Prior pharmacologic androgen ablation for prostate cancer is allowed only if the onset of androgen ablation (both LHRH agonist and oral anti-androgen) is =<  days prior to the date of registration
Patients on long term (>  months) anti-androgen therapy (e.g., flutamide, bicalutamide, nilutamide) will need to be off anti-androgen for  weeks (wash out period) and show evidence of disease progression off the anti-androgen; patients that have been on an anti-androgen  months or less will need to discontinue anti-androgen therapy prior to treatment start (no wash out period required)
Preceding line of treatment included response to anti-androgen, progression documented after withdrawal of the anti-androgen.
Patients treated with first generation anti-androgen as most recent systemic therapy (bicalutamide, nilutamide) must have at least  weeks elapsed from treatment discontinuation to start of protocol therapy with evidence of disease progression by Prostate Cancer Working Group  (PCWG) criteria following discontinuation of prior anti-androgen
Androgen deprivation therapy prior to radiation is allowed. However, it is not acceptable if continued during radiation or as adjuvant therapy.
standard of care androgen deprivation treatment
progressive disease while receiving androgen deprivation therapy
Patients with hormone sensitive disease who received prior androgen deprivation therapy as part of primary/salvage local treatment or patients receiving intermittent androgen deprivation therapy will be allowed to participate
Subjects on long term (>=  months) first generation anti-androgen therapy (e.g. flutamide, bicalutamide, nilutamide) will need to discontinue anti-androgen therapy for  weeks prior to registration (wash out period) and show evidence of disease progression off the anti-androgen; subjects that have been on a first generation anti-androgen  months or less will need to discontinue therapy prior to registration (no wash out period required)
Subjects on second generation anti-androgen therapy (enzalutamide) or androgen bio-synthesis inhibitor (abiraterone acetate) will need to discontinue therapy  weeks prior to registration (wash out period)
More than one prior line of therapy with a second generation anti-androgen (enzalutamide, ARN-, etc.) or androgen bio-synthesis inhibitor (abiraterone acetate, etc.); subject may have had one second generation anti-androgen or androgen bio-synthesis inhibitor but not both sequentially; subjects that have received combination therapy with second generation anti-androgen plus an androgen bio-synthesis inhibitor would be eligible (e.g., enzalutamide plus abiraterone acetate as one line of therapy on a clinical trial)
Patients receiving denosumab or bisphosphonates for any cancer, or undergoing androgen deprivation therapy for prostate cancer, are eligible for this therapy
Prior androgen deprivation therapy and/or first generation anti-androgen (e.g. bicalutamide, nilutamide, flutamide) for biochemically recurrent prostate cancer. Prior ADT and/or first generation anti-androgen in the (neo)adjuvant and/or salvage setting before, during, and/or following radiation or surgery is allowed provided last effective dose of ADT and/or first-generation anti-androgen is >  months prior to date of randomization and total duration of prior therapy is ?  months.
Prior or planned androgen deprivation or bilateral orchiectomy
Previous androgen deprivation therapy lasting more than  months
Any investigational medicinal product or other systemic chemotherapy, or antibody therapy within  weeks prior to the first dose of study treatment, or within  weeks after immunotherapy, whichever is the most appropriate and as judged by the Investigator. Note: androgen-deprivation therapy is permitted for patients with prostate cancer.
A minimum of  weeks elapsed off of anti-androgen therapy prior to enrollment for flutamide and  weeks for bicalutamide and nilutamide without evidence of an anti-androgen withdrawal response; patients who NEVER HAD A PSA decline with the most recent anti-androgen therapy or in whom the response to the most recent anti-androgen was for <  months require only a  week washout period prior to first dose of study drug
Prior anti-androgen therapy
Previous androgen suppression therapy for prostate cancer.
Prior androgen suppression therapy for prostate cancer for more than  months
Expansion Phase: Patients must have progressed while receiving an androgen-directed therapy, as follows:
Received prior nd generation anti-androgen and require urgent disease response or stabilization
Prior androgen deprivation therapy is allowed and may have been initiated up to  months prior to the date of the HDR implant; the complete duration of androgen deprivation therapy can range from  months to  months provided it has been initiated no more than  months prior to the date of the HDR implant
PSA >= . prior to start of androgen deprivation treatment
Is a candidate for, in the opinion of the investigator, at least  year of continuous androgen deprivation therapy for the management of androgen-sensitive advanced prostate cancer with one of the following clinical disease state presentations:
Advanced localized disease not suitable for local primary surgical intervention with curative intent (radiotherapy, cryotherapy, or high frequency ultrasound are allowed after  months of androgen deprivation therapy);
In the investigator's opinion, is likely to require chemotherapy or surgical therapy for symptomatic disease management within  months of initiating androgen deprivation therapy;
Previously received GnRH analog or other form of androgen deprivation therapy (estrogen or antiandrogen) for >  months total duration. If androgen deprivation therapy was received for ?  months total duration, then that therapy must have been completed at least  months prior to baseline. If the dosing interval of the depot is longer than  months, then the prior androgen deprivation therapy must have been completed at least as long as the dosing interval of the depot;
Willing to undergo the following therapy: (st) systemic chemo-hormonal therapy with up to -months (around  weeks) of neoadjuvant androgen deprivation and up to  cycles of chemotherapy, (nd) definitive local tumor control with adjuvant radiation therapy, and (rd) consolidative stereotactic radiation to oligometastatic lesions; additionally, must be willing to be treated with a full two years of androgen deprivation
Hormonal therapy (e.g., androgen receptor [AR] antagonists,  alpha reductase inhibitors, estrogens)
Prior docetaxel as first line therapy in addition to androgen deprivation is allowed
A minimum of  weeks elapsed off of antiandrogen therapy prior to registration (i.e. flutamide, nilutamide, and bicalutamide) without evidence of an anti-androgen withdrawal response; an anti-androgen withdrawal response is a PSA level at  weeks (or more) off of anti-androgen equal or higher than PSA level when anti-androgen therapy stopped
Prior androgen deprivation or chemotherapy is allowed if discontinued at least  days prior to enrollment
Has recovered from all therapy-related toxicity to =< grade  (except alopecia, anemia and any signs or symptoms of androgen deprivation therapy) at the time of registration
Willing to undergo the following therapy: (st) Systemic chemo-hormonal therapy with up to -months (~ weeks) of neoadjuvant androgen deprivation and up to  cycles of chemotherapy, (nd) definitive local tumor control with prostatectomy +/- adjuvant radiation therapy, and (rd) consolidative stereotactic radiation to oligometastatic lesions; additionally, must be willing to be treated with a full year of androgen deprivation
Prior or second primary malignancies within the last two years (except carcinoma in situ of the cervix, non-metastatic prostate cancer, or basal cell or squamous cell carcinoma of the skin which were treated with local resection only; prior adjuvant androgen deprivation therapy in the case of prostate cancer is permitted, but current adjuvant androgen deprivation therapy is not)
Prior treatment for CaP by surgery, irradiation, local ablative (e.g. cryosurgery or high intensity focused ultrasound) or androgen deprivation therapy.
Up to a total of  year of androgen deprivation allowed
Use of hormonal therapy or androgen deprivation therapy, including enzalutamide, except in the following setting:
Patients can be on androgen deprivation therapy
Patient deemed eligible for complete androgen blockade, and androgen deprivation therapy by treating physician (this includes consideration of baseline liver function prior to initiation of therapy, if necessary at physicians discretion); for patients not eligible for anti-testosterone therapy, hormone therapy with gonadotrophin releasing hormone (LHRH) agonist alone will be permitted on case by case by study principal investigator; AS can be any LHRH agonists, LHRG antagonists or anti-androgens that are approved for androgen suppression for the treatment of prostate cancer
Participation in a previous clinical trial of enzalutamide or an investigational agent that inhibits the androgen receptor (ARN-) or androgen synthesis
Patients progressing on LHRH agonist plus an anti-androgen as first line therapy must be off anti-androgen for  weeks prior to first treatment with testosterone
Prior pharmacologic androgen ablation for prostate cancer is allowed only if the onset of androgen ablation is =<  days prior to the date of registration
Patient must currently be on androgen deprivation or anti-androgen therapy with castrate levels of testosterone (<  ng/dl)\r\n* Medical castration should continue until disease progression
Radiographic progression at study entry while on androgen deprivation therapy (or after bilateral orchiectomy).
A prior course of hormone therapy (androgen deprivation) of greater than  months duration
Standard of care medical management of current prostate cancer disease status by the patients local oncologist, e.g. androgen deprivation therapy is allowed
Prior use of androgen deprivation including enzalutamide
Progression on a prior regimen/line of an androgen synthesis inhibitor for prostate cancer
Subjects must not have had prior androgen deprivation therapy in the past  months
History of androgen deprivation therapy within the past  months
Willingness to be treated with radiation therapy and androgen deprivation therapy
No ongoing anti-androgen therapy; patients must be off anti-androgen therapy for at least  days
Patients must have had prior treatment with bilateral orchiectomy or androgen\n             deprivation therapy with an LHRH-blocker with evidence of treatment failure
All patients must have a histologically or cytologically proven diagnosis of adenocarcinoma of the prostate; all patients must have metastatic disease as evidenced by soft tissue and/or bony metastases prior to initiation of androgen deprivation therapy
Disease progression despite Androgen Deprivation Therapy
Myocardial infarction or cerebrovascular accident within one year from consultation, or other major vascular risk factor which would prevent a patient from receiving appropriate androgen deprivation therapy
Progressive disease on androgen deprivation therapy at enrollment;
Specific eligibility criteria for Part  CRPC expansion cohort: Persistent disease with evidence of disease progression following standard therapy(ies) including prior treatment with androgen/androgen receptor directed therapy, including enzalutamide and/or abiraterone
Androgen deprivation therapy started after prostatectomy and prior to step  registration for >  weeks ( days)
Androgen suppression or anti-androgen therapy within the  months prior to dosing, for prostate cancer.
Any prior androgen-deprivation therapy or finasteride as neoadjuvant or adjuvant therapy or for biochemical recurrence must have been discontinued at least  months prior to registration.
Patients must have started androgen deprivation therapy (bilateral orchiectomy versus luteinizing hormone-releasing hormone [LHRH] agonist, and with or without androgen antagonist) at least one month ( weeks) prior to enrollment and no more than six months ( weeks) prior to enrollment; patients must continue the androgen deprivation therapy throughout the study period, and patients are not permitted to change the type of androgen deprivation therapy (e.g. by adding an androgen antagonist) during the course of investigational therapy
Patients 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  [PCWG] criteria as a % increase in serum PSA and an absolute increase of  ng/mL over nadir)
Patient under medications that can affect PSA for the last  months prior to MRgFUS treatment (Androgen Deprivation Treatment; alpha reductase inhibitors)
Androgen deprivation therapy (if applicable) initiated >  months prior to registration; patients who have undergone bilateral orchiectomy will be eligible if they meet all other criteria; NOTE: patients with a history of locally recurrent hormone refractory cancer are eligible for this study, not patients with metastatic hormone refractory prostate cancer
Patients who have received TOK- (Galeterone) or any other investigational product directed towards the androgen receptor or androgen biosynthesis.
Castration-resistant prostate cancer demonstrated during continuous androgen deprivation therapy (ADT), defined as  rises of PSA, at least  week apart with the last androgen deprivation therapy (PSA) >=  nanogram per milliliters (ng/mL)
Patients who received a first generation anti-androgen (e.g., bicalutamide, flutamide, nilutamide) as part of their first-line hormonal therapy must have shown progression of disease off the anti-androgen prior to enrollment
Patients who are receiving an anti-androgen as part of their first-line hormonal therapy must have shown progression of disease off the anti-androgen prior to enrollment
Patients may either be untreated for their newly diagnosed metastatic disease (preferred as much as possible) or have started androgen deprivation therapy; patients who have started androgen deprivation therapy for the treatment of their newly diagnosed metastatic disease are eligible as long as the duration of treatment is less than or equal to  weeks ( days) prior to registration; the start date of androgen deprivation is considered the day the patient first received an injection of a LHRH agonist/antagonist (or orchiectomy), not the date when an oral antiandrogen started
Patients must have a minimum PSA >=  ng/mL within  days of registration or prior to the initiation of androgen deprivation for patients who have started androgen deprivation therapy
Prior use, or participation in a clinical trial, of an investigational agent that blocks androgen synthesis (e.g., abiraterone acetate, TAK-, TAK-, TAK-) or agents that block the androgen receptor (e.g., ARN-)
>=  days of antiandrogen therapy monotherapy without androgen deprivation therapy
Subjects who received combined androgen blockade with an anti-androgen must have shown PSA(prostate specific antigen) progression after discontinuing the anti-androgen prior to enrollment.
Prior androgen deprivation, chemotherapy, surgery, or radiation for prostate cancer
Progressive disease on androgen deprivation therapy
Prior participation in a clinical trial of an investigational agent that inhibits the androgen receptor or androgen synthesis (unless the treatment was placebo)
Previous anti-androgen therapy and progression after withdrawal; patients who received combined androgen blockade with an anti-androgen must have shown PSA progression after discontinuing the anti-androgen prior to enrollment (>=  weeks since last flutamide, >=  weeks since last bicalutamide or nilutamide)
Androgen deprivation therapy based on clinician judgment is permitted on study
No prior anti-androgen therapy (bicalutamide, flutamide or nilutamide) is permitted
Patients may have been treated with up to  months of androgen deprivation therapy
No prior androgen deprivation therapy (ADT) or anti-androgen for biochemical relapse
Patients who have received androgen ablative therapy for less than  weeks immediately prior to initiation of study drug are eligible provided they had only PSA evidence of progression (as defined above) with no visible metastases by CT-scan and bone scan (within  weeks) prior to starting androgen ablation
For cohort  only: - months of androgen deprivation therapy (gonadotropin hormone releasing analogs with or without an anti-androgen) prior to prostatectomy with a castrate testosterone level of <  ng/dL within  month prior to prostatectomy
Prior treatment with an luteinizing hormone-releasing hormone (LHRH) agonist or nonsteroidal antiandrogen, except in the following circumstances: Neoadjuvant/adjuvant androgen deprivation therapy administered with radiation therapy or at the time of prostatectomy is acceptable, provided that there was no evidence of PSA progression while on treatment; in this situation, patients must not have received more than  months of androgen deprivation treatment, and must not have been treated within  months prior to screening; other treatment with androgen deprivation therapy is prohibited
Have been on androgen deprivation therapy for a minimum of  months, and continue that therapy or an equivalent therapy to suppress testosterone during this trial
For patients who have been on anti-androgen therapy and had evidence of response to the addition of an anti-androgen (i.e., PSA reduction), patients must have discontinued anti-androgen therapy for at least six weeks ( weeks for flutamide) without current evidence of an anti-androgen withdrawal response
Has recovered from all therapy-related toxicity to =< grade  (except alopecia, anemia and any signs or symptoms of androgen deprivation therapy)
Patients who have had prior treatment for prostate cancer by surgery, irradiation, local ablative (i.e., cryosurgery or high-intensity focused ultrasound), or androgen-deprivation therapy are not eligible
Progressive disease despite ongoing androgen deprivation therapy.
Prior treatment with investigative androgen receptor (AR) agents
Progressive metastatic (M) disease on androgen deprivation therapy
Subjects must have discontinued additional hormonal (eg bicalutamide, abiraterone, estrogen) therapy prior to the first dose of cabozantinib; no anti-androgen withdrawal period is required
Patients who have received prior anti-androgen therapy
Prior investigational new generation potent anti-androgen therapy (such as ARN ).
Serum testosterone level: i) Subjects with no history of androgen deprivation therapy:
A single measurement greater than  ng/dL or . nmol/L within  months of enrollment ii) Subjects with a history of androgen deprivation therapy (either in adjuvant or biochemical relapse setting):
Concurrent use of other investigational agents or other prostate cancer therapies (e.g., androgen deprivation therapy)
Prior androgen deprivation therapy for prostate cancer
Ongoing androgen deprivation therapy
Prior therapy with other CYP inhibitor(s) or investigational agent(s) targeting the androgen receptor for metastatic prostate cancer
Concurrent anti-androgen therapy
Previous anti-androgen therapy and progression after withdrawal
Patients may be enrolled if they have had prior palliative radiation therapy; however, this has to have been commenced within  days of starting androgen deprivation
Prior or current androgen deprivation therapy
Patients, who have experienced disease progression despite 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 anti-androgen withdrawal prior to being eligible; the minimum timeframe to document failure of anti-androgen withdrawal will be four weeks; patients on second-line (or beyond) hormonal maneuvers, and patients who had no PSA decline on combined androgen blockade as first line therapy, need not progress through anti-androgen withdrawal (AAW) in order to be eligible
Starting or have started androgen deprivation therapy (oral or injection) for prostate cancer treatment within the last  months
Have received prior investigational anti-androgen therapy, including ARN-
Have a diagnosis of prostate cancer and are scheduled to receive radiotherapy with androgen deprivation therapy
Patient had prior treatment for prostate cancer (surgery, radiation, local ablative therapy, anti-androgen therapy or androgen deprivation therapy)
ELIGIBILITY FOR THE -YEAR EXTENSION: Patient has had prior treatment for prostate cancer (surgery, radiation, local ablative therapy, anti-androgen therapy or androgen deprivation therapy)
Have had prior treatment for prostate cancer by surgery, irradiation, local ablative (i.e., cryosurgery or high-intensity focused ultrasound), or androgen-deprivation therapy
Patients on long term (>  months) anti-androgen therapy (e.g. flutamide, bicalutamide, nilutamide) will need to be off anti-androgen for  weeks (wash out period) and show evidence of disease progression off the anti-androgen; patients that have been on an anti-androgen  months or less will need to discontinue anti-androgen therapy prior to treatment start (no wash out period required)
Patient under medications that can affect PSA for the last  months prior to MRgFUS treatment (Androgen Deprivation Treatment; alpha reductase inhibitors)
Patients with prior androgen deprivation therapy or any investigational neoadjuvant agent or intervention Cohort B Only: [Enrollment is Complete; No longer recruiting subjects]
No prior history of androgen deprivation therapy within the last month; however patients who will receive neoadjuvant and concurrent and adjuvant hormonal therapy will be eligible
Patients who have received androgen deprivation therapy or prior surgery for prostate cancer
Must be treatment naive (not have received neoadjuvant chemotherapy, radiation therapy, hormonal therapy, androgen deprivation therapy, or focal ablation techniques (e.g., high intensity focused ultrasound [HiFu])
SUB-STUDY I: Androgen deprivation therapy for prostate cancer
SUB-STUDY II: Androgen deprivation therapy for prostate cancer
SUB-STUDY III: Radiation therapy or start of standard of care systemic therapy (chemotherapy, androgen deprivation therapy) within  days prior to study PET
Androgen deprivation therapy or other neoadjuvant treatments prior to PET imaging and surgery
Not on current androgen deprivation therapy or plan for withdrawal of androgen deprivation therapy
Androgen deprivation therapy prior to PET imaging
Prior androgen deprivation therapy
Current or prior androgen deprivation therapy; a history of use of a -alpha reductase inhibitor is allowed, provided it was discontinued at least one month prior to study entry
Hormone deprivation therapy
Can be on androgen deprivation therapy if dose is stable for >=  week
Patient can remain on androgen deprivation therapy if on the same regimen prior to documentation of progressive metastatic disease
Prior radiation therapy, chemotherapy, or androgen-deprivation therapy within  weeks prior to study radiotracer administration (washout is one half-life of the drug or  weeks, whichever is longest)
Androgen ablation (hormone treatment) within the last  months
Androgen deprivation therapy or chemotherapy prior to PET imaging
Participants should not have had prior curative local treatment for prostate cancer, including no radiotherapy or prostatectomy; a maximum  days of systemic androgen deprivation therapy prior to registration is allowed
Current or prior androgen deprivation therapy; previous use of a -alpha reductase inhibitor is allowed, provided it was discontinued at least one month prior to study entry
- No androgen deprivation, anti-androgen therapy, chemotherapy, or investigational systemic therapy prior to CTT PET imaging
- Must remain on androgen deprivation therapy for duration of trial if no prior bilateral orchiectomy
Patients must be eligible for and must be planning to undergo androgen deprivation therapy
Prior use of androgen deprivation therapy or radiation therapy
Must be willing to continue androgen deprivation therapy while on study, if no prior orchiectomy