Darolutamide+ADT Post-RP w/o ePLND in hrPC: Briganti 2019

Official title

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

Overview

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

• Drug Darolutamide (BAY 1841788)
  Darolutamide 600 mg bid + ADT x 12 months

Primary outcome measures

• Percentage of patients who remained biochemical recurrence free for 2 years [Time frame: 2 years]

Secondary outcome measures (3)

• 2-year rate of radiological progression-free survival (rPFS) [Time frame: 2 years]
• 6-month/ 12-month/ 24-month PSA undetectable rate [Time frame: 2 years]
• TEAEs [Time frame: 2 years]

Eligibility criteria

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.

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

• Peking University First Hospital — Beijing

Identifiers

NCT: NCT07282197 · 23096

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗