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

Overview

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.

Interventions

• Drug Darolutamide combined with 177Lu-PSMA-617
  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.

Primary outcome measures

• pCR + MRD [Time frame: Screening, End of Neoadjuvant Treatment( 12 weeks after baseline)]

Secondary outcome measures (7)

• Patient Sexual Function [Time frame: 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) [Time frame: 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 [Time frame: Screening, End of Neoadjuvant Treatment (12 weeks after baseline)]
• 1-year biochemical recurrence-free survival, bRFS [Time frame: 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 [Time frame: Perioperative Period]
• Patient Quality of Life [Time frame: Day 1 of Cycle 1&2 ( each cycle is 6 weeks), 1 month after treatment, 3 and 6 months after treatmnet,6 months until 2 years]
• Tumor Radiation Absorbed Dose: The maximum absorbed dose of 177Lu-PSMA-617 treatment for the prostate (measured in Gray [Gy]) [Time frame: Screening, End of Neoadjuvant Treatment(12 weeks after baseline)]

Eligibility criteria

Inclusion criteria

• 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

Exclusion criteria

• 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

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

N/A

Model

Single group

Masking

Open label

Primary purpose

Treatment

Study locations

China · 1 center

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

Identifiers

NCT: NCT07677566 · 23232

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗