Studio di fase 2 su darolutamide rispetto alla terapia di deprivazione androgenica nel tumore della prostata ormonosensibile

Inclusion Criteria:

* Histologically confirmed prostate cancer (all stages) for whom continuous androgen-deprivation therapy (ADT) is indicated for a minimum period of 24 weeks
* Patient presenting with a maximum of 4 confirmed metastatic lesions, including bone, extra-pelvic lymph nodes, and pelvic lymph nodes > 2 cm on baseline Computed tomography(CT) or Magnetic resonance imaging (MRI) and/or Tc bone scintigraphy. Visceral metastases are excluded
* Asymptomatic for metastatic prostate cancer; urinary symptoms are allowed
* Baseline testosterone ≥ 8 nmol/L or 230 ng/dL
* Two subsequent PSA values ≥ 2 ng/ml, taken at minimum 2-week interval, with the second being equal to or higher than the first one
* WHO performance status (PS) of 0-1
* G8 score ≥ 14 for patients aged ≥ 70 years old
* A life expectancy of at least 12 months
* Able to swallow the study drug and comply with the study requirements
* Adequate bone marrow function (absolute neutrophil count (ANC) ≥ 1.5 10exp9/L; hemoglobin ≥ 10.0 g/dl, platelets ≥ 100 10exp9/L)
* Adequate renal function: creatinine clearance/eGFR within normal limits to baseline assessed as per local standard method
* Albumin > 25 g/L
* Adequate hepatic function:

Bilirubin: total bilirubin ≤ to 1.5 X upper limit of normal (ULN)

* Aspartate aminotransferase (AST) and/or Alanine aminotransferase(ALT) ≤ 2.5 X ULN
* Normal cardiac function according to local standard by 12-lead Electrocardiogram (ECG) (complete, standardized 12-lead recording)
* Before patient registration/randomization, written informed consent must be given according to International Conference on Harmonization on Good Clinical Practices (ICH/GCP), and national/local regulations.

Exclusion Criteria:

* any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule
* Previously or currently receiving hormonal therapy with intent to treat prostate cancer disease (surgical castration or other hormonal manipulation, e.g. GnRH agonists, GnRH antagonists, anti-androgens, oestrogens, 5α-reductase inhibitor). For patients that have received (neo)adjuvant ADT before radiotherapy, it should have been stopped for more than 1 year
* Prior use of investigational agents that block androgen synthesis or block androgen receptor
* Use of herbal products that may have hormonal anti-prostate cancer activity and/or are known to decrease PSA levels (e.g. saw palmetto)
* Has received systemic glucocorticoids within 24 weeks prior to enrollment or is expected to require systemic glucocorticoids during the study period
* Radiation therapy for treatment of the primary tumor within 3 months prior to enrollment
* Use of an investigational agent within 4 weeks prior to enrollment is not allowed. The maximum allowed duration may be extended to comply with national regulations in the participating countries.
* Gastrointestinal disorder affecting absorption (e.g. gastrectomy, active peptic ulcer disease within 3 months prior to enrollment)
* Known hypersensitivity to the study treatment or any of its ingredients (refer to Investigator's brochure).
* Severe or uncontrolled concurrent disease, infection or co-morbidity including active viral hepatitis, known human immunodeficiency virus infection with detectable viral load (Human immunodeficiency virus (HIV)) or chronic liver disease
* History of prior malignancy. Adequately treated basal cell or squamous cell carcinoma of skin or superficial bladder cancer that has not spread behind the connective tissue layer (i.e. pTis, pTa, and pT1) is allowed, as well as any other cancer for which chemotherapy has been completed ≤ 5 years ago and from which the patient has been disease-free.
* Clinically significant cardiovascular disease including:
* Myocardial infarction within six months prior to randomization
* Uncontrolled angina within 3 months prior to randomization
* Coronary/peripheral artery bypass within 6 months prior to randomization
* Stroke within 6 months prior to randomization
* Congestive heart failure New York Heart Association (NYHA) class 3 or 4, or subjects with history of congestive heart failure NYHA class 3 or 4 in the past, unless a screening echocardiogram or multi-gated acquisition scan (MUGA) performed within 3 months results in a left ventricular ejection fraction that is ≥ 45%
* History of clinically significant ventricular arrhythmias (e.g., ventricular tachycardia, ventricular fibrillation, torsades de pointes)
* History of Mobitz II second degree or third degree heart block without a permanent pacemaker in place
* Uncontrolled hypertension as indicated by a resting systolic blood pressure >170 mm Hg or diastolic blood pressure > 105 mm Hg at the screening visit