Radiometabolic Therapy (RMT) With 177Lu PSMA 617 in Advanced Castration Resistant Prostate Cancer (CRPC)

Radiometabolic Therapy (RMT) with 177Lu PSMA 617 in advanced castration resistant prostate cancer (CRPC): efficacy and toxicity evaluation. Single-center, prospective, non controlled, open label, phase II trial. The main objective of this study is to evaluate the Disease Control Rate (DCR) and the safety as co-primary objective.

The secondary objectives are: late toxicity, PFS, OS, biochemical response and dosimetry.

Inclusion criteria

• Male, Age > 18 years.
• Patients must have histologically or cytologically confirmation of advanced prostate cancer castration resistant defined according to PCWG3 criteria
• Measurable disease according to RECIST 1.1. criteria; also patients with bone lesions only could be enrolled
• Patients with documented disease will be admitted to therapeutic phase only if the diagnostic PET/CT 68Ga-PSMA images demonstrate a significant uptake (tumor to background ratio >2.5) at metastatic tumour site (or in the primary when present, or both)
• Patients with documented radiological progression (in soft tissue and / or bone) and / or biochemical progression (sequence of 3 PSA rising values from a screening PSA value ≥ 2 ng / ml) according to PCWG3 in pre-study period, refractory or unfit to conventional standard treatments (hormonal or chemotherapeutic treatment such as abiraterone, enzalutamide and docetaxel)
• Concomitant LHRH analogs assumption is allowed
• Life expectancy greater than 6 months.
• ECOG performance status <2
• Adequate haematological, liver and renal function: haemoglobin >= 9 g/dL, absolute neutrophil count (ANC) >= 1.5 x 109 /L, platelets >= 100 x 109 /L, bilirubin ≤1.5 X upper normal limit (UNL), alanine aminotransferase (ALT) and Aspartate aminotransferase (AST) <2.5 X UNL (< 5 X UNL in presence of liver metastases, creatinine < 2 mg/dL).
• Participant is willing and able to give informed consent for participation in the study
• Other known malignant neoplastic diseases in the patient's medical history with a disease-free interval of less than 3 years (except for previously treated basal cell carcinoma).

Exclusion criteria

• Patients treated with chemotherapy and 223Ra radiotherapy within 4 weeks and treated within 2 weeks with palliative radiotherapy.
• All acute toxic effects of any prior therapy (including surgery, radiation therapy, chemotherapy) must have resolved to a grade ≤ 1 according to National Cancer Institute Common Terminology Criteria for Adverse Events Version 4.03 (CTCAE)
• ECOG performance status >2
• Participation in another clinical trial with any investigational agents within 30 days prior to study screening.
• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
• Assessed bone marrow invasion > 50%