Darolutamide with hormone therapy after prostate cancer surgery in high-risk patients

Trial details

Who runs it

Peking University First Hospital

Trial code

NCT07282197

Record updated

15 December 2025

Original description

The goal of this clinical trial is to evaluate whether adjuvant darolutamide plus androgen-deprivation therapy (ADT) can reduce post-operative recurrence and improve disease control in high-risk prostate cancer patients-defined by the Briganti 2019 nomogram-who have undergone radical prostatectomy (RP) without extended pelvic lymph node dissection (ePLND). The main questions it aims to answer are:Read full original descriptionShow less

Efficacy and Safety Evaluation of Darolutamide+ADT Adjuvant After Radical Prostatectomy (RP) Without ePLND, in High-risk Prostate Cancer Patients Based on Briganti 2019 Nomogram: A Phase II, Single-center, Single-arm, Prospective Study

The goal of this clinical trial is to evaluate whether adjuvant darolutamide plus androgen-deprivation therapy (ADT) can reduce post-operative recurrence and improve disease control in high-risk prostate cancer patients-defined by the Briganti 2019 nomogram-who have undergone radical prostatectomy (RP) without extended pelvic lymph node dissection (ePLND). The main questions it aims to answer are:

1. What proportion of participants remains biochemical-recurrence-free at 2 years, using NCCN criteria (PSA increase >0.1 ng/mL above post-treatment nadir confirmed by two tests ≥2 weeks apart)? 2. What proportion of participants is the 2-year radiographic progression-free survival (rPFS)?

Additional key outcomes include:

* PSA undetectable rates at 6, 12, and 24 months (PSA <0.01 ng/mL). * Safety and tolerability assessed by CTCAE v5.0. * Exploratory** patient-reported outcomes: urinary symptoms (IPSS) and quality of life (EQ-5D-3L).

Study type \& design: Phase II, single-center, single-arm, prospective interventional study. Enrollment occurs within 12 weeks after RP. ADT is delivered with a GnRH agonist (physician's choice); orchiectomy is excluded. Target sample size is approximately 40 participants; the statistical plan uses a one-sample log-rank framework. Primary and secondary endpoints are assessed over 2 years.

Participants will: Provide informed consent and undergo eligibility confirmation (high-risk per Briganti 2019; post-RP without ePLND; enrollment ≤12 weeks after surgery). Receive darolutamide + ADT according to protocol (GnRH agonist; no orchiectomy). Attend scheduled visits for PSA monitoring, safety labs, and adverse-event assessments (CTCAE v5.0). Undergo radiologic evaluations as per protocol to determine rPFS (RECIST 1.1/PCWG3). Complete IPSS and EQ-5D-3L questionnaires at specified time points to assess urinary symptoms and quality of life.

Primary endpoint: 2-year biochemical-recurrence-free rate. Key secondary endpoints: 2-year rPFS; PSA <0.01 ng/mL at 6/12/24 months; treatment-emergent adverse events.

Exploratory endpoints: IPSS and EQ-5D-3L changes over 2 years.

This trial aims to balance oncologic control with quality of life in a population for whom the therapeutic value of ePLND remains uncertain, by testing whether early adjuvant darolutamide + ADT after RP can meaningfully delay recurrence and progression while maintaining acceptable tolerability.

Inclusion: The patient volunteers to participate and signs the informed consent form (ICF); Age 18-75 years (inclusive), male; Histologically or cytologically confirmed prostatic adenocarcinoma; No non-regional lymph-node metastasis, bone metastasis, or other distant metastasis (e.g., visceral) by conventional imaging (bone scan, CT or MRI) or by PET/CT; i.e., M0; High-risk per the Briganti 2019 nomogram, i.e., risk >7%; PSA <0.1 ng/mL at 6 weeks after radical prostatectomy (RP); Has undergone RP without pelvic lymph-node dissection; Not suitable for adjuvant/salvage radiotherapy (RT) after RP, or the patient declines RT; Patients with lymph-node involvement (LNI) indicated by PSMA-PET who did not undergo extended pelvic lymph-node dissection (ePLND) may be enrolled; Patients with negative intraoperative obturator lymph-node biopsy who did not undergo ePLND may be enrolled; Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0-1; Adequate hematologic and organ function:; Absolute neutrophil count (ANC) ≥1.5 × 10⁹/L (1500/µL); Hemoglobin ≥90 g/L (9.0 g/dL); Platelet count ≥100 × 10⁹/L (100,000/µL) (without transfusion and/or growth factors within 3 months prior to starting study treatment); Serum potassium ≥3.5 mmol/L; Total bilirubin (TBIL) ≤2.0 × ULN (for Gilbert syndrome, TBIL >1.5 × ULN is not eligible; if indirect bilirubin ≤1.5 × ULN, enrollment is allowed); AST and ALT ≤2.5 × ULN; Serum albumin ≥30 g/L (3.0 g/dL); Serum creatinine <2 × ULN; Patients of childbearing potential must agree to use effective contraception throughout the study and for 3 months after the last dose.

Exclusion: Prior prostate cancer treatments including any of the following:; Systemic therapy, including but not limited to: >2 months of ADT; >2 months of conventional hormonal therapy (e.g., flutamide, bicalutamide); next-generation hormonal agents (e.g., darolutamide, abiraterone, apalutamide, enzalutamide, relugolix); chemotherapy (e.g., docetaxel); immunotherapy; targeted therapy; Local radiotherapy; Concurrent participation in, or planned participation in, another clinical trial; Any concomitant disease or condition that, in the investigator's judgment, presents a serious risk to patient safety, may confound study results, or may interfere with completion of the study (e.g., severe cardiovascular disease, active infection, gastrointestinal disease, neurologic or psychiatric disorders, etc.); A malignancy other than prostate cancer within the past 5 years or concurrently, except for cured basal cell carcinoma of the skin; Any other condition deemed by the investigator to make the patient unsuitable for this study; Histologic features of neuroendocrine differentiation or small-cell carcinoma; Planned bilateral orchiectomy during the study treatment period; Inability to tolerate darolutamide or ADT.

ClinicalTrials.gov NCT07282197