 and 6 months after treatment, 6 months until 2 years

• PSA Response Rate (defined as a decrease in PSA of 50% or more)

  Day 1 of Cycle 1&2 (each cycle is 6 weeks), End of Neoadjuvant Treatment (12 weeks after baseline). The last week of each month for the first 3 months after the periprocedural, thereafter the last week of every 3rd month for a total duration of 1 year

• PSMA Response Rate

  Screening, End of Neoadjuvant Treatment (12 weeks after baseline)

• 1-year biochemical recurrence-free survival, bRFS

  The last week of each month for the first 3 months after the periprocedural, thereafter the last week of every 3rd month for a total duration of 1 year

• Perioperative Complications

  Perioperative Period

Other Outcomes (1)

• Adverse Event

  From Day 1 of cycle 1 to the 30 days after study completion, an average of 1year and 4 months.

Study Arms (1)

Experimental Arm

EXPERIMENTAL

Drug: Darolutamide combined with 177Lu-PSMA-617

Interventions

Darolutamide combined with 177Lu-PSMA-617 DRUG

177Lu-PSMA-617: Eligible participants must start receiving 177Lu-PSMA-617 within 14 days. Participants will receive a dosage of 7.4 GBq (± 10%) of 177Lu-PSMA-617, administered once every 6 weeks (± 7 days), for a total of two doses. Darolutamide: Administered at a dosage of 1200 mg orally in two divided doses with meals, starting from the first injection of 177Lu-PSMA-617 and continuing until 6 weeks after the second injection, for a total duration of 12 weeks.

Experimental Arm

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: male
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients must be ≥ 18 and ≤75 years of age
• All patients must have a histologically or cytologically diagnosis of prostate cancer，without distant metastasis, and suitable for radical prostatectomy
• All patients meet at least one of the following criteria： multi-parameter MRI or PSMA PET / CT shows clinical staging of primary tumor ≥ T2c； Gleason score of primary tumor ≥ 8； prostate specific antigen (PSA) ≥20 ng/ml； Radiographic assessment of regional lymph node metastases (N1)
• Eastern Cooperative Oncology Group (ECOG) physical condition score 0- 1
• Primary lesion SUVmax ≥ 20.0 as assessed by PSMA-PET examination.
• Adequate organ function: Complete Blood Count: White blood cell count (WBC) ≥ 3.0 × 10\^9/L, platelet count ≥ 100 × 10\^9/L, hemoglobin ≥ 9 g/dL. Renal Function: Serum creatinine ≤ 2 × ULN. Liver Function: Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 2.5 × ULN, total bilirubin (TBIL) ≤ 1.5 × ULN. Coagulation Function: International normalized ratio (INR) \< 1.5.
• Voluntary Participation: Participants must voluntarily agree to participate and sign the informed consent form (ICF), indicating their understanding of the purpose of the study and the required procedures, as well as their willingness to participate in the research. Participants must be willing to comply with the prohibitions and restrictions outlined in the study protocol.
• Patients of childbearing potential must be willing to take high-efficiency contraceptive measures during the study period and within 120 days after the last dose of treatment

You may not qualify if:

• Patients with prostate having neuroendocrine, small cell, or sarcoma-like features are not eligible
• Patients with low-risk and medium-risk, localized prostate cancer (the following conditions are met at the same time) are not eligible: prostate specific antigen (PSA) \<20 ng/mL multiparameter MRI or PSMA PET / CT shows clinical staging of primary tumor \< T3, Gleason score of primary tumor \< 8
• Patients with clinical or radiological evidence of regional or extra-regional lymph node metastases or bone metastases or visceral metastases (any M1）
• Primary lesion SUVmax \< 20.0 as assessed by PSMA-PET examination.
• Patients who have previously received androgen deprivation therapy (medical or surgical) more than 3 months or focal treatment of prostate cancer or prostate cancer radiotherapy or prostate cancer chemotherapy
• Patients with severe or uncontrolled concurrent infections
• Patients must not have New York Heart Association Class III or IV congestive heart failure at the time of screening. Patients must not have any thromboembolic event, unstable angina pectoris, myocardial infarction within 6 months prior to registration
• Uncontrolled severe hypertension, persistently uncontrolled diabetes, oxygen-dependent lung disease, chronic liver disease, or HIV infection
• Patients with a history of other malignancies within the past 5 years, except for prostate cancer, are not eligible; however, cured basal cell carcinoma or squamous cell carcinoma of the skin may be eligible
• Patients with mental illness, mental disability, or inability to provide informed consent

Sponsors & Collaborators

• The Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical School: lead
• Bayer: collaborator

Study Sites (1)

Nanjing Drum Tower Hospital The Affiliated Hospital of Nanjing University Medical School

Nanjing, Jiangsu, China

Location

MeSH Terms

Conditions

Prostatic Neoplasms

Interventions

Pluvicto

Condition Hierarchy (Ancestors)

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

Central Study Contacts

Hongqian Guo

CONTACT

+86 (025)-83106666; dr.ghq@nju.edu.cn

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Director

Study Record Dates

• First Submitted: June 18, 2026
• First Posted: July 1, 2026
• Study Start: July 1, 2026
• Primary Completion (Estimated): July 1, 2027
• Study Completion (Estimated): December 31, 2028
• Last Updated: July 1, 2026

Record last verified: 2026-06

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)