ENZALUTAMIDE for Metastatic castration-resistant prostate cancer

Inclusion criteria

• {"criterion_text":"- Willing and able to provide written informed consent\n- Male aged 18 years and above\n- Histologically or cytological confirmed adenocarcinoma of the prostate\n- Metastatic disease documented by positive bone scan or metastatic lesions other than liver or visceral metastasis on CT, MRI. If lymph node metastasis is the only evidence of metastasis, it must be ≥ 2 cm in diameter. Alternatively, metastatic disease can be diagnosed by PET-Choline or PSMA.\n- Prostate cancer progression documented by PSA according to PCWG2 or radiographic progression according to modified RECIST criteria\n- At least one negative prognostic features between: I. Mildly symptomatic prostate cancer defined as per BPI Question #3 (worst pain in last 24 hours) value 2 or 3 or II. Asymptomatic prostate cancer defined as per BPI Question #3 (worst pain in last 24 hours) value 0 or 1 and at least one between - PSA≥80 ng/dl ; - Gleason Score ≥ 8; - PSA doubling time ≤ 3 months; - Time from start ADT to CRPC less < 1 year\n- No evidence of mutation in BRCA1 or genes or tumor tissue not evaluated for quality reasons (status unknown)\n- Surgically or medically castrated, with testosterone levels of < 50 ng/dL (< 2.0 nM)\n- Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 2\n- Adequate bone marrow and chemistry values defined as: a. Hemoglobin ≥ 10.0 g/dL independent of transfusion b. Neutrophil count ≥1500 x 109/L c. Platelet count ≥100,000/μL d. Serum albumin ≥ 3.5 g/dL e. Serum creatinine < 1.5 x ULN or a calculated creatinine clearance ≥ 60 mL/min f. Serum potassium ≥ 3.5 mmol/L g. Liver function: - Serum bilirubin < 1.5 x ULN (except for patients with documented Gilbert’s disease); - AST or ALT < 2.5 x ULN\n- Able to swallow the study drug whole as a tablet\n- Life expectancy of at least 6 months\n- Patients who have partners of childbearing potential must be willing to use a method of birth control with adequate barrier protection as determined to be acceptable by the principal investigator and sponsor during the study and for 13 weeks after last study drug administration"}

Exclusion criteria

• {"criterion_text":"- Active infection or other medical condition that would make prednisone/prednisolone (corticosteroid) use contraindicated\n- Pathological finding consistent with small cell carcinoma of the prostate greater than 10%\n- Known brain metastasis\n- Use of major opiate analgesics for cancer-related pain (codeine and tramadol are allowed)\n- Previous cytotoxic chemotherapy, or biologic therapies for the treatment of castrationsensitive or castration-resistant prostate cancer (prior use of bicalutamide is permitted). Previous use of new generation androgen receptor inhibitors for castration-sensitive disease is permitted if at least one year has passed since their discontinuation or if treatment has lasted longer than 36 months without evidence of biochemical and radiological progression\n- Radiation therapy for treatment of the primary tumour within 6 weeks of Cycle 1, Day 1\n- Radiation or radionuclide therapy for treatment of metastatic CRPC and CSPC\n- Bicalutamide, nilutamide within 6 weeks of Cycle 1 Day 1\n- A marked baseline prolongation of QT/QTc interval (e.g., repeated demonstration of a QTc interval >450 ms) or history of additional risk factors for “torsaides de pointes” (e.g., heart failure, hypokalemia, family history of Long QT Syndrome) or the use of concomitant medications that prolong the QT/QTc interval (at least those of class IA and III).\n- Active or symptomatic viral hepatitis or chronic liver disease\n- Clinically significant heart disease as evidenced by myocardial infarction, or arterial thrombotic events in the past 6 months, severe or unstable angina, or New York Heart Association (NYHA) Class II-IV heart disease or cardiac ejection fraction measurement of < 50% at baseline\n- Uncontrolled Atrial Fibrillation, or other uncontrolled cardiac arrhythmia requiring therapy\n- Other malignancy with a previous diagnosis within 5 years (with the exclusions of NMIBC)\n- Concomitant medications as reported in section 7\n- Known hypersensitivity to docetaxel, abiraterone or enzalutamide active principles and any excipients\n- Uncontrolled hypertension (systolic BP ≥ 160 mmHg or diastolic BP ≥ 95 mmHg). Patients with a history of hypertension are allowed provided blood pressure is controlled by antihypertensive treatment"}

Primary endpoints

• {"endpoint_text":"- To compare the radiographic Progression-Free Survival (rPFS) rate at 9 months of chemotherapy (Arm A, docetaxel plus prednisone) versus androgen receptor targeted therapy (Arm B, enzalutamide or abiraterone acetate plus prednisone) in mCRPC BRCA negative or unknown patients with adverse prognostic factors","definition_or_measurement_approach":"Radiographic Progression-Free Survival (rPFS) rate measured at 9 months (radiographic progression-free survival assessed radiographically; endpoint specified as rPFS rate at 9 months)."}

Secondary endpoints

• {"endpoint_text":"- To compare efficacy of docetaxel plus prednisone to enzalutamide or abiraterone acetate plus prednisone for: - PSA response rate; - Median rPFS; - Overall survival\n- To compare the safety of each treatment amog docetaxel abiraterone end enzalutamide\n- To compare Health-Related Quality Of Life (HRQOL) according to FACT-P questionnaire and Health status/utility (EQ-5D-5L) test","definition_or_measurement_approach":"Efficacy: PSA response rate, median rPFS, overall survival as comparative measures; Safety: comparison of adverse events between arms; HRQOL: assessed by FACT-P questionnaire and EQ-5D-5L."}

Italy

Earliest CTIS Part Ii Submission Date

01-10-2024

Latest Decision Or Authorization Date

26-11-2024

Processing Time Days

56

Number Of Sites

21

Number Of Participants

68

Primary sponsor

Full Name

Fondazione Policlinico Universitario Agostino Gemelli IRCCS

Organisation Type

Hospital/Clinic/Other health care facility

Country Of Registered Address

Italy