Testosterone > 50 ng/dL within 90 days prior to Step 1 registration Serum testosterone concentration ?50 ng/dL sustained by medical or surgical castration Parts A,B or D (TNBC) Serum testosterone concentration ?50 ng/dL sustained by medical or surgical castration. Serum testosterone <50 ng/dL Currently taking testosterone, methyltestosterone, oxandrolone (Oxandrin), oxymetholone, danazol, fluoxymesterone (Halotestin), or testosterone-like agents. Serum testosterone level < 50 ng/mL Serum testosterone ? 50 ng/dL Surgically or medically castrated, with testosterone ? 50 ng/dL (? 1.7 nmol/L). Testosterone level =< 100 ng/dL Serum testosterone < 50 ng/ml Screening serum testosterone > 150 ng/dL Be surgically or medically castrated, with serum testosterone levels of ? 50 ng/dL (1.73 nM) Subjects 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 eligible Testosterone level < 50 ng/dL Patient must have hormone-sensitive prostate cancer as evident by a serum total testosterone level > 150 ng/dL within 12 weeks prior to randomization Serum testosterone level < 50 ng/dL at screening Testosterone =< 50 ng/dL Not a candidate for standard effective therapy NOTE: In men with prostate cancer, baseline testosterone levels must also be ?50ng/dL (? 2.0nM) and surgical or ongoing medical castration must be maintained throughout the duration of the study. Serum 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 supplements Serum testosterone > 200 ng/mL Does not have castration resistant disease\r\n* Castration resistance defined as progression of disease despite serum testosterone level of < 50 ng/dL Serum testosterone level =< 50 ng/dL at the screening visit Baseline testosterone >= 100 ng/dl Testosterone level ? 100 ng/dL Asymptomatic 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 metastases Men with baseline serum testosterone < 100 ng/dL Serum 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. Surgically or ongoing medically castrated, with baseline testosterone levels of =< 50 ng/dL =< 2.0 nM). Eugonadal state (serum testosterone > 150 ng/dL). Serum testosterone ? 1.73 nmol/L (50 ng/dL) at screening. Has a serum testosterone at the Screening visit of ? 150 ng/dL (5.2 nmol/L); Serum testosterone >= 150 ng/dl Baseline testosterone > 150 ng/dL if patient has not initiated hormonal therapy; for those patients who have already initiated hormonal therapy, baseline testosterone is not required Serum testosterone >= 150 ng/dL Serum testosterone >= 150 ng/dL Surgically or ongoing medically castrated, with baseline testosterone levels of =< 50 ng/dL (=< 2.0 nM) Requires estrogen or testosterone Ongoing androgen deprivation with serum testosterone < 50 ng/dl Patients may be receiving continuous hormonal ablation with surgical or medical castration with baseline testosterone < 50ng/dL Serum testosterone >= 100 ng/dL Bilirubin < 2.0 ng/dl Creatinine < 3.0 ng/dl Serum testosterone levels < 50 ng/L after surgical or continued chemical castration Patients must have ongoing therapy to maintain serum testosterone < 50 ng/dL Androgens (testosterone, dihydroepiandrosterone, etc.); Testosterone =< 50 ng/dL (documented at any time while on LHRH agonist or antagonists or s/p orchiectomy) Castration 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 progression Serum testosterone ? 150 ng/dL (5.2 nmol/L). Testosterone ? 50 ng/dL (? 1.73 nmol/L) at screening; Known 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 hypogonadism Specific 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. Patients must have a serum testosterone < 50 ng/dL demonstrated within 1 month of study entry Be surgically or medically castrated, with serum testosterone levels of ? 50 ng/dL (1.73 nM) Testosterone or testosterone-like agents (methyltestosterone, oxandrolone, oxymetholone, danazol, fluoxymesterone, dehydroepiandrosterone, androstenedione) other androgenic compounds or anti-androgens within 30 days prior to day 1 of protocol therapy Testosterone >= 125 ng/dL Baseline testosterone >= 100 ng/dl Serum testosterone levels less than (<) 50 nanogram per deciliter (ng/dL) determined within 4 weeks prior to start of study drug Patients must have a serum total testosterone level >= 150 ng/dL at the time of enrollment within 4 weeks prior to randomization Testosterone ? 1.73 nmol/L (? 50 ng/dL) at screening; Hypogonadism or severe androgen deficiency as defined by screening serum testosterone < 200 ng/dL Surgically or medically castrated, with testosterone levels of less than (<) 50 nanogram per deciliter (ng/dL) Castration-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 drug Medical or surgical castration with testosterone less than 50 ng/dL (1.7nmol/L). Hypogonadism or severe androgen deficiency as defined by screening serum testosterone less than 50 ng/dL below the normal range for the institution Participants must have a testosterone level < 50 ng/dL Serum testosterone level: ? 50 ng/dL (1.7 nmol/L) Testosterone =< 50 ng/dL (1.7 nmol/L) Participants must have a testosterone levels < 50 ng/dL Testosterone >= 50 ng/dL per laboratory reference range Testosterone < 50 ng/dL Serum testosterone > 150 ng/dL at study entry Patients must have a serum testosterone of 150 ng/dL or greater Ongoing androgen blockade demonstrated by serum testosterone concentration of less than 50 ng/dL Evidence of castration resistance defined as disease progression despite a testosterone level < 50 ng/dL (or surgical castration) Total 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 duration Serum testosterone at screening < 50 ng/dL Serum testosterone >= 240 ng/dL determined within 2 months prior to enrollment Prior orchiectomy or serum testosterone levels <50 ng/dL determined within 4 weeks prior to start of study drug. Hormone-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 randomization Serum testosterone level < 50 ng/dL at Screening visit Testosterone ? 1.73 nmol/L (? 50 ng/dL) at screening. Serum testosterone levels < 50ng/ml Serum testosterone level < 50 ng/dL Testosterone < 50 ng/dL; patients must continue primary androgen deprivation with an LHRH analogue if they have not undergone orchiectomy Serum testosterone < 50 ng/dL determined within 4 weeks of first administration of study drug Both measurements are greater than 150 ng/dL or 5.2 nmol/L; Effective castration (serum testosterone levels ?0.5 ng/mL). Serum testosterone (total) less than 25 ng/ml at time of enrollment Serum 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 measurements Patients with hypogonadism or severe androgen deficiency as defined by serum testosterone less than 100 ng/dL will not be eligible Serum testosterone <50 nanogram per deciliter (ng/dL) (1.7 nanomole per liter [nM/L]) Surgical or medical castration with testosterone less than 50 ng/dL Serum testosterone levels < 50 ng/dL Medical or surgical castration with testosterone less than 50 ng/dL Eugonadal state (serum testosterone > 150 ng/dL) Serum testosterone, measured by liquid chromatography (LC)–mass spectrometry (MS)/MS, < 300 ng/dL and/or calculated free testosterone < 60 pg/mL Baseline hypogonadism as defined as a testosterone < 50 ng/dL Serum total testosterone >= 150 ng/dL (5.2 nmol/L) Hypogonadism or severe androgen deficiency as defined by screening serum testosterone < 200 ng/dL Serum testosterone =< 50 ng/dL Serum testosterone < 50 ng/dL determined within 4 weeks of first administration of study drug Patients may be receiving continuous hormonal ablation with surgical or medical castration with baseline testosterone < 50 ng/dL Patients must have testosterone levels >= 100 ng/dL Ongoing androgen deprivation with serum testosterone < 50 ng/dL (< 1.7 nM) Patients receiving testosterone supplementation Testosterone levels ? 100 ng/dL Patients must have castrate serum level of testosterone of < 50 ng/dL (< 1.73 nmol/L) For 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 therapy Evidence of castrate testosterone level < 50 ng/dL (or surgical castration) Patients 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. Progressive metastatic prostate cancer despite castrate levels of testosterone (< 50 ng/dL) castrate serum level of testosterone of ? 50 ng/dL (? 1.73 mmol/L) Non-castrate testosterone level, > 50 ng/dl, at study enrollment Documented castrate level of serum testosterone (< 50 ng/dl) Non-castrate level of testosterone: >= 50 ng/dL (prior androgen deprivation therapy [ADT] allowed; must be >= 6 months since last dose of ADT) Patients must have castrate levels of testosterone (< 50 ng/dL [1.74 nmol/L]). Castrate testosterone level (< 50ng/dl or 1.7nmol /L); (patients with a malignancy other than prostate cancer are excluded from this criterion) Castrate testosterone level (< 50ng/dl or 1.7nmol /L) Patient 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) Progression of metastatic prostate cancer in the setting of castrate levels of testosterone or history of bilateral orchiectomy at study entry Castrate testosterone level (< 50ng/dl or 1.7nmol /L) Metastatic castration resistant prostate cancer with castrate-level testosterone (< 50 ng/dL)\r\n* Subjects must maintain a castrate-level testosterone during the study Tumor 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. Castrate levels of serum total testosterone (=< 50 ng/dl) OR ongoing documented androgen deprivation therapy (ADT) unless pure small cell prostate cancer is present Men with metastatic castrate-resistant prostate cancer (prostate cancer progressing despite castrate levels of testosterone [< 50 ng/dL]), using standard measures of progression defined by Prostate Cancer Working Group 2 (PCWG2) Subjects must be castration resistant with evidence of progressive prostate cancer despite castrate levels of testosterone (=< 50 ng/dL) according to the PCWG3 criteria Castrate testosterone level (< 50 ng/dl or 1.7 nmol/L) Progression of metastatic prostate cancer in the setting of castrate levels of testosterone or history of bilateral orchiectomy at study entry mCRPC EXPANSION COHORT: Patients must have castrate levels of testosterone (< 50 ng/dl [1.74 nmol/l]) PHASE 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]) Documented castrate level of serum testosterone (< 50 ng/dl) Castrate level of testosterone (< 50 ng/dL) Patient 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) Known castrate-resistant disease with serum testosterone level less than or equal to (= 150 ng/dL) Maintain castrate levels of testosterone within 4 weeks prior to randomization and throughout the study Participants must have progressive disease despite ongoing androgen deprivation therapy (ADT) and castrate levels of testosterone, defined as castration resistant prostate cancer (CRPC) Castrate testosterone level (< 50 ng/dl or 1.7 nmol/L) Castrate serum testosterone level, =< 1.73 nmol/L (50 ng/dL), at the screening visit For cohorts 1, 2, and 4 only: non-castrate testosterone level (> 100 ng/dL) Castrate levels of serum testosterone of less than or equal to 50 ng/dL Castrate serum testosterone (< 50 ng/dL) The 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) Castrate 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 orchiectomy Patient 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) Castrate 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/dL Patient 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) Testosterone 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 study Patients 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. Castrate-resistant prostate cancer (CRPC) with bone metastasis: --Progressive Disease in the setting of castrate level of testosterone Castrate serum testosterone level: =< 50 ng/dL (=< 1.7 nmol/L) Histologically 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 enzalutamide Metastatic disease that has progressed despite castrate levels of testosterone (surgically or medically castrated, with testosterone levels of < 50 ng/dL) SUB-STUDY III: Castrate-levels of testosterone (total testosterone < 50 ng/dL) Multifocal metastatic disease in either castrate sensitive or castrate resistant patients At 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 therapy Must continue ongoing androgen deprivation therapy with castrate levels of serum testosterone <50 nanogram/deciliter (ng/dL)