Patients may also be on concomitant drugs to prevent bone loss, including bisphosphonates and denosumab. Other supportive care with blood components, antibiotics, analgesics, general medical therapy, etc., will be delivered as required. Use caution when co-administering medication which may lower the seizure threshold. Consistent with the PREVAIL trial which demonstrated improved survival in mCRPC and led to FDA approval in the chemotherapy-naïve subgroup, palliative radiation will be allowed for patients on this study. They will be allowed to continue enzalutamide (with/without vaccine). There is no concern for overlapping toxicity.[36] 3.8.1 Excluded medications While patients on protocol treatment, all medications required for the health of the patient are allowed with the following exceptions: Concurrent chemotherapy Concurrent immunotherapy Concurrent anti-cancer radionuclides Concurrent systemic corticosteroid use (daily or every other day for continued use > 14 days) Concomitant use of secondary hormonal treatments 3.8.2 Treatment of vaccinia vaccination complication 3.8.2.1 Vaccinia Immune Globulin: First-line treatment of some of the complications of vaccinia caused by dissemination of vaccinia virus (severe cases of inadvertent inoculation involving extensive lesions or if comorbid conditions exist, severe cases of generalized vaccinia in patients that are systemically ill and whose condition might be toxic or who have serious underlying immunosuppressive illnesses, eczema vaccinatum, and progressive vaccinia) is with VIG. VIG is contraindicated, however, for the treatment of isolated vaccinial keratitis. VIG is a sterile solution of the immunoglobulin fraction of pooled plasma from individuals inoculated with vaccinia vaccine. VIG is an investigational agent available through the CDC’s Strategic National Pharmaceutical Stockpile under an IND protocol by contacting the CDC’s Smallpox Vaccine Adverse Events Clinician Information Line at 1-877-554-4625. Upon receipt of a call from a patient or upon direct observation of a patient or contact who manifests signs and symptoms of any of the above conditions, the investigator should place a call to the CDC as soon as possible: 32 Short Title: Enzalutamide Vaccine in mCRPC Version Date: 03/29/2022 1. To initiate review of the clinical case, 2.