153Sm-EDTMP With or Without a PSA/TRICOM Vaccine To Treat Men With Androgen-Insensitive Prostate Cancer

Background * There are no standard therapy options shown to prolong survival for patients with progressive disease on first-line docetaxel-based regimens for men with metastatic castration resistant prostate cancer (CRPC). * Ninety percent of men in this population have bone metastasis. * PSA/TRICOM vaccines as single agents can induce generation of PSA-specific T cells in the majority of patients and objective responses and PSA declines in a minority of patients. Furthermore, the generation of at least a 6-fold increase in PSA-specific T cells was significantly correlated with evidence of clinical benefit. * Radiation can alter the phenotype of tumor cells (increase Fas, increase major histocompatibility complex (MHC), increase tumor-associated molecules and increase ICAM), making them much more amenable to immune-mediated killing. * (153)Sm EDTMP is a beta emitter (with some gamma emissions) that targets osteoblastic bone lesions (such as those found in prostate cancer). * (153)Sm EDTMP, at Food And Drug Administration (FDA)-approved doses used clinically for palliation of prostate cancer, can cause phenotypic changes in tumor cells, leading to improved killing of those cells in a cytotoxic T-cell assay in vitro. * The combination of vaccine and radiation greatly increases antitumor efficacy in a murine subcutaneous tumor model. Objectives * Primary-A comparison of progression-free survival at 4 months between Arm A (153)Sm EDTMP alone) and Arm B (153Sm EDTMP with vaccine). * Secondary-Objective responses, PSA outcomes, immunologic responses, toxicity, palliation and overall survival. Eligibility * Patients with metastatic CRPC who have 2 or more bone lesions consistent with prostate cancer and who have been treated with a docetaxel-based regimen. * Patients with symptomatic soft tissue disease or parenchymal disease will be excluded. Design * Randomized phase 2.5 study. * Sixty-eight patients to be enrolled and randomized to: * Arm A: (153)Sm-EDTMP: 1 mCi/kg intravenous (IV) over one minute on day 8. (153)Sm-EDTMP will be repeated every 12 weeks if there is adequate hematologic recovery. Arm B: PROSTAC-V/TRICOM (vaccinia) 2 x 10\^8 plaque forming unit (pfu) subcutaneously on day 1. * (153)Sm-EDTMP: 1 mCi/kg IV over one minute on day 8. (153)Sm-EDTMP will be repeated every 12 weeks if there is adequate hematologic recovery. PROSTVAC-F/TRICOM (fowlpox) 1 x 10\^9 pfu subcutaneously on days 15, 29, and then every 4 weeks.