A Randomized Trial of Neoadjuvant Leuprorelin, Darolutamide or Both Prior to Radical Prostatectomy for Intermediate or High-risk Prostate Cancer
A Randomized Trial of Neoadjuvant Leuprorelin, Darolutamide or Both Prior to Radical Prostatectomy for Intermediate or High-risk Prostate Cancer. Prospective, randomized, parallel group, open-label with blinded endpoint adjudication multicenter clinical trial.To assess, among patients with unfavorable intermediate to high-risk prostate cancer, whether a neoadjuvant combined treatment with leuprorelin (Leuprorelin) and darolutamide is superior to monotherapy in terms of complete or almost complete pathological response.A total of 144 patients with unfavorable intermediate to high-risk prostate cancer scheduled for radical prostatectomy with extended pelvic lymph node dissection will be randomized 1:1:1 to oral darolutamide, SC leuprorelin (Leuprorelin) or both (48 patients per arm) for 24 weeks.
• Men ≥18 years of age;
• Histologically confirmed unfavorable intermediate or high/very high risk non metastatic (by conventional imaging) prostate adenocarcinoma intended for surgery without neuroendocrine differentiation or small cell features;
• Unfavorable intermediate-risk:
‣ ISUP grade 3, and/or \> 50% positive biopsy cores and/or at least two intermediate-risk factors. Intermediate-risk factors:
• Clinical tumor stage T2b or T2c (MRI based);
∙ ISUP grade 2 or 3;
∙ Prostate-specific antigen (PSA) level of 10-20 ng/mL.
• High-risk or very high-risk:
‣ ≥cT3a (MRI based) or ISUP 4-5 or PSA\>20 ng/mL;
⁃ cN1.
• ECOG 0-1;
• Baseline testosterone \> 230 ng/dL;
• No prior prostate cancer treatment;
• Sexually active male subjects must agree to use condoms as an effective barrier method and refrain from sperm donation, and/or their female partners of reproductive potential to use a method of effective birth control, during the treatment with darolutamide and for 1 week after the end of treatment with darolutamide to prevent pregnancy;
• Written informed consent.