Patients must have castrate serum level of testosterone of < 50 ng/dL (< 1.73 nmol/L)
Testosterone > 50 ng/dL within 90 days prior to Step 1 registration
For 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 enzalutamide
Evidence of castrate testosterone level < 50 ng/dL (or surgical castration)
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
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.
Serum testosterone ? 50 ng/dL
Progressive metastatic prostate cancer despite castrate levels of 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
castrate serum level of testosterone of ? 50 ng/dL (? 1.73 mmol/L)
Non-castrate testosterone level, > 50 ng/dl, at study enrollment
Screening serum testosterone > 150 ng/dL
Documented castrate level of serum testosterone (< 50 ng/dl)
Ongoing 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 randomization
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 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/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
Non-castrate level of testosterone: >= 50 ng/dL (prior androgen deprivation therapy [ADT] allowed; must be >= 6 months since last dose of ADT)
Serum testosterone level < 50 ng/dL at screening
Testosterone =< 50 ng/dL
Serum testosterone < 50 ng/dL. Subjects must continue primary androgen deprivation with an LHRH analogue (agonist or antagonist) if they have not undergone orchiectomy
Patients must have castrate levels of testosterone (< 50 ng/dL [1.74 nmol/L]).
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.
Concurrent use of gonadotrophin releasing hormone (GnRH) analogue (i.e. medical castration) with testosterone at screening < 50 ng/dL
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)
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
Histologically 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.
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
Castrate testosterone level (< 50ng/dl or 1.7nmol /L)
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).
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
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
Castration resistant disease with confirmed testosterone level ?50 ng/ml under prior androgen deprivation therapy (ADT)
Subjects must be castration resistant with evidence of progressive prostate cancer despite castrate levels of testosterone (=< 50 ng/dL) according to the PCWG3 criteria
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
Treated 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)
Castrate testosterone level (< 50 ng/dl or 1.7 nmol/L)
Serum testosterone >= 150 ng/dL
mCRPC EXPANSION COHORT: Patients must have castrate levels of testosterone (< 50 ng/dl [1.74 nmol/l])
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
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])
Patients may be receiving continuous hormonal ablation with surgical or medical castration with baseline testosterone < 50ng/dL
Prior surgical castration or concurrent use of gonadotropin-releasing hormone (GnRH) analogue (i.e. medical castration) with testosterone at screening < 50 ng/dL
Documented castrate level of serum testosterone (< 50 ng/dl)
Serum testosterone >= 100 ng/dL
Bilirubin < 2.0 ng/dl
Creatinine < 3.0 ng/dl
Patient 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 progression
Baseline serum testosterone obtained within 60 days prior to registration
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.);
Castrate level of testosterone (< 50 ng/dL)
Current use of exogenous testosterone
Surgically 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 period
Known 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 study
Testosterone =< 50 ng/dL (documented at any time while on LHRH agonist or antagonists or s/p orchiectomy)
Patient 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)
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).
Castration-resistant prostate cancer (CRPC) with castrate level of serum testosterone.
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 prior and/or ongoing androgen-deprivation therapy and a castrate level of serum testosterone (<50 ng/dL).
Patients must have a castrate level of serum testosterone (< 50 ng/dL)
Ongoing androgen deprivation therapy (ADT) with a Gonadotropin-releasing hormone (GnRH) analogue or a surgical/medical castration with testosterone level of ?1.73nmol/L (50ng/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
Patients may have received prior androgen deprivation therapy (ADT) in the neoadjuvant, adjuvant and/or salvage setting, but must be off therapy for at least 3 months and have a testosterone level > 150 ng/dl
Testosterone ? 1.73 nmol/L (? 50 ng/dL) at screening;
Patients must have castrate levels of testosterone (<50 ng/dl [1.74 nmol/l]).
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)
Tumor 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 study
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
Castrate levels of serum testosterone < 50 ng/dL determined within 4 weeks prior to starting treatment
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)
Patients must have non-castrate levels of serum testosterone (>= 150 ng/dL)
Testosterone =< 50 ng/dL (1.7 nmol/L)
Maintain castrate levels of testosterone within 4 weeks prior to randomization and throughout the study
Participants must have a testosterone levels < 50 ng/dL
Testosterone >= 50 ng/dL per laboratory reference range
Baseline testosterone >= lower limit of normal
Castrate testosterone level (< 50 ng/dl or 1.7 nmol/L)
Testosterone < 50 ng/dL
Castrate 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.
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
Castrate serum testosterone level, =< 1.73 nmol/L (50 ng/dL), at the screening visit
Evidence of castration resistance defined as disease progression despite a testosterone level < 50 ng/dL (or surgical castration)
For cohorts 1, 2, and 4 only: non-castrate testosterone level (> 100 ng/dL)
For 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 prostatectomy
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
Castrate levels of serum testosterone of less than or equal to 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
Be currently taking or have previously taken testosterone, methyltestosterone, oxandrolone (Oxandrin®), oxymetholone, danazol, fluoxymesterone (Halotestin®), testosterone-like agents (such as dehydroepiandrosterone, androstenedione, and other androgenic compounds, including herbals), or anti-androgens
Serum testosterone level < 50 ng/dL at Screening visit
Testosterone ? 1.73 nmol/L (? 50 ng/dL) at screening.
Serum testosterone levels < 50ng/ml
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)
Serum testosterone level < 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
Testosterone < 50 ng/dL; patients must continue primary androgen deprivation with an LHRH analogue if they have not undergone orchiectomy
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
Serum testosterone < 50 ng/dL determined within 4 weeks of first administration of study drug
Serum testosterone level: i) Subjects with no history of androgen deprivation therapy:
Both measurements are greater than 150 ng/dL or 5.2 nmol/L;
Effective castration (serum testosterone levels ?0.5 ng/mL).
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
Serum testosterone (total) less than 25 ng/ml at time of enrollment
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.
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
Castrate serum testosterone level: =< 50 ng/dL (=< 1.7 nmol/L)
A history of androgen deprivation therapy; patients receiving hormonal therapy in the adjuvant and/or neoadjuvant setting must have discontinued therapy at least 6 months prior to day 1 of treatment AND have a serum testosterone level >= 50 ng/dL and cannot have received more than 18 months of previous ADT
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
Prior 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 consent
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
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)
Patients must have testosterone levels >= 100 ng/dL
Ongoing androgen deprivation with serum testosterone < 50 ng/dL (< 1.7 nM)
Patients receiving testosterone supplementation
Patients on testosterone replacement therapy who are unwilling to discontinue
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
Testosterone levels ? 100 ng/dL
Must continue ongoing androgen deprivation therapy with castrate levels of serum testosterone <50 nanogram/deciliter (ng/dL)