This clinical trial is for men with progressive metastatic castration resistant prostate cancer. The purpose of this study is to find the highest dose level of the study drug, 225Ac-J591 that can be given without severe side effects. The research study is being done because the standard treatments for prostate cancer that has spread beyond the prostate gland are intended to minimize the adverse effects of the disease. These treatments, however, are not curative. Patients who choose to participate in this study will have a screening visit to determine whether or not they are eligible to participate in the study. The treatment phase is comprised of 8 weeks for the fractionated dose cohort and 8 weeks past last dose of 225Ac-J591 for the multiple dose regimen (for subjects receiving 4 cycles, 26 weeks is expected). Following treatment, short-term follow up is planned until radiographic progression, expected to be 6 months.The study medication is called 225Ac-J591, and will be administered as a single fractionated cycle day 1 and day 15 in the fractionated dose regimen and as a single dose per cycle repeated every 6 weeks in the multiple dose regimen. Upon completion of investigational treatment with 225Ac-J591, subjects will undergo 68Ga-PSMA-HBED-CC injection and same day PET/CT/ at the end of study visit to document treatment response. 68Ga-PSMA-HBED-CC is comprised of gallium-68, which is a PET emitting radionuclide linked to PSMA-HBED-CC (aka PSMA11), which is a small molecule targeting PSMA. 68Ga-PSMA-HBED-CC will be administered intravenously prior to PET/CT at screening and at follow up imaging x2. Subsequently survival data and additional treatment(s) information will be captured from their routine Standard of care (SOC) visits.During the other study visits, participants will undergo routine tests and procedures, such as physical examinations, and routine blood tests. Some blood tests will be done for research purposes only. After completion of therapy, participants may be contacted on a periodic basis to see how they are doing.~Key eligibility:~Open to men age 18 and older.~Diagnosis of progressive metastatic prostate cancer~Have been previously treated for their disease with particular types of therapy
The purpose of the initial (phase I) portion of this study is to find a dose level and administration schedule of the study drug, 225Ac-J591 that can be given without severe side effects.