Carboplatin and Cabazitaxel versus Lutetium-177-PSMA-617 for the Treatment of Metastatic Castration-Resistant Prostate Cancer, CATCH-177 Trial

Inclusion Criteria

• Subjects must have histologically or cytologically confirmed metastatic castrate-resistant prostate cancer that has previously been treated with an androgen receptor pathway inhibitor. Prior docetaxel exposure is recommended but not mandatory. Tissue is not mandatory, but a pathologic report is required at time of enrollment
• Patients must have a PSMA-positive 18^F-rhPSMA-7.3 performed within 12 weeks from cycle 1 day 1 (C1D1) with ≥ 1 site with standard uptake value maximum (SUVmax) ≥ 10 mCRPC with progression on prior novel hormonal agent to include at least one of the following: * PSMA SUVmean < 10 * ≥ 1 visceral metastasis * ≥ 5 bone metastases OR two of the following * TP53 * PTEN * RB1 mutation
• Age > 18 years
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2
• Absolute neutrophil count > 1000/uL * Note: Subjects must not have received any growth factors within 7 days or blood transfusions within 14 days prior to the hematologic laboratory values obtained at screening)
• Platelet count > 90,000/uL * Note: Subjects must not have received any growth factors within 7 days or blood transfusions within 14 days prior to the hematologic laboratory values obtained at screening)
• Hemoglobin > 8.5 g/dL * Note: Subjects must not have received any growth factors within 7 days or blood transfusions within 14 days prior to the hematologic laboratory values obtained at screening)
• Total bilirubin (TBIL) < 2.5 x the upper limit of normal (ULN) at screening, except subjects with documented Gilbert's syndrome who must have a TBIL < 3 mg/dL
• Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) < 5 ULN at screening
• Creatinine clearance ≥ 40 mL/min and/or estimated glomerular filtration rate (eGFR) ≥ 30
• Albumin > 30 g/L (3.0 g/dL) at screening
• Subjects receiving bisphosphonates or other approved bone-targeting therapy (e.g., denosumab) must be on a stable dose for at least 14 days before the start of study treatment
• Subjects of child-producing potential agree to use highly effective contraceptive methods (i.e., barrier contraception measures such as a male condom with spermicide during intercourse) and avoid sperm donation during the study treatment and for 3 months after the last dose of study treatment. A man is considered to be of child-producing potential, unless he has had a bilateral vasectomy with documented aspermia or a bilateral orchiectomy. Partners of patients must also practice approved forms of birth control
• Subjects must have the ability to understand and the willingness to sign a written informed consent form (ICF)
• Members of all races and ethnic groups are eligible for this trial

Exclusion Criteria

• Evidence of hormone-sensitive prostate cancer (HSPC)
• Evidence of small cell prostate cancer
• Subjects receiving any other investigational agents
• Diagnosis of another clinically significant malignancy within the previous 2 years other than curatively treated non-melanomatous skin cancer or superficial urothelial carcinoma and other in situ or noninvasive malignancies, as determined by the principal investigator (PI) or co-PI
• Subjects with brain metastases/central nervous system (CNS) disease that are treated prior to enrollment will be allowed in this clinical trial
• Known or suspected significant hypersensitivity to any components of the formulation used for cabazitaxel, carboplatin or 177Lu-PSMA-617
• 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 considered by the Investigator to limit compliance with study requirements
• Prior treatment toxicities not resolved to ≤ grade 2 according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0