Targeted Alpha Therapy With 225Actinium-PSMA-I&T of Castration-resISTant Prostate Cancer (TATCIST). (TATCIST)

This is an interventional treatment trial for Metastatic Castration Resistant Prostate Cancer Read More

Inclusion Criteria:

• Signing informed consent
• Adenocarcinoma of Prostate proven by histopathology
• Life expectancy of 6 months or more
• Unresectable metastases
• Progressive disease, with docetaxel/cabazitaxel or declined taxane therapy by the patient
• 177Lu-PSMA-617 naive or 177Lu-PSMA-617/177Lu-PSMA-I&T treated
• If BRCA mutations or microsatellite instability is present, patients should have received FDA approved therapies such as PARP inhibitors and pembrolizumab, and progressed
• Castration-resistant disease with confirmed testosterone level ≤50 ng/ml under prior androgen deprivation therapy (ADT)
• Positive 68Ga-PSMA-11 PET/CT for the majority of measurable diseases defined as SUV ≥2.0
• ECOG 0-2
• Hemoglobin concentration ≥ 9.0 g/dL
• Platelet counts ≥100 × 109/L
• White blood cell count ≥ 2.0 × 109/L), ANC>1.5 x109/L
• Glomerular Filtration Rate (GFR) ≥ 60 ml/min
• AST and ALT ≤ 5xULN
• Billirubin ≤ 3x ULN
• Albumin ≥ 25 g/L
• Serum/plasma creatinine ≤1.5 × ULN or creatinine clearance ≥50 mL/min based on Cockcroft-Gault formula
• Received at least one ARAT in the past
• Patients on anti-androgen therapy are allowed to continue their treatment at the discretion of their oncologists

Exclusion Criteria:

• Inclusion Criteria:
• Signing informed consent.
• Adenocarcinoma of Prostate proven by histopathology
• Life expectancy of 6 months or more.
• Unresectable metastases.
• Progressive disease, with docetaxel/cabazitaxel or declined taxane therapy by the patient.
• 177Lu-PSMA-617 naive or 177Lu-PSMA-617/177Lu-PSMA-I&T treated.
• If BRCA mutations or microsatellite instability is present, patients should have received FDA approved therapies such as PARP inhibitors and pembrolizumab, and progressed
• Castration resistant disease with confirmed testosterone level ≤50 ng/mlunder prior androgen deprivation therapy (ADT)
• Positive 68Ga-PSMA-11 PET/CT for the majority of measurable disease defined as SUV ≥2.0.
• ECOG 0-2
• Hemoglobin concentration ≥ 9.0 g/dL
• Platelet counts ≥100 × 109/L
• White blood cell count ≥ 2.0 × 109/L), ANC>1.5 x109/L
• Glomerular Filtration Rate (GFR) ≥ 60 ml/min
• AST and ALT ≤ 5xULN
• Billirubin ≤ 3x ULN
• Albumin ≥ 25 g/L.
• Serum/plasma creatinine ≤1.5 × ULN or creatinine clearance ≥50 mL/min based on Cockcroft-Gault formula
• Received at least one ARAT in the past.
• Patients on anti-androgen therapy are allowed to continue their treatment at the discretion of their oncologists.

Exclusion Criteria:

• Less than 6 weeks since last myelosuppressive therapy (including Docetaxel, Cabazitaxel, 223Ra, 153Sm, 177Lu-PSMA-617, 177Lu-PSMA-I&T) or other radionuclide therapy permitted (including 223Ra, 153Sm)
• Urinary tract obstruction as evidenced by Tc-99m DTPA renal scan with diuretics
• Abnormal renal function (eGFR <60 mL/min), baseline Hgb <9g/dL, ANC<1.5 x109/L, platelets <100 x109/L, and PT, INR or PTT ≥1.5xULN
• Persistent baseline dry eye or dry mouth from prior RLT
• Persistent prior AEs >Grade 1 from prior anti-cancer therapies
• Administration of an investigational agent ≤60 days or 5 half-lives, whichever is shorter, prior to randomization
• The known presence of central nervous system metastases
• Active malignancy other than low-grade non-muscle-invasive bladder cancer and non-melanoma skin cancer
• Concurrent illness that may jeopardize the patient's ability to undergo study procedures.
• Symptomatic cord compression, or clinical or radiologic findings indicative of impending cord compression
• Concurrent serious (as determined by the investigator) medical conditions, including, but not limited to, New York Heart Association class III or IV congestive heart failure
• Major surgery ≤30 days prior to randomization
• Planning to conceive pregnancy during the treatment and up to 6 months after the last treatment