Treatment of Castration Resistant Prostate Cancer Using Multi-Targeted Recombinant Ad5 PSA/MUC1/Brachyury Based Immunotherapy Vaccines

* INCLUSION CRITERIA: * Age more than or equal to 18 years (male). * Ability to understand and provide signed informed consent that fulfills Institutional Review Board (IRB)s guidelines. * Cytologically or histologically confirmed prostate cancer for which no curative standard approved therapy is available by either the Laboratory of Pathology at the National Institutes of Health (NIH) Clinical Center or Walter Reed National Military Medical Center at Bethesda prior to starting this study. If no pathologic specimen is available, patients may enroll with a pathologists report showing a histological diagnosis of prostate cancer and a clinical course consistent with the disease. * Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1. * Subjects who have received prior prostate specific antigen (PSA), mucin1 (MUC1), and/or brachyury-targeted immunotherapy (e.g. vaccine) are eligible for this trial if this treatment was discontinued at least 3 months prior to enrollment. * Resolution of all toxic side effects of prior chemotherapy, radiotherapy, or surgical procedures to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Grade less than or equal to1. * Adequate hematologic function at screening, as follows: * Absolute neutrophil count (ANC) greater than or equal to x 10 to the ninth power/L * Hemoglobin more than or equa to 9 g/dL * Platelets more than or equal to 75,000/microliter. * Prothrombin (PT)-international normalized ratio (INR) \< 1.5. * Partial thromboplastin time (PTT) \< 1.5 x upper limit of normal (ULN). * Adequate renal and hepatic function at screening, as follows: --Serum creatine less than or equal to 1.5x upper limit of normal (ULN) OR creatinine clearance (CrCl) more than or equal to 40mL/min (if using the Cockcroft-Gault formula below): 1. Female CrCl = \[(140 - age in years) x weight in kg x 0.85\] / \[72 x serum creatinine in mg/dL\] 2. Male CrCl = \[(140 - age in years) x weight in kg x1.00\] / \[72 x serum creatinine in mg/dL\] * Total bilirubin less than or equal to 1.5 x ULN OR in subjects with Gilberts syndrome, a total bilirubin less than or equal to x ULN * Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) less than or equal to 2.5 x ULN, unless liver metastasis are present, then values must be less than or equal to 5 x ULN) * The effects of ETBX-051, ETBX-061 and ETBX-071 vaccines on the developing human fetus are unknown. For this reason subjects must agree to use a condom and acceptable contraceptive method with their partner during the study and for one month after the last dose of vaccines. * Ability to attend required study visits and return for adequate follow up, as required by this protocol. * Castrate testosterone level (\<50ng/dl or 1.7nmol /L) * Metastatic disease documented by at least one of the following: * Metastatic bone disease on an imaging study, or * Soft tissue disease documented by computed tomography (CT)/magnetic resonance imaging (MRI) * Progressive disease at study entry defined as one or more of the following criteria occurring in the setting of castrate levels of testosterone: * Radiographic progression defined as any new or enlarging bone lesions or growing lymph node disease, consistent with prostate cancer OR * PSA progression defined by sequence of rising values separated by \>1 week (2 separate increasing values over a minimum of 2ng/ml (Prostrate Cancer Working Group 2 (PCWG2) PSA eligibility criteria). If patients had been on flutamide, PSA progression is documented 4 weeks or more after withdrawal. For patients on bicalutamide or nilutamide disease progression is documented 6 or more weeks after withdrawal. The requirement for a 4-6 week withdrawal period following discontinuation of flutamide, nilutamide or bicalutamide only applies to patients who have been on these drugs for at least the prior 6 months. For all other patients, they must stop bicalutamide, nilutamide or flutamide the day prior to enrollment. * Patients must agree to continue to continuation of androgen deprivation therapy (ADT) with a gonadotropin-releasing hormone analogue/antagonist or bilateral orchiectomy * Prior treatment with immunotherapy, hormonal therapy, radium 223, chemotherapy and/or other experimental therapy is allowed. EXCLUSION CRITERIA: * Treatment with an investigational drug study within 28 days of before starting on study treatment. * Subjects with concurrent cytotoxic chemotherapy or radiation therapy. There must be at least 28 days between any other prior chemotherapy (or radiotherapy) and study treatment. Prior antibody therapy must be discontinued 8 weeks prior to start of study treatment. Prior hormonal therapy can be discontinued 24 hours prior to start of study treatment. * Any prior PSA, MUC1, and/or brachyury-targeted immunotherapy (e.g., vaccine) must have been discontinued at least 12 weeks before initiation of study treatment. Subjects must have recovered from all acute toxicities from prior treatment prior to screening for this study. * Prior treatment with Adenovirus-Based vectors immunotherapy * Known active brain or central nervous system metastasis, or seizures requiring anticonvulsant treatment, cerebrovascular accident, or transient ischemic attack (\< 6 months prior to enrollment). * Subjects with a history of autoimmune disease (active or past), such as but not restricted to inflammatory bowel disease, systemic lupus erythematosus, ankylosing spondylitis, scleroderma, or multiple sclerosis. Autoimmune-related thyroid disease, type I diabetes and vitiligo are permitted if the condition is well controlled. * Subjects with serious intercurrent chronic or acute illness, such as cardiac or pulmonary disease, hepatic disease, or other illness considered by the Investigator as high risk for investigational drug treatment. * Subjects with a history of heart disease, such as congestive heart failure (class II, III, or IV defined by the New York Heart Association functional classification), history of unstable or poorly controlled angina, or history (\< 1 year prior to enrollment) of ventricular arrhythmia. * Subjects with a medical or psychological impediment that would impair the ability of the subject to receive therapy per protocol or impact ability to comply with the protocol or protocol-required visits and procedures. * Presence of a known active acute or chronic infection, including human immunodeficiency virus (HIV, as determined by enzyme-linked immunosorbent assay \[ELISA\] and confirmed by western blot) and hepatitis B and hepatitis C virus (HBV/HCV, as determined by Hepatitis B surface antigen (HBsAg) and hepatitis C serology). * Subjects on systemic intravenous or oral steroid therapy (or other immunosuppressive, such as azathioprine or cyclosporin A) are excluded on the basis of potential immune suppression. Subjects must have had at least 6 weeks of discontinuation of any steroid therapy (except that used as premedication for chemotherapy or contrast-enhanced studies) prior to enrollment. Physiologic (replacement) doses of steroids as well as nasal, topical or inhaled steroids are allowed. * Subjects with known allergy or hypersensitivity to any component of the investigational product will be excluded. * Subjects with acute or chronic skin disorders that will interfere with injection into the skin of the extremities or subsequent assessment of potential skin reactions will be excluded. * Subjects vaccinated with a live (attenuated) vaccine (e.g., FluMist) or a killed (inactivated)/subunit vaccine (e.g., PNEUMOVAX, Fluzone) within 28 days or 14 days, respectively, of the first planned dose of ETBX vaccine. * Patients with second malignancy within 3 years of enrollment; Patients curatively treated non-melanoma skin cancers or carcinoma in situ of the bladder, are not excluded. * Use of herbal products that may decrease PSA levels (e.g. saw palmetto) * Patients who have received radiation therapy, radionuclide therapy or undergone surgery within certain duration (4 weeks) of enrollment