This is a phase II, multicenter, randomized open-label and comparative trial designed to study the effectiveness and the safety of androgen receptor antagonist (darolutamide) combined with surgery in patients with high-risk and/or locally advanced prostate cancer. In this trial, patients will be assigned in one of the two following treatments arms: * Arm A (control arm): Surgery alone (radical prostatectomy with lymph node dissection) * Arm B (experimental arm): Peri-operative darolutamide + surgery (radical prostatectomy with lymph node dissection) A total of 240 patients will have to be randomized with 120 patients in the control arm and 120 patients in the experimental arm.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
240
Radical prostatectomy with lymph node dissection will be performed.
Darolutamide: 600 mg (2 tablets of 300 mg) twice daily with food, equivalent to a total daily dose of 1200 mg; for a total duration of 9 months. Darolutamide will start at day 1. Surgery: radical prostatectomy with lymph node dissection will be performed after at least 3 months of darolutamide treatment.
Chu Angers
Angers, France
CHU Bordeaux
Bordeaux, France
Institut Bergonié
Bordeaux, France
Chu Henri Mondor
Créteil, France
CHU Grenoble
Grenoble, France
Hopital Claude Huriez
Lille, France
CHU Lyon - Hôpital Edouard Herriot
Lyon, France
Institut Paoli-Calmettes
Marseille, France
Hopital Paris Saint-Joseph
Paris, France
Hopital Europeen Georges-Pompidou
Paris, France
...and 9 more locations
The non-curable progression-free survival (NC-PFS) defined as the time from randomization to non-curable event.
Time frame: 5 years for each patient
Metastatic-Free Survival (MFS) defined as the time from randomization to the appearance of distant metastasis or death from any cause.
Time frame: 5 years for each patient
PSA-RFS (Recurrence-Free survival) defined as the time from randomization to PSA recurrence according to the European Association of Urology (EAU) criteria or death from any cause.
Time frame: 5 years for each patient
Overall Survival (OS) defined as the time from randomization to death from any cause.
Time frame: 5 years for each patient
pathological Complete Response (pCR) rate defined as the number of patients presenting a pathological complete response (i.e., absence of residual tumor found in the surgery specimens) divided by the number of patients in the experimental arm.
Time frame: 5 years for each patient
Safety assessed using the NCI-CTCAE Version 5.0.
Time frame: 3 years for each patient
Quality of life will evaluated using the Functional Assessment of Cancer Therapy-Prostate (FACT-P) questionnaire.
Subscale Domains: Physical Well-Being, Social/Family Well-Being, Emotional Well-Being, Functional Well-Being, Prostate Cancer Subscale. Responses to questions use a five-point Likert-type scale ranging from 0 ("not at all") to 4 ("very much so").
Time frame: 1 year for each patient
Quality of life will evaluated using the 5-level EuroQol 5-Dimensional (EQ5D-5L) questionnaire.
The descriptive system comprises five dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Each dimension has 5 levels: no problems, slight problems, moderate problems, severe problems and extreme problems.
Time frame: 1 year for each patient
Quality of life will evaluated using the International Prostate Symptom Score (IPSS) questionnaire.
The I-PSS is based on the answers to seven questions concerning urinary symptoms. Each question is assigned points from 0 (never) to 5 (almost always).
Time frame: 1 year for each patient
Quality of life will evaluated using the International Index of Erectile Function (IIEF-15) questionnaire.
The IIEF is a 15-item questionnaire containing five domains including erectile function, orgasmic function, sexual desire, intercourse satisfaction, and overall satisfaction. Each item is rated from 0 (or 1) (Severe ED/No sexual activity) to 5 (Mild/No ED).
Time frame: 1 year for each patient
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