Prostate Cancer
Conditions
Keywords
Prostate Cancer, Radical Prostatectomy, Darolutamide, Neoadjuvant
Brief summary
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.
Interventions
darolutamide 600 mg PO BID for 24 weeks
DRUGleuprorelin
leuprorelin depot 22.5 mg SC every 12 weeks
Sponsors
Brazilian Clinical Research Institute
Bayer
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Outcomes Assessor)
Eligibility
Sex/Gender
MALE
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* 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.
Exclusion criteria
* Unresectable prostate cancer; * Histology of small cell carcinoma prostate cancer or adenocarcinoma with neuroendocrine features; * Any prior prostate cancer treatment; * Any active infection requiring IV antibiotics; * Known additional malignancy that has a life-expectancy \< 2 years; * Had any of the following within 6 months before randomization: stroke, myocardial infarction, severe/unstable angina pectoris, coronary/peripheral artery bypass graft, heart failure with New York Heart Association Class Functional III or IV; * Uncontrolled severe hypertension as indicated by a resting systolic BP ≥ 180 mmHg or diastolic BP ≥ 110 mmHg despite medical management; * A gastrointestinal (GI) disorder or procedure which is expected to interfere significantly with absorption of darolutamide; * Inability to swallow oral medications; * Receipt of medications (e.g. finasteride, dutasteride) or agents that are likely to alter serum PSA levels within \<= 42 days or 5 half-lives prior to registration, whichever is shorter.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Proportion of patients with minimal residual disease | Patients are expected to undergo surgery after no more than 30 days after completion of the neoadjuvant regimen therapy, which will last for 24 weeks after randomization in all 3 groups. | Proportion of patients with minimal residual disease, defined as residual cancer burden (RCB) ≤ 0.25 cm3 (tumor volume ≤ 0.5 cm3 × tumor cellularity ≤ 50%) or complete pathological response, assessed by pathology of surgical specimen obtained from prostatectomy. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Complete biochemical response assessed by serum PSA with the rate of PSA<0,2 ng/dL | 24 weeks | — |
| Treatment emergent adverse events and serious adverse events. | 24 weeks | — |
| PSA levels at 3 months after prostatectomy. | in 42 weeks | — |
| Testosterone levels. | in 42 weeks | — |
| Number of positive lymph nodes. | 30 weeks | — |
| Number of positive surgical margins. | 30 weeks | — |
| Perioperative complications. | 42 weeks | — |
| Quality of life using IEEF5 and HRQoL questionnaires pre and post neoadjuvant treatment. | 42 weeks | — |
| Downstaging (changes in TNM - Classification of Malignant Tumours stage) based on surgical specimen. | 30 weeks | Prostate cancer TNM (Classification of Malignant Tumours) staging AJCC (American Joint Committee on Cancer) UICC (Union for International Cancer Control) 8th edition |
Countries
Brazil
Contacts
STUDY_CHAIRFernando C Maluf, MD
Brazilian Clinical Research Institute
Outcome results
None listed