Patients must have castrate serum level of testosterone of < 50 ng/dL (< 1.73 nmol/L)Xx_NEWLINE_xXPathologically (histologically or cytologically) proven diagnosis of prostatic adenocarcinoma within 180 days of registration at moderate- to high-risk for recurrence as determined by one of the following combinations:             \r\n* Gleason score 7-10 + T1c-T2b (palpation) + prostate-specific antigen (PSA) < 50 ng/mL (includes intermediate- and high-risk patients)\r\n* Gleason score 6 + T2c-T4 (palpation) + PSA < 50 ng/mL OR Gleason score 6 + >= 50% (positive) biopsies + PSA < 50 ng/ml\r\n* Gleason score 6 + T1c-T2b (palpation) + PSA > 20 ng/mL\r\n* Patients previously diagnosed with low risk prostate cancer undergoing active surveillance who are re-biopsied and found to have unfavorable intermediate risk disease or favorable high risk disease according to the protocol criteria are eligible for enrollment within 180 days of the repeat biopsy procedureXx_NEWLINE_xXBaseline PSA nadir >= 0.2 ng/ml (post-operative value is never undetectable) obtained prior to step 1 registrationXx_NEWLINE_xXPost-prostatectomy patients with a detectable serum PSA (>= 0.1, but =< 1.0 ng/mL) at study entry (within 90 days of Step 1 registration) and at least one of the following:\r\n* Gleason score 7-10 (International Society of Urological Pathology [ISUP] grade group 2 to 5)\r\n* ISUP grade group:\r\n** Grade group 1?=?Gleason score?=<?6, \r\n** Grade group 2?=?Gleason score 3?+?4?=?7,\r\n** Grade group 3?=?Gleason score 4?+?3?=?7, \r\n** Grade group 4?=?Gleason score 8, \r\n** Grade group 5?=?Gleason scores 9 and 10\r\n* >= T3a disease\r\n* Persistent elevation of PSA after prostatectomy measured within 90 days after surgery (PSA never became undetectable) of > 0.04 but < 0.2 ng/mL (PSA nadir)Xx_NEWLINE_xXTestosterone > 50 ng/dL within 90 days prior to Step 1 registrationXx_NEWLINE_xXPreviously untreated localized adenocarcinoma of the prostate with the following clinical findings:\r\n* Clinical stage by digital rectal exam of either T1c or T2a/b (limited to one side of the gland); (American Joint Committee on Cancer [AJCC], version 7) or cT1a-c or 2a or 2b, stage group IIA or IIB (AJCC, version 8); both versions 7 and 8 staging should be recorded\r\n* Patients in active surveillance who elect to be treated are eligible if they meet protocol requirements\r\n* Stages T1a-T1b are eligible if patient underwent transurethral prostatic resection (TURP) previously Gleason score must be Gleason 7(3+4) with a PSA < 20 ng/mL, or Gleason 6(3+3) with a PSA > 10 ng/mL and < 20 ng/mL; (AJCC, version 7) or group grade 1 or 2, stage Group IIA or IIB (AJCC version 8)\r\n** If patient is receiving a 5-alpha reductase inhibitor at the time of enrollment the baseline PSA value will be assumed to be double the initial value and the medication should be discontinued but does not need to have a washout period to participate, to remain eligible a PSA drawn while still on the medicine must be:\r\n*** < 10 ng/mL to remain eligible if Gleason 7(3+4) \r\n**** Stratification level 1 if PSA < 5 ng/mL and level 2 if less than 10 ng/mL\r\n*** > 5 ng/mL and less than 10 ng/mL for Gleason 6(3+3) \r\n**** Stratification level 3\r\n* Percent of submitted positive core biopsies must be < 50% of all sextants\r\n** NOTE: all cores from a targeted lesion will be counted as an N of 1 core for calculating percent positive cores in total\r\n* The prostate volume must be < 60 cc as reported at time of biopsy or by separate measure with ultrasound or other imaging modalities including magnetic resonance imaging (MRI) or computed tomography (CT) scanXx_NEWLINE_xXDocumented progressive metastatic (m)CRPC based on at least one of the following criteria:\r\n* PSA progression defined as 25% increase over baseline value with an increase in the absolute value of at least 2 ng/mL that is confirmed by another PSA level with a minimum of a 1 week interval and a minimum PSA of 2 ng/mL\r\n* Soft-tissue progression defined as an increase >= 20% in the sum of the longest diameter (LD) of all target lesions based on the smallest sum LD since treatment started or the appearance of one or more new lesions\r\n* Progression of bone disease (evaluable disease) or (new bone lesion[s]) by bone scanXx_NEWLINE_xXHave testosterone < 50 ng/dL; patients must continue primary androgen deprivation with an luteinizing hormone-releasing hormone (LHRH) analogue (agonist or antagonist) if they have not undergone orchiectomyXx_NEWLINE_xXRecurrent prostate cancer following primary therapy as defined by:\r\n* Post-radical prostatectomy: Any PSA >= 0.4 ng/ml\r\n* Post-primary radiotherapy: PSA >= 2 ng/ml above a post-radiotherapy nadir\r\n* Post-primary androgen-deprivation therapy: A confirmed rise of PSA >= 2 ng/ml above a post-therapy nadirXx_NEWLINE_xXFor patients with non-castrate levels of circulating androgen levels (testosterone >= 50 g/dl)\r\n* PSA levels should be increasing on at least two occasions >= 1 week apart\r\n* Patients should not be considered candidates for radiation therapyXx_NEWLINE_xXFor patients with castrate levels of circulating androgen levels (testosterone < 50 ng/dl):\r\n* PSA levels must be >= 0.4 ng/ml (if history of radical prostatectomy) or >= 2 ng/ml (if history of non-surgical primary treatment) and found to be increasing on at least two occasions >= 1 week apart\r\n* At least 4 weeks must have elapsed since any changes to hormonal therapy, including at least 4 weeks since flutamide and at least 6 weeks since bicalutamide, nilutamide, or enzalutamideXx_NEWLINE_xXEvidence of castrate testosterone level < 50 ng/dL (or surgical castration)Xx_NEWLINE_xXPSA at screening must be ?2 µg/L.Xx_NEWLINE_xXSerum testosterone concentration ?50 ng/dL sustained by medical or surgical castration Parts A,B or D (TNBC)Xx_NEWLINE_xXSerum testosterone concentration ?50 ng/dL sustained by medical or surgical castration.Xx_NEWLINE_xXLast PSA value should have increase of ? 25% of the first PSA value and an absolute increase of ?2 ng/mL over the first PSA valueXx_NEWLINE_xXFor the diagnosis of pure germinoma, HCGbeta (serum and CSF) must be =< 100 mIU/ml, serum AFP must be =< 10 IU/l (ng/ml) and =< institutional norm and initial CSF AFP =< 2 IU/l (ng/ml) and =< institutional norm with histologically proven diagnosis of germinoma at diagnosis or subsequent relapseXx_NEWLINE_xXFor histologically unconfirmed MMGCT, serum and/or CSF tumor markers of HCGbeta > 100 mIU/ml or any elevation of above AFP > 10 IU/L (ng/ml) and/or above institutional norm in the serum and CSF AFP >= 2 IU/L (ng/ml) and/or institutional normXx_NEWLINE_xXSerum testosterone <50 ng/dLXx_NEWLINE_xXSerum testosterone level < 50 ng/mLXx_NEWLINE_xXCuratively treated cervical intraepithelial neoplasia or prostate carcinoma with current prostate specific antigen < 0.01 ng/mL; orXx_NEWLINE_xXSerum testosterone < 50 ng/dL; patients must continue primary androgen deprivation with a luteinizing-releasing hormone (LHRH) analogue (agonist or antagonist) if they have not undergone orchiectomyXx_NEWLINE_xXPatients must have histologically documented adenocarcinoma of the prostate with progressive systemic (clinically metastatic disease documented on bone, CT, or magnetic resonance imaging (MRI) scan) disease despite castrate levels of testosterone (<50 ng/dL) due to orchiectomy or luteinizing hormone-releasing hormone (LHRH) agonist. Castrate levels of testosterone must be maintained.Xx_NEWLINE_xXProstate- specific antigen (PSA) Progression: An elevated PSA ?2 ng/ml that has risen serially on at least two occasions, each at least one week apart (PSA1 < PSA2 < PSA3). If the 3rd PSA value is less than the 2nd PSA value, than an additional test for rising PSA is required to document progression. (For the purposes of the nomogram calculator, the last PSA value recorded prior to initiation of the intervention will be considered the baseline PSA)Xx_NEWLINE_xXPSA ? 2 ng/mlXx_NEWLINE_xXSerum testosterone ? 50 ng/dLXx_NEWLINE_xXSurgically or medically castrated. The testosterone levels do not need to be checked if the patient has undergone surgical castration for >4 months. Patients receiving chemical castration should have testosterone levels checked at baseline and confirmed to be in the castrate levels (<0.5 ng/mL or 1.735 nM). In all cases the luteinizing hormone-releasing hormone (LHRH) antagonist/agonist is to be continued in these patients.Xx_NEWLINE_xXCastrate testosterone levels (< 50 ng/dL) achieved by orchiectomy or maintenance on a luteinizing hormone-releasing hormone (LHRH) agonist or antagonistXx_NEWLINE_xXProgressive metastatic prostate cancer despite castrate levels of testosterone (< 50 ng/dL)Xx_NEWLINE_xXProgressive disease during (or within 4 weeks of completion) with abiraterone, enzalutamide, and/or androgen receptor antagonist ARN-509 (ARN-509) based on any one of the following:\r\n* For patients with measurable disease, progression by the Response Evaluation Criteria in Solid Tumors (RECIST)\r\n* PSA evidence for progressive prostate cancer consists of a PSA level of at least 2 ng/ml which has risen on at least 2 successive occasions, at least one week apart; if the confirmatory PSA value is less than the screening PSA value, then an additional test for rising PSA will be required to document progression for the purposes of eligibility\r\n* Radionuclide bone scan: at least two new foci consistent with metastatic lesionsXx_NEWLINE_xXTestosterone < 50 ng/dL; patients must continue primary androgen deprivation with an gonadotrophin releasing hormone (LHRH) analogue if they have not undergone orchiectomyXx_NEWLINE_xXSurgically or medically castrated, with testosterone ? 50 ng/dL (? 1.7 nmol/L).Xx_NEWLINE_xXProgressive prostate cancer by either serum PSA levels, soft tissue or bone disease as defined by the PCWG2 criteria.Xx_NEWLINE_xXPSA relapse within 4 years of prostatectomy defined by persistently detectable or rising PSA after surgeryXx_NEWLINE_xXEvidence of disease recurrence or progression as evidenced by a PSA > 0.20; this requires 2 consecutive rises in PSA, at least 1 week apart, over the post-prostatectomy nadir or one PSA value above 0.20 ng/mL if the patient failed to achieve a post-prostatectomy nadir of < 0.2 ng/mLXx_NEWLINE_xXPSA > 4.0 ng/mLXx_NEWLINE_xXTestosterone level =< 100 ng/dLXx_NEWLINE_xXConfirmation of detectable PSA after radical prostatectomy, OR presence of extracapsular extension, seminal vesicle invasion or positive surgical margin if postoperative PSA is undetectable (adjuvant RT)Xx_NEWLINE_xXBaseline (pre-treatment) serum troponin T (TnT) >= 0.03 ng/mL; Troponin T levels may be rechecked and therapy given if levels decrease to < 0.03 ng/mLXx_NEWLINE_xXInclusion Criteria include:\n\n          -  Localized prostate cancer meeting the NCCN criteria of Intermediate Risk or patients\n             having only one NCCN high-risk feature\n\n               -  NCCN Intermediate Risk is defined as having at least one of the following: PSA\n                  10-20 ng/ml, Gleason score =7, T2b-T2c\n\n               -  High Risk with a single high risk feature is defined as having only one of the\n                  following: PSA>20 ng/ml, Gleason score 8-10, or T3a\n\n               -  Excluded are those in the following risk groups: Low risk; High risk with more\n                  than 1 high risk factor; Locally advanced/very high risk=T3b-T4; Metastatic: N1\n                  or M1\n\n          -  Planning to undergo standard prostate-only external beam radiation therapy\n\n          -  ECOG Performance Status 0-2\n\n        Exclusion Criteria include:\n\n          -  Liver disease, including known cirrhosis or active hepatitis\n\n          -  Patients on systemic corticosteroids (>10mg prednisone per day) or other\n             immunosuppressive drugs\n\n          -  Known HIV+ patients\n\n          -  Regional lymph node involvement or distant metastases\n\n          -  Patients planning to receive whole pelvic irradiation\n\n          -  Prior treatment for prostate cancer, except TURP or ADT. For ADT, it may only be given\n             for a maximum of 6 months\n\n          -  Patients who had or plan to have orchiectomy as the form of hormonal ablation\n\n          -  Known sensitivity or allergic reactions to acyclovir or valacyclovirXx_NEWLINE_xXPSA values < 10 ng/ml within 90 days prior to randomization. Either done prior to biopsy or at least 21 days after prostate biopsy.Xx_NEWLINE_xXBiochemical progression (rising PSA) after medical or surgical castrationXx_NEWLINE_xXRising PSA as defined above and either:Xx_NEWLINE_xXAbsolute PSA > 20 ng/mL AND/ORXx_NEWLINE_xXPSA doubling time < 8 monthsXx_NEWLINE_xXSerum testosterone < 50 ng/mlXx_NEWLINE_xXcastrate serum level of testosterone of ? 50 ng/dL (? 1.73 mmol/L)Xx_NEWLINE_xXCastration-resistant prostate cancer requires the following criteria:\r\n* A castrate level of testosterone (< 50 ng/dL)\r\n* Prostate cancer progression on or since last treatment as documented by PSA rise or bone progression according to Prostate Cancer Working Group 2 (PCWG2) or soft tissue radiographic progression according to Response Evaluation Criteria in Solid Tumors (RECIST) criteria version 1.1\r\n* If on anti-androgen, will need to show no PSA decline after at least a 6 week withdrawal period from the last dose of bicalutamide or nilutamide or 4 weeks from last flutamide dose\r\n* Will require a 2 week washout period from last dose of ketoconazole, abiraterone acetate or radiationXx_NEWLINE_xXEvidence of rising PSA, on 2 separate occasions, at least one week apart; baseline PSA must be >= 0.2 ng/mL at the time of screening; radiographic evidence of disease is not allowedXx_NEWLINE_xXPatients must have sufficient PSA time points prior to enrollment (a minimum of 3 PSA levels within a six month period) to calculate a baseline PSA doubling timeXx_NEWLINE_xXPatients must not be on active luteinizing hormone-releasing hormone (LHRH) agonist/antagonist therapy and must have testosterone level > 50 ng/dLXx_NEWLINE_xXVery fast PSA doubling time of less than 4 weeks, if the absolute PSA is > 2 ng/mL or an absolute PSA value of greater than or equal to 20 ng/mlXx_NEWLINE_xXDocumented progressive metastatic CRPC based on at least one of the following criteria: \r\n* PSA progression defined as 25% increase over baseline value with an increase in the absolute value of at least 2 ng/mL that is confirmed by another PSA level with a minimum of a 1 week interval and a minimum PSA of 2 ng/mL\r\n* Soft-tissue progression defined as an increase >= 20% in the sum of the longest diameter (LD) of all target lesions based on the smallest sum LD since treatment started or the appearance of one or more new lesions or the appearance of new lesions\r\n* Documented appearance of new lesions by bone scanXx_NEWLINE_xXTestosterone =< 50 ng/dL; subjects must continue primary androgen deprivation with an luteinizing hormone-releasing hormone (LHRH) analogue (agonist or antagonist) if they have not undergone orchiectomyXx_NEWLINE_xXNon-castrate testosterone level, > 50 ng/dl, at study enrollmentXx_NEWLINE_xXSubject must not have had more than 24 months of hormonal therapy in combination with prostatectomy or radiation in the setting of localized disease and must not have shown any evidence of disease recurrence within 12 months after stopping hormonal therapy; disease recurrence after hormonal therapy is defined as PSA > 0.2 ng/dl after prostatectomy + hormonal therapy or PSA that is 2.0 ng/dl more than the PSA nadir after radiotherapy + hormonal therapy; previous hormonal therapy to the prostate must have stopped at least 12 months prior to enrollmentXx_NEWLINE_xXBiochemically recurrent prostate cancer with PSA doubling time ? 9 months at the time of study entry. Calculation of PSA doubling time should include the use of all available PSA values obtained within past 12 months prior to randomization, with a minimum of 3 values separated by at least 2 weeks apart. PSA values obtained prior to localized therapy will be excluded. PSA doubling time to be estimated using Memorial Sloan Kettering Cancer Center online calculator (https://www.mskcc.org/nomograms/prostate/psa-doubling-time)Xx_NEWLINE_xXScreening PSA > 0.5 ng/mLXx_NEWLINE_xXScreening serum testosterone > 150 ng/dLXx_NEWLINE_xXDocumented castrate level of serum testosterone (< 50 ng/dl)Xx_NEWLINE_xXMust have had disease progression while on abiraterone acetate alone or abiraterone acetate in combination with other investigational agents based on: \r\n* PSA progression defined as an increase in PSA, as determined by 2 separate measurements taken at least 1 week apart and/or\r\n* Radiographic disease progression, based on RECIST 1.1 in patients with measurable soft tissue lesions or PCWG2 for patients with bone diseaseXx_NEWLINE_xXScreening PSA must be >= 1.0 ng/mLXx_NEWLINE_xXProstate specific antigen (PSA) < 20, within 6 months of study entry\r\n* Participants who are currently receiving dutasteride (or have received it within the last 90 days) or finasteride (or have received it within the last 30 days) must have a PSA of =< 10Xx_NEWLINE_xXOngoing androgen deprivation with gonadotropin-releasing hormone (GnRH) analog or bilateral orchiectomy, with serum testosterone <= 50 ng/dL (<= 1.7 nmol/L) within 28 days before randomizationXx_NEWLINE_xXBe surgically or medically castrated, with serum testosterone levels of ? 50 ng/dL (1.73 nM)Xx_NEWLINE_xXSubjects must be receiving antiandrogen therapy (ADT) with a GnRH agonist or antagonist, with or without an anti-androgen, with a current testosterone level documented to be < 50 ng/dL at enrollment; subjects whose ADT is interrupted may enroll or continue on study as long as the testosterone is documented to remain < 50 ng/dL for the entire duration of study participation; subjects who have undergone orchiectomy are also eligibleXx_NEWLINE_xXTestosterone level < 50 ng/dLXx_NEWLINE_xXPSA doubling time of < 6 months, measured over the 3 months prior to enrollmentXx_NEWLINE_xXClinical stage T1-2 N0 M0, Gleason score =< 7, PSA 20-100 ng/mL, or clinical stage any T N0 M0, Gleason score 8 -10, PSA =< 100 ng/mL, or clinical stage T3-4 N0 M0, any Gleason score, PSA =< 100 ng/mL, or clinical stage T1-2 N0 M0, Gleason score 4 + 3, PSA 10-20 ng/mLXx_NEWLINE_xXPSA < 15 ng/ml or PSA density < 0.15 ng/ml2 in patients with a PSA > 15 ng/mlXx_NEWLINE_xXPatient may have had prior neoadjuvant and/or adjuvant therapy (chemotherapy, vaccines or experimental agents) within 4 weeks prior to randomization, if the PSA rise and PSADT were documented after the testosterone level was > 150 ng/dLXx_NEWLINE_xXPatient must have hormone-sensitive prostate cancer as evident by a serum total testosterone level > 150 ng/dL within 12 weeks prior to randomizationXx_NEWLINE_xXPSA must be < 30 ng/mL at study entryXx_NEWLINE_xXPatient must have evidence of biochemical failure after primary therapy and subsequent progression; biochemical failure is declared when the PSA reaches a threshold value after primary treatment and it differs for radical prostatectomy or radiation therapy\r\n* For radical prostatectomy the threshold for this study is PSA >= 0.2 ng/mL\r\n* For radiation therapy the threshold is a PSA rise of 2 ng/mL above the nadir PSA achieved post radiation with or without hormone therapy (2006 Radiation Therapy Oncology Group [RTOG]-American Society for Radiation Oncology [ASTRO] Consensus definition)\r\n* PSA progression requires a PSA rise above the threshold measured at any time point since the threshold was reachedXx_NEWLINE_xXPSA doubling time between 3 and 9 months; PSA calculation requires at least two consecutive PSA rises (PSA2 and PSA3) above the threshold PSA (at least 3 PSA values); PSA2 and PSA3 must be obtained within 12 months of study entry; all baseline PSAs should be obtained at the same reference laboratory (lab); patient's PSA doubling time must be calculatedXx_NEWLINE_xXCastrate-resistant prostate cancer, in the setting of castrate levels of testosterone (=< 50 ng/dL), defined as current or historical evidence of disease progression concomitant with surgical castration or androgen deprivation therapy (ADT), as demonstrated by two consecutive rises in prostate-specific androgen (PSA) OR new lesions on bone scan:\r\n* PSA progression will be defined as 2 rising PSA values compared to a reference value, measured at least 7 days apart and the second value is >= 2 ng/mL; it must be documented within 2 months of screening\r\n* Appearance of one or more new areas of abnormal uptake on bone scan when compared to imaging studies acquired during castration therapy or against the pre-castration studies if there was no response; increased uptake of pre-existing lesions on bone scan does not constitute progression; it must be documented within 4 months of screeningXx_NEWLINE_xXSerum PSA >= 2.0 ng/mLXx_NEWLINE_xXPSA doubling time (PSADT) >= 3 months and =< 15 months:\r\n* Patients must have >= 3 PSA measurements over >= 3 months\r\n* The interval between PSA measurements must be >= 4 weeksXx_NEWLINE_xXFor patients following radical prostatectomy: 2 absolute PSA values > 0.2 ng/mlXx_NEWLINE_xXNon-castrate level of testosterone: >= 50 ng/dL (prior androgen deprivation therapy [ADT] allowed; must be >= 6 months since last dose of ADT)Xx_NEWLINE_xXSerum testosterone level < 50 ng/dL at screeningXx_NEWLINE_xXProgressive disease by PSA or imaging in the setting of medical or surgical castration; disease progression for study entry is defined as one or more of the following three criteria:\r\n* PSA evidence for progressive prostate cancer which consists of a PSA level of at least 2 ng/ml which has risen on at least 2 successive occasions, at least 1 week apart; if the confirmatory PSA value is less than the screening value, then an additional PSA value greater than #2 will be required to document progression of >= 1 week\r\n** PSA values to be obtained >= 1 week apart\r\n* Soft tissue disease progression defined by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1\r\n* Bone disease progression defined by two or more new lesions on bone scanXx_NEWLINE_xXHistory of progressive disease after androgen deprivation, defined by one OR both of the following:\r\n* Objective radiographic progression defined by Prostate Cancer Clinical Trials Working Group 2 (PCWG2) or Response Evaluation Criteria in Solid Tumors (RECIST) criteria\r\n* Prostate-specific antigen (PSA) evidence for progressive prostate cancer which consists of a PSA level of at least 2 ng/ml, which has risen on at least 2 successive occasions, at least 1 week apart; if the confirmatory PSA value is not greater than the screening PSA value, then an additional test for rising PSA will be required to document progressionXx_NEWLINE_xXIf no prior orchiectomy has been performed, patients must remain on luteinizing hormone-releasing hormone (LHRH) agonist or antagonist (e.g. degarelix) therapy; patients who are receiving an antiandrogen as part of primary androgen ablation must demonstrate disease progression following discontinuation of the antiandrogen, defined as two consecutive rising PSA values, obtained at least two weeks apart, or documented osseous or soft tissue progression; at least one of the PSA values must be obtained at least four weeks (flutamide) or six weeks (bicalutamide or nilutamide) after discontinuationXx_NEWLINE_xXPSA >= 2 ng/mLXx_NEWLINE_xXTestosterone =< 50 ng/dLXx_NEWLINE_xXSerum PSA =< 10.0 ng/mlXx_NEWLINE_xXPSA values < = 20 ng/ml within 90 days prior to randomization. Obtained prior to biopsy or at least 21 days after prostate biopsy.Xx_NEWLINE_xXDocumented progressive metastatic castrate resistant prostate cancer (mCRPC) based on at least one of the following criteria:\r\n* PSA progression defined as 25% increase over baseline value with an increase in the absolute value of at least 1.0 ng/mL that is confirmed by another PSA level with a minimum of a 1 week interval and a minimum PSA of 1.0 ng/mL\r\n* Soft-tissue progression defined as an increase >= 20% in the sum of the longest diameter (LD) of all target lesions based on the smallest sum LD since treatment started or the appearance of one or more new lesions\r\n* Progression of bone disease (evaluable disease) or two or more new bone lesions by bone scanXx_NEWLINE_xXSerum testosterone < 50 ng/dL. Subjects must continue primary androgen deprivation with an LHRH analogue (agonist or antagonist) if they have not undergone orchiectomyXx_NEWLINE_xXPSA values < 2 ng/ml within 90 days prior to enrollment. Obtained at least 6 weeks after surgeryXx_NEWLINE_xXPatients must have progressive metastatic castration-resistant prostate cancer (mCRPC). There must be radiographic evidence of disease progression or biochemically (rising PSA levels on successive measurements) recurring disease despite adequate testosterone suppression.Xx_NEWLINE_xXProgression must be evidenced and documented by any of the following parameters:\r\n* PSA progression defined by a minimum of two rising PSA levels with an interval of >= 1 week between each determination\r\n* Appearance of one or more new lesions consistent with prostate cancer on bone scan\r\n* New or growing lesions on computed tomography (CT) scanXx_NEWLINE_xXPatients must have castrate levels of testosterone (< 50 ng/dL [1.74 nmol/L]).Xx_NEWLINE_xXConcurrent use of gonadotrophin releasing hormone (GnRH) analogue (i.e. medical castration) with testosterone at screening < 50 ng/dLXx_NEWLINE_xXRadiological confirmation of metastatic disease, or \r\n* Progressive disease at study entry defined as one or more of the following criteria occurring in the setting of castrate levels of testosterone: \r\n** Radiographic progression defined as any new or enlarging bone lesions or growing lymph node disease, consistent with prostate cancer OR \r\n** Prostate specific antigen (PSA) progression defined by sequence of rising values separated by > 1 week (2 separate increasing values over a minimum of 1 ng/ml [prostate cancer working group 3 (PCWG3) 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 enrollmentXx_NEWLINE_xXCastrate testosterone level (< 50ng/dl or 1.7nmol /L)Xx_NEWLINE_xXProgressive disease at study entry defined as one or more of the following criteria occurring in the setting of castrate levels of testosterone:\r\n* Radiographic progression defined as any new or enlarging bone lesions or growing lymph node disease, consistent with prostate cancer\r\n* PSA progression defined by sequence of rising values separated by > 1 week (2 separate increasing values over a minimum of 2ng/ml (Prostate 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 enrollmentXx_NEWLINE_xXPatient must have evidence of castrate resistant prostate cancer as evidenced by a confirmed rising PSA (per PCWG3 criteria) and a castrate serum testosterone level (i.e. =< 50 mg/dL)Xx_NEWLINE_xXTreatment failure of either abiraterone and/or enzalutamide as evidenced by a confirmed rising PSA (per PCWG3 criteria) and a castrate serum testosterone level (i.e. =< 50 mg/dL) while receiving treatment with either abiraterone and/or enzalutamideXx_NEWLINE_xXPrior surgical or chemical castration with serum testosterone <1.7 nmol/L (50 ng/dL). If the method of castration is use of a luteinizing hormone releasing hormone (LHRH) analogue,there must be a plan to maintain effective LHRH analogue treatment for the duration of the trialXx_NEWLINE_xXProgressive disease by PSA or imaging after most recent prior therapy. PSA ?1 ng/mL, if a confirmed rise in PSA is the only indication of progression. Progression by PSA requires rising PSA over a previous reference value by at least 2 measurements obtained ? 1 week apart.Xx_NEWLINE_xXSerum testosterone of 150 ng/dL or greater (if initial T is < 150 it can be repeated [recommended before 10 AM] and if > 150 patient will be considered eligible). If patient was on testosterone supplementation, testosterone measurements need to be obtained > 4 weeks off supplementsXx_NEWLINE_xXMust be considered either low-risk (T1-T2a, Gleason =< 6, prostate specific antigen [PSA] < 10 ng/mL) or favorable intermediate-risk (Gleason 3 + 4 = 7, percentage of positive biopsy cores < 50%, no more than one National Comprehensive Cancer Network [NCCN] intermediate risk factor)Xx_NEWLINE_xXHistologically confirmed prostate adenocarcinoma without significant small- cell/neuroendocrine or other variant histologies, with rising PSA and/or radiographic progression in the setting of castration-level testosterone (< 50 ng/dL) indicating mCRPC. Patients must have either undergone surgical castration or continue on GnRH agonist/antagonist on the appropriate schedule throughout the study period.Xx_NEWLINE_xXTwo rising PSA values separated by at least 1 week, one showing a rise of at least 0.5 ng/mL and one confirmatory value not showing a decline, while on abiraterone therapy.Xx_NEWLINE_xXA minimum of 10 core biopsies must be obtained at baseline. A prostate biopsy within 6 months from screening is allowed for entry requirements. Patients must meet intermediate risk criteria from Gleason score, T stage, and prostate specific antigen (PSA) value by National Comprehensive Cancer Network (NCCN) criteria: cT2b-T2c or Gleason 7 (3+4 or 4+3) or PSA 10-20 ng/mL. In addition, the Gleason 3+4 or 4+3 must be presentXx_NEWLINE_xXSerum testosterone > 200 ng/mLXx_NEWLINE_xXIndications for post-prostatectomy radiation exist:\r\n* Disease progression (detectable PSA on two measurements obtained at least one month apart) or\r\n* Indications for adjuvant radiation exist (if undetectable PSA): pathologic T3, T4, N+ disease or positive margins (within 1 year of prostatectomy)Xx_NEWLINE_xXPatients must have histologically confirmed progressive, metastatic castration resistant prostate adenocarcinoma by meeting ALL the following:\r\n* Pathology of prostate gland or metastatic disease must confirm the diagnosis of prostate adenocarcinoma; mixed histology with other variants including but not limited to small cell or neuroendocrine differentiation must be discussed with the study principal investigator (PI) \r\n* Metastasis must be documented by radiographic evidence\r\n* Castration resistance must be documented with surgical or medical castration with serum testosterone < 50 ng/d (< 2.0 nM); if the patient is being treated with luteinizing hormone-releasing hormone (LHRH) agonists (patient who has not undergone orchiectomy), this therapy must have been initiated at least 4 weeks prior to cycle 1, day 1 and must be continued throughout the study\r\n* Progression must be evidenced and documented by any of the following parameters\r\n** Two consecutively rising PSA values, above the baseline, at a minimum of 1-week intervals; the minimal value to enter the study is 1.0 ng/ml or greater; the reference value (#1) is the last PSA measured before increases are documented, with subsequent values obtained a minimum of 1 week apart; if the PSA at time point 3 (value #3A) is greater than that at point 2, then eligibility has been met; if the PSA is not greater than point 2 (value #3B), but value #4 is, the patient is eligible assuming that other criteria are met, if values 3A or #4 are 1 ng/mL or higher (Prostate Cancer Working Group 3)\r\n** Appearance of one or more new lesions on bone scan\r\n** Progressive disease by RECIST 1.1Xx_NEWLINE_xXDoes not have castration resistant disease\r\n* Castration resistance defined as progression of disease despite serum testosterone level of < 50 ng/dLXx_NEWLINE_xXPSA >= 0.2 prior to start of androgen deprivation treatmentXx_NEWLINE_xXSerum testosterone level =< 50 ng/dL at the screening visitXx_NEWLINE_xXProgressive disease defined as one or more of the following three criteria (NOTE: Patients who received an antiandrogen must demonstrate disease progression following discontinuation of antiandrogen): \r\n* PSA progression defined by a minimum of two rising PSA levels with an interval of >= 1 weeks between each determination. The PSA value at the screening visit should be >= 2 ng/mL \r\n* Soft tissue disease progression as defined by the Response Evaluation Criteria in Solid Tumors (RECIST) \r\n* Bone disease progression defined by two or more new lesions on bone scanXx_NEWLINE_xXHigh risk prostate cancer defined as extracapsular extension (cT3a) or seminal vesicle involvement (cT3b) or invasion of adjacent structures (cT4), serum PSA > 20 ng/mL or Gleason score of 8 to 10 and/or regional lymph node orXx_NEWLINE_xXHas a serum vitamin D level of ? 50 ng/mLXx_NEWLINE_xXAndrogen independent prostatic adenocarcinoma; subjects must have current or historical evidence of disease progression concomitant with surgical or medical castration, as demonstrated by PSA progression OR progression of measurable disease OR progression of non-measurable disease as defined below:\r\n* PSA: two consecutive PSA values, at least 14 days apart, each >= 5.0 ng/mL and >= 50% above the minimum PSA observed during castration therapy or above the pre-treatment value if there was no response\r\n* Measurable disease: at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study); in addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm; the change will be measured against the best response to castration therapy or against the pre-castration measurements if there was no response\r\n* Non-measurable disease: soft tissue disease: the appearance of 1 or more new lesions, and/or unequivocal worsening of non-measurable disease when compared to imaging studies acquired during castration therapy or against the pre-castration studies if there was no response\r\n* Bone disease: appearance of 2 or more new areas of abnormal uptake on bone scan when compared to imaging studies acquired during castration therapy or against the pre-castration studies if there was no response; increased uptake of pre-existing lesions on bone scan does not constitute progression\r\n* Serum PSA >= 5.0 ng/mL\r\n* Castration levels of testosterone (< 50 ng/dL) achieved via medical or surgical castration; surgical castration must have occurred at least 3 months prior to registration; subjects who are not surgically castrate must be receiving medical castration therapy, have initiated such therapy at least 3 months prior to registration, and continue such therapy until the time of confirmed objective disease progressionXx_NEWLINE_xXCastrate testosterone level (< 50ng/dl or 1.7nmol /L)Xx_NEWLINE_xXProgressive disease at study entry defined as one or more of the following criteria occurring in the setting of castrate levels of testosterone:\r\n* Radiographic progression defined as any new or enlarging bone lesions or growing lymph node disease, consistent with prostate cancer OR\r\n* PSA progression defined by sequence of rising values separated by > 1 week (2 separate increasing values over a minimum of 2ng/ml [Prostate 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 withdrawalXx_NEWLINE_xXBiochemical progression defined as follows:\r\n* For patients following definitive radiation therapy: a rise in PSA of >= 2 ng/mL above the nadir (per Radiation Therapy Oncology Group [RTOG]- American Society for Radiation Oncology [ASTRO] consensus criteria)\r\n* For patients following radical prostatectomy: rising PSA after surgical procedure (patients must have a PSA >= 0.8 ng/mL)Xx_NEWLINE_xXPatients must have a rising PSA as confirmed by 3 values a minimum of 1 week apart over at least a 1 month period of timeXx_NEWLINE_xXPatients must have a PSA doubling time of 5-15 monthsXx_NEWLINE_xXBaseline testosterone >= 100 ng/dlXx_NEWLINE_xXPSA =< 30 ng/mLXx_NEWLINE_xXSerum PSA ?10 ng/mL.Xx_NEWLINE_xXPSA relapse within 4 years of prostatectomy defined by persistently detectable or rising PSA after surgeryXx_NEWLINE_xXEvidence of disease recurrence or progression as evidenced by a PSA > 0.20 ng/ml; this requires 2 consecutive rises in PSA, at least 1 week apart, over the post-prostatectomy nadir or one PSA value above 0.20 ng/mL if the patient failed to achieve a post-prostatectomy nadir of < 0.2 ng/mLXx_NEWLINE_xXPSA ? 4.0 ng/mLXx_NEWLINE_xXTestosterone level ? 100 ng/dLXx_NEWLINE_xXAsymptomatic or symptomatic hormone naive men with testosterone levels >= 100 ng/dL with previously treated localized prostate cancer who now have rising PSA’s and five or fewer bone metastasesXx_NEWLINE_xXMen with baseline serum testosterone < 100 ng/dLXx_NEWLINE_xXSerum testosterone > 150 ng/dL. For patients treated up to 1 month of LHRH agonist, a testosterone measurement prior to the LHRH treatment will be used to determine eligibility, and must have been > 150 ng/dL. If no testosterone level is available from before LHRHa injection up to 30 days prior to study entry, the patient will be ineligible.Xx_NEWLINE_xXPatients must meet at least one of the following AVPC criteria: \r\n* Histologically proven small cell (neuroendocrine) prostate carcinoma.\r\n* Exclusive visceral metastases. \r\n* Predominantly lytic bone metastases identified by plain x-ray or CT scan. \r\n* Bulky (>= 5 cm in longest dimension) lymphadenopathy or high-grade tumor mass in prostate/pelvis. \r\n* Low PSA (=< 10 ng/mL) at initial presentation (prior to androgen ablation or at symptomatic progression in the castrate-setting) plus high volume (>= 20) bone metastases. \r\n* Elevated serum lactate dehydrogenase (>=2 x upper limit of normal) or elevated serum carcinoembryonic antigen (>= 2 x upper limit of normal) in the absence of other etiologies. \r\n* Short interval (=< 180 days) to castrate-resistant progression following initiation of hormonal therapy. \r\n* Known loss or mutation (by Clinical Laboratory Improvement Act [CLIIA] certified molecular testing, immunohistochemistry staining method [IHC] and/or DNA sequencing) in at least 2 of the following: Tp53, RB1 and PTEN.Xx_NEWLINE_xXPatients must have documented evidence of progressive disease as defined by any of the following: \r\n* PSA progression: minimum of 2 rising values (3 measurements) obtained a minimum of 7 days apart with the last result being at least >= 1.0 ng/mL.\r\n* New or increasing non-bone disease (RECIST).\r\n* Positive bone scan with 2 or more new lesions (Prostate Cancer Working Group 2 [PCWG2]).Xx_NEWLINE_xXSurgically or ongoing medically castrated, with baseline testosterone levels of =< 50 ng/dL =< 2.0 nM).Xx_NEWLINE_xXPSA >= 4 ng/mlXx_NEWLINE_xXPSA failure after definitive radiation as defined by the Phoenix criteria (PSA elevation at least 2 ng/dL above post-radiotherapy nadir)Xx_NEWLINE_xXPSA >= 20 ng/dLXx_NEWLINE_xXMetastatic castration resistant prostate cancer with castrate-level testosterone (< 50 ng/dL)\r\n* Subjects must maintain a castrate-level testosterone during the studyXx_NEWLINE_xXDisease progression defined by one or more of the following three criteria:\r\n* PSA > 2.0 ng/mL and rising PSA by at least 2 consecutive measurements a minimum of 1-week apart\r\n* Soft tissue progression as defined by RECIST v1.1 criteria\r\n* Bone disease progression as defined by Prostate Cancer Working Group 3 (PCWG3)Xx_NEWLINE_xXTumor progression while on hormone therapy with castrate levels serum testosterone (=< 1.7 nmol/L or 50 ng/dL) defined by prostate-specific antigen (PSA) and/or radiographic criteria according to the Prostate Cancer Working Group 3 (PCWG3). Castrate levels of testosterone must be maintained by surgical or medical means throughout the conduct of the study.Xx_NEWLINE_xXDocumented progressive metastatic castration resistant prostate cancer (CRPC) based on at least one of the following criteria:\r\n* PSA progression defined as 25% increase over baseline value with an increase in the absolute value of at least 2.0 ng/mL that is confirmed by another PSA level with a minimum of a 1 week interval and a minimum PSA of 2.0 ng/mL; Note: if confirmed rise is the only indication of progression, a minimal starting value of 1.0 ng/mL is acceptable, unless pure small-cell carcinoma\r\n* Soft-tissue progression based on new lesions or growth of existing soft tissue metastases\r\n* Progression of bone disease (evaluable disease) or (new bone lesion[s]) by bone scanXx_NEWLINE_xXCastrate levels of serum total testosterone (=< 50 ng/dl) OR ongoing documented androgen deprivation therapy (ADT) unless pure small cell prostate cancer is presentXx_NEWLINE_xXEugonadal state (serum testosterone > 150 ng/dL).Xx_NEWLINE_xXSerum testosterone ? 1.73 nmol/L (50 ng/dL) at screening.Xx_NEWLINE_xXA minimum of 3 rising PSA values with an interval of at least 1 week between determinations. The screening central laboratory PSA value must be ? 2 ?g/L (2 ng/mL) if qualifying solely by PSA progression.Xx_NEWLINE_xXProstate-specific antigen (PSA) progression: minimum of 2 rising values (3 measurements) obtained a minimum of 7 days apart with the last result being at least >/= 1.0 ng/mL;Xx_NEWLINE_xXHas a serum testosterone at the Screening visit of ? 150 ng/dL (5.2 nmol/L);Xx_NEWLINE_xXHas a serum PSA concentration at the Screening visit of > 2.0 ng/mL (2.0 ?g/L), or, when applicable, post radical prostatectomy of > 0.2 ng/mL (0.2 ?g/L) or post radiotherapy, cryotherapy, or high frequency ultrasound > 2.0 ng/mL (2.0 ?g/L) above the post interventional nadir;Xx_NEWLINE_xXCreatinine =< 1.4 ng/mL for females; =< 1.5 ng/mL for males; patients with creatinine =< 2.0 ng/mL may still be eligible if in the opinion of the investigator, the benefits of treatment outweigh the risksXx_NEWLINE_xXAbsolute PSA >=1 ng/ml; prior undetectable PSA post-prostatectomy is not requiredXx_NEWLINE_xXSerum testosterone >= 150 ng/dlXx_NEWLINE_xXCastration resistant disease with confirmed testosterone level ?50 ng/ml under prior androgen deprivation therapy (ADT)Xx_NEWLINE_xXSubjects must be castration resistant with evidence of progressive prostate cancer despite castrate levels of testosterone (=< 50 ng/dL) according to the PCWG3 criteriaXx_NEWLINE_xXSubjects must have progressive disease at study entry defined as 1 or more of the following 3 criteria that occurred while the subject was on androgen deprivation therapy:\r\n* PSA progression defined by a minimum of two rising PSA levels with an interval of >= 1 week between each determination; subjects who received an anti-androgen as part of their primary hormonal therapy must demonstrate progression after withdrawal; the PSA value at screening should be >= 2 ug/L (2 ng/mL)\r\n* Soft tissue disease progression defined by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1\r\n* Bone disease progression defined by PCWG3 with two or more new lesions on bone scan\r\n* Note: for subjects enrolling on the basis of soft tissue or bone progression, the baseline scan must show progression relative to a comparison scan performed during prior therapy; if the comparison scan is not available, the baseline scan report must reference the previous scan to document progressionXx_NEWLINE_xXPSA progression defined by a minimum of two rising PSA levels with an interval of >= 1 week between each determination; patients who received an anti-androgen must have progression documented by a minimum of two rising PSA levels with an interval of >= 1 week between each determination such that at least the second of these rises is > 4 weeks since last flutamide or > 6 weeks since last bicalutamide or nilutamide; the PSA value at the screening should be > 2 ug/L (2 ng/mL)Xx_NEWLINE_xXDocumented progressive mCRPC based on at least one of the following criteria:\r\n* PSA progression defined as 25% increase over baseline value with an increase in the absolute value of at least 2.0 ng/mL that is confirmed by another PSA level with a minimum of a 1 week interval and a minimum PSA of 2.0 ng/mL\r\n* Progression of bidimensionally measurable soft tissue or nodal metastasis assessed within 42 days prior to registration by a computed tomography (CT) scan or magnetic resonance imaging (MRI)\r\n* Progression of bone disease (evaluable disease) (new bone lesion[s]) by bone scanXx_NEWLINE_xXSerum testosterone < 50 ng/dL; patients must continue primary anti-androgen therapy (ADT) with a luteinizing hormone-releasing hormone (LHRH) analogue (agonist or antagonist) if they have not undergone orchiectomyXx_NEWLINE_xXPSA > 2 ng/mL at baseline or prior to initiation of hormonal therapyXx_NEWLINE_xXBaseline testosterone > 150 ng/dL if patient has not initiated hormonal therapy; for those patients who have already initiated hormonal therapy, baseline testosterone is not requiredXx_NEWLINE_xXTreated with continuous androgen ablative therapy (either surgical castration or gonadotrophin releasing hormone [LHRH] agonist/antagonist) with documented castrate level of serum testosterone (< 50 ng/dl)Xx_NEWLINE_xXScreening PSA must be >= 1.0 ng/mLXx_NEWLINE_xXOngoing androgen deprivation therapy (ADT) using an luteinizing hormone-releasing hormone (LHRH) agonist (e.g. leuprolide, goserelin) or antagonist (e.g. degarelix) must continue on therapy unless prior bilateral orchiectomy has been performed; OR screening serum testosterone must be =< 50 ng/dlXx_NEWLINE_xXEvidence of disease progression on ADT as evidenced by one of the following:\r\n* 2 consecutive PSA levels 50% or greater above the PSA nadir achieved on ADT and separated at least 1 week apart, OR\r\n* Computed tomography (CT) or magnetic resonance imaging (MRI) based evidence of disease progression (soft tissue, nodal or visceral disease progression) according to Prostate Cancer Working Group 3 (PCWG3) criteria or Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1) criteria, or at least 1 new bone scan lesion as compared to the most immediate prior radiologic studies, OR\r\n* Absolute rise in PSA of 2.0 ng/mL or greater, minimum 2 consecutive rising PSA levels with an interval of >= 1 week between each PSA levelXx_NEWLINE_xXBaseline serum ferritin level >= 300 ng/mLXx_NEWLINE_xXPatients must have CaP deemed to be castration-resistant by one or more of the following criteria (despite androgen deprivation when applicable):\r\n* Progression of unidimensionally measurable disease assessed within 42 days prior to initial administration of drug\r\n* Progression of evaluable but not measurable disease assessed within 42 days prior to initial administration of drug for PSA evaluation and for imaging studies (e.g, bone scans)\r\n* Rising PSA, defined as at least two consecutive rises in PSA to be documented over a reference value (measure 1); the first rising PSA (measure 2) should be taken at least 7 days after the reference value; a third confirmatory PSA measure (2nd beyond the reference level) should be greater than the second measure, and it must be obtained at least 7 days after the 2nd measure; if this is not the case, a fourth PSA measurement is required to be taken and be greater than the second measureXx_NEWLINE_xXPatients must have been surgically or medically castrated; if the method of castration was luteinizing hormone-releasing hormone (LHRH) agonists (leuprolide or goserelin) or antagonists (degarelix), then the patient must be willing to continue the use of LHRH agonists or antagonists; serum testosterone must be at castration levels (< 50 ng/dL) within 3 months prior to registrationXx_NEWLINE_xXCastrate testosterone level (< 50 ng/dl or 1.7 nmol/L)Xx_NEWLINE_xXProgressive disease at study entry defined as one or more of the following criteria occurring in the setting of castrate levels of testosterone\r\ni. Radiographic progression defined as any new or enlarging bone lesions or growing lymph node disease, consistent with prostate cancer OR\r\nii. PSA progression defined by sequence of rising values separated by > 1 week (2 separate increasing values over a minimum of 2 ng/ml [Prostate Cancer Working Group (PCWG)2 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 withdrawalXx_NEWLINE_xXSerum testosterone >= 150 ng/dLXx_NEWLINE_xXCastration resistant disease defined as evidence of radiological and/or prostate specific antigen (PSA) progression despite castrate levels of testosterone (serum testosterone < 50 ng/dL [1.7 nmol/L]); for PSA progression, there must be at least 2 sequential rises at a minimum of 1-week intervals; the first PSA value must be >= 4 (Prostate Cancer Working Group 2 [PCWG2] criteria)Xx_NEWLINE_xXOngoing androgen deprivation therapy with a luteinizing hormone-releasing hormone (LHRH) \super-agonist\ or antagonist, or bilateral orchiectomy and serum testosterone level < 50 ng/dL (< 0.5 ng/mL, < 1.7 nmol/L) at screening.Xx_NEWLINE_xXSubjects with a rising PSA value > 2 ng/mL in at least 2 measurements, at least 1 week apart. If the confirmatory PSA value is less than the screening PSA value, then an additional test for the rising PSA is required to document progression.Xx_NEWLINE_xXPatients must have CaP deemed to be castration-resistant by one or more of the following criteria (despite androgen deprivation when applicable):\r\n* Progression of unidimensionally measurable disease assessed within 42 days prior to initial administration of drug\r\n* Progression of evaluable but not measurable disease assessed within 42 days prior to initial administration of drug for PSA evaluation and for imaging studies (e.g, bone scans)\r\n* Rising PSA, defined as at least two consecutive rises in PSA to be documented over a reference value (measure 1); the first rising PSA (measure 2) should be taken at least 7 days after the reference value; a third confirmatory PSA measure (second [2nd] beyond the reference level) should be greater than the second measure, and it must be obtained at least 7 days after the 2nd measure; if this is not the case, a fourth PSA measurement is required to be taken and be greater than the second measureXx_NEWLINE_xXPatients must have been surgically or medically castrated; if the method of castration was luteinizing hormone-releasing hormone (LHRH) agonists (leuprolide or goserelin) or antagonists (degarelix), then the patient must be willing to continue the use of LHRH agonists or antagonists; serum testosterone must be at castration levels (< 50 ng/dL) within 3 months prior to registrationXx_NEWLINE_xXmCRPC EXPANSION COHORT: Patients must have castrate levels of testosterone (< 50 ng/dl [1.74 nmol/l])Xx_NEWLINE_xXSerum ferritin < 50 ng/mLXx_NEWLINE_xXFavorable risk prostate cancer as defined by:\r\n* Very low-risk:\r\n** Clinical stage T1c disease\r\n** PSA density (PSAD) < 0.15 ng/mL\r\n** Gleason score 6\r\n** =< 2 core biopsies with =< 50% involvement of any biopsy core with cancer, or unilateral disease =< 2 core biopsies with any percentage involvement OR\r\n* Low risk:\r\n** Clinical stage =< T2a\r\n** PSA < 10 ng/mL\r\n** Gleason score 6 OR\r\n* Low-intermediate risk:\r\n** Clinical stage T1c\r\n** PSA < 10 ng/ml\r\n** Gleason 3+4 present in =< 50% of one core/site as detected by systematic biopsy or MRI/transrectal ultrasound (TRUS) fusion guided biopsy\r\n** Gleason 6 disease in all other cores (maximum of 2 cores with =< 50% involvement of any core, or if unilateral disease, any percentage involvement)Xx_NEWLINE_xXSerum testosterone >= 150 ng/dLXx_NEWLINE_xXPatients must have documented evidence of progressive disease as defined by any of the following: \r\n* Prostate-specific antigen (PSA) progression: minimum of 2 rising values (3 measurements) obtained a minimum of 7 days apart with the last result being at least >= 1.0 ng/mL; \r\n* New or increasing non-bone disease (Response Evaluation Criteria in Solid Tumors [RECIST] 1.1); \r\n* Positive bone scan with 2 or more new lesions (Prostate Cancer Clinical Trials Working Group [PCWG]3)Xx_NEWLINE_xXSurgically or ongoing medically castrated, with baseline testosterone levels of =< 50 ng/dL (=< 2.0 nM)Xx_NEWLINE_xXEvidence of rising PSA on ADTXx_NEWLINE_xXMen with a diagnosis of very low risk (< 5% risk of disease relapse after primary treatment, criteria; cT1c, Gleason =< 6, prostate-specific antigen (PSA) < 10 ng/mL, fewer than 3 positive biopsy cores =< 50% cancer in any core, PSA density < 0.15 ng/mL/g); low risk (10% risk of disease relapse after primary treatment, criteria; cT1-2a, Gleason =< 6, PSA < 10 ng/mL) prostate cancerXx_NEWLINE_xXBaseline serum vitamin D total 25-hydroxy level below 66 ng/mlXx_NEWLINE_xXPatients with vitamin D total 25-hydroxy level above 66 ng/ml at baseline testingXx_NEWLINE_xXKnown castration?resistant disease, defined according to Prostate Cancer Working Group 2 (PCWG2) criteria as:\r\n* Castrate serum testosterone level: =< 50 ng/dL (=< 1.7 nmol/L)\r\n* Subjects who have failed initial hormonal therapy, either by orchiectomy or by using a gonadotropin-releasing hormone (GnRH) agonist in combination with an anti?androgen, must first progress through antiandrogen withdrawal prior to being eligible; the minimum timeframe to document failure of anti?androgen withdrawal will be four weeks\r\n* Serum PSA progression defined as two consecutive increases in PSA over a previous reference value within 6 months of first study treatment, each measurement at least one week apart; serum PSA at screening >= 2 ng/mL OR\r\n** Documented bone lesions by the appearance of two or more new lesions by bone scintigraphy OR\r\n** Bidimensionally?measureable soft tissue metastatic lesion assessed by computed tomography (CT) or magnetic resonance imaging (MRI)Xx_NEWLINE_xXCastration resistant prostate cancer as defined by rising PSA when serum testosterone < 50 ng/ml (note: current testosterone results are not required if the potential subject has not missed any GnRH analogue/antagonist doses since their last result was received) AND one of the following:\r\n* PSA level of at least 2 ng/ml that has risen on at least 2 successive occasions at least 1 week apart\r\n* Evaluable disease progression by modified RECIST (Response Evaluation Criteria in Solid Tumors)\r\n* Progression of metastatic bone disease on bone scan with > 2 new lesionsXx_NEWLINE_xXProstate specific antigen (PSA) =< 80 ng/ml, obtained within 3 monthsXx_NEWLINE_xXPatients belonging in the National Comprehensive Cancer Network (NCCN) high recurrence risk group:\r\n* High risk:\r\n** Clinical stage T3a, or Gleason score = 8-10, or PSA > 20 ng/mLXx_NEWLINE_xXPatient has a PSA of greater than 80 ng/ml obtained no greater than 3 months prior to randomizationXx_NEWLINE_xXOngoing androgen deprivation with serum testosterone < 50 ng/dlXx_NEWLINE_xXCastration resistant prostate cancer as defined by serum testosterone < 50 ng/ml and at least one of the following:\r\n* PSA level of at least 2 ng/ml that has risen on at least 2 successive occasions at least 1 week apart\r\n* Evaluable disease progression by modified RECIST 1.1\r\n* Progression of metastatic bone disease on bone scan with > 2 new lesionsXx_NEWLINE_xXSerum PSA <20 ng/mlXx_NEWLINE_xXPSA >= 0.1 after radical prostatectomy (value w/in 3 months of registration) AND at least 1 unfavorable risk factor listed below\r\n* Gleason 8-10\r\n* PSA > 0.5\r\n* Pathologically positive lymph nodes\r\n* pT3 or pT4\r\n* PSA doubling time (DT) < 10 months\r\n* Negative margins\r\n* Persistent PSA after radical prostatectomy (RP) (PSA never dropped below 0.1 after RP)\r\n* Local/regional recurrence on imaging\r\n* Decipher “high risk” (a Medicare-reimbursed test for risk of metastases after prostatectomy)Xx_NEWLINE_xXPSA > 10 ng/mL in screeningXx_NEWLINE_xXCastrate-resistant disease, defined as follows:\r\n* All patients must have received (and be receiving) standard of care androgen deprivation treatment (surgical castration versus gonadotropin-releasing hormone [GnRH] analogue or antagonist treatment); subjects receiving GnRH analogue or antagonist must continue this treatment throughout the time on this study\r\n* Patients may or may not have been treated previously with a nonsteroidal antiandrogen; for patients previously treated with an antiandrogen, they must be off use of anti-androgen for at least 4 weeks (for flutamide) or 6 weeks (for bicalutamide or nilutamide) prior to registration; moreover, subjects who demonstrate an anti-androgen withdrawal response, defined as a >= 25% decline in PSA within 4-6 week of stopping a nonsteroidal antiandrogen, are not eligible until the PSA rises above the nadir observed after antiandrogen withdrawal\r\n* Patients must have a castrate serum level of testosterone (< 50 ng/dL) within 6 weeks of day 1Xx_NEWLINE_xXPHASE II STUDY METASTATIC CASTRATE-RESISTANT PROSTATE CANCER COHORT 4 ELIGIBILITY CRITERIA (MEDI+O ONLY):\r\nPatients must have castrate levels of testosterone (< 50 ng/dl [1.74 nmol/l])Xx_NEWLINE_xXMost recent prostate specific antigen (PSA) within 60 days of enrollmentXx_NEWLINE_xXMaximum PSA =< 20 ng/ml (not within 20 days after biopsy)Xx_NEWLINE_xXHave metastatic castration-resistant prostate cancer, are chemo-naïve for mCRPC (however, six cycles of docetaxel are allowed in hormone-sensitive disease), and have progressed on abiraterone treatment (patients may have had prior therapy including sipuleucel-T, radium-223, abiraterone, ketoconazole, and/or Tak-700); progression on abiraterone is defined as\r\n* Radiologic progression by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 and Prostate Cancer Working Group (PCWG)2 criteria, or \r\n* PSA progression on abiraterone:\r\n** For responders to abiraterone: 25% or greater increase and an absolute increase of 2 ng/mL or more from the nadir, confirmed by a second value obtained 2 or more weeks later\r\n** For non-responders to abiraterone: 25% increase above baseline with an increase in absolute value of 2 ng/mL or more after 12 weeks of treatmentXx_NEWLINE_xXPSA > 100 ng/mLXx_NEWLINE_xXOne of the following pathologic classifications\r\n* T3N0 disease with or without a positive surgical margin or\r\n* T2N0 disease with or without a positive surgical margin\r\n** Those with T2N0 disease and a negative margin must have a detectable prostate-specific antigen (PSA) following radical prostatectomy or\r\n** Must have had an undetectable PSA after prostatectomy and has since had a rise in post-operative PSA to 0.2 ng/mL or greaterXx_NEWLINE_xXPrior surgical castration or concurrent use of gonadotropin-releasing hormone (GnRH) analogue (i.e. medical castration) with testosterone at screening < 50 ng/dLXx_NEWLINE_xXPatients must have at least one of the following criteria:\r\n* The serum PSA should be greater than or equal to 20 ng/ml OR study entry PSA must not be obtained during the following time frames: (1) 10-day period following prostate biopsy; (2) following initiation of antiandrogen therapy (ADT)\r\n* The Gleason score should be greater than or equal to 8 OR\r\n* Eligible patients must have appropriate staging studies identifying them as American Joint Committee on Cancer (AJCC) stage T3+ adenocarcinoma of the prostate gland; (MR stage T3a without other high risk factors permitted at investigator discretion)Xx_NEWLINE_xXPSA < 150 ng/mLXx_NEWLINE_xXPSA >= 150 ng/mLXx_NEWLINE_xXPatients must have histologically or cytologically confirmed prostate cancer with a Gleason score available or interpretable; patients must have prostate cancer deemed to be castration-resistant by one or more of the following criteria (despite androgen deprivation and anti-androgen withdrawal when applicable):\r\n* Progression of unidimensionally measurable disease assessed within 28 days prior to initial administration of drug\r\n* Progression of evaluable but not measurable disease assessed within 28 days prior to initial administration of drug for PSA evaluation and within 42 days for imaging studies (e.g, bone scans)\r\n* NOTE: rising PSA, defined as at least two consecutive rises in PSA to be documented over a reference value (measure 1); the first rising PSA (measure 2) should be taken at least 7 days after the reference value; a third confirmatory PSA measure (2nd beyond the reference level) should be greater than the second measure, and it must be obtained at least 7 days after the 2nd measure; if this is not the case, a fourth PSA is required to be taken and be greater than the second measure; measurable disease is not requiredXx_NEWLINE_xXPatients must have been surgically or medically castrated; if the method of castration was luteinizing hormone-releasing hormone (LHRH) agonists (leuprolide or goserelin), then the patient must be willing to continue the use of LHRH agonists; serum testosterone must be at castrate levels (< 50 ng/dL) at least 14 days prior to registrationXx_NEWLINE_xXFor patients with metastatic prostate cancer, PSA >= 2 ng/mL, except for patients who have recently started androgen deprivation therapy with PSA < 2 ng/mLXx_NEWLINE_xXProstate specific antigen (PSA) =< 10 ng/mL within 90 days prior to registration; PSA should not be obtained within 10 days after prostate biopsyXx_NEWLINE_xXDocumented castrate level of serum testosterone (< 50 ng/dl)Xx_NEWLINE_xXPatients with rising PSA on two successive measurements at least 2 weeks apartXx_NEWLINE_xXSerum testosterone >= 100 ng/dLXx_NEWLINE_xXPatients must be candidates for long-term androgen deprivation in combination with EBRT for the treatment of high-risk or locally-advanced prostate cancer by the following criteria:\r\n* High risk disease: T3a or Gleason 8-10 or serum PSA > 20 ng/mL\r\n* Gleason 7 also allowed if > 50% of cores positive for cancer or PSA velocity > 2 ng/mL/year in preceding 12 months\r\n* Locally advanced (very high risk) disease: T3b-T4Xx_NEWLINE_xXSerum PSA > 160 ng/dLXx_NEWLINE_xXPathologically (histologically or cytologically) proven diagnosis of prostatic adenocarcinoma within 180 days of registration at moderate to high risk for recurrence as determined by one of the following combinations:\r\n* Gleason score 7-10 + T1c-T2b (palpation) + prostate specific antigen (PSA) < 75 ng/ml (includes intermediate and high risk patients)\r\n* Gleason score 6 + T2c-T4 (palpation) or > 50% (positive) biopsies + PSA < 75 ng/ml\r\n* Gleason score 6 + T1c-T2b (palpation) + PSA > 20 ng/mlXx_NEWLINE_xXBaseline vitamin D level greater than 50 ng/mLXx_NEWLINE_xXClinical stage T1-2b (American Joint Committee on Cancer [AJCC] 7th edition) and PSA < 20 ng/mL within 90 days prior to registration; PSA should not be obtained within 10 days after prostate biopsyXx_NEWLINE_xXNational Comprehensive Cancer Network (NCCN) risk category very low, low, or intermediate risk:\r\n* Combined Gleason score =< 7\r\n* Prostate specific antigen (PSA) within three months of enrollment < 20 ng/ml\r\n* Clinical stage T1a-cN0M0 or clinical stage T2aN0M0Xx_NEWLINE_xXBilirubin < 2.0 ng/dlXx_NEWLINE_xXCreatinine < 3.0 ng/dlXx_NEWLINE_xXPatient must currently be on androgen deprivation or anti-androgen therapy with castrate levels of testosterone (< 50 ng/dl)\r\n* Medical castration should continue until disease progressionXx_NEWLINE_xXProstate specific antigen (PSA) >= 0.2 ng/ml that is confirmed with a second PSA measurementXx_NEWLINE_xXPSA >= 2.0 ng/mLXx_NEWLINE_xXEvidence of castration resistant disease in the setting of ongoing ADT (medical or surgical) as evidenced by one of the following:\r\n* Absolute rise in PSA of 2.0 ng/mL or an increase > 25% from the nadir, minimum 2 consecutive rising PSA levels with an interval of >= 1 week between each PSA level, OR\r\n* Computed tomography (CT) or magnetic resonance imaging (MRI) based evidence of disease progression (soft tissue, nodal or visceral disease progression) according to RECIST 1.1 criteria, OR\r\n* At least 1 new bone scan lesion as compared to the most immediate prior radiologic studiesXx_NEWLINE_xXProstate cancer categorized (as determined by central pathology review) as low risk is defined as T1c-T2a, PSA<10, N0, M0 (or presumed N0, M0 if CT/bone scan not done due to low risk of metastases), GS ? 6, ECOG status ?2 and estimated life expectancy >5 years OR intermediate risk is defined as T2b-T2c, PSA<20, N0, M0 (or presumed N0, M0 if CT/bone scan not done), GS ?7 (3+4 pattern only), ECOG status ? 2 and estimated life expectancy > 5 years. Prostate cancer categorized (as determined by central pathology review) to the very low risk category (T1c, GS ?6, PSA <10 ng/mL, fewer than 3 prostate biopsy cores positive, ?50% cancer in any core, PSA density <0.15 ng/mL/g) is not included.Xx_NEWLINE_xXVery low risk category (T1c, GS ?6, PSA <10 ng/mL, fewer than 3 prostate biopsy cores positive, ?50% cancer in any core, PSA density <0.15 ng/mL/g)Xx_NEWLINE_xXIntermediate or high risk for recurrence according to the following criteria:\r\n* Two or more of the following intermediate risk features for recurrence\r\n** Gleason score = 7\r\n** Prostate-specific antigen (PSA) 10-20 ng/ml\r\n** Clinical stage T2b-T2c\r\n** Percent positive biopsy cores >= 50% OR\r\n* One or more of the following high risk features for recurrence\r\n** Gleason score 8-10\r\n** PSA > 20 ng/ml\r\n** Clinical stage T3a-T4Xx_NEWLINE_xXStudy entry PSA and serum testosterone must not be obtained during the following time frames: (1) 10-day period following prostate biopsy; (2) following initiation of oral androgen manipulation; (3) within 30 days after discontinuation of finasteride or dutasterideXx_NEWLINE_xXFor the diagnosis of pure germinoma, HCGB (serum and CSF) must be =< 100 mIU/ml, serum AFP must be =< 10 IU/l (ng/ml) and =< institutional norm and CSF AFP =< 2 IU/l (ng/ml) and =< institutional norm with histologically proven diagnosis of germinoma at diagnosis or relapseXx_NEWLINE_xXFor histologically unconfirmed MMGCT, serum and/or CSF tumor markers of HCG? > 100 mIU/ml or any elevation of AFP > 10 IU/L (ng/ml) and/or institutional norm in the serum and CSF AFP > 2 IU/L (ng/ml) and/or institutional normXx_NEWLINE_xXEligible patients will have clinical stage T1c, T2a, or T2b, a pre-biopsy PSA level < 15 ng/mL and a biopsy Gleason score of 3+3 (or 3+4 if fewer than 50% of the total number of biopsy cores are involved by grade 3+4)Xx_NEWLINE_xXPSA values < 20 ng/ml within 90 days prior to registration, done either prior to prostate biopsy or at least 21 days after prostate biopsyXx_NEWLINE_xXPSA of greater than 10ng/mlXx_NEWLINE_xXProstate specific antigen (PSA) =< 20 ng/dLXx_NEWLINE_xXPatients belonging in one of the following risk groups:\r\n* Low: clinical stage (CS( T1b-T2a and Gleason 2-6 and PSA =< 10, or\r\n* Intermediate: CS T2b and Gleason 2-6 and PSA =< 10, or CS T1b-T2b, and Gleason 2-6 and PSA =< 20 ng/dL, or Gleason 7 and PSA =< 10 ng/dLXx_NEWLINE_xX25(OH) D3 level less than 40 ng/ml within 3 months of initiation of study; most recent 25 hydroxy D level within last 3 months would be usedXx_NEWLINE_xXMost recent PSA value more than 18 months agoXx_NEWLINE_xXProstate specific antigen (PSA) of less than 10 ng/mlXx_NEWLINE_xXPSA > 10 ng/mlXx_NEWLINE_xXA minimum of three PSA values, each at least 4 weeks apart, to calculate PSA-doubling time (DT); the last PSA level prior to enrollment must be at least 1.0 ng/mL and be rising over the prior valueXx_NEWLINE_xXSerum testosterone levels < 50 ng/L after surgical or continued chemical castrationXx_NEWLINE_xXPatients must have ongoing therapy to maintain serum testosterone < 50 ng/dLXx_NEWLINE_xXInclusion Criteria include:\n\n          -  Histologically confirmed adenocarcinoma of the prostate\n\n          -  Patients choosing active surveillance\n\n          -  Patients meeting definition of NCCN low risk, intermediate risk OR patients having\n             only one NCCN high-risk feature\n\n               -  NCCN Low Risk is defined as having all of the following: PSA < 10 ng/ml, Gleason\n                  ? 6, T1-T2a\n\n               -  NCCN Intermediate Risk is defined as having at least one of the following and no\n                  high risk features: PSA 10-20 ng/ml, Gleason score =7, T2b-T2c\n\n               -  High Risk with a single high risk feature is defined as having only one of the\n                  following: PSA>20 ng/ml, Gleason score 8-10, or T3a\n\n               -  Excluded are those in the following risk groups: High risk with more than 1 high\n                  risk factor; Locally advanced/very high risk=T3b-T4; Metastatic: N1 or M1\n\n          -  Patients must be planning and medically able to tolerate multiple transrectal\n             ultrasound guided injections.\n\n          -  ECOG Performance status 0-2\n\n        Exclusion Criteria include:\n\n          -  Active liver disease, including known cirrhosis or active hepatitis\n\n          -  Patients on systemic corticosteroids (>10 mg prednisone per day) or other\n             immunosuppressive drugs\n\n          -  Known HIV+ patients\n\n          -  Regional lymph node involvement or distant metastases\n\n          -  Other current malignancy (except squamous or basal cell skin cancers)\n\n          -  Other serious co-morbid illness or compromised organ function that, in the opinion of\n             the investigator, would interfere with treatment or follow up\n\n          -  Prior treatment for prostate cancer except TURP. If prior TURP, patients must be\n             deemed able to receive prostate biopsy and multiple intra-prostatic injections by the\n             investigator\n\n          -  Patients taking 5-alpha-reductase inhibitors (e.g. finasteride, dutasteride)\n\n          -  Patients who had or plan to use ADT or have history of an orchiectomy.\n\n          -  Patients who are planning to undergo radical treatment for prostate cancer within 12\n             months.\n\n          -  Known sensitivity or allergic reactions to acyclovir or valacyclovirXx_NEWLINE_xXKey Eligibility Criteria:\n\n          -  Patients must have documented histological or cytological evidence of adenocarcinoma\n             of the prostate.\n\n          -  Must have progressive, metastatic castration-resistant prostate cancer (mCRPC). There\n             must be radiographic evidence of disease after primary treatment with surgery or\n             radiotherapy that has continued to progress radiographically or biochemically (rising\n             PSA levels on successive measurements) despite adequate androgen-deprivation therapy,\n             which is defined as having undergone bilateral surgical castration or continued\n             treatment on GnRH agonists or antagonists.\n\n          -  All patients in this trial must have been treated with enzalutamide.\n\n          -  Patients in Cohort 1 will not be allowed to have received prior chemotherapy; patients\n             in Cohort 2 must have received one (and not more) prior course of chemotherapy for\n             mCRPC.\n\n          -  Progression must be evidenced and documented by any of the following parameters:\n\n               -  PSA progression defined by a minimum of two rising PSA levels with an interval of\n                  ? 1 week between each determination\n\n               -  Appearance of one or more new lesions on bone scan\n\n               -  Progressive measurable disease by RECIST 1.1Xx_NEWLINE_xXCEA plasma levels > 5 ng/mL.Xx_NEWLINE_xXPatients with CEA plasma levels > 1000 ng/mL are excluded during dose escalation, but may be included after the MTD is determined.Xx_NEWLINE_xXInclusion Criteria: All of the following criteria are mandatory for inclusion:\n\n          -  Histological confirmation of prostate adenocarcinoma with a minimum of 10 biopsy cores\n             taken within 18 months of randomisation.\n\n          -  Gleason score ? 3+4\n\n          -  Men aged ?18\n\n          -  Clinical and MRI stage T1c -T2c, N0-X, M0-X (TNM 6th Edition [72], See Appendix 1)\n\n          -  PSA ? 20 ng/ml\n\n          -  Pre-enrollment PSA must be completed within 60 days of randomisation\n\n          -  Patients belonging in one of the following risk groups according to the National\n             Comprehensive Cancer Network (www.nccn.org):\n\n               -  Low risk: Clinical stage T1-T2a and Gleason ? 6 and PSA < 10 ng/ml, or\n\n               -  Intermediate risk includes any one of the following:\n\n               -  Clinical stage T2b orT2c\n\n               -  PSA 10-20 ng/ml or\n\n               -  Gleason 3+4\n\n          -  WHO performance status 0 - 2\n\n          -  Prostate volume ? 90 cc measured within 6 months of randomisation (height*width*length\n             *?/6)\n\n          -  Ability of the research subject to understand and the willingness to sign a written\n             informed consent document\n\n        Exclusion criteria: One of the following criteria is sufficient for exclusion:\n\n          -  Clinical stage T3 or greater\n\n          -  Gleason score ? 4 + 3\n\n          -  High risk disease defined by National Comprehensive Cancer Network (www.nccn.org)\n\n          -  Previous malignancy within the last 2 years (except basal cell carcinoma or squamous\n             cell carcinoma of the skin), or if previous malignancy is expected to significantly\n             compromise 5 year survival\n\n          -  Prior pelvic radiotherapy\n\n          -  Prior androgen deprivation therapy (including LHRH agonists and antagonists and\n             anti-androgens)\n\n          -  Any prior active treatment for prostate cancer. Patients previously on active\n             surveillance are eligible if they continue to meet all other eligibility criteria.\n\n          -  Life expectancy <5 years\n\n          -  Bilateral hip prostheses or any other implants/hardware that would introduce\n             substantial CT artifacts\n\n          -  Medical conditions likely to make radiotherapy inadvisable eg inflammatory bowel\n             disease, significant urinary symptoms\n\n          -  Anticoagulation with warfarin/ bleeding tendency making fiducial placement or surgery\n             unsafe in the opinion of the clinician (see section 11, Treatment).\n\n          -  Participation in another concurrent treatment protocol for prostate cancerXx_NEWLINE_xXCastrate level of testosterone (< 50 ng/dL)Xx_NEWLINE_xXPatient must have evidence of castration resistant prostate cancer as evidenced by PSA progression (per Prostate Cancer Working Group 3 [PCWG3] criteria) and a castrate serum testosterone level (i.e., ? 50 mg/dL)Xx_NEWLINE_xXPSA must be at least 1 ng/ml and rising on two successive measurements at least two weeks apartXx_NEWLINE_xXCastration resistant prostate cancer as defined by serum testosterone < 50 ng/ml and PSA level of at least 2 ng/ml that has risen on at least 2 successive occasions at least 1 week apartXx_NEWLINE_xXCEA plasma levels > 5 ng/mLXx_NEWLINE_xXPatients with CEA plasma levels > 1000 ng/mL must be approved in advance by the Sponsor.Xx_NEWLINE_xXProgressive, castration-resistant prostate cancer demonstrated during continuous antiandrogen therapy (ADT), defined as 3 PSA rises at least 1 week apart, with the last PSA > 2 ng/mLXx_NEWLINE_xXSurgically or medically castrated, with testosterone levels of < 50 ng/dL; if the patient is medically castrated, continuous dosing with luteinizing hormone-releasing hormone (LHRH) analogue must have been initiated at least 4 weeks prior to randomization and must be continued throughout the study to maintain castrate levels of testosterone including post-treatment follow up periodXx_NEWLINE_xXPatients who received a first generation anti-androgen (e.g., bicalutamide, flutamide, nilutamide) as most recent treatment must have at least a 6-week washout prior to randomization and must show continuing disease (PSA) progression (an increase in PSA) after washoutXx_NEWLINE_xXCastration resistance will be defined as the development of disease progression, defined as one of the following:\r\n* Rising PSA x 2 values >= 2 weeks apart; minimum absolute PSA value 2 ng/mL\r\n* Radiographic progression, with at least 1 new site of metastasis\r\n* Symptomatic progression (ex: increase in pain despite stable imaging) AND despite ongoing luteinizing hormone-releasing hormone (LHRH) therapy OR testosterone level < 50Xx_NEWLINE_xXPatients must have CaP deemed to be castration-resistant by one or more of the following criteria (despite androgen deprivation when applicable):\r\n* Progression of unidimensionally measurable disease assessed within 42 days prior to initial administration of drug\r\n* Progression of evaluable but not measurable disease assessed within 42 days prior to initial administration of drug for PSA evaluation and for imaging studies (e.g, bone scans)\r\n* Rising PSA, defined as at least two consecutive rises in PSA to be documented over a reference value (measure 1); the first rising PSA (measure 2) should be taken at least 7 days after the reference value; a third confirmatory PSA measure (2nd beyond the reference level) should be greater than the second measure, and it must be obtained at least 7 days after the 2nd measure; if this is not the case, a fourth PSA measurement is required to be taken and be greater than the second measureXx_NEWLINE_xXPatients must have been surgically or medically castrated; if the method of castration was luteinizing hormone-releasing hormone (LHRH) agonists (leuprolide or goserelin) or antagonists (degarelix), then the patient must be willing to continue the use of LHRH agonists or antagonists; serum testosterone must be at castration levels (< 50 ng/dL) within 3 months prior to registrationXx_NEWLINE_xXSurgically or medically castrated, with testosterone levels of <=50 nanograms per deciliter (ng/dL) (<2.0 nanometer [nM]). If the patient is being treated with luteinizing hormone-releasing hormone (LHRH) agonists/antagonists (patient who have not undergone orchiectomy) this therapy must have been initiated at least 4 weeks prior to Cycle 1 Day 1 and must be continued throughout the study.Xx_NEWLINE_xXDocumented prostate cancer progression as assessed by the investigator with one of the following: PSA progression defined by a minimum of 3 rising PSA levels with an interval of >=1 week between each determination. The PSA value at screening must be >=5 microgram (µg)/L (5 ng/mL) if PSA is the only indication of progression; subjects on systemic glucocorticoids for control of symptoms must have documented PSA progression by PCWG3 while on systemic glucocorticoids prior to commencing Cycle 1 Day 1 treatment.Xx_NEWLINE_xXKnown castrate-resistant disease with serum testosterone level less than or equal to (</=) 50 nanograms per deciliter (ng/dL) with prior surgical castration or ongoing androgen deprivation for the duration of the studyXx_NEWLINE_xXProstate cancer with a current PSA level < 0.1 ng/mL.Xx_NEWLINE_xXMust have a vitamin D level >= 30 ng/mL after repletionXx_NEWLINE_xXAt least one of the following:\r\n* Two or more high risk features OR\r\n** Gleason score 8-10\r\n** PSA >= 20 ng/mL within two months prior to registration\r\n** Clinical stage >= T3 disease, as determined by standard digital rectal examination (DRE)\r\n** Radiographic stage >= T3 disease as determined by a >= 75% probability of extracapsular extension or seminal vesicle invasion per reading radiologist\r\n* Any Gleason 9 or 10 disease OR\r\n* > 4 cores of Gleason 8 diseaseXx_NEWLINE_xXIntermediate risk or high risk prostate cancer patients who are candidates for radiation therapy:\r\n* Gleason >= 7 or\r\n* Clinical or pathological > T2b disease or\r\n* Prostate-specific antigen (PSA) >= 10 ng/mLXx_NEWLINE_xXSerum ferritin < 50 ng/mL.Xx_NEWLINE_xXNo distant metastases on bone scan (only necessary if prostate specific antigen [PSA] >= 10 ng/ml and/or Gleason score >= 7)Xx_NEWLINE_xXNormal serum CEA levels (< 3 ng/ml) at the time of registrationXx_NEWLINE_xXCastration-resistant prostate cancer requires the following 3 criteria:\r\n* Progression after surgical castration or on gonadotrophin releasing hormone (GnRH) agonist or antagonist\r\n* A castrate level of testosterone (< 50 ng/dL)\r\n* Prostate cancer progression documented by PSA rise or bone progression according to Prostate Cancer Clinical Trials Working Group (PCWG2)Xx_NEWLINE_xXTestosterone =< 50 ng/dL (documented at any time while on LHRH agonist or antagonists or s/p orchiectomy)Xx_NEWLINE_xXPatients must have rising PSA on two successive measurements, at least 2 weeks apartXx_NEWLINE_xXPatient must be treated with continuous androgen ablative therapy (e.g. goserelin, leuprolide, triptorelin, or degarelix, if he has not had prior surgical castration) and have castrate levels of testosterone (< 50 ng/dL or 1.7 nmol/L)Xx_NEWLINE_xXSerum prostate specific antigen (PSA) level < 20 ng/mlXx_NEWLINE_xXSerum PSA level > 20 ng/mlXx_NEWLINE_xXProstate-specific antigen (PSA) < 10 ng/ml (this will be the PSA level prompting the initial prostate biopsy)Xx_NEWLINE_xXCastration-resistant based on a current or historical evidence of disease progression despite surgical or medical castration as demonstrated by one or more of the following:\r\n* Prostate-specific antigen (PSA) progression (defined as two consecutive PSA measurements at least 14 days apart >= 2.0 ng/ml and >= 50% above the minimum PSA during castration therapy or above pre-treatment value if no response)\r\n* Progression of measurable disease based on Response Evaluation Criteria in Solid Tumors (RECIST) (>= 20% increase in the sum of the diameters of all target lesions or the development of any new lesions)\r\n* Progression of non-measureable disease based on imaging studiesXx_NEWLINE_xXSerum PSA >= 2.0 ng/ml at study enrollmentXx_NEWLINE_xXCastration levels of testosterone defined as =< 50 ng/dL at study enrollment; must be at least 3 months from surgical castration or must have received medical castration therapy for at least 3 months and be receiving such therapy at the time of confirmed disease progressionXx_NEWLINE_xXNeutralizing antibodies less than or equal to 75% neutralization of 200 ng/ml of LMB-2Xx_NEWLINE_xXStatus post radical prostatectomy with sampling of the pelvic lymph nodes with histologically confirmed adenocarcinoma of the prostate, with the patients falling into either the “adjuvant high risk group” or the “salvage high risk group” as indicated below; in those cases where patients undergo a prostatectomy without any sampling of the pelvic lymph nodes, patients will be also considered eligible if they are found to have a negative pelvic computed tomography (CT) or magnetic resonance imaging (MRI) scan which shows no evidence of lymphatic nodal metastases after the prostatectomy\r\n* “Adjuvant High Risk Group” (undetectable, persistent or decreasing PSA levels before starting therapy) who have NO evidence of metastatic disease (i.e. no clinical symptoms or radiologic evidence) who MUST be able to start RT treatments within 6 months of radical prostatectomy with at least one of the 3 disease features:\r\n** Pathologic T2N0 disease and Gleason score >= 8, or\r\n** Pathologic T3aN0 disease with extracapsular extension and Gleason score >= 8, or\r\n** Pathologic T3bN0 disease with any Gleason score\r\n* “Salvage High Risk Group” are those patients with PSA biochemical failure defined by at least 1 detectable PSA level >= 0.2 ng/ml or at least 2 consecutive increases over baseline PSA levels at least one month apart, who have NO other evidence of metastatic disease (i.e. no clinical symptoms or radiologic evidence), and WITH AT LEAST ONE of the high risk disease features as defined below:\r\n** Pathologic T3bN0 disease with any Gleason score, or\r\n** Pathologic T2-3aN0 disease with Gleason score >= 8, or\r\n** Pathologic T2-3aN0 disease with PSA doubling time =< 10 months, or\r\n** Pathologic T2-3aN0 disease with pre-radiation therapy PSA level >= 1.0 ng/mlXx_NEWLINE_xXPatients with prostate cancer on active surveillance at low risk for progression, defined as Prostate-Specific Antigen (PSA) < 10 ng/dL, Gleason score 6 and clinical stage tumor-1 (cT1) are permitted to be in the study at the discretion of the investigator (see exclusion criterion 10).Xx_NEWLINE_xXPatients must have a PSA >= 2 ng/mL obtained within 90 days prior to registrationXx_NEWLINE_xXSerum PSA <10 ng/mL undergoing active surveillance may be enrolled with agreement of the sponsor.Xx_NEWLINE_xXSubjects must have castrate levels of testosterone (?50 ng/dl [1.7 nmol/L]) and have progressive disease at Screening defined as PSA rise determined by a minimum of 2 rising PSA values ?1 week between each assessment. The PSA value at the Screening visit must be ?2ng/mL with or without:Xx_NEWLINE_xXHas prostate cancer progression within 6 months prior to screening, as determined by the investigator, by means of one of the following: PSA progression as defined by a minimum of 2 rising PSA levels with an interval of ?1 week between each assessment where the PSA value at screening should be ?2 ng/mL; radiographic disease progression in soft tissue based on Response Evaluation Criteria In Solid Tumors Version 1.1 criteria with or without PSA progression; radiographic disease progression in bone defined as the appearance of 2 or more new bone lesions on bone scan with or without PSA progressionXx_NEWLINE_xXHas ongoing androgen deprivation with serum testosterone <50 ng/dL (<2.0 nM). Treatment with luteinizing hormone-releasing hormone agonists or antagonists must have been initiated ?4 weeks prior to first dose of study therapy and must be continued throughout the studyXx_NEWLINE_xXPSA doubling time ? 9 months;Xx_NEWLINE_xXScreening PSA by the central laboratory ? 1 ng/mL for patients who had radical prostatectomy (with or without radiotherapy) as primary treatment for prostate cancer and at least 2 ng/mL above the nadir for patients who had radiotherapy only as primary treatment for prostate cancer;Xx_NEWLINE_xXSerum testosterone ? 150 ng/dL (5.2 nmol/L).Xx_NEWLINE_xXPSA ? 15 ng/mlXx_NEWLINE_xXCastration resistant disease defined as ongoing androgen deprivation therapy with gonadotropin-releasing hormone (GnRH) analogue or bilateral orchiectomy and serum testosterone level ? 1.73 nmol/l (50 ng/dL) at screening visit. Individuals who have not had a bilateral orchiectomy must have a plan to maintain effective GnRH-analogue therapy for the duration of the trial.Xx_NEWLINE_xXPatient must fit D’Amico intermediate-risk criteria by clinical stage (T2b-T2c), prostate-specific antigen (PSA) (10-20 ng/mL), and/or Gleason score (Gleason 7)Xx_NEWLINE_xXPSA > 20 ng/mlXx_NEWLINE_xXUp to 3 months of ADT with LHRH agonists or antagonists or orchiectomy with or without concurrent antiandrogens prior to day 1, with no radiographic evidence of disease progression or rising PSA levels prior to day 1;Xx_NEWLINE_xXProstate-specific antigen doubling time of ? 10 months and PSA > 2ng/ml.Xx_NEWLINE_xXTestosterone ? 50 ng/dL (? 1.73 nmol/L) at screening;Xx_NEWLINE_xXPSA and the screening PSA assessed by the central laboratory (central PSA) should be ? 2 µg/L (2 ng/mL:Xx_NEWLINE_xXPSA doubling time ? 10 months;Xx_NEWLINE_xXAdenocarcinoma of the prostate proven by biopsy within 180 days of study registration with one of the following high risk criteria:\r\n* Gleason score 7 with PSA =< 20 ng/ml and clinical T1-2, or\r\n* Gleason score 8-10, PSA =< 20 ng/ml and clinical T1-2, or\r\n* PSA 10.1-40 ng/ml with Gleason score (GS) < 7 and clinical T1-2, or\r\n* Clinical T3 with Gleason score < 7 and PSA =< 10 ng/mlXx_NEWLINE_xXKnown serum testosterone =< 150 ng/dl or symptoms of hypogonadism (fatigue, hot flashes, hair loss, loss of muscle mass, osteoporosis, low libido, depression) prior to ADT initiation not explained by other medical co-morbidity OR history of testosterone supplement; if questionable, serum testosterone level greater than 150 ng/dl can be used to exclude hypogonadismXx_NEWLINE_xXSpecific eligibility criteria for Part 2 CRPC expansion cohort: Ongoing androgen deprivation therapy with a serum testosterone level <1.7 nanomoles/L or <50 ng/dL.Xx_NEWLINE_xXSpecific eligibility criteria for Part 2 CRPC expansion cohort: Prostate-Specific Antigen (PSA) levels >=2.0 ng/mL. Note: If PSA level has been obtained within 14 days of Screening, this test does not need to be repeated and the result previously obtained may be used for the Screening value.Xx_NEWLINE_xXPSA progression defined as 25% increase over baseline value with an increase in the absolute value of at least 2 ng/mL that is confirmed by another PSA level with a minimum of a 1 week interval and a minimum PSA of 2 ng/mL.Xx_NEWLINE_xXPatients must have prior and/or ongoing androgen-deprivation therapy and a castrate level of serum testosterone (<50 ng/dL).Xx_NEWLINE_xXPSA progression defined as 25% increase over a baseline value of > 2 ng/ml with an increase in the absolute value of at least 2 ng/mL that is confirmed by another PSA level with a minimum of a 1-week interval. Baseline is defined as the PSA nadir level since commencing most recent prior therapyXx_NEWLINE_xXPatients must have a castrate level of serum testosterone (< 50 ng/dL)Xx_NEWLINE_xXA post-radical prostatectomy study entry PSA >= 45 days after prostatectomy and within 30 days prior to step 1, < 2.0 ng/mLXx_NEWLINE_xXA post-prostatectomy PSA nadir >= 0.2 ng/mL AND Gleason >= 7Xx_NEWLINE_xXpT2 with a negative surgical margin and PSA < 0.1 ng/mLXx_NEWLINE_xXSerum prostate-specific antigen (PSA) ? 15ng/mL.Xx_NEWLINE_xXPSA ? 20 ng/mL;Xx_NEWLINE_xXPSA > 20 ng/mLXx_NEWLINE_xXPatients must have a serum testosterone < 50 ng/dL demonstrated within 1 month of study entryXx_NEWLINE_xXPatients must have evidence of response to androgen deprivation as defined by a documented decline in serum PSA values from pre-androgen deprivation treatment baseline and without evidence of PSA progression while on androgen deprivation (defined by Prostate Cancer Working Group 2 [PCWG2] criteria as a 25% increase in serum PSA and an absolute increase of 2 ng/mL over nadir)Xx_NEWLINE_xXPatients previously treated with neoadjuvant and/or adjuvant androgen deprivation (e.g. with radiation therapy) prior to the 6-month eligibility period are allowed, assuming they did not meet criteria for progression (defined by PCWG2 criteria as a 25% increase in serum PSA and an absolute increase of 2 ng/mL over nadir) while on treatmentXx_NEWLINE_xXPSA progression defined as 25% increase over baseline value with an increase in the absolute value of at least 2 ng/mL that is confirmed by another PSA level with a minimum of a 1 week interval with a minimum PSA of 2 ng/ml.Xx_NEWLINE_xXPatients with a prostate serum antigen (PSA), equal to, or more than, 5 ng/mL.Xx_NEWLINE_xXPatients with prior surgical or chemical castration with a serum testosterone of <50 ng/mL. If the method of castration is luteinizing hormone releasing level hormone (LHRH) agonists, the patient must be willing to continue the use of LHRH agonists during protocol treatment.Xx_NEWLINE_xXIncreasing PSA level: at least two consecutive rising PSA values over a reference value (PSA #1) taken at least 1 week apart. A third PSA (PSA #3) is required to be greater than PSA #2; if not, a fourth PSA (PSA #4) is required to be greater than PSA #2. Inclusion criterion only for patients entering phase Ib expansion cohort:Xx_NEWLINE_xXPatients must be receiving continuous enzalutamide treatment and show a rise in PSA level: at least two consecutive rising PSA values over a reference value (PSA #1) taken at least 1 week apart. A third PSA (PSA #3) is required to be greater than PSA #2; if not, a fourth PSA (PSA #4) is required to be greater than PSA #2.Xx_NEWLINE_xXProstate adenocarcinoma without distant metastatic disease with either Gleason score >= 7, PSA >= 10 ng/ml, or T2b or greater diseaseXx_NEWLINE_xXProstate cancer with a current PSA level < 0.1 ng/mL.Xx_NEWLINE_xXAdenocarcinoma of the prostate with intermediate risk disease T2b-T2c or Gleason score 7 or prostate specific antigen (PSA) 10-20 ng/ml, without metastatic diseaseXx_NEWLINE_xXPatient with PSA less than or equal to 10 ng/mLXx_NEWLINE_xXA diagnosis of progressive castrate metastatic prostate cancer defined as one or more of the following three criteria: \r\n* Soft tissue progression defined by Response Evaluation Criteria In Solid Tumors (RECIST) 1.0 \r\n* Bone disease progression defined by Prostate Cancer Working Group 2 (PCWG2) with two or more new lesions on bone scan \r\n* Post-hormonal therapy rising PSA values from a hormone therapy nadir on >= 3 successive determinations at least two weeks apart, where the increase above the nadir is the greater of >= 2.0 ng/mL or a >= 10% change; (subjects with a rise in PSA but no evidence of metastases at any time by imaging studies will NOT be eligible)Xx_NEWLINE_xXCastrate level of serum testosterone (< 50 ng/mL) achieved by prior hormonal therapy consisting of either a) orchiectomy or b) luteinizing hormone-releasing hormone (LHRH) agonists with or without an anti-androgenXx_NEWLINE_xXPathologically (histologically) proven diagnosis of prostatic adenocarcinoma, at intermediate risk for recurrence, within 180 days prior to registration as determined by having one or more of the following intermediate-risk features: \r\n* Gleason score 7\r\n* Prostate specific antigen (PSA) > 10 but =< 20\r\n* Clinical stage T2b-T2c\r\n* Patients previously diagnosed with low risk (Gleason score =< 6, clinical stage < T2a, and PSA < 10) prostate cancer undergoing active surveillance who are re-biopsied and found to have intermediate risk disease according to the protocol criteria are eligible for enrollment within 180 days of the repeat biopsy procedureXx_NEWLINE_xXPSA < 10 ng/mL =< 30 days prior to registrationXx_NEWLINE_xXBe surgically or medically castrated, with serum testosterone levels of ? 50 ng/dL (1.73 nM)Xx_NEWLINE_xXProstatic specific antigen doubling time (PSADT) < 15 months; PSA doubling time (PSADT) will be calculated using as many PSA values that are available from time of relapse (PSA > 0.2); to calculate PSADT, the Memorial Sloan Kettering Cancer Center Prostate Cancer Prediction Tool will be usedXx_NEWLINE_xXPSA >= 0.5 but =< 50Xx_NEWLINE_xXTestosterone >= 125 ng/dLXx_NEWLINE_xXBiochemical progression after definitive radiation or surgery defined as follows:\r\n* For patients following definitive radiation therapy: a rise in PSA of >= 2 ng/mL above the nadir (per Radiation Therapy Oncology Group [RTOG]-American Society for Radiation Oncology [ASTRO] consensus criteria)\r\n* For patients following radical prostatectomy: rising PSA after surgical procedure; (patients must have a PSA >= 0.8 ng/ml)Xx_NEWLINE_xXPatients must have a PSA doubling time of 5-15 monthsXx_NEWLINE_xXPatients must have a rising PSA as confirmed by 3 values done at least 1 week apart and over no less than 1 monthXx_NEWLINE_xXBaseline testosterone >= 100 ng/dlXx_NEWLINE_xXPSA =< 30 ng/mLXx_NEWLINE_xXSerum testosterone levels less than (<) 50 nanogram per deciliter (ng/dL) determined within 4 weeks prior to start of study drugXx_NEWLINE_xXPatients with prior history of prostate cancer that is not under active systemic treatment (except hormonal therapy), but with undetectable PSA (<0.2 ng/mL).Xx_NEWLINE_xXPatients must have PSA progression after local treatment:\r\n* PSA values for patients after surgery (or surgery and salvage/adjuvant radiation) must be greater than 0.2 ng/mL, determined by two measurements, at least 1 month apart and at least 6 months after prostatectomy OR\r\n* PSA values for patients after radiation must be greater than or equal to 2.0 ng/ml greater than the nadir achieved after radiation, determined by two measurements at 1 month apart and at least 6 months after the radiation treatment is completed; (patients who received adjuvant or salvage radiation after prostatectomy must have PSA of greater than or equal to 0.2)\r\n* The first two PSA values, along with a third (study baseline) value must all be rising (i.e., there must be an overall rising trajectory, such that the third value cannot be lower than the first value)\r\n* PSA doubling time using the mkscc.org PSA doubling time calculator must be greater than 4 monthsXx_NEWLINE_xXPatients must have a serum total testosterone level >= 150 ng/dL at the time of enrollment within 4 weeks prior to randomizationXx_NEWLINE_xXTestosterone ? 1.73 nmol/L (? 50 ng/dL) at screening;Xx_NEWLINE_xXProgressive disease on androgen deprivation therapy at screening defined as a minimum of two sequentially rising prostate-specific antigen (PSA) values (PSA1 < PSA2 < PSA3);Xx_NEWLINE_xXThe screening PSA (PSA3) must be ? 2 ?g/L (? 2 ng/mL).Xx_NEWLINE_xXPatients must have a minimum serum PSA level of >2 ng/ml that is rising based on the Prostate Cancer Working Group 2 criteria.Xx_NEWLINE_xXPatients must have castrate levels of testosterone (<50 ng/dl [1.74 nmol/l]).Xx_NEWLINE_xXThe serum PSA should be less than or equal to 15 ng/ml; study entry PSA must not be obtained during the following time frames: (1) 10-day period following prostate biopsy; (2) following initiation of androgen deprivation therapy (ADT); (3) within 30 days after discontinuation of finasteride; or (4) within 90 days after discontinuation of dutasterideXx_NEWLINE_xXHave a PSA or radiographic progression on enzalutamide; PSA progression is defined as two consecutive increases in PSA with the second level obtained at least 3 weeks after the first, and the second level of at least 0.5 ng/mL; soft tissue disease progression defined by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria or >= 2 new lesions on bone scanXx_NEWLINE_xXHave had either surgical castration OR be on luteinizing hormone-releasing hormone (LHRH) agonist or antagonist therapy with serum testosterone < 50 ng/dl AND agree to stay on LHRH agonist or antagonist therapy during the studyXx_NEWLINE_xXIntermediate risk prostate cancer patients will be eligible for this study; intermediate risk grouping will be assessed per National Comprehensive Cancer Network (NCCN) guidelines as: \r\n* Pathologically-proven diagnosis of prostate adenocarcinoma\r\n* PSA 10-20 ng/mL or\r\n* Gleason = 7 or\r\n* Clinical stage T2b/cXx_NEWLINE_xXParticipants must have the following features:\r\n* Intermediate-risk disease defined as Gleason 4+3 = 7 disease OR\r\n* High-risk disease defined as Gleason 8-10 OR PSA > 20 ng/mL OR T3 disease (by prostate MRI)Xx_NEWLINE_xXHypogonadism or severe androgen deficiency as defined by screening serum testosterone < 200 ng/dLXx_NEWLINE_xXCastration-resistant prostate cancer demonstrated during continuous androgen deprivation therapy (ADT), defined as 3 rises of PSA, at least 1 week apart with the last androgen deprivation therapy (PSA) >= 2 nanogram per milliliters (ng/mL)Xx_NEWLINE_xXParticipants who received a first generation anti-androgen (eg, bicalutamide, flutamide, nilutamide) must have at least a 6-week washout prior to randomization and must show continuing disease (PSA) progression (an increase in PSA) after the washout periodXx_NEWLINE_xXProstate-specific antigen (PSA) < 20 ng/dlXx_NEWLINE_xXThe subject must have castration-resistant prostate cancer (CRPC) with castrate levels of serum testosterone less than 50 ng/dL; Note: subjects must maintain a castrate state; if they have not had an orchiectomy must continue to receive luteinizing-hormone-releasing hormone (LHRH) or gonadotropin-releasing hormone (GnRH) agonists unless intolerantXx_NEWLINE_xXCastration resistant prostatic adenocarcinoma; subjects must have castrated levels of serum testosterone (< 50 ng/dL) achieved by orchiectomy or luteinizing hormone-releasing hormone (LHRH) agonist or antagonist therapyXx_NEWLINE_xXEvidence of disease progression on or after the most recent systemic treatment disease defined by the following criteria:\r\n* PSA: increasing PSA levels as defined by the Prostate Cancer Clinical Trials Working Group (PCWG2), determined by 2 consecutive measurements (compared to a baseline or nadir value); if the third measurement is below the second, then a fourth measurement must be greater than the second; the confirming third or fourth measurement must be >= 2 ng/mL; PSA progression must have occurred within 15 months of registration with at least 7 days between each PSA measurement; additionally the PSA progression as described above should have occurred during or after the most recent systemic treatment for prostate cancer\r\n* Measurable disease: >= 20% increase in the sum of the short axis diameter of all measurable lymph nodes or the development of any new measurable lymphadenopathy by Response Evaluation Criteria In Solid Tumors (RECIST) 1.1 and PCWG2 criteria\r\n* Non-measurable disease:\r\n** Lymph node disease: appearance of 1 or more new lymphadenopathy, and/or unequivocal worsening of non-measurable disease when compared to imaging studies acquired during castration therapy or against the pre-castration studies if there was no response\r\n** Bone disease: appearance of 2 or more new areas of abnormal uptake on bone scan when compared to imaging studies acquired during castration therapy or against the pre-castration studies if there was no response; increased uptake of pre-existing lesions on bone scan does not constitute progressionXx_NEWLINE_xXSurgically or medically castrated, with testosterone levels of less than (<) 50 nanogram per deciliter (ng/dL)Xx_NEWLINE_xXTumor progression while on hormone therapy with castrate levels serum testosterone (=< 1.7 nmol/L or 50 ng/dL) defined as biopsy-proven, PSA and/or radiographic criteria according to the Prostate Cancer Working Group 2 (PCWG2); castrate levels of testosterone must be maintained by surgical or medical means throughout the conduct of the studyXx_NEWLINE_xXCastration-resistant prostate cancer: patients must have surgical or ongoing chemical (androgen deprivation therapy) castration, with baseline testosterone level =< 50 ng/dL determined within 4 weeks of starting study drugXx_NEWLINE_xXCastrate levels of serum testosterone < 50 ng/dL determined within 4 weeks prior to starting treatmentXx_NEWLINE_xXPatients must have a minimum PSA >= 5 ng/mL within 60 days of registration or prior to the initiation of androgen deprivation for patients who have started androgen deprivation therapyXx_NEWLINE_xXAll patients who have not initiated hormone therapy (early induction patients) must have elevated PSA >= 4 ng/ml within 28 days prior to registration; for late induction registrations, PSA must be >= 4 ng/ml prior to start of androgen deprivation therapy; either antiandrogen or LHRH analogue or gonadotropin-releasing hormone (GNRH) antagonist; if patients are on antiandrogen, this will need to be discontinued for at least 7 days prior to registrationXx_NEWLINE_xXRising serum PSA levels documented by 3 values over the last 6 months prior to study enrollment. Each value must be greater than 2 weeks from the previous value.Xx_NEWLINE_xXPatients with rising PSA must have had either 1) prior definitive therapy including surgery or radiation therapy (hormone-naïve, defined as hormone-naïve patients and patients who received hormone therapy in the past who currently have total testosterone greater than 50 ng/dL), or 2) hormone suppressive therapy as documented by surgical castration or a serum testosterone value less than 50 ng/dL (hormone-independent). Patients must have completed these therapies for at least 6 months but no longer than 20 years prior to enrollmentXx_NEWLINE_xXPSA value within 4 weeks of starting therapy less than 20 ng/mL for hormone-naïve patients (defined as hormone-naïve patients and patients who received hormone therapy in the past who currently have total testosterone greater than 50 ng/dL) or less than 60 ng/mL for hormone-independent patients.Xx_NEWLINE_xXProgressive disease (PSA, radiologic, symptomatic) following abiraterone acetate and/or enzalutamide (prior chemotherapy and sipuleucel-T is allowed); PSA progression is defined as baseline increase followed by any PSA increase >= 1 week apartXx_NEWLINE_xXAn elevated PSA level of > 2 ng/mL for patients progressing by PSA criteria is required (last confirmatory sample must be > 2 ng/mL)Xx_NEWLINE_xXCurrently on androgen ablation hormone therapy (a luteinizing hormone-releasing hormone [LHRH] agonist/antagonist or orchiectomy) with testosterone level < 50 ng/dL)Xx_NEWLINE_xXMedical or surgical castration with testosterone less than 50 ng/dL (1.7nmol/L).Xx_NEWLINE_xXSerum PSA ?2 ng/mL (?g/L)Xx_NEWLINE_xXParticipants must have histologically confirmed malignancy and are candidates for external beam radiation therapy; patients eligible for this study must have intermediate risk disease defined as PSA values between 10-20 ng/ml and/or T2b-c and/or Gleason grade 7; if all three are present, less than 50% of the core biopsies can be positiveXx_NEWLINE_xXHypogonadism or severe androgen deficiency as defined by screening serum testosterone less than 50 ng/dL below the normal range for the institutionXx_NEWLINE_xXParticipants must have progressive disease as defined by one or more of the following:\r\n* Castrate resistant disease as defined by Prostate Cancer Working Group (PCWG)2; participants must have a rise in PSA on two successive determinations at least one week apart and PSA levels >= 2 ng/ml (only the screening PSA needs to be >= 2 ng/ml) and testosterone levels < 50 ng/dL\r\n* Soft tissue progression defined by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1\r\n* Bone disease progression defined by PCWG2 with two or more new lesions on bone scanXx_NEWLINE_xXParticipants must have a testosterone level < 50 ng/dLXx_NEWLINE_xXSerum testosterone level: ? 50 ng/dL (1.7 nmol/L)Xx_NEWLINE_xXSerum PSA (Prostate specific antigen) progression defined as 2 subsequent increases in PSA over a previous reference value (a minimum of 2 ng/mL [?g/L]) ORXx_NEWLINE_xXCOHORT B: Histologically confirmed prostate cancer with progressive disease, defined as:\r\n* Rising PSA (50% or more increase to a level of 1 ng/mL or more, based on at least 3 PSA determinations obtained at least 1 week apart); the 50% rise in PSA is across the 3 determinations, and these determinations do not need to be sequential\r\n* PSA doubling time of =< 12 months as calculated according to the Memorial Sloan-Kettering Cancer Center nomogramXx_NEWLINE_xXProstate-Specific Antigen (PSA) progression defined by a minimum of 2 rising PSA levels with an interval of at least 1 week between each draw;Xx_NEWLINE_xXCandidate for abiraterone therapy with documented evidence of metastatic castration-resistant prostate cancer. Metastatic status is defined as at least one documented metastatic lesion on either bone scan or CT/MRI scan. Castration resistant prostate cancer is defined as rising PSA or other signs of disease progression despite treatment with androgen deprivation therapy and the presence of a castrate level of testosterone (?50 ng/dL).Xx_NEWLINE_xXSerum PSA > 2.0 ng/mL; prostate cancer progression documented by PSA according to Prostate Cancer Working Group 2 (PCWG2) or radiographic progression according to modified Response Evaluation Criteria in Solid Tumors (RECIST) criteriaXx_NEWLINE_xXSurgically or medically castrated, with testosterone levels of < 50 ng/dL (< 2.0 nM); if the patient is being treated with luteinizing hormone-releasing hormone (LHRH) agonists (patient who have not undergone orchiectomy), this therapy must have been initiated at least 4 weeks prior to cycle 1 day 1 and must be continued throughout the studyXx_NEWLINE_xXPatients must have evidence of biochemical (PSA) relapse after prostatectomy, defined by one rise in PSA above a baseline detectable value (>= 0.05 ng/mL) using measurements taken at least 4 weeks apart from each other (all PSA values must be within 12 months of study entry)Xx_NEWLINE_xXPatients must have an absolute PSA level between > 0.05 and < 0.7 ng/mL at the time of study entryXx_NEWLINE_xXPatients must have non-castrate levels of serum testosterone (>= 150 ng/dL)Xx_NEWLINE_xXPatients must have progressive disease at study entry defined as one or more of the following three criteria that occurred while the patient was on androgen deprivation therapy; for patients enrolling on the basis of soft tissue or bone progression, the baseline scan must show progression relative to a comparison scan; if the comparison scan is not available, the baseline scan report must reference the previous scan to document progression\r\n* PSA progression defined by a minimum of two rising PSA levels with an interval of >= 1 week between each determination; patients who received an anti-androgen must have progression documented by a minimum of two rising PSA levels with an interval of >=1 week between each determination such that at least the second of these rises is >= 4 weeks since last flutamide, bicalutamide or nilutamide; the PSA value at the screening should be >= 2 ug/L (2 ng/mL)\r\n* Soft tissue disease progression defined by at least 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study)\r\n* Bone disease progression defined by PCWG2 with two or more new lesions on bone scanXx_NEWLINE_xXTestosterone =< 50 ng/dL (1.7 nmol/L)Xx_NEWLINE_xXCastration-resistant prostate cancer demonstrated during continuous ADT, defined as 3 PSA rises, at least 1 week apart, with the last PSA greater than (>) 2 nanogram per milliliter (ng/mL)Xx_NEWLINE_xXPatients who received a first generation anti-androgen (for example, bicalutamide, flutamide, nilutamide) must have at least a 4-week washout prior to randomization AND must show continuing disease (PSA) progression (an increase in PSA) after washoutXx_NEWLINE_xXParticipants must have progressive disease as defined by either:\r\n* Castrate resistant disease as defined by Prostate Cancer Working Group (PCWG); participants must have a rise in PSA on two successive determinations at least one week apart and PSA levels >= 2 ng/ml (only the screening PSA needs to be >= 2 ng/ml) and testosterone levels < 50 ng/dL, OR\r\n* Soft tissue progression defined by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1, OR\r\n* Bone disease progression defined by PCWG2 with two or more new lesions on bone scanXx_NEWLINE_xXParticipants must have a testosterone levels < 50 ng/dLXx_NEWLINE_xXOngoing androgen-deprivation therapy (ADT) using a luteinizing hormone-releasing hormone (LHRH) agonist (e.g. leuprolide, goserelin) or antagonist (e.g. degarelix) must continue on therapy unless prior bilateral orchiectomy has been performed; screening serum testosterone must be =< 50 ng/dlXx_NEWLINE_xXPSA >= 2.0 ng/mLXx_NEWLINE_xXEvidence of disease progression on ADT as evidenced by one of the following:\r\n* Absolute rise in PSA of 2.0 ng/mL or greater, minimum 2 consecutive rising PSA levels with an interval of >= 1 week between each PSA level, OR\r\n* 2 consecutive PSA levels 50% or greater above the PSA nadir achieved on ADT and separated at least 1 week apart, OR\r\n* Computed tomography (CT) or magnetic resonance imaging (MRI) based evidence of disease progression (soft tissue, nodal or visceral disease progression) according to modified Prostate Cancer Working Group 2 (PCWG2) criteria or modified Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria, or at least 1 new bone scan lesion as compared to the most immediate prior radiologic studiesXx_NEWLINE_xXPatients must have undergone a radical prostatectomy (any surgical technique is permitted) within 3 months from study entry and have high-risk disease define by any of the following:\r\n* Pathological stage T3a, T3b, T4 (any grade or initial prostate-specific antigen [iPSA])\r\n* Gleason sum >= 8 (any stage or iPSA)\r\n* Initial pre-operative PSA >= 20 ng/mL (any Gleason score [GS] or pT stage)\r\n* Any stage/PSA/Gleason patients with a 35% or greater chance of biochemical failure at 5 years based on Kattan's nomogram\r\n* Patients with lymph node (LN) positive disease, regardless of iPSA, pT stage or GS provided their post-operative PSA 6-8 weeks after surgery is =< 0.4 ng/mL (lymph node dissection is desired but not mandated)Xx_NEWLINE_xXTestosterone >= 50 ng/dL per laboratory reference rangeXx_NEWLINE_xXBaseline post-radical prostatectomy (RP) PSA =< 0.4Xx_NEWLINE_xXProstate specific antigen (PSA) value can be undetectable up to a value of 2.0 within 30 days prior to study entryXx_NEWLINE_xXPatient must have a histological diagnosis of adenocarcinoma of the prostate and 2 rising pre-study PSA values >= 1 ng/ml at least 1 week apart within 28 days prior to enrollmentXx_NEWLINE_xXPatients must be unresponsive to androgen-deprivation therapy (ADT), as indicated by a rising PSA level above the ADT nadirXx_NEWLINE_xXBiochemical progression defined as follows:\r\n* For patients following definitive radiation therapy: a rise in PSA of >= 2 ng/mL above the nadir (per Radiation Therapy Oncology Group [RTOG]-American Society for Radiation Oncology [ASTRO] consensus criteria)\r\n* For patients following radical prostatectomy: rising PSA after surgical procedure (patients must have a PSA >= 2 ng/ml)Xx_NEWLINE_xXPatients must have a PSA doubling time of 12 months or lessXx_NEWLINE_xXPatients must have a rising PSA as confirmed by 3 values done at least 1 week apart and over no less than 1 monthXx_NEWLINE_xXPSA =< 20 ng/mLXx_NEWLINE_xXCastrate testosterone level (< 50 ng/dl or 1.7 nmol/L)Xx_NEWLINE_xXProgressive disease at study entry defined as one or more of the following criteria occurring in the setting of castrate levels of testosterone:\r\n* Radiographic progression defined as any new or enlarging bone lesions or growing lymph node disease, consistent with prostate cancer OR\r\n* PSA progression defined by sequence of rising values separated by > 1 week (2 separate increasing values over a minimum of 2 ng/ml [Prostate Cancer Clinical Trials Working Group (PCWG2) PSA eligibility criteria]); if patient has 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 enrollmentXx_NEWLINE_xXAll patients must meet one or more of the following disease features: clinical stage >= T3; primary Gleason score of 4 OR Gleason score of 8, 9 or 10; serum PSA >= 20 ng/mL; prostate magnetic resonance imaging (MRI) findings consistent with T3 disease; any clinical stage and PSA > 10 and Gleason score 7; a Kattan nomogram predicted probability of being free from biochemical progression at 5 years after surgery of < 60%Xx_NEWLINE_xXPatients must have a PSA >= 2 ng/mL at the time of diagnosis of prostate cancer or laterXx_NEWLINE_xXPSA > 2 ng/mLXx_NEWLINE_xXTestosterone < 50 ng/dLXx_NEWLINE_xXCastrate levels of testosterone (testosterone < 50 ng/dL) on androgen deprivation therapy (ADT). Patients who have not undergone orchiectomy will continue gonadotropin releasing hormone (GnRH) agonist or antagonist therapy.Xx_NEWLINE_xXEvidence of disease progression on ADT. Patients must have two serial rises in PSA from nadir, with at least 1 week between PSA measurements, with a minimum PSA of 2 ng/mL, OR patients must have radiographic evidence of progression. Nadir is defined as the lowest PSA value after beginning the most recent therapy for metastatic CRPC.Xx_NEWLINE_xXPSA doubling time less than or equal to 12 monthsXx_NEWLINE_xXMinimum PSA 1.0 ng/mL if prior radical prostatectomy +/- adjuvant or salvage radiation; nadir + 2.0 ng/mL if prior RT without prior radical prostatectomyXx_NEWLINE_xXSerum testosterone > 150 ng/dL at study entryXx_NEWLINE_xXProstate cancer recurrence after definitive local therapy (radical prostatectomy and/or radiation therapy) as evidenced by rising serum PSA, without evidence of metastases by bone scan or CT scan. a) After radiation: A rising PSA taken to indicate recurrent prostate cancer in patients with previous definitive external beam radiotherapy will be defined as PSA of 1.0, b) After Radical Prostatectomy: A rising PSA taken to indicate recurrent prostate cancer in patients with previous radical prostatectomy will be defined by the criteria of the American Urological Association as any PSA measurement of 0.2, with a subsequent measurement >0.2 ng/mLXx_NEWLINE_xXHistologically confirmed prostate cancer (per standards at institution of participant registration) currently with progressive disease, defined as:\r\n* Rising PSA (50% or more increase to a level of 1 ng/mL or more, based on at least 3 PSA determinations obtained at least 1 week apart); the 50% rise in PSA is across the 3 determinations, and these determinations do not need to be sequential; AND\r\n* Prostate-specific antigen doubling time (PSADT) =< 9 months as calculated according to the Memorial Sloan-Kettering Cancer Center nomogramXx_NEWLINE_xXPatients must have a serum testosterone of 150 ng/dL or greaterXx_NEWLINE_xXAndrogen dependent disease measured by declining prostate-specific antigen (PSA) and do not display signs of progression demonstrated by a rising PSAXx_NEWLINE_xXOngoing androgen blockade demonstrated by serum testosterone concentration of less than 50 ng/dLXx_NEWLINE_xXCastrate-resistant disease, defined as follows:\r\n* All patients must have received standard of care androgen deprivation treatment before trial entry (surgical castration versus gonadotropin-releasing hormone [GnRH] analogue or antagonist treatment), and subjects receiving GnRH analogue or antagonist must continue this treatment throughout the time on this study\r\n* Patients may have been treated previously with a nonsteroidal antiandrogen, with evidence of disease progression subsequently; subjects must be off use of anti-androgen for at least 4 weeks (for flutamide) or 6 weeks (for bicalutamide or nilutamide) prior to registration\r\n** Subjects who demonstrate an anti-androgen withdrawal response, defined as a >= 25% decline in PSA within 4-6 week of stopping a nonsteroidal antiandrogen are not eligible until the PSA rises above the nadir observed after antiandrogen withdrawal\r\n* Castration levels of testosterone (< 50 ng/dL) within 2 weeks of registrationXx_NEWLINE_xXMust have >= 3 serum PSA values obtained over at least a 12 week period of time prior to registration, including the day of screening, to calculate a PSA doubling time; Note: PSA’s are not required to be obtained at the same laboratory; use all PSA values that have been done in last 6 months to calculate PSA doubling timeXx_NEWLINE_xXCastrate serum testosterone level, =< 1.73 nmol/L (50 ng/dL), at the screening visitXx_NEWLINE_xXMust have metastatic, progressive, castrate resistant prostate cancer (CRPC); there must be radiographic evidence of disease after primary treatment with surgery or radiotherapy that has continued to progress radiographically or biochemically (rising prostate specific antigen [PSA] levels on successive measurements) despite adequate androgen-deprivation therapy, which is defined as having undergone bilateral surgical castration or continued treatment on gonadotropin-releasing hormone (GnRH) agonists or antagonists\r\n* Progression must be evidenced and documented by any of the following parameters:\r\n** Two consecutively rising PSA values, above the baseline, at a minimum of 1-week intervals\r\n** Appearance of one or more new lesions on bone scan\r\n** Progressive measurable disease by RECIST 1.1\r\n* The use of androgen receptor inhibitors is not required prior to study entry; for those patients receiving an anti-androgen agent (flutamide, bicalutamide, or nilutamide), for at least 6 consecutive months immediately prior to study entry, and are entering the trial due to a rise in PSA, they must demonstrate a continued rise in PSA within 4 weeks after stopping flutamide and within 6 weeks after stopping bicalutamide or nilutamide; flutamide, nilutamide and bicalutamide disease progression requirements only apply to patients who have been on these drugs for at least the prior 6 monthsXx_NEWLINE_xXProstate specific antigen (PSA) > 1 ng/ml, unless anaplastic features are presentXx_NEWLINE_xXPatients with \anaplastic\ features are eligible for this trial as defined by at least one of the following: a) any of the following metastatic presentations: exclusive visceral metastases, radiographically predominant lytic bone metastases identified by plain X-ray or CT scan, bulky (> 5 cm in longest dimension) lymphadenopathy or high-grade (Gleason > 8) tumor mass in the prostate/pelvis; b) low PSA (=< 10 ng/ml) at initial presentation (prior to androgen ablation or at symptomatic progression in the castrate-setting) plus high volume (>= 20) bone metastases; c) elevated serum lactate dehydrogenase (LDH) (>= 2 x ULN) or elevated serum carcinoembryonic antigen (CEA) (>= 2 x ULN) in the absence of other etiologies; d) short interval (=< 180 days) to castrate-resistant progression following initiation of hormonal therapyXx_NEWLINE_xXHave progressive metastatic castration-resistant prostate cancer, on androgen-deprivation therapy, based on at least one of the following criteria:\r\n* PSA progression defined as 25% increase over baseline value with an increase in the absolute value of at least 2 ng/mL that is confirmed by another PSA level with a minimum of a 1-week interval with a minimum PSA of 2 ng/mL\r\n* Progression of bidimensionally measurable soft tissue (nodal metastasis) assessed within one month prior to registration by a computed tomography (CT) scan or magnetic resonance imaging (MRI) of the abdomen and pelvis\r\n* Progression of bone disease (evaluable disease) (new bone lesion[s]) by bone scanXx_NEWLINE_xXHave testosterone < 50 ng/dL; patients must continue primary androgen-deprivation with a luteinizing hormone-releasing hormone (LHRH) analogue if they have not undergone orchiectomyXx_NEWLINE_xXPatient must have biochemical evidence of prostate-specific antigen (PSA) including one of the following:\r\n* Biochemical recurrence (defined as nadir + 2 rises measured at least 2 weeks apart)\r\n* PSA doubling time of less than or equal to 6 months OR\r\n* Persistently elevated PSA (PSA post prostatectomy of 0.2 ng/mL if standard assay or greater than 0.05 if ultrasensitive PSA assay)Xx_NEWLINE_xXHistologically or cytologically confirmed prostate cancer with progressive disease defined as either:\r\n* 2 or more new lesions on bone scan or\r\n* Progressive disease on computed tomography (CT)/magnetic resonance imaging (MRI) according to Response Evaluation Criteria In Solid Tumors (RECIST) 1.1 criteria or\r\n* Rising PSA: PSA evidence for progressive prostate cancer consists of a minimum PSA level of at least 2 ng/ml, which has subsequently risen on at least 2 successive occasions, at least 2 weeks apartXx_NEWLINE_xXEvidence of castration resistance defined as disease progression despite a testosterone level < 50 ng/dL (or surgical castration)Xx_NEWLINE_xXFor cohorts 1, 2, and 4 only: non-castrate testosterone level (> 100 ng/dL)Xx_NEWLINE_xXFor cohort 3 only: 1-6 months of androgen deprivation therapy (gonadotropin hormone releasing analogs with or without an anti-androgen) prior to prostatectomy with a castrate testosterone level of < 50 ng/dL within 1 month prior to prostatectomyXx_NEWLINE_xXA PSA of > 0.2 ng/ml after 6-18 months of androgen suppression therapy, which may consist of luteinizing hormone-releasing hormone (LHRH) agonist or antagonist alone or the combination of an LHRH agonist or antagonist plus an antiandrogen, such as bicalutamide; androgen suppression therapy will continue without interruptionXx_NEWLINE_xXTotal testosterone < 50 ng/ml, except in patients with prior orchiectomy, where testosterone does not need to be measured; patients must continue their LHRH agonist therapy throughout study durationXx_NEWLINE_xXAdenocarcinoma of the prostate with locally advanced prostate cancer without distant metastatic with unfavorable risk features that are defined below: \r\n* Gleason Score >= 8; prostate-specific antigen (PSA) any; T-Stage any\r\n* Gleason Score 7; PSA >= 20; T-Stage any\r\n* Gleason Score 7; PSA any; T-Stage T3/T4Xx_NEWLINE_xXPatients must have high-risk clinical stage D0 disease defined by the following:\r\n* In patients previously treated by prostatectomy, must have evidence of rising prostate specific antigen (PSA) with measurements at least two weeks apart, and final serum PSA value must be >= 2 ng/mL\r\n* In patients previously treated with ablative radiation therapy, an absolute increase in serum PSA by at least 2 ng/mL over nadir PSA value after radiation therapy\r\n* All patients must have at least four serum PSA values determined over a 12-week-to-six-month period of time prior to study entry from the same clinical laboratory; all available PSA values during this period (up to 6 months) will be used to calculate a PSA doubling time, according to the Memorial Sloan-Kettering Cancer Center nomogram\r\n* The PSA doubling time calculated from this nomogram, up to and including the value obtained at screening, must be < 12 monthsXx_NEWLINE_xXSerum testosterone at screening < 50 ng/dLXx_NEWLINE_xXI 04. Effective castration (serum testosterone levels ?0.50 ng/mL) by orchiectomy and/or luteinizing hormone-releasing hormone (LHRH) agonists or antagonist with or without anti-androgens.Xx_NEWLINE_xXSerum testosterone levels < 50 ng/dL (unless surgically castrate); patients must continue androgen deprivation with an luteinizing hormone releasing hormone (LHRH) agonist if they have not undergone orchiectomyXx_NEWLINE_xXPSA > 2 ng/mL (at the time of enrollment or prior to initiation of docetaxel)Xx_NEWLINE_xXSerum prostate specific antigen (PSA) < 10 ng/mL            \r\n* NOTE: baseline PSA for determination of eligibility must be measured after discontinuation of any 5-alpha reductase inhibitorsXx_NEWLINE_xXProgressive disease despite androgen deprivation therapy as defined by rising PSA levels or progressive soft tissue or bony diseaseXx_NEWLINE_xXHistologically or cytologically proven prostate cancer with high risk for development of metastases, defined as either a PSA value >=8 ng/mL within the last 3 months or PSA Doubling Time <=10 monthsXx_NEWLINE_xXCastrate levels of serum testosterone of less than or equal to 50 ng/dLXx_NEWLINE_xXEvidence of measurable disease either by RECIST 1.1 or elevation of serum tumor markers (AFP > 15 ng/mL or HCG > 2.2 mIU/ml)Xx_NEWLINE_xXBiopsy proven intermediate risk prostate cancer, which includes patients with any one of the following variables:\r\n* Gleason 7 disease\r\n* Prostate-specific antigen (PSA) 10-20 ng/ml\r\n* Clinical T2b-T2c disease\r\n* Note: Patients who only have radiographic evidence of T3 disease (i.e. extracapsular extension, or seminal vesical invasion radiographically) will not be excludedXx_NEWLINE_xXSerum testosterone >= 240 ng/dL determined within 2 months prior to enrollmentXx_NEWLINE_xXMust have shown clinical characteristics of acquired resistance to enzalutamide or apalutamide defined as: decline in serum PSA ?50% compared to baseline serum levels by week 12 (±4 weeks) of enzalutamide or apalutamide treatment and before disease progression by PCWG3 PSA criteria, OR disease progression by PCWG3 radiographic criteria. (Part 2 only) Parts 1 and 2:Xx_NEWLINE_xXPrior orchiectomy or serum testosterone levels <50 ng/dL determined within 4 weeks prior to start of study drug.Xx_NEWLINE_xXPatients with microscopic and/or gross extra thyroidal disease extension without RAI uptake but with a) FDG-PET positive disease or b) suppressed thyroglobulin >1 ng/mL or c) stimulated thyroglobulin >10 ng/L.Xx_NEWLINE_xXPatients with histologically proven prostate cancer and tumors limited to the prostate (including seminal vesicle involvement, provided all visible disease was surgically removed) that have completed local therapy and have an elevated PSA after surgery or rising PSA after radiation therapyXx_NEWLINE_xXHormone-sensitive prostate cancer as evident by a serum total testosterone level > 150 ng/dL or > 6 nmol/L at the time of enrollment within 4 weeks prior to randomizationXx_NEWLINE_xXAll patients must have evidence of biochemical progression as determined by a reference PSA value followed by 1 confirmatory rising PSA value, higher than the previous value, obtained at least 2 weeks apart; all of these PSA values must be obtained at the same reference lab, and all must be done within 6 months prior to enrollmentXx_NEWLINE_xXThe most recent of the PSA values must be >= 2.0 ng/ml; this measurement must be obtained within 1 month prior to enrollmentXx_NEWLINE_xXThe PSA doubling time (PSA-DT) must be less than 12 monthsXx_NEWLINE_xXserum prostate specific antigen (PSA) ?0.5 ng/mL and ?10 ng/mL;Xx_NEWLINE_xXPre-registration serum PSA level =< 100 ng/mLXx_NEWLINE_xXOngoing androgen deprivation therapy with a luteinizing hormone-releasing hormone (LHRH) agonist or antagonist, or bilateral orchiectomy and serum testosterone level < 50 ng/dL (< 0.5 ng/mL, < 1.7 nmol/L) at screeningXx_NEWLINE_xXDemonstrated PSA progression within 12 weeks of study participationXx_NEWLINE_xXCRPC participants must maintain ongoing androgen deprivation therapy with a gonadotropin releasing hormone (GnRH) analogue, antagonist or orchiectomy providing serum testosterone is <50 ng/dL (<1.7 nmol/L)Xx_NEWLINE_xXPSA progression according to PCWG2 criteria with 3 consecutive rising PSA measurements, all collected at least 1 week apartXx_NEWLINE_xXSerum testosterone level < 50 ng/dL at Screening visitXx_NEWLINE_xXTestosterone ? 1.73 nmol/L (? 50 ng/dL) at screening.Xx_NEWLINE_xXSerum testosterone levels < 50ng/mlXx_NEWLINE_xXEvidence of disease progression (PSA progression, or radiographic/clinical progression [Prostate Cancer Working Group (PCWG2)])\r\n* PSA progression is defined as at least two consecutive rises in serum PSA, obtained at a minimum of 1-week intervals, and each value >= 2.0 ng/mL\r\n* Radiographic progression is defined for soft tissue lesions using Response Evaluation Criteria in Solid Tumors (RECIST) criteria, i.e an increase greater than 20% in the sum of the longest diameter of all target lesions based on the smallest sum longest diameter since treatment started or the appearance of one of more new lesions with a confirmatory scan 6 or more weeks later; radiographic progression will be defined for bone lesions as the appearance of two new lesions with a confirmatory scan performed 6 or more weeks later that shows at least 2 or more additional new lesionsXx_NEWLINE_xXCastrate serum testosterone (< 50 ng/dL)Xx_NEWLINE_xXTwo consecutively rising PSA values or two out of three rising PSA values (2.0 ng/mL is the minimum ending value for PSA) at a minimum of 1-week intervalsXx_NEWLINE_xXThe subject must currently have castration resistant prostate cancer defined as 2 serial rising prostate-specific antigens (PSAs) with a castrate level of testosterone (< 50 ng/dL)Xx_NEWLINE_xXSerum testosterone level < 50 ng/dLXx_NEWLINE_xXSerum neutralization antibody assay shows >= 75% neutralization of the SS1 (dsFv) PE38 activity at 200 ng/mlXx_NEWLINE_xXHad a second malignancy within the previous 5 years, except for basal cell carcinoma, cervical intra-epithelial neoplasia or treated prostate cancer with a prostate-specific antigen (PSA) of <2.0 ng/mL;Xx_NEWLINE_xXCastrate levels of serum testosterone (=< 50 ng/dL or 1.0 mmol/L) confirmed within two weeks prior to day 1 of treatment; testosterone levels will not be required for patients who have had bilateral orchiectomyXx_NEWLINE_xXPatient must have evidence of castrate resistant prostate cancer as evidenced by a confirmed rising PSA (per Prostate Cancer Working Group 2 [PCWG2] criteria) and a castrate serum testosterone level (i.e. =< 50 mg/dL)Xx_NEWLINE_xXAll patients must have a PSA >= 2 ng/mLXx_NEWLINE_xXProgressive disease based on any one of the following:\r\n* For patients with measurable disease, progression will be defined by the Response Evaluation Criteria in Solid Tumors (RECIST) criteria\r\n* For patients with non-measurable disease, a positive bone scan and elevated PSA will be required; PSA evidence for progressive prostate cancer consists of a PSA level of at least 2 ng/ml which has risen on at least 2 successive occasions, at least one week apart; if the confirmatory PSA value is less than the screening PSA value, then an additional test for rising PSA will be required to document progression for the purposes of eligibility\r\n* Radionuclide bone scan: new metastatic lesions\r\n* Patients whose sole manifestation of progression is an increase in disease-related symptoms are not eligibleXx_NEWLINE_xXTestosterone < 50 ng/dL; patients must continue primary androgen deprivation with an LHRH analogue if they have not undergone orchiectomyXx_NEWLINE_xX300 ng/mL < serum ferritin < 1,500 ng/mL (Values within 10% difference above 1500 ng/ml or 10% difference below 300 ng/ml may be accepted at the investigator's discretion.Xx_NEWLINE_xXCastrate resistant progression of prostate carcinoma, as shown by:\r\n* Serum testosterone level =< 30 ng/dL or prior bilateral orchiectomy; treatment to remain castrate levels of testosterone should continue, and\r\n* Either symptomatic progression, or, if patient is asymptomatic then a rising serum PSA in two occasions at least 1 week apart, with minimum pre-treatment serum PSA of 5 ng/dLXx_NEWLINE_xXSerum testosterone < 50 ng/dL determined within 4 weeks of first administration of study drugXx_NEWLINE_xXProstate cancer with a current PSA level < 0.1 ng/mL.Xx_NEWLINE_xXPatient must have evidence of castration resistant prostate cancer as evidenced by a confirmed rising PSA (per Prostate Cancer Working Group 2 [PCWG2] criteria) and a castrate serum testosterone level (i.e. =< 50 mg/dL)Xx_NEWLINE_xXAfter radical prostatectomy, two PSA measurements of ? 1.0 ng/mL at least one week apart;Xx_NEWLINE_xXAfter cryosurgery, two PSA measurements of ? 2.0 ng/mL at least one week apart;Xx_NEWLINE_xXBoth measurements are greater than 150 ng/dL or 5.2 nmol/L;Xx_NEWLINE_xXPSA doubling time (PSA-DT) of ? 3 months, using 2 PSA values at least 4 weeks apart, calculated according to the Memorial Sloan-Kettering Cancer Center nomogram (https://www.mskcc.org/nomograms/prostate/psa-doubling-time);Xx_NEWLINE_xXRising PSA defined (PCWG2).Xx_NEWLINE_xXA PSA value of at least 2 ng/mL is required at study entry.Xx_NEWLINE_xXEffective castration (serum testosterone levels ?0.5 ng/mL).Xx_NEWLINE_xXBiochemical disease progression after radical prostatectomy and/or radiation therapy (external-beam radiation therapy and/or brachytherapy), and no radiographic evidence of metastases\r\n* Men with history of radical prostatectomy are required to have baseline PSA > 0.5 ng/mL (prior treatment with neoadjuvant, adjuvant, or salvage radiation therapy is allowed, again, with screening PSA greater than or equal to 0.5 ng/mL required for eligibility)\r\n* Men treated with primary radiation therapy are required to have baseline PSA >= 1.0 ng/mL above their post radiation nadir for men who were treated with primary radiation therapy (external beam and/or brachytherapy); men who had primary radiation therapy followed by salvage prostatectomy are eligible if screening PSA is greater than or equal to 0.5 ng/mL\r\n* Men with previous neoadjuvant adjuvant hormone therapy are eligible if testosterone level at screening is non-castrate (>= 50 ng/dl); men previously treated with intermittent hormonal therapy are also eligible if level of testosterone at screening is non-castrate (>= 50 ng/dl)Xx_NEWLINE_xXCuratively treated cervical intraepithelial neoplasia or prostate carcinoma with current prostate specific antigen (PSA) < 0.01 ng/mL; orXx_NEWLINE_xXPatients must have castrate levels of testosterone (< 50 ng/dL) on gonadotropin-releasing hormone (GnRH) analogues or have had prior orchiectomy; GnRH analogues must be continued while on studyXx_NEWLINE_xXLocalized prostate cancer with at least one of the following National Comprehensive Cancer Network (NCCN) high-risk features:\r\n* Gleason sum >= 8\r\n* PSA > 20 ng/mL\r\n* Clinical stage >= T3Xx_NEWLINE_xXPSA at least 2 ng/mLXx_NEWLINE_xXTestosterone level < 50 ng/dL; patients receiving luteinizing hormone-releasing hormone (LHRH) agonists or antagonists must be continued to maintain castrate levels of testosterone while on studyXx_NEWLINE_xXPatients must have evidence of disease progression during current or prior therapy with abiraterone with either:\r\n* Biochemical progression as defined as rising PSA by Prostate Cancer Clinical Trials Working Group (PCWG2) from a nadir or baseline (whichever was lowest) confirmed on a second determination at least 1 week later that must be higher than the first and must have reached >=2 ng/ml (if no other evidence of progression); or\r\n* New metastases on bone scan (at least 2); or\r\n* Progression of measurable disease on computed tomography (CT) scan by Response Evaluation Criteria in Solid Tumors (RECIST) criteriaXx_NEWLINE_xXSerum testosterone (total) less than 25 ng/ml at time of enrollmentXx_NEWLINE_xXDevelopment of liver metastases in the absence of PSA progression as defined by PCWG2Xx_NEWLINE_xXPatients with pure small cell neuroendocrine carcinoma on histology are not required to have received prior androgen deprivation therapy (ADT) or castrate levels of testosterone, but their testosterone state should be maintained for the duration of the study. Other patients are required to have surgical or ongoing chemical castration, with baseline testosterone level <50ng/dL.Xx_NEWLINE_xXAmyloid cardiac biomarker stage III disease, defined as both NT-proBNP ? 332 pg/mL and troponin T ? 0.035 ng/mL. If troponin T is not available at local institution, troponin I may be used, but cut-off is ? 0.1 ng/mLXx_NEWLINE_xXBiochemically relapsed disease with a rising PSA on at least two successive measurements at least two weeks apart after prior definitive local therapy (radical prostatectomy, external beam radiation, or brachytherapy) or combination of radical prostatectomy and radiotherapy (RT) with curative intent; if the confirmatory PSA value is less than the screening PSA value, then an additional test for rising PSA will be required to documents progressionXx_NEWLINE_xXMinimum PSA:\r\n* If no prior androgen deprivation therapy (ADT) for biochemical relapse:\r\n** 1.0 ng/mL if prior radical prostatectomy with or without adjuvant/salvage radiation therapy, confirmed by repeat measurement at least 2 weeks later, or\r\n** Nadir + 2 ng/mL if prior RT alone without prior radical prostatectomy, confirmed by repeat measurement at least 2 weeks later\r\n* If prior ADT for biochemical relapse:\r\n** 4.0 ng/mL or > 2 ng/mL above nadir on prior cycle of ADT, whichever is higher, confirmed by repeat measurement at least 2 weeks laterXx_NEWLINE_xXSerum testosterone level:\r\n* If no prior androgen deprivation therapy:\r\n** A single measurement greater than 150 ng/dL within 3 months of day 1 of protocol therapy\r\n* If prior androgen deprivation therapy (either in adjuvant or biochemical relapse setting):\r\n** The two most recent measurements of serum testosterone prior to day 1 of protocol therapy must fulfill the following criteria:\r\n*** Both measurements are greater than 150 ng/dL\r\n*** The two measurements are spaced at least 14 days apart\r\n*** Both must be measured within 3 months of day 1 of protocol therapy\r\n*** There must not be an increase of > 50 ng/dL between these two successive measurementsXx_NEWLINE_xXPSA doubling time (PSADT) =< 15 months, calculated based upon all serum PSA measurements obtained within 3 months prior to day 1 of protocol therapy, with a minimum of three PSA measurements spaced at least 14 days apart ; PSA values obtained when serum testosterone was known to be less than 150 ng/dL, prior to local therapy, or within three months of last dose of LHRH agonist/antagonist or antiandrogen will be excluded from the calculation of the PSADTXx_NEWLINE_xXCastrate-resistant disease, as evidenced by either:\r\n* Rising PSA on 2 consecutive measurements at least 2 weeks apart with concurrent documented serum testosterone < 50 ng/dL at the time of PSA measurement, or\r\n* Rising PSA on 2 consecutive measurements at least 2 weeks apart measured within 3 months after last LHRH agonist/antagonist injectionXx_NEWLINE_xXPatients must be candidates for short or long term androgen deprivation in combination with external beam radiation therapy (RT) based on the following criteria:\r\n* Intermediate risk disease: T2b/c, or Gleason 7, or prostate-specific antigen (PSA) 10-20\r\n* High risk disease: Gleason 8-10, or PSA > 20, or T3/4Xx_NEWLINE_xXPatients with hypogonadism or severe androgen deficiency as defined by serum testosterone less than 100 ng/dL will not be eligibleXx_NEWLINE_xXPSA progression defined by a minimum of two rising PSA levels with an interval of ? 1 week between each determination. The PSA value at the Screening visit should be ? 2 ng/mLXx_NEWLINE_xXSerum testosterone <50 nanogram per deciliter (ng/dL) (1.7 nanomole per liter [nM/L])Xx_NEWLINE_xXIntermediate risk prostate cancer patients will be eligible for this study; risk groups will be assigned as per National Comprehensive Cancer Network (NCCN) guidelines; intermediate risk patients will be defined as:\r\n* PSA 10-20 ng/ml or\r\n* Gleason score = 7 or\r\n* Clinical stage T2b/T2cXx_NEWLINE_xXPatients will need to have documentation of metastatic disease in bone and/or soft tissue, and a baseline PSA of >= 5 ng/ml; patients with biochemical failures, with rising PSA (baseline PSA does not need to be >= 5 ng/ml to be eligible), without metastatic disease are also eligible if castration therapy is indicated for a minimum of 7 months and for these patients any PSA value is permittedXx_NEWLINE_xXMetastatic castration resistant prostate cancer as defined by serum testosterone < 50 ng/ml and one of the following:\r\n* Prostate specific antigen (PSA) level of at least 2 ng/ml that has risen on at least 2 successive occasions at least 1 week apart\r\n* Evaluable disease progression by modified RECIST (Response Evaluation Criteria in Solid Tumors) \r\n* Progression of metastatic bone disease on bone scan with > 2 new lesionsXx_NEWLINE_xXSurgical or medical castration with testosterone less than 50 ng/dLXx_NEWLINE_xXInclusion Criteria:\n\n        Men, ?18years of age with documented asymptomatic or minimally symptomatic metastatic\n        castration-resistant prostate cancer.\n\n        Documented progressive disease post surgical castration or during androgen suppression\n        therapy, or during complete androgen blockade therapy and withdrawal. Documented by either\n        criterion a (Radiological progression), OR criterion b (PSA progression).\n\n          1. Radiological progression defined as any new/enlarging bone metastases or new/enlarging\n             lymph node disease, consistent with prostate cancer.\n\n             OR\n\n          2. PSA progression defined by sequence of rising values separated by > 1 week (2 separate\n             increasing values) over a threshold minimum of 2.0 ng/ml. (PCWG2 PSA eligibility\n             criteria).\n\n        Chemotherapy naïve and Vaccinia-experienced (previous smallpox vaccination). Currently\n        using a GnRH agonist or antagonist (unless surgically castrated).\n\n        Exclusion Criteria:\n\n        Cancer-related pain requiring scheduled opioid narcotics for control (as needed, ? 2x per\n        week is allowed).\n\n        Metastasis to organ systems other than lymph nodes and/or bone. Estimated PSA doubling time\n        of <1 month as established within 6 months of the anticipated first dose of vaccine or\n        placebo.\n\n        Concurrent or prior Provenge (sipuleucel-T) immunotherapy for prostate cancer. Receipt of\n        an investigational agent within 30 days (or 60 days for an antibody-based therapy) of the\n        first planned dose of PROSTVAC-V/F.\n\n        History of prior malignancies other than prostate cancer within the past 3 years, excluding\n        successfully resected basal or squamous cell carcinoma of the skin.\n\n        Congestive heart failure (NYHA Class II, III, or IV), unstable angina, ventricular or\n        hemodynamically significant atrial arrhythmia, or cardiovascular disease such as stroke or\n        myocardial infarction (current or within the past 6 months) Confirmed positive for HIV,\n        hepatitis B, and /or hepatitis C. Immunodeficiency or splenectomy. History of or active\n        autoimmune disease, persons with vitiligo are not excluded. Diabetics are not excluded if\n        the condition is well controlled.\n\n        History of atopic dermatitis or active skin condition (acute, chronic, exfoliative) that\n        disrupts the epidermis.Xx_NEWLINE_xXSerum testosterone levels < 50 ng/dLXx_NEWLINE_xXHave documented disease progression while receiving or following hormonal therapy as determined by increasing Serum Prostate Specific Antigen (PSA) level, Radiological Progression, or ?2 new bone lesionsXx_NEWLINE_xXMedical or surgical castration with testosterone less than 50 ng/dLXx_NEWLINE_xXEugonadal state (serum testosterone > 150 ng/dL)Xx_NEWLINE_xXPatient must have evidence of castration resistant prostate cancer as evidenced by a confirmed rising PSA (per Prostate Cancer Working Group 3 [PCWG3] criteria) and a castrate serum testosterone level (i.e. =< 50 mg/dL); if a subject also received an anti-androgen, he must first progress through antiandrogen withdrawal prior to being eligible; the minimum timeframe to document failure of anti-androgen withdrawal will be four weeksXx_NEWLINE_xXSerum prostate specific antigen equal to or less than 10 ng/mLXx_NEWLINE_xXHave a PSA less than 10 ng/mL,Xx_NEWLINE_xXHave a PSA density less than 0.15 ng/ml/cc,Xx_NEWLINE_xXHave a PSA velocity less than 2 ng/ml yearly in the year prior to diagnosis,Xx_NEWLINE_xXBiochemical recurrence following prostatectomy or radiation to the prostate, defined as at least 3 PSA rises, with each PSA determination at least 4 weeks apart, and each PSA value >= 0.2 ng/mLXx_NEWLINE_xXPSA must be < 50 ng/mL at study entryXx_NEWLINE_xXScreening PSA >= 0.5 ng/mL for men who had a prostatectomy; prior treatment with neoadjuvant, adjuvant or salvage radiation therapy is allowed, again, with screening PSA >= 0.5 ng/mL required for eligibilityXx_NEWLINE_xXScreening PSA >= 1.0 ng/mL above their postradiation nadir for men who were treated with primary radiation therapy (external beam and/or brachytherapy); men who had primary radiation therapy followed by salvage prostatectomy are eligible if screening PSA >= 0.5 ng/mLXx_NEWLINE_xXPSA doubling time between 3 and 36 monthsXx_NEWLINE_xXProstate cancer, with organ-localized disease with very low risk of disease recurrence, as indicated by stage pT2, N0, M0 lesions (if American Joint Committee on Cancer [AJCC] staging is not available in medical records, the investigators will infer the staging based on extensive review of the pathology report), combined Gleason score of 7 (3+4) or less, and preoperative PSA < 10 ng/mlXx_NEWLINE_xXStable and undetectable PSA level (PSA < 0.1 ng/mL using an assay that has a functional sensitivity of 0.1 ng/mL) for at least two years after radical prostatectomyXx_NEWLINE_xXSerum testosterone, measured by liquid chromatography (LC)–mass spectrometry (MS)/MS, < 300 ng/dL and/or calculated free testosterone < 60 pg/mLXx_NEWLINE_xXCastrate serum testosterone level: =< 50 ng/dL (=< 1.7 nmol/L)Xx_NEWLINE_xXKnown progressive castration-resistant disease, defined as: \r\n* Serum PSA progression defined as two consecutive increases in PSA over a previous reference value within 6 months of first treatment, each measurement at least one week apart; serum PSA at screening >= 2 ng/mL; or \r\n* Documented appearance of new lesions by bone scintigraphyXx_NEWLINE_xXProstate-specific antigen (PSA) level of 0.1 - 50 ng/dlXx_NEWLINE_xXPSA > 50 ng/dlXx_NEWLINE_xXBaseline hypogonadism as defined as a testosterone < 50 ng/dLXx_NEWLINE_xXPSA < 0.5 ng/dLXx_NEWLINE_xXSerum vitamin D 25, hydroxy (OH) < 12 ng/mLXx_NEWLINE_xXDetectable PSA, defined as PSA >= 0.01 ng/mlXx_NEWLINE_xXSerum total testosterone >= 150 ng/dL (5.2 nmol/L)Xx_NEWLINE_xXPatients must have the following features:\r\n* Gleason >= 4+3 = 7 OR\r\n* Gleason 3+4 = 7 AND at least one of the following: PSA > 20 ng/mL, or T3 disease (as determined by MRI)Xx_NEWLINE_xXHypogonadism or severe androgen deficiency as defined by screening serum testosterone < 200 ng/dLXx_NEWLINE_xXRising PSA after prostatectomy or radiation with PSA doubling time =< 6 monthsXx_NEWLINE_xXPersistent PSA after prostatectomy for PSA >= 0.2 ng/mLXx_NEWLINE_xXVitamin D insufficiency, defined as 25(OH)D =< 32 ng/mlXx_NEWLINE_xXFerritin >= 800 ng/mLXx_NEWLINE_xXHistologically documented adenocarcinoma of the prostate with systemic bone or node metastatic disease despite castrate levels of testosterone (< 50 ng/dL) due to orchiectomy or luteinizing hormone-releasing hormone (LHRH) agonist; castrate levels of testosterone must be maintained while on study; men can be enrolled prior to starting abiraterone and/or enzalutamide OR already be receiving treatment with abiraterone and/or enzalutamideXx_NEWLINE_xXProstate-specific antigen (PSA) >= 0.2 ng/mlXx_NEWLINE_xXSerum testosterone =< 50 ng/dLXx_NEWLINE_xXDiagnostic prostate specific antigen (PSA) =< 10 ng/mlXx_NEWLINE_xXA priori, we will allow men with concurrent benign prostatic hyperplasia (prostate volume > 50 g) to have a PSA between 10-15 ng/ml; and include men with low volume Gleason 3+4 disease, because such men have similar outcomes on active surveillance to those with Gleason =< 3+3Xx_NEWLINE_xXSubjects with anemia (defined as a hemoglobin < 12) who have a ferritin < 40 ng/mL and iron percentage of saturation (% sat) < 20%Xx_NEWLINE_xXPrior androgen deprivation therapy allowed, provided there is documented evidence of testosterone recovery to > 150 ng/dL and greater than 12 months duration between last “effective” date of ADT and date of study consentXx_NEWLINE_xXSerum vitamin D level >= 10 ng/mlXx_NEWLINE_xXSevere vitamin D deficiency with serum 25-OH vitamin D < 10 ng/ml (25 nmol/l) \r\n* Patients with vitamin D levels < 10 ng/ml may be treated with vitamin D and reconsidered for enrollment when levels are sufficientXx_NEWLINE_xXSerum testosterone < 50 ng/dL determined within 4 weeks of first administration of study drugXx_NEWLINE_xXPatients may be receiving continuous hormonal ablation with surgical or medical castration with baseline testosterone < 50 ng/dLXx_NEWLINE_xXNo restrictions on stage of cancer, Gleason score, and pre-treatment prostate-specific antigen (PSA) levelXx_NEWLINE_xXMetastatic disease that has progressed despite castrate levels of testosterone (surgically or medically castrated, with testosterone levels of < 50 ng/dL)Xx_NEWLINE_xXPSA of 2-10 ng/mLXx_NEWLINE_xX25(OH)D3 level less than 20 ng/ml prior to stage 2 initiationXx_NEWLINE_xXPost-operative prostate-specific antigen (PSA) < 0.2 ng/mL by 120 days after prostatectomyXx_NEWLINE_xXMust have one or more of the following:\r\n* pT3b or pT4 primary tumor\r\n* Gleason score 8-10\r\n* pN1 lymph node disease\r\n* Positive surgical margins\r\n* Pre-operative PSA of >= 10 ng/mLXx_NEWLINE_xXPSA < 25Xx_NEWLINE_xXHave a PSA < 25Xx_NEWLINE_xXScreening serum PSA < 20 ng/mL; for men treated with 5-alpha-reductase inhibitors (e.g., finasteride, dutasteride), PSA needs to be < 10 ng/mLXx_NEWLINE_xXParticipants must have had a standard-of-care biopsy within 13 months of the baseline study visit and must have been diagnosed with low-grade, clinically localized prostate cancer (Gleason score =< 3+3 with a PSA at baseline < 10 ng/ml in participants < 70 years of age, OR Gleason score =< 3+4 with a PSA at baseline =< 15 ng/ml in participants >= 70 years of age); eligible participants will be those men who are able and willing to undergo AS with PSA monitoring and a scheduled biopsy performed at the end of the studyXx_NEWLINE_xXDocumented progressive metastatic CRPC based on at least one of the following criteria:\r\n* PSA progressive defined as 25% increased over baseline value with an increase in the absolute value of at least 2 ng/mL that is confirmed by another PSA level with a minimum of a 1 week interval and a minimum PSA of 2 ng/mL\r\n* Soft-tissue progression defined as an increase >= 20% in the sum of the longest diameter (LD) of all target lesions based on the smallest sum LD since treatment started or the appearance of one or more new lesions\r\n* Progression of bone disease (evaluable disease) or (new bone lesion[s]) by bone scanXx_NEWLINE_xXHave testosterone < 50 ng/dL; patients must continue primary androgen deprivation with an luteinizing hormone-releasing hormone (LHRH)/GnRH analogue (agonist or antagonist) if they have not undergone orchiectomyXx_NEWLINE_xXPSA within the past 2 months is between 3 and 20 ng/ml if patient received local radiation OR between 0.4 and 20 ng/ml if patient received prior radical prostatectomyXx_NEWLINE_xXPatient with PSA less than or equal to 20 ng/mLXx_NEWLINE_xXAt least high risk prostate cancer defined by NCCN Guidelines Version 3.2016 (clinical stage ?T3a or PSA >20 ng/mL or Gleason score ?8).Xx_NEWLINE_xXCOHORT I: Biochemical recurrence defined as any of the following:\r\n* PSA >= 0.2 ng/mL in at least two consecutive tests within 6 months of date of consent for patients treated with surgery, radiation therapy, brachytherapy, or cryotherapy\r\n* PSA >= 0.2 ng/ml above the most recent therapy nadir for patients who have received additional treatment in the recurrent settingXx_NEWLINE_xXDetectable prostate-specific antigen (PSA)Xx_NEWLINE_xXPatients must have castrate levels of testosterone (< 50 ng/dL) on luteinizing hormone-releasing hormone (LHRH) analogue or have had prior bilateral orchiectomy, with evidence of castration-resistant disease by Prostate Cancer Working Group 2 (PCWG2) criteriaXx_NEWLINE_xXProstate-specific antigen (PSA) >= 0.1 ng/ml at time of enrollment.Xx_NEWLINE_xXProven biochemical recurrence as defined by American Urological Association (AUA) recommendation: PSA greater than or equal to 0.2 ng/mL measured more than 6 weeks after radical prostatectomyXx_NEWLINE_xXPSA values ranging from 0.2 ng/mL to 2 ng/mLXx_NEWLINE_xXRising PSA after definitive therapy with prostatectomy or radiation therapy (external beam or brachytherapy)\r\n* Post radical prostatectomy (RP) – American Urological Association (AUA) recommendation\r\n** PSA greater than 0.2 ng/mL measured more than 6 weeks after RP and,\r\n** Confirmatory persistent PSA greater than 0.2 ng/mL\r\n* Post-radiation therapy –American Society for Therapeutic Radiology and Oncology (ASTRO) (ASTRO)-Phoenix consensus definition\r\n** Nadir + greater than or equal to 2 ng/mL rise in PSAXx_NEWLINE_xXRising PSA after definitive therapy with prostatectomy or radiation therapy (external beam or brachytherapy)\r\n* If post-radical prostatectomy, PSA > 0.2 ng/mL measured > 6 weeks post-operatively and confirmatory persistent PSA greater than 0.2 ng/mL (American Urological Association [AUA] recommendation for biochemical recurrence)\r\n* If post-radiation therapy, PSA that is equal to, or greater than, a 2 mg/mL rise above PSA nadir (American Society for Radiation Oncology [ASTRO] recommendation for biochemical recurrence)Xx_NEWLINE_xXIntermediate to high-risk disease (as determined by elevated prostate specific antigen [PSA] [PSA > 10], tumor [T]-stage [T2b or greater], Gleason score [Gleason score > 6] or other risk factors)Xx_NEWLINE_xXRising PSA (at least two consecutive rising PSAs) after definitive therapy with prostatectomy or radiation therapy (external beam or brachytherapy)\r\n* Post radical prostatectomy (RP) – American Urological Association (AUA) recommendation for biochemical recurrence after radical prostatectomy\r\n** PSA greater than or equal to 0.2 ng/mL measured more than 6 weeks after RP\r\n* Post-radiation therapy–American Society for Radiation Oncology (ASTRO)-Phoenix consensus definition of biochemical recurrence after radiation therapy\r\n** Nadir + greater than or equal to 2 ng/mL rise in PSAXx_NEWLINE_xXSUB-STUDY II: Biochemical recurrence with PSA > 0.2 ng/mL on two successive testsXx_NEWLINE_xXSUB-STUDY III: Two consecutive rising PSA valuesXx_NEWLINE_xXSUB-STUDY III: Castrate-levels of testosterone (total testosterone < 50 ng/dL)Xx_NEWLINE_xXPatients fit criteria for one of the following categories:\r\n* COHORT 1\r\n** Known localized high risk prostate cancer (PSA > 10, Gleason 8-10 or clinical stage > T2c) with evidence of disease on standard imaging or\r\n* COHORT 2\r\n** Nonspecific or no evidence of disease on standard imaging modality AND biochemical prostate cancer relapse with a PSA >= 0.2 ng/mLXx_NEWLINE_xXIntermediate to high-risk disease (as determined by elevated PSA [PSA > 10], T-stage [T2b or greater], Gleason score [Gleason score > 6] or other risk factors)Xx_NEWLINE_xXProstate carcinoma patients at high risk for metastasis with prostate–specific antigen (PSA) more than 20 ng/ml and/or Gleason score = 8/ > 8.Xx_NEWLINE_xXUnfavorable risk intermediate prostate cancer eligible for standard of care surgery\r\n* Grade group 2 (Gleason score 3+4) with either PSA 10 - < 20 or clinical stage T2b-c, OR grade group 3 (Gleason 4+3) with PSA < 20Xx_NEWLINE_xXPersistently elevated PSAXx_NEWLINE_xXRising PSA after definitive therapy with prostatectomy or radiation therapy.\r\n* Post radical prostatectomy (RP)\r\n** PSA equals to or greater than 0.2 ng/mL measured more than 6 weeks after RP\r\n* Post-radiation therapy – American Society for Therapeutic Radiation and Oncology (ASTRO)-Phoenix consensus definition\r\n** Nadir + greater than or equal to 2 ng/mL rise in PSAXx_NEWLINE_xXIntermediate to high-risk disease (as determined by elevated PSA [PSA > 10], T-stage [T2b or greater], Gleason score [Gleason score > 6] or other risk factors)Xx_NEWLINE_xXProstate specific antigen (PSA) measurement =< 42 days prior to study enrollmentXx_NEWLINE_xXPatients must have rising serum PSA level defined as at least 2 consecutive rises in PSA documented over a reference value; the first rising PSA (2nd measure) should be taken at least 14 days after the reference value; a confirmatory PSA measure (3rd measure) obtained at least 14 days after the 2nd measure is required and must be greater than the 2nd measure; initial (reference) PSA must be >= 4 and the two consecutive rises must all be >= 0.5 over the previous PSA measureXx_NEWLINE_xXElevated PSA level (>= 4) and a prior negative standard biopsy of the prostateXx_NEWLINE_xXPSA < 0.1 ng/ml at enrollmentXx_NEWLINE_xXPatient will have suspicion of recurrent prostate carcinoma as defined by: older American Society for Radiation Oncology (ASTRO) criteria of three consecutive rises of PSA or earlier if clinically appropriate, and/or nadir + 2.0 ng/ml (ASTRO-Radiation Therapy Oncology Group [RTOG] Phoenix criteria)Xx_NEWLINE_xXPatients must have histopathology confirmed prostate cancer that is Gleason score =< 7 (4+3) clinical stage =< T2aN0M0 with a PSA below 15 ng/mLXx_NEWLINE_xXPSA >= 15 ng/mLXx_NEWLINE_xXIntermediate to high-risk disease (as determined by elevated prostate-specific antigen [PSA] [PSA > 10], T-stage [T2b or greater], Gleason score [Gleason score > 6] or other risk factors)Xx_NEWLINE_xXRising PSA after definitive therapy with prostatectomy or radiation therapy (external beam or brachytherapy\r\n* Post radical prostatectomy (RP) – American Urological Association (AUA) recommendation\r\n** PSA greater than 0.2 ng/mL measured 6–13 weeks after RP\r\n** Confirmatory persistent PSA greater than 0.2 ng/mL\r\n* Post-radiation therapy – American Society for Therapeutic Radiology and Oncology (ASTRO)-Phoenix consensus definition \r\n** Nadir plus (+) greater than or equal to 2 ng/mL rise in PSAXx_NEWLINE_xXMust have previously untreated (with definitive therapy) prostate cancer with intermediate or high risk features defined as:\r\n* Intermediate risk:\r\n** Prostate specific antigen (PSA) level is between 10 and 20 ng/ml or\r\n** Gleason score is 7 or\r\n** Stage T2b or T2c\r\n* High risk:\r\n** Gleason 8 and higher OR\r\n** PSA > 20 at the time of diagnosis OR\r\n** Seminal vesicle involvement OR\r\n** Possible (on magnetic resonance [MRI]) extra-capsular extension (T3 disease)Xx_NEWLINE_xXPatients must have testosterone levels >= 100 ng/dLXx_NEWLINE_xXPSA < 25 ng/mLXx_NEWLINE_xXNewly diagnosed high-risk, localized or locally advanced prostate cancer pathologically proven by prostate biopsy within the past 12 months:\r\n* Clinical T3 or greater, or\r\n* PSA > 20 ng/ml, or\r\n* Clinically N1, or\r\n* Prostate biopsy histology grade ? Gleason 8-10Xx_NEWLINE_xXSerum prostate specific antigen (PSA) =< 20 ng/ml within 3 months of study enrollmentXx_NEWLINE_xXINCLUSION CRITERIA (NEXT 60 PATIENTS WITH LOCALLY ADVANCED PROSTATE CANCER): Pathologically confirmed clinically localized intermediate risk or higher prostate cancer (clinical stage >= T2b or Gleason sum >= 7 or PSA >= 10 ng/mL)Xx_NEWLINE_xXPatients with moderate to high-risk disease as defined by D' Amico risk stratification and having at least one of the following:\r\n* Prostate-specific antigen (PSA) level > 10 ng/ml\r\n* Gleason score >= 7\r\n* Clinical stage >= T2cXx_NEWLINE_xXRising PSA on two observations taken at least 1 week apartXx_NEWLINE_xXHaving elevated prostate specific antigen (PSA) (> 2.5 ng/ml) and no palpable nodule on digital rectal exam (DRE)Xx_NEWLINE_xXSubjects with concurrent clinical diagnosis of evidence of active iron overload defined by the following 1) ferritin >= 250 ng/mL in men or >= 200 ng/mL in women AND 2) transferrin saturation, the ratio of plasma iron to transferrin, expressed as percent, >= 45%Xx_NEWLINE_xXNational Comprehensive Cancer Network (NCCN) high risk disease (cT3 or Gleason score 8-10 or prostate specific antigen [PSA] > 20)Xx_NEWLINE_xXRising PSA after definitive therapy with prostatectomy or radiation therapy (external beam or brachytherapy)\r\n* Post radical prostatectomy (RP) – American Urology Association (AUA) recommendation\r\n** PSA greater than 0.2 ng/mL measured 6–13 weeks after RP\r\n** Confirmatory persistent PSA greater than 0.2 ng/mL\r\n* Post-radiation therapy –American Society for Radiation Oncology (ASTRO)-Phoenix consensus definition\r\n** Nadir + greater than or equal to 2 ng/mL rise in PSAXx_NEWLINE_xXProstate-specific antigen (PSA) within 4 months prior to study consent or within 30 days after study consent < 10 ng/mLXx_NEWLINE_xXDocumented metastatic prostate cancer progression as assessed by the treating oncologist with either one or both of the following:\r\n* Rising PSA over a minimum 1-week interval\r\n* Radiographic progression in soft tissue and/or boneXx_NEWLINE_xXOngoing androgen deprivation with serum testosterone < 50 ng/dL (< 1.7 nM)Xx_NEWLINE_xXSerum PSA level >= 0.2 ng/mL at least 45 days prior to study enrollmentXx_NEWLINE_xXTwo PSA values >= 0.2 ng/mL at least 4 weeks after prostatectomyXx_NEWLINE_xXPSA recurrence not verified by elevated PSA as discussed in the eligibility sectionXx_NEWLINE_xXPatient will have suspicion of recurrent prostate carcinoma as defined by: the American Society for Therapeutic Radiology and Oncology (ASTRO)-Radiation Therapy Oncology Group (RTOG) Phoenix criteria of elevated prostate-specific antigen (PSA) greater than nadir plus 2 ng/ml with absolute PSA >= 4.0 ng/ml with any doubling time (DT) or with PSA 2.0-3.99 ng/ml with DT =<10 monthsXx_NEWLINE_xXRising PSA after definitive therapy with prostatectomy or radiation therapy (external beam or brachytherapy)\r\n* Post radical prostatectomy (RP) – American Urological Association (AUA) recommendation\r\n** PSA greater than 0.2 ng/mL measured more than 6 weeks after RP and\r\n** Confirmatory persistent PSA greater than 0.2 ng/mL\r\n* Post-radiation therapy –American Society for Radiation Oncology (ASTRO)-Phoenix consensus definition\r\n* Nadir + greater than or equal to 2 ng/mL rise in PSAXx_NEWLINE_xXPatient has suspected recurrence based on biochemical data (prostate-specific antigen [PSA] > 2 ng/mL)Xx_NEWLINE_xXPSA < 10 ng/ml (this will be the PSA level prompting the initial prostate biopsy)Xx_NEWLINE_xXPSA levels to be taken within 2 weeks of antibody administrationXx_NEWLINE_xXAbnormal prostate-specific antigen (PSA) blood test\r\n* > 2.5 ng/mL for men < 50 years (yrs) of age\r\n* > 3.5 ng/mL for men < 60 yrs of age\r\n* > 4.5 ng/mL for men < 70 yrs of ageXx_NEWLINE_xXProstate specific antigen (PSA) < 10 ng/mLXx_NEWLINE_xXINCLUSION CRITERIA:\n\n          -  Ability to provide informed consent and willingness to comply with protocol\n             requirements\n\n          -  Life expectancy ? 6 months\n\n        Cohort A only:\n\n          -  A diagnostic trans-rectal ultrasound (TRUS)-guided biopsy within 12 months of\n             enrollment showing adenocarcinoma of the prostate gland\n\n          -  Within 90 days of consent, serum PSA ? 15.0 ng/mL or ? 7.5 ng/mL if on 5 ?-reductase\n             inhibitors.\n\n          -  Candidates for active surveillance and/or a Gleason score ?3+4\n\n          -  Scheduled to undergo radical prostatectomy (RP) with or without pelvic lymph node\n             dissection (PLND)\n\n        Cohort B only:\n\n          -  Very low risk (VLR) prostate cancer defined by 2016 NCCN Guideline criteria:\n\n          -  T1c stage, and\n\n          -  PSA < 10 ng/mL, and\n\n          -  Gleason score ? 6 with < 3 biopsy cores cancer positive and ? 50% cancer in any core\n             based on prior prostate biopsy within 24 months of enrollment, and\n\n          -  PSA density < 0.15 mg/mL/g\n\n          -  Scheduled to undergo a reassessment of prostate cancer staging that includes prostate\n             biopsy as part of routine follow-up\n\n        EXCLUSION CRITERIA:\n\n          1. Subjects administered a radioisotope within 5 physical half-lives prior to study drug\n             injection.\n\n          2. Previous treatment with hormonal therapy, surgery (except biopsy), radiation therapy,\n             LHRH analogs, and non-steroidal anti-androgens, for the treatment of prostate cancer\n             or benign prostatic hyperplasia (BPH)\n\n          3. Planned androgen or anti-androgen therapy prior to RP surgery or biopsy\n\n          4. Subjects with any medical condition or other circumstances that, in the opinion of the\n             investigator, would significantly interfere with obtaining reliable data, achieving\n             study objectives, or completing the study\n\n          5. Malignancy (not including curatively treated basal or squamous cell carcinoma of the\n             skin) within the previous 5 years. (Ta stage transitional cell carcinoma bladder\n             cancer with negative surveillance cystoscopy within the past 2 years may be included).Xx_NEWLINE_xXARM II ONLY: For patients status post prostatectomy, a PSA >= 0.2 ng/mlXx_NEWLINE_xXSerum PSA ? 20ng/ml within the previous 3 monthsXx_NEWLINE_xXPost prostatectomy: Detectable or rising PSA level that is >0.2 ng/mL with a second confirmatory level of >0.2 ng/mLXx_NEWLINE_xXPost non-prostatectomy: PSA rise ? 2ng/mL over nadirXx_NEWLINE_xXPatient has suspected recurrence based on biochemical data (prostate specific antigen [PSA] > 2 ng/mL)Xx_NEWLINE_xXIncreased PSA level >4 ng/mLXx_NEWLINE_xXDetectable PSA, defined as PSA detectable and rising on 2 or more subsequent determinationsXx_NEWLINE_xXFailure of PSA to nadir after surgeryXx_NEWLINE_xXbiochemical progression (PSA)Xx_NEWLINE_xXAbnormal serum PSA (total > 2.5 ng/ml or other clinically important biomarker parameters, including PSA velocity and density) associated with or without normal digital rectal examinationXx_NEWLINE_xXA history of antibiotic use within one month prior to initial PSA level measurementXx_NEWLINE_xXAt the time of enrollment, patients must demonstrate evidence of castration-resistant prostate cancer with a documented castrate level of serum total testosterone (< 50 ng/dL) while on continuous androgen deprivation therapyXx_NEWLINE_xXMinimally-symptomatic or asymptomatic, castrate-resistant metastatic prostate cancer, as evidenced by all of the following:\r\n* Histologically-confirmed diagnosis of adenocarcinoma of the prostate\r\n* Evidence of adequate androgen deprivation, as evidence by one of the following:\r\n** Bilateral orchiectomy\r\n** Ongoing luteinizing hormone-releasing hormone (LHRH) agonist (e.g. leuprolide, goserelin) and serum testosterone =< 50 ng/dl\r\n** Ongoing LHRH antagonist (e.g. degarelix) and serum testosterone =< 50 ng/dl\r\n* Evidence of prostate cancer resistance to castration, as evidenced by at least one of the following:\r\n** 2 consecutive prostate-specific antigen (PSA) levels that are >= 50% above the PSA nadir achieved on androgen deprivation therapy (ADT) and obtained at least 1 week apart\r\n** Computed tomography (CT) or magnetic resonance imaging (MRI) based evidence of disease progression (soft tissue or nodal) according to Prostate Cancer Working Group 2 (PCWG2) criteria or Response Evaluation Criteria In Solid Tumors (RECIST) 1.1 criteria, or at least 1 new bone scan lesion as compared to the most immediate prior radiologic studies\r\n* Presence of non-visceral metastases on imaging\r\n* Absence of major symptoms directly attributable to prostate cancer, with the following permissible exceptions:\r\n** Ureteral obstruction secondary to pelvic or retroperitoneal lymphadenopathy\r\n** Bladder outlet obstruction secondary to locally recurrent prostate cancerXx_NEWLINE_xXTestosterone levels ? 100 ng/dLXx_NEWLINE_xXPatients must have progressive prostate cancer as indicated by either PSA progression (PSA progression is defined as two consecutively rising PSAs above the nadir post-definitive therapy and an absolute value greater than 1.0 ng/mL separated by at least 2 weeks) or radiographic progression based on Response Evaluation Criteria in Solid Tumors (RECIST) version (v) 1.1 or Prostate Cancer Working Group 3 (PCWG3).Xx_NEWLINE_xXUse of any medications known to affect the serum androgen levels or the PSAXx_NEWLINE_xXMust continue ongoing androgen deprivation therapy with castrate levels of serum testosterone <50 nanogram/deciliter (ng/dL)Xx_NEWLINE_xXA rise in prostate-specific antigen (minimal value 2 ng/milliliter (mL); ?3 consecutive rising values)Xx_NEWLINE_xXThe presence of liver lesion(s) (as defined in a.) with AFP ? 400 ng/mL.Xx_NEWLINE_xXProstate-specific antigen (PSA) < 50 ng/mLXx_NEWLINE_xXPSA<50Xx_NEWLINE_xXPSA > 20Xx_NEWLINE_xXAt least 2 of the following 3 factors: Gleason score(GS) 3+4=7 and/or PSA 10-20 and/or T2b/cXx_NEWLINE_xXGreater than 50% of biopsy cores positive and at least one other risk factor: Gleason score (GS) 7 and/or PSA 10-20 and/or T2b/cXx_NEWLINE_xXBaseline serum PSA value performed with an FDA-approved assay within 120 days prior to registration. Study entry PSA should not be obtained within 10-day period following prostate biopsy or following initiation of hormonal therapyXx_NEWLINE_xX