Prostate Cancer
Conditions
Brief summary
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.
Interventions
Darolutamide 600 mg bid + ADT x 12 months
Sponsors
Peking University First Hospital
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
MALE
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
* 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 criteria
* Histologic features of neuroendocrine differentiation or small-cell carcinoma; * 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; * Planned bilateral orchiectomy during the study treatment period; * Inability to tolerate darolutamide or ADT; * Concurrent participation in, or planned participation in, another clinical trial; * A malignancy other than prostate cancer within the past 5 years or concurrently, except for cured basal cell carcinoma of the skin; * 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.); * Any other condition deemed by the investigator to make the patient unsuitable for this study.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of patients who remained biochemical recurrence free for 2 years | 2 years | biochemical recurrence defined as a PSA increase \>0.1 ng/ml above the post-treatment nadir (confirmed by two consecutive measures at least 2 weeks apart), according to NCCN criteria |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 2-year rate of radiological progression-free survival (rPFS) | 2 years | rPFS define as the first date of darolutamide+ ADT to the date of first documented radiological progression per RECIST 1.1 for soft tissue or per Prostate Cancer Working Group 3 (PCWG3) for bone lesions, the development of symptoms or complications attributable to cancer progression |
| 6-month/ 12-month/ 24-month PSA undetectable rate | 2 years | defined as the rate of patients with PSA \<0.01 ng/mL |
| TEAEs | 2 years | Measured by the number of participants with treatment-related adverse events as assessed by the Common Terminology Criteria for Adverse Events (CTCAE) v5.0 |
Other
| Measure | Time frame | Description |
|---|---|---|
| Changes in urinary symptoms | 2 years | International Prostate Symptom Score (IPSS) questionnaire |
| PRO | 2 years | EQ-5D-3L questionnaire |
Countries
China
Contacts
Primary ContactKan Gong
Outcome results
None listed