Patients must have a thyroid-stimulating hormone (TSH) with reflex free T3/free T4 (if TSH is out of normal range) and electrocardiogram (EKG) obtained within 7 days prior to sub-study registration
Patients must have adequate thyroid function, as evidenced by either thyroid-stimulating hormone (TSH) or, free thyroxine (T4) serum tests demonstrating values within the normal range, within 28 days prior to registration; Note: TSH, with reflex T4 is allowable if per institutional standard; otherwise, both TSH and free-T4 must be obtained
Adjuvant chemotherapy after surgery other than that specified in this protocol is not allowed; luteinizing hormone-releasing hormone (LHRH) agonists and adjuvant bisphosphonate or denosumab use is allowed
Hormone replacement therapy of any type, megestrol acetate, or raloxifene within one week prior to registration
Thyroid stimulating hormone (TSH) within normal limits (WNL); supplementation is acceptable to achieve a TSH WNL; in patients with abnormal TSH if free T4 is normal and patient is clinically euthyroid, patient is eligible
Pre/peri- and postmenopausal women and all men are eligible for this trial; postmenopausal is defined as:\r\n* Age >= 55 years and one year or more of amenorrhea\r\n* Age < 55 years and one year or more of amenorrhea, with estradiol < 20 pg/ml\r\n* Age < 55 with prior hysterectomy but intact ovaries, with estradiol < 20 pg/ml\r\n* Prior bilateral oophorectomy\r\nNOTE: Women who do not fit the criteria for being postmenopausal as above are deemed pre-or peri-menopausal; pre/perimenopausal women and all men can enroll provided they agree to receive concomitant luteinizing hormone-releasing hormone (LHRH) agonist; pre/perimenopausal women must have commenced treatment with LHRH agonist at least 4 weeks prior to randomization; if patients have received alternative LHRH agonist prior to study entry, they must switch to goserelin for the duration of the trial
Thyroid-stimulating hormone (TSH) within normal limits (WNL); supplementation is acceptable to achieve a TSH WNL; in patients with abnormal TSH, if free T4 is normal and patient is clinically euthyroid, patient is eligible
Thyroid stimulating hormone (TSH) within normal limits (WNL); supplementation is acceptable to achieve a TSH WNL; in patients with abnormal TSH however if the Free T4 is normal and patient is clinically euthyroid, patient is eligible
A serum thyroid-stimulating hormone (TSH) must be obtained within 28 days prior to step 2 registration to obtain a baseline value
All patients must be receiving standard of care androgen deprivation treatment (surgical castration versus LHRH agonist or antagonist treatment); subjects receiving LHRH agonist or antagonist must continue treatment throughout the time on this study
Previous hormonal therapy, such as LHRH agonists (e.g., leuprolide, goserelin, buserelin, triptorelin) or LHRH antagonist (e.g. degarelix), anti-androgens (e.g., flutamide, bicalutamide, cyproterone acetate), estrogens (e.g., diethylstilbestrol [DES]), or surgical castration (orchiectomy)
Prior pharmacologic androgen ablation for prostate cancer is allowed only if the onset of androgen ablation (both LHRH agonist and oral anti-androgen) is =< 45 days prior to the date of registration
Thyroid-stimulating hormone (TSH) within normal limits (TSH < ULN allowed in euthyroid patients on thyroid replacement therapy)
Prior androgen deprivation (luteinizing hormone-releasing hormone [LHRH] agonist and/or non-steroidal anti-androgen) is allowed if discontinued at least 90 days prior to study enrollment and given for =< 90 days duration\r\n* For example: Patients on prior LHRH analogs (post-prostatectomy), the discontinuation date should be calculated based on the expected duration of the sustained release injection, not simply the injection date of the drug; for instance, if a 22.5 mg sustained release dose of leuprolide acetate is given (3 month duration), then the expected duration of such a dose would be 90 days after the injection date; for a 7.5 mg leuprolide (1 month duration), the discontinuation date would be 30 days after the injection date\r\n* Please note: Finasteride or dutasteride must be stopped before treatment but should not determine eligibility
Prior androgen deprivation therapy (luteinizing hormone-releasing hormone [LHRH] agonist and/or non-steroidal anti-androgen) is allowed if discontinued at least 90 days prior to Step 1 registration and given for =< 90 days duration\r\n* For example: patients on prior LHRH analogs (post-prostatectomy), the discontinuation date should be calculated based on the expected duration of the sustained release injection, not simply the injection date of the drug; for instance, if a 22.5 mg sustained release dose of leuprolide acetate is given (3 month duration), then the expected duration of such a dose would be 90 days after the injection date; for a 7.5 mg leuprolide (1 month duration), the discontinuation date would be 30 days after the injection date \r\n* Please note: finasteride or dutasteride must be stopped before treatment starts but prior usage will not affect eligibility
Have 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 orchiectomy
Hormonal-acting agents (including DES, aldosterone, and spironolactone but not including gonadotropin-releasing hormone [GnRH] agonists or antagonists) are forbidden during the trial and must be stopped prior to treatment start; no washout period will be required for any of these agents
an intrauterine device (IUD) or hormone-releasing system (IUS)
Subjects not using hormone replacement therapy (HRT) must have experienced total cessation of menses for >= 1 year and be greater than 45 years in age, OR, in questionable cases, have a follicle stimulating hormone (FSH) value > 40 mIU/mL and an estradiol value < 40pg/mL (< 140 pmol/L)
Must have undergone bilateral orchiectomy (surgical castration) or be willing to continue gonadotropin-releasing hormone (GnRH) analog or antagonist (medical castration)
Postmenopausal status or receiving ovarian ablation with a gonadotropin-releasing hormone (GnRH) agonist such as goserelin or leuprolide; postmenopausal status is defined by any one of the following criteria:\r\n* Prior bilateral oophorectomy\r\n* Prior ovarian radiation for the purpose of ablation\r\n* Age >= 60 years\r\n* Age < 60 and amenorrhea for 12 or more months (in the absence of chemotherapy, tamoxifen, or ovarian suppression) and follicle stimulating hormones (FSH), luteinizing (LH), and estradiol in the postmenopausal range per local normal
Cohort A Dose Escalation (Ribociclib + PDR001): Breast participants:\r\n* Hormone receptor (HR)-positive, HER2-negative metastatic breast cancer according to American Society of Clinical Oncology (ASCO) College of American Pathologists (CAP) guidelines\r\n* Men are eligible, as long as on a gonadotropin releasing hormone (GNRH) agonist for at least 6 weeks prior to study entry; men MUST remain on the GnRH agonist for the duration of protocol\r\n* Prior Chemotherapy: Participants may have received any number of prior lines of chemotherapy for advanced breast cancer, as long as the last dose is >= 21 days prior to first dose of study treatment.
Cohort B Safety Run-In (Ribociclib + PDR001 + Fulvestrant): Women must be postmenopausal as defined as:\r\n* Age > 60 years or\r\n* Age > 45 with intact uterus and amenorrhea for >= 12 consecutive months or follicle stimulating hormone (FSH) levels within postmenopausal range according to the ranges established by the testing facility OR\r\n* Premenopausal women who have been on a GnRH agonist for at least 6 weeks prior to study entry; women in this group MUST remain on the GnRH agonist for the duration of protocol treatment OR\r\n* Status post bilateral oophorectomy, after adequate healing post-surgery
Expansion Cohort B (Ribociclib + PDR001 + Fulvestrant): Women must be postmenopausal as defined as:\r\n* Age > 60 years or\r\n* Age > 45 with intact uterus and amenorrhea for >= 12 consecutive months or follicle stimulating hormone (FSH) levels within postmenopausal range according to the ranges established by the testing facility OR\r\n* Premenopausal women who have been on a GnRH agonist for at least 6 weeks prior to study entry; women in this group MUST remain on the GnRH agonist for the duration of protocol treatment OR\r\n* Status post bilateral oophorectomy, after adequate healing post-surgery
Ongoing androgen deprivation therapy with a GnRH analogue, GnRH antagonist, or bilateral orchiectomy
Postmenopausal women as defined as:\r\n* Age > 60 years or\r\n* Age >= 45 with intact uterus and amenorrhea for >= 12 consecutive months or follicle stimulating hormone (FSH) levels within postmenopausal range according to the ranges established by the testing facility or\r\n* Premenopausal women who have been on a gonadotrophin releasing hormone (GnRH) agonist for at least 6 weeks prior to study entry; women in this group MUST remain on the GnRH agonist for the duration of protocol treatment or\r\n* Status post bilateral oophorectomy, after adequate healing post-surgery
Serum 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 orchiectomy
On Androgen Deprivation Therapy (ADT) with a Gonadotropin-releasing hormone (GnRH) agonist/antagonist or prior bilateral orchiectomy. All patients will be required to be on ADT throughout the study;
Surgically 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.
Menopausal status\r\n* Both pre- and post-menopausal patients are permitted into the study; for patients in Cohort C who are pre-menopausal, therapy with a gonadotropin-releasing hormone analogue (leuprolide acetate preferred) must be commenced at least 4 weeks before commencing trial therapy; post-menopausal status is defined either by \r\n** Prior bilateral oophorectomy\r\n** Age greater than 60\r\n** Age less than 60 years with an intact uterus and amenorrhoeic for at last 12 months. \r\n** For patients aged less than 60 years with amenorrhea for less than 12 months (including patients with prior hysterectomy, those who have received hormone replacement therapy, or those rendered amenorrhoeic by chemotherapy), follicle-stimulating hormonal (FSH) levels in the post-menopausal range define the post-menopausal state
Castrate testosterone levels (< 50 ng/dL) achieved by orchiectomy or maintenance on a luteinizing hormone-releasing hormone (LHRH) agonist or antagonist
Testosterone < 50 ng/dL; patients must continue primary androgen deprivation with an gonadotrophin releasing hormone (LHRH) analogue if they have not undergone orchiectomy
More than 1 month of prior hormone exposure or hormone exposure within 30 days of registration; prior enzalutamide, ketoconazole, abiraterone, or TAK700 prohibited; prior 5alpha-reductase inhibitors are allowed
For all Parts except Part F and H: Participants must have either post-menopausal status or pre-menopausal status if continuing or beginning ovarian suppression with a luteinizing hormone-releasing hormone (LHRH) agonist such as goserelin.
Receipt of any type of small molecule kinase inhibitor (including investigational kinase inhibitor) within 14 days before the first dose of study treatment. Note: Subjects with prostate cancer currently receiving luteinizing hormone releasing hormone (LHRH) or gonadotropin-releasing hormone (GnRH) agonists may be maintained on these agents
Have received systemic anti-cancer treatment or radiotherapy less than 2 weeks before the first dose of AG-270. Subjects with castration-resistant prostate cancer may continue therapy with a luteinizing hormone releasing hormone (LHRH) agonist while participating in this study. Continuation of supportive therapy with bisphosphonates or denosumab is also allowed, regardless of the underlying malignancy.
Patients with a history of autoimmune-related hypothyroidism on a stable dose of thyroid replacement hormone may be eligible for this study.
Age <60 and amenorrhea for 12 or more months (in the absence of chemotherapy, tamoxifen, toremifen, or ovarian suppression) and follicle-stimulating hormone (FSH) value >40 milli-international units per milliliter (mIU/mL) and an estradiol value <40 picograms per milliliter (pg/mL) (140 picomoles per liter [pmol/L]). Or ii. Premenopausal or perimenopausal concurrently given a luteinizing hormone-releasing hormone (LHRH) agonist starting at least 4 weeks before the start of trial therapy and is planned to continue LHRH during the study.
an intrauterine device (IUD) or hormone releasing system (IUS)
Patients must not be on active luteinizing hormone-releasing hormone (LHRH) agonist/antagonist therapy and must have testosterone level > 50 ng/dL
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
Testosterone =< 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 orchiectomy
intra-uterine hormone-releasing systems (IUSs),
The participant has received prior treatment with a small molecule kinase inhibitor or a hormonal therapy (including investigational kinase inhibitors or hormones) within 4 weeks or five half-lives of the compound or active metabolites, whichever is longer, before the first dose of study treatment; note: participants with prostate cancer currently receiving luteinizing hormone-releasing hormone (LHRH) or gonadotropin-releasing hormone (GnRH) agonists may be maintained on these agents
Treated with continuous androgen ablative therapy (either surgical castration or luteinizing hormone- releasing hormone [LHRH] agonist/antagonist)
Prior treatment with one additional second line hormone therapy is permitted
Prior docetaxel for hormone-sensitive prostate cancer is permitted if =< 6 doses were given in conjunction with first-line androgen deprivation therapy and > 12 months since last dose of docetaxel
Prior or planned androgen deprivation or bilateral orchiectomy
No other anticancer-therapy (chemotherapy, immunotherapy, hormonal anti-cancer therapy, radiotherapy [except for palliative local radiotherapy]), biological therapy or other novel agent is to be permitted while the patient is receiving study medication; patients on luteinizing hormone-releasing hormone (LHRH) analogue treatment for more than 6 months are allowed entry into the study and may continue at the discretion of the investigator
Women under 50 years old would be considered postmenopausal if they have been amenorrheic for 12 months or more, following cessation of exogenous hormonal treatments, and with luteinizing hormone (LH) and follicle-stimulating hormone (FSH) levels in the post-menopausal range for the laboratory.
Any isolated laboratory abnormality suggestive of a serious autoimmune disease (e.g. hypothyroidism): antinuclear antibody, thyroid-stimulating hormone (TSH), free thyroxine (FT4), rheumatoid factor
Patients must be castrate-resistant (i.e., developed progression of metastases following surgical castration or during medical androgen ablation therapy). Patients receiving medical castration therapy with gonadotropin-releasing hormone analogues should continue this treatment during this study.
Hypothyroidism (e.g., following Hashimoto's disease) stable on hormone replacement
Thyroid stimulating hormone (TSH) OR free thyroxine (T4) within the normal limits
Patient may not have had therapy modulating testosterone levels (such as luteinizing hormone, releasing-hormone agonists/antagonists and antiandrogens) within 6 months prior to randomization; agents such as 5 alpha reductase inhibitors, ketoconazole, abiraterone, systemic steroids, or herbal supplements known to decrease PSA levels including any dose of megestrol acetate, finasteride (e.g., saw palmetto and prostate cancer [PC]-SPES, African pygeum extract, lycopene, alanine, glutamic acid and glycine, beta-sitosterol, lycopene, nettle root extract, quercetin, Belizian Man Vine extract, muira puama extract and epimedium extract campesterol, stigmasterol, sitostanol and brassicasterol) are not permitted at any time during the period that the PSA values are being collected
Patients with a history of autoimmune-related hypothyroidism on a stable dose of thyroid replacement hormone are eligible
Subject has prior use of any hormones, including luteinizing hormone-releasing hormone (LHRH) agonists, ketoconazole, antiandrogens (such as bicalutamide, flutamide, or nilutamide), or 5-alpha-reductase inhibitors
Known uncompensated hypothyroidism (defined as greater than 2x upper limit of normal not treated with replacement hormone)
Ongoing androgen deprivation therapy with a gonadotropin-releasing hormone (GnRH) analogue or orchiectomy (i.e., surgical or medical castration); patients who have not had an orchiectomy must maintain effective GnRH-analogue therapy for the duration of the trial
If 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 discontinuation
Patients with prostate cancer can continue to receive treatment with gonadotropin releasing hormone (GnRH) agonists while on study, as long as there is evidence of disease progression on therapy
Part B2: Participants must have advanced, recurrent, or metastatic breast cancer that is refractory to aromatase inhibitors (AI) with either disease recurrence or disease progression; must be hormone receptor positive (HR+) and human epidermal growth factor receptor 2 (HER2)-negative; must be of postmenopausal status or beginning ovarian suppression with a luteinizing hormone-releasing hormone (LHRH) agonist
Patients with a history of autoimmune hypothyroidism (such as atrophic thyroiditis) on a stable dose of thyroid replacement hormone may be eligible.
Thyroid stimulating hormone (TSH) =< 1 x ULN.
Patients must have undergone bilateral surgical castration or must continue on gonadotrophin releasing hormone (GnRH) agonists/antagonists for the duration of the study.
Patients must agree to continuation of androgen deprivation therapy (ADT) with a gonadotropin-releasing hormone analogue/antagonist or bilateral orchiectomy; (patients with a malignancy other than prostate cancer are excluded from this criterion)
Patients must agree to continue to continuation of androgen deprivation therapy (ADT) with a gonadotropin-releasing hormone analogue/antagonist or bilateral orchiectomy
Current systemic therapy (other than a gonadotrophin releasing hormone [GnRH] agonist/antagonist) for CRPC including:\r\n* CYP-17 inhibitors (e.g. ketoconazole, abiraterone)\r\n* Antiandrogens (e.g. bicalutamide, nilutamide)\r\n* Second generation antiandrogens (e.g. enzalutamide, ARN-509, Galeterone)\r\n* Immunotherapy (e.g. sipuleucel-T, ipilimumab)\r\n* Chemotherapy (e.g. docetaxel, cabazitaxel)
Prior 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 trial
Ongoing or anticipated therapy with hormone therapy (other than LHRH antagonist), including any dose of megestrol acetate (Megace), finasteride (Proscar), dutasteride (Avodart) or received abiraterone within 28 days prior to the first dose of enzalutamide and/or CORT125281
More than 2 months of prior ADT with gonadotrophin releasing hormone (GnRH) antagonist/agonist at time of consent. Bicalutamide given for =< 2 months at the time of registration as flare prevention is allowed
Currently treated with hormone therapy-based regimen, including selective estrogen receptor modulators (SERMs), aromatase inhibitors, selective estrogen receptor down regulators (SERDs), CYP17A1 inhibitors, gonadotrophin releasing hormone (GnRH) agonists/antagonists, and antiandrogens; concurrent anti-HER2 therapy and other targeted therapy (e.g., CDK4/6 inhibitor, mTOR inhibitor) is permitted; must have started the current regimen at least 4 weeks prior to enrollment
Women under 50 years old would be considered postmenopausal if they have been amenorrheic for 12 months or more following cessation of exogenous hormonal treatments and with luteinizing hormone and follicle-stimulating hormone levels in the post-menopausal range for the institution
Prior hormone therapy for prostate cancer including orchiectomy, antiandrogens, ketoconazole, or estrogens (5-alpha reductase inhibitors allowed), or luteinizing hormone-releasing hormone (LHRH) agonists/antagonists
Adequately controlled thyroid function, with no symptoms of thyroid dysfunction; patients can be on thyroid hormone replacement medication; asymptomatic patients with elevated thyroid-stimulating hormone (TSH) with normal T4/T3 are allowed to enroll, and recommended to follow with routine thyroid function test especially if they are randomized to cediranib/olaparib arm
Thyroid-stimulating hormone (TSH) WNL\r\n* Supplementation is acceptable to achieve a TSH WNL; in patients with abnormal TSH, if free T4 is normal and patient is clinically euthyroid, patient is eligible
Initiated 28 (+ 7) days of androgen deprivation therapy (ADT) prior to day 1 of protocol therapy\r\n* Only luteinizing hormone-releasing hormone (LHRH) agonist treatment is considered ADT, bicalutamide or other antiandrogens used alone do not count
Ongoing androgen deprivation therapy with a gonadotropin releasing hormone (GnRH) analogue or orchiectomy (i.e., surgical or medical castration)
Postmenopausal female patients with metastatic histologically or cytologically confirmed invasive breast cancer; pre or perimenopausal women allowed with the addition of goserelin; postmenopausal status will be defined as following:\r\n* Age >= 60 years\r\n* Age < 60 years and 12 months of amenorrhea plus follicle stimulating hormone and plasma estradiol levels within postmenopausal range by local laboratory assessment in the absence of oral contraceptive pills, hormone replacement therapy, or gonadotropin-releasing hormone (GnRH) agonist or antagonist\r\n* Prior bilateral oophorectomy
Ongoing androgen deprivation therapy (ADT) with a gonadotropin-releasing hormone (GnRH) analogue or bilateral orchiectomy
Patients must agree to continuation of androgen deprivation therapy (ADT) with a gonadotropin-releasing hormone agonist/antagonist or bilateral orchiectomy
More than 1 month of prior hormone exposure or hormone exposure within 30 days of enrollment (up to 1 month of prior luteinizing hormone-releasing hormone (LHRH) agonist and/or anti-androgen therapy as neoadjuvant therapy prior to prostatectomy is allowed); prior enzalutamide, apalutamide, ketoconazole, abiraterone, or TAK700 for prostate cancer are prohibited; prior antiandrogen therapy (including but not limited to bicalutamide, flutamide, nilutamide, enzalutamide, and apalutamide) and prior estrogen therapy (including estrogen patch) are not allowed; all investigational agents are prohibited within 30 days of enrollment
Men who have had gonadotrophin releasing hormone (LHRH) agonist or antagonist hormone therapy in the prior six months
Prior hormone therapy for prostate cancer including orchiectomy, antiandrogens, ketoconazole, or estrogens (5-alpha reductase inhibitors allowed), or LHRH agonists/antagonists (Note: LHRH allowed if begun within 1 month of day 1).
Patients undergoing any systemic therapy (except for luteinizing hormone-releasing [LHRH] hormone agonist or antagonist treatment for prostate cancer, and bisphosphonates or receptor activator of nuclear factor [Nf] kappa [RANK] ligand inhibitors for bone strengthening), major surgery or radiotherapy for the treatment of prostate cancer within 2 weeks of study entry.
No prior hormonal therapy with the exception of oral 5-alpha-reductase inhibitors (finasteride, dutasteride, etc.); patients who have received prior oral anti-androgen therapies (bicalutamide, flutamide, nilutamide, etc.) must be off treatment for at least 6 weeks prior to enrollment; patients who have received prior luteinizing hormone-releasing hormone (LHRH) agonist or antagonist therapy (leuprolide, goserelin acetate, etc.) are eligible provided serum testosterone is > 50 mg/dl
Adequate thyroid function within 14 days prior to registration defined as serum thyroid-stimulating hormone (TSH) within the normal range
Female patients of no childbearing potential must be post-menopausal; post-menopausal female subjects should be defined prior to protocol enrollment by any of the following:\r\n* Subjects at least 60 years of age; OR\r\n* Subjects under 60 years of age and naturally (spontaneous, no alternative pathologic or physiological cause) amenorrhea for at least 12 months; OR\r\n* Medical ovarian failure confirmed by follicle-stimulating hormone (FSH) and estradiol levels in the post menopausal range per local institutional normal range; OR\r\n* Prior bilateral oophorectomy; OR\r\n* Prior radiation castration with amenorrhea for at least 6 months; OR\r\n* Treatment with a luteinizing hormone-releasing hormone (LH-RH) agonist (such as goserelin acetate or leuprolide acetate) is permitted for induction of ovarian suppression as long as it has been initiated at least 28 days prior to study enrollment
Patients who have had chemotherapy, radiotherapy, immunotherapy or anticancer agents within 4 weeks (6 weeks for nitrosoureas or mitomycin C) of the first dose of study treatment, except hormonal therapy with luteinizing hormone-releasing hormone (LHRH) analogues for medical castration in patients with prostate cancer and breast cancer, which are permitted
Last dose of any antineoplastic therapy >= 2 weeks (including chemotherapy, small molecule inhibitors, radiation, and/or other investigational anticancer agents); patients receiving hormone manipulation (e.g. selective estrogen receptor modulators [SERMs], aromatase inhibitors, luteinizing hormone releasing hormone [LHRH] agonist, etc.) for reasons other than treatment of metastatic breast cancer may continue this treatment at the discretion of the investigator
Prior hormone therapy for prostate cancer including orchiectomy, antiandrogens, ketoconazole, or estrogens (5-alpha reductase inhibitors allowed), or luteinizing hormone-releasing hormone (LHRH) agonists/antagonists.
Bilateral orchiectomy or ongoing androgen deprivation therapy with a gonadotropin-releasing hormone (GnRH) agonist/antagonist (surgical or medical castration).
For women with irregular menstrual periods and on hormone replacement therapy (HRT), a documented serum follicle stimulating hormone (FSH) level > 35 mIU/mL
Post-menopausal (if female) defined as: 1) prior bilateral oophorectomy, 2) age 60 or over, or 3) < 60 years and amenorrheic for at least 12 months with follicle-stimulating hormone (FSH) and estradiol in the postmenopausal range per institutional parameters); use of luteinizing hormone-releasing hormone (LHRH) agonists to induce chemical ovarian ablation will not be allowed for this study
Subjects must be receiving endocrine therapy consisting of 1) letrozole +/- palbociclib; or 2) exemestane +/ everolimus; or 3) fulvestrant +/- palbociclib; or 4) anastrozole; or 5) tamoxifen; pre-menopausal women must also be receiving a gonadotrophin releasing hormone (LHRH) agonist with endocrine therapy options 1 through 4; option 5 can be used without LHRH agonists for pre-menopausal women
The following ongoing treatments are permitted:\r\n* Hormone-replacement therapy or oral contraceptives\r\n* Hormone therapy for primary prevention of breast cancer
Patients must maintain ongoing androgen deprivation therapy with a GnRH analogue, antagonist, or bilateral orchiectomy (i.e., surgical or medical castration)
Postmenopausal is defined either by age >= 60, prior bilateral oophorectomy, or age < 60 with intact uterus and no spontaneous menses over 12 consecutive months; follicule stimulating hormone (FSH) and luteinizing hormone (LH) will not be utilized to define menopausal status, unless history of prior total hysterectomy; premenopausal patients are eligible to participate; medication-induced amenorrhea will not categorize a patient as post-menopausal; these patients should be treated as pre-menopausal; premenopausal and peri-menopausal patients should receive ongoing treatment with luteinizing hormone-releasing hormone (LHRH) agonists (goserelin or leuprolide); premenopausal patients must be enrolled directly into the treatment phase of the study
Patients receiving concurrent exogenous hormone therapy (hormone replacement therapy, oral or any other hormonal contraceptives such as hormonal contraceptive coil are not eligible
The subject has received prior treatment with a small molecule kinase inhibitor or a hormonal therapy (including investigational kinase inhibitors or hormones) within 14 days or 5 half-lives of the compound or active metabolites, whichever is longer, before the first dose of study treatment -OR- the subject has ever taken Cabozantinib; Note: subjects with prostate cancer currently receiving luteinizing hormone releasing hormone (LHRH) or gonadotropin releasing hormone (GnRH) agonist may be maintained on these agents
Serum 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 orchiectomy
Postmenopausal status or receiving ovarian ablation with a gonadotropin-releasing hormone (GnRH) agonist such as goserelin\r\n* Postmenopausal status is defined by any one of the following criteria:\r\n** Prior bilateral oophorectomy\r\n** Age >= 60 years\r\n** Age < 60 and amenorrhea for 12 or more months (in the absence of chemotherapy, tamoxifen, toremifene, or ovarian suppression) and follicle-stimulating hormone (FSH), luteinizing hormone (LH), and estradiol in the postmenopausal range per local normal\r\n* If the patient does not meet criteria for postmenopausal status but is receiving ovarian ablation therapy with a GnRH agonist such as goserelin, the patient is eligible for this study, provided that the GnRH agonist is started at least 2 weeks prior to cycle 1 day 1 (C1D1) of anti-estrogen therapy
Adequately controlled thyroid function, with no symptoms of thyroid dysfunction; elevated thyroid stimulating hormone (TSH) with normal T3 and T4 are allowed; patients on thyroid replacement therapy are allowed
Treatment naive, defined as less than 2 months of standard of care ADT (e.g. gonadotrophin releasing hormone [GNRH] agonist or antagonist with or without antiandrogen, including abiraterone) for metastatic hormone-sensitive prostate cancer prior to enrollment (at time of consent)
Ongoing 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/dl
Any hormonal therapy being taken as a treatment for cancer must be discontinued at least one week prior to registration; continuation of hormone replacement therapy e.g. thyroid hormone replacement therapy is permitted
Women under 50 years-of-age would be considered postmenopausal if they have been amenorrhoeic for at least 12 months following the cessation of exogenous hormonal treatments, and have serum follicle-stimulating hormone and luteinizing hormone levels in the postmenopausal range for the institution.
Planned total, near-total or completion thyroidectomy requiring lifelong thyroid hormone replacement
Patients 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 registration
Patients must agree to continue to continuation of androgen deprivation therapy (ADT) with a gonadotropin-releasing hormone agonist/antagonist or bilateral orchiectomy
Ongoing 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.
Patients 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 registration
Patients may have had a recent previous hospital admission (within 30 days) or be admitted preoperatively but not for the following conditions\r\n* Unstable angina\r\n* Congestive heart failure\r\n* Severe hypothyroidism thyroid-stimulating hormone (TSH) >10\r\n** Endocrine consult and intervention may allow participation at the discretion of the principal investigator (PI) for a TSH > 10
The use of any prior hormones including luteinizing hormone–releasing hormone (LHRH) agonists, LHRH antagonists, antiandrogens such as bicalutamide, flutamide and nilutamide, and/or the use of 5-alpha reductase inhibitors, PCSPES (or PC-x product), megestrol acetate, or estrogen containing nutraceuticals within 6 months of\r\nstudy treatment initiation
mCRPC EXPANSION COHORT: Patients must have undergone bilateral surgical castration or must agree to continue on gonadotrophin releasing hormone (GnRH) agonists/antagonists for the duration of the study
Concurrent standard long-term anticancer hormonal therapy with drugs including, but not limited to, selective estrogen receptor modulators or Gonadotropin-releasing hormone (GnRH) analogs if started at least six months before the first dose of ARQ 751 is allowed
Women may be premenopausal or postmenopausal; however, premenopausal women and men must be treated with concurrent luteinizing hormone-releasing hormone (LHRH) agonist (goserelin preferred) initiated at least 4 weeks prior to enrollment; NOTE: Postmenopausal status is defined by at least one of the following criteria:\r\n* Age >= 60 years\r\n* Age < 60 and cessation of regular menses for at least 12 consecutive months with no alternative pathological or physiological cause; and serum estradiol and follicle stimulating hormone (FSH) level within the laboratory’s reference range for postmenopausal females\r\n* Documented bilateral oophorectomy; or,\r\n* Medically confirmed ovarian failure
Clinically euthyroid; Note: patients are permitted to receive thyroid hormone supplements to treat underlying hypothyroidism
Is currently participating and receiving study therapy or concurrent chemotherapy, immunotherapy, biologic, or hormonal therapy for cancer treatment at the time of administration of first dose of trial treatment; continuation of hormone replacement therapy is permitted; stable regimens of hormonal therapy i.e. for prostate cancer (e.g. leuprolide, a gonadotrophin releasing hormone [GnRH] agonist), ovarian, or breast cancer are not exclusionary
Treatment within 28 days of cycle1 day1: any other systemic therapy for prostate cancer (with the exception of luteinizing hormone-releasing hormone [LHRH] agonists and LHRH antagonists for testosterone suppression, and bisphosphonates and RANK-ligand inhibitors for bone metastases which are allowed); any other investigational product
Post-menopausal status defined by: a) age ? 60 years; b) age < 60 years and cessation of regular menses for at least 12 consecutive months with no alternative pathological or physiological cause; c) documented bilateral oophorectomy; d) medically confirmed ovarian failure OR\r\n* Pre/peri-menopausal, ie, not meeting the criteria for being postmenopausal who are also receiving ongoing treatment with gonadotrophin releasing hormone (LHRH) agonists (goserelin or leuprolide); the first injection should occur at least two weeks before study start
Patients must be off prior chemotherapy, hormonal therapy, or biological therapy for at least 4 weeks or > 3 half-lives whichever comes first; patients with prostate cancer may continue to receive luteinizing hormone–releasing hormone (LHRH) agonist (unless orchiectomy has been performed)
Currently using hormone replacement therapy (oral or patch) or/and phytoestrogen supplements (i.e. black cohosh)
Intrauterine hormone-releasing system ( IUS)
Triiodothyronine measurement (T3), thyroxine (T4) or thyroid-stimulating hormone (TSH) =< 3.0 x IULN
Post-menopausal women with clinical stage I-IV, ER positive/HER2 negative, breast cancer that will be managed by surgical resection; the subject is post-menopausal if:\r\n* She has had a prior bilateral oophorectomy\r\n* Age is 60 or greater\r\n* Age is under 60 but she has had at least 12 months or amenorrhea and with both follicle-stimulating hormone and estradiol levels in the post-menopausal range; treatment with a luteinizing hormone-releasing hormone is not allowed for induction of ovarian suppression on this trial\r\n* Patients with metastatic disease at diagnosis are eligible if clinically appropriate; the patient must have had a baseline magnetic resonance imaging (MRI) performed as standard-of-care that can be used to calculate the distance(s) of the longest dimension(s) of the primary tumor(s)
Concurrent use of other anticancer agents or treatments, with the following exceptions:\r\n* Ongoing treatment with luteinizing hormone-releasing hormone (LHRH) agonists or antagonists, denosumab (Prolia) or bisphosphonate (eg, zoledronic acid) is allowed; ongoing treatment should be kept at a stable schedule; however, if medically required, a change of dose, compound, or both is allowed
Ongoing gonadal androgen deprivation therapy with gonadotropin-releasing hormone (GnRH) analogues, antagonists or orchiectomy; patients who have not had an orchiectomy must be maintained on effective GnRH analogue/antagonist therapy
Ongoing gonadal androgen deprivation therapy with gonadotropin-releasing hormone (GnRH) analogues, antagonists or orchiectomy; patients who have not had an orchiectomy must be maintained on effective GnRH analogue/antagonist therapy
Female patients should be either:\r\n* Postmenopausal, as defined by at least one of the following criteria:\r\n* Age >= 60 years\r\n* Age =< 60 years and cessation of regular menses for at least 12 consecutive months with no alternative pathological or physiological cause\r\n* Documented bilateral oophorectomy\r\n* Medically confirmed ovarian failure\r\nOR\r\n* Pre/peri-menopausal women, ie, not meeting the criteria for being postmenopausal who are also receiving ongoing treatment with luteinizing hormone-releasing hormone (LHRH) agonists (goserelin or leuprolide); the first injection should occur at least two weeks before study start
Receipt of any type of small molecule kinase inhibitor (including investigational kinase inhibitor) within 14 days before the first dose of study treatment; note: subjects with prostate cancer currently receiving luteinizing hormone-releasing hormone (LHRH) or gonadotropin-releasing hormone (GnRH) agonists may be maintained on these agents
Clinically euthyroid; note: patients are permitted to receive thyroid hormone supplements to treat underlying hypothyroidism
Castrate-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 1
For subjects enrolled in the Carboplatin Plus Paclitaxel Arm or Paclitaxel Arm, concurrent standard long-term anticancer hormonal therapy with drugs including but not limited to selective estrogen receptor modulators or Gonadotropin-releasing hormone (GnRH) analogs if started at least six months before the first dose of study treatment is allowed
For patients who are not postmenopausal or surgically sterile (absence of ovaries and/or uterus), agreement to remain abstinent or to use two adequate methods of contraception (e.g., condoms, diaphragm, vasectomy/vasectomized partner, tubal ligation), during the treatment period and for at least 30 days after the last dose of study treatment or 3 months after discontinuation of taselisib and/or enzalutamide, whichever is longer; hormone based oral contraceptives are not allowed on study; postmenopausal is defined as:\r\n* Age >= 60 years\r\n* Age =< 60 years and amenorrheic for 12 months in the absence of chemotherapy, tamoxifen, toremifene, or ovarian suppression; or follicle stimulating hormone and estradiol in the postmenopausal range
Adequately controlled thyroid function, with no symptoms of thyroid dysfunction and thyroid stimulating hormone (TSH) within normal limits
Participants with DTC must be receiving thyroxine suppression therapy and levels of thyroid stimulating hormone (TSH) should not be elevated (TSH should be less than or equal to 5.50 milliunits per liter (mU/L)). When tolerated by the participant, thyroxine dose should be changed to achieve TSH suppression (TSH less than 0.50 mU/L).
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 physician’s 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
Patients 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 registration
Hormonal therapy (luteinizing hormone-releasing hormone [LHRH] agonist or oral anti-androgen) exceeding 4 months prior to registration
Previous hormonal therapy, such as luteinizing hormone-releasing hormone (LHRH) agonists (e.g., goserelin, leuprolide) or LHRH antagonists (e.g., degarelix), anti-androgens (e.g., flutamide, bicalutamide), estrogens (e.g., diethylstilbestrol [DES]), or surgical castration (orchiectomy)
Progressing on continuous androgen ablative therapy (either surgical castration or luteinizing hormone-releasing hormone [LHRH] agonist)
For castration-only Cohort C, patients must have developed castrate resistant prostate cancer after progressing on first line hormone therapy with either surgical castration or LHRH agonist or LHRH agonist plus an anti-androgen
Patients progressing on LHRH agonist plus an anti-androgen as first line therapy must be off anti-androgen for 4 weeks prior to first treatment with testosterone
Prior docetaxel for hormone-sensitive prostate cancer is permitted if =< 6 doses were given in conjunction with first-line androgen deprivation therapy and > 12 months since last dose of docetaxel
Patients who received hormone therapy before prostatectomy
Previous hormonal therapy, such as luteinizing hormone-releasing hormone (LHRH) agonists (e.g., leuprolide, goserelin, buserelin, triptorelin) or LHRH antagonist (e.g. degarelix), anti-androgens (e.g., flutamide, bicalutamide, cyproterone acetate), estrogens (e.g., diethylstilbestrol [DES]), or surgical castration (orchiectomy)
Thyroid-stimulating hormone (TSH) and free thyroxine (T4) within normal limits (patients may be on thyroid hormone replacement)
COHORTS 1 AND 2: HEALTHY VOLUNTEERS: Any female with symptoms and/or serum hormone levels consistent with perimenopause
COHORT 3: ATOPIC DERMATITIS PATIENTS: Any female with symptoms and/or serum hormone levels consistent with perimenopause
Bisphosphonates, hormone modification therapy, and trastuzumab are permitted without restriction
Any hormonal therapy directed at the malignant tumor must be discontinued at least one week prior to registration (study enrollment); continuation of hormone replacement therapy is permitted; stable regimens of hormonal therapy i.e. for prostate cancer (e.g. leuprolide, a gonadotropin-releasing hormone [GnRH] agonist), ovarian or breast cancer are not exclusionary
Subjects not using hormone replacement therapy (HRT) must have experienced total cessation of menses for >= 1 year and be greater than 45 years in age, OR, in questionable cases, have a follicle stimulating hormone (FSH) value > 40 mIU/mL and an estradiol value < 40 pg/mL (< 140 pmol/L)
Ongoing 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
Ongoing therapy with LHRH analog or bilateral orchiectomy.
Radiographic progression at study entry while on androgen deprivation therapy (or after bilateral orchiectomy).
Prior hormonal therapy (luteinizing hormone-releasing hormone [LHRH] agonist/antagonist with or without antiandrogen) up to 8 weeks is permitted
Prior hormonal therapy, such as luteinizing hormone-releasing hormone (LHRH) agonists (e.g., goserelin, leuprolide), antiandrogens (e.g., flutamide, bicalutamide), estrogens (e.g., diethylstilbestrol [DES]), or bilateral orchiectomy
A prior course of hormone therapy (androgen deprivation) of greater than 3 months duration
No hormone ablation for two months prior to enrollment, or during treatment
Androgen suppression therapy within past year; defined as: luteinizing hormone-releasing hormone (LHRH) agonist or antagonist, or androgen blocker, not 5-alpha reductase inhibitor
At least 28 days elapsed between last anti-cancer treatment administration and the initiation of study treatment (except for Luteinizing Hormone-releasing Hormone [LHRH] or Gonadotropin-releasing Hormone [GnRH]), or resolution of all previous treatment related toxicities to CTCAE version 4.03 grade of ? 1 (except for chemotherapy induced alopecia and grade 2 peripheral neuropathy or grade 2 urinary frequency which are allowed). Prior major surgery must be at least 12 weeks prior to study entry.
Oestrogens, including hormone replacement therapy;
Current progestin-based hormone replacement therapy.
hormone-containing contraceptive intrauterine device with a failure rate of < 1% per year,
No other anticancer-therapy (chemotherapy, immunotherapy, hormonal anti-cancer therapy, radiotherapy [except for palliative local radiotherapy]), biological therapy or other novel agent is to be permitted while the patient is receiving study medication; patients on luteinizing hormone-releasing hormone (LHRH) analogue treatment for more than 6 months are allowed entry into the study and may continue at the discretion of the investigator
A serum thyroid-stimulating hormone (TSH), free T4, and AM (morning) cortisol must be obtained within 14 days prior to randomization to obtain a baseline value and be within normal limits for the local laboratory
Ongoing gonadal androgen deprivation therapy with gonadotropin-releasing hormone (GnRH) analogues, antagonists or orchiectomy; patients who have not had an orchiectomy must be maintained on effective GnRH analogue/antagonist therapy
Pre/perimenopausal women with a known hypersensitivity to gonadotrophin releasing hormone (gnRH).
Patients 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 registration
Non-pregnant and not nursing; women of childbearing potential must take the pregnancy test and must commit to receive luteinizing hormone-releasing hormone (LHRH) agonist Zoladex (goserelin) for two years starting from the commencement of the study medications
Surgically 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.
Any anticancer therapy including; small molecules, immunotherapy, chemotherapy monoclonal antibodies or any other experimental drug within five half-lives but maximum four weeks before first infusion. Accepted exceptions are bisphosphonates, denosumab and gonadotropin-releasing hormone agonist or antagonist.
Received hormonal therapy (apart from luteinizing hormone releasing hormone agonist/antagonist for prostate cancer and hormone replacement therapy) within 2 weeks prior to the first dose of study treatment
Received hormonal therapy (apart from luteinizing hormone releasing hormone agonist/antagonist for prostate cancer and hormone replacement therapy) within 2 weeks prior to the first dose of study treatment
Thyroid stimulating hormone (TSH) within normal limits
Patients with hypothyroidism that is clinically stable and have normal TSH levels with hormone replacement, or patients with vitiligo or psoriasis not requiring treatment remain eligible for the study
intrauterine hormone-releasing system (IUS)
TUMOR BIOPSY SEQUENCING: Patients with bone metastases or hypercalcemia on intravenous bisphosphonate treatment, denosumab, or similar agents areare eligible to participate and may continue this treatment; patients with prostate cancer may continue luteinizing hormone-releasing hormone (LHRH) agonists or antagonists
Adequately controlled thyroid function, with no symptoms of thyroid dysfunction; patients can be on thyroid hormone replacement medication; asymptomatic patients with elevated thyroid stimulating hormone (TSH) with normal T4/T3 are allowed to enroll, and recommended to follow with routine thyroid function test
Adequately controlled thyroid function, with no symptoms of thyroid dysfunction and thyroid-stimulating hormone (TSH) within normal limits
Prior history of up to 8 weeks of androgen deprivation therapy defined as luteinizing-hormone releasing hormone (LHRH) or other medical castration therapy prior to registration is acceptable; this will be in addition to the 6 months of ADT on study
Subject is post-menopausal defined as age over 60 or status post bilateral oophorectomy; in subjects aged 50-60 years they shall be considered eligible if follicle stimulating hormone (FSH)/luteinizing hormone (LH) and estradiol is within institutional post-menopausal range at the time of study entry
Prior orchiectomy or must be on ongoing luteinizing hormone-releasing hormone (LHRH) agonist or antagonist (e.g., degarelix) therapy
Women are considered post-menopausal and not of child-bearing potential if they have had 12 months of natural (spontaneous) amenorrhea with an appropriate clinical profile (e.g. age appropriate, history of vasomotor symptoms) or have had surgical bilateral oophorectomy (with or without hysterectomy) at least six weeks ago; for women with therapy-induced amenorrhea, oophorectomy or serial measurements of follicle stimulating hormone (FSH) and/or estradiol are needed to ensure postmenopausal status; NOTE: ovarian radiation or treatment with a luteinizing hormone-releasing hormone (LH-RH) agonist (goserelin acetate or leuprolide acetate) is not permitted for induction of ovarian suppression
Men who have received any hormonal manipulation (antiandrogens; luteinizing hormone-releasing hormone [LHRH] agonist; 5-alpha-reductase inhibitors) within the previous 6 months
Normal thyroid function testing (thyroid stimulating hormone [TSH]) within 14 days prior to registration
Patients who require thyroid replacement therapy are not eligible if they have not been receiving a stable replacement dose for at least 28 days prior to study enrollment; patients who enter the study on thyroid replacement should have their medication adjusted to maintain thyroid-stimulating hormone (TSH) in the normal range
Clinically euthyroid; note: patients are permitted to receive thyroid hormone supplements to treat underlying hypothyroidism
Patients with prostate cancer can continue to receive treatment with gonadotropin-releasing hormone (GnRH) agonists while on study, as long as there is evidence of disease progression on therapy
Thyroid-stimulating hormone (TSH) up to 4 times ULN if thyroxine (T4) is normal
Thyroid-stimulating hormone (TSH) within institutional/laboratory normal limits
Thyroid stimulating hormone (TSH) within institutional normal range – patients with thyroid disease are eligible if euthyroid on suppressive or replacement therapy
Thyroid-stimulating hormone (TSH) within normal limits (WNL); supplementation is acceptable to achieve a TSH WNL; in patients with abnormal TSH however free T4 and free thyroxine index (FTI) are normal and patient is clinically euthyroid, patient is eligible
Thyroid stimulating hormone (TSH) within normal limits
Prior treatment with an anti-androgen, luteinizing hormone-releasing hormone (LHRH) agonist, or a combination of the two
Patients must be postmenopausal defined as:\r\n* Age >= 55 years and one year or more of amenorrhea\r\n* Age < 55 years and one year or more of amenorrhea, with an estradiol assay < 20 pg/mL\r\n* Surgical menopause with bilateral oophorectomy (at least 28 days must elapse from surgery to time of study registration)\r\n* The use of gonadotropin-releasing hormone (GnRH) analogues to achieve postmenopausal status is not allowed
Normal (=< upper limit of normal) levels of thyroid stimulating hormone (TSH), free T4, adrenocorticotropic hormone (ACTH), morning AM cortisol, amylase and lipase are required for entry to cohorts 4, 5 and 6 (AM cortisol testing may be taken up to 5 pm per Moffit Cancer Center guidelines)
Patient must not have pre-existing thyroid abnormality with thyroid stimulating hormone that cannot be maintained at less than or within the normal range with medication
There are two patient populations eligible for the study: those who have not started any therapy with LHRH agonist or antagonist (or orchiectomy) (Early Induction Group) and those who have already started therapy with LHRH agonist or antagonist (or orchiectomy) within the 30 days prior to registration (Late Induction Group); patients must be registered within 30 days of first injection of the LHRH agonist or antagonist (or orchiectomy)
Patients who have not yet started androgen deprivation therapy (LHRH agonist/antagonist or orchiectomy) and will not have an LHRH agonist injection until after randomization (early induction group) must have radiographic assessments of all disease including bone scan (or positron emission tomography [PET] scan) within 42 days prior to registration; patients who have started androgen deprivation therapy (LHRH agonist/antagonist or orchiectomy) prior to registration (late induction group) must have radiographic assessments including bone scan (or PET scan) within 42 days prior to start of androgen deprivation therapy (if scans have not been obtained prior to LHRH agonist/antagonist or orchiectomy they must be done within 42 days prior to registration); all disease must be assessed and documented on the Baseline Tumor Assessment Form; NOTE: Androgen deprivation therapy does not include treatment with anti-androgens such as bicalutamide or flutamide or five alpha reductase inhibitors such as finasteride or dutasteride
In the late induction group, patients must have had no more than 30 days of prior castration (medical or surgical) for metastatic prostate cancer prior to registration; the start date of medical castration is considered the day the patient first received an injection of a LHRH agonist/antagonist (or orchiectomy), not an oral antiandrogen\r\n* If the method of castration was luteinizing hormone releasing hormone (LHRH) agonists (i.e., leuprolide or goserelin), the patient must be willing to continue the use of LHRH agonist and add bicalutamide or TAK-700 (according to randomization) during protocol treatment\r\n* If the patient was on an antiandrogen (e.g. bicalutamide, flutamide), the patient must be willing to switch over to bicalutamide or TAK-700 (according to randomization); there is no limit on how many days a patient may have been on an antiandrogen (e.g. bicalutamide, flutamide) or a five alpha reductase inhibitor (e.g. finasteride or dutasteride) prior to going on study and no washout is required\r\n* If the method of castration was LHRH antagonists (i.e. Degarelix), the patient must be willing to switch to an LHRH agonist during protocol treatment
Subjects must have undergone orchiectomy, or have ongoing LHRH analogue therapy prior to drug initiation. Subjects on LHRH analogues must remain on these agents for the duration of the study.
Has 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 study
Patients should have normal baseline thyroid-stimulating hormone (TSH); patients with elevated TSH level (between 4.5-10 mU/L in the absence of symptoms of hypothyroidism) must have a normal free thyroxine (T4); TSH that is 10 mU/L or higher is exclusionary\r\n* A history of hypothyroidism and/or hyperthyroidism is allowed, as long as the patient has stable well-controlled thyroid function for a minimum of 2 months
negative serum pregnancy test at baseline (within 14 days prior to randomization) and agree to use medically approved precautions to prevent pregnancy during the study and for 12 weeks following the last dose of abemaciclib id menopause induced by gonadotropin-releasing hormone (GnRH) agonist or radiation
Follicle stimulating hormone measurement elevated into the menopausal range
If letrozole is selected as the control therapy, patients must be postmenopausal, either following bilateral oophorectomy or at least 5 years after spontaneous menopause; patients within 5 years of spontaneous menopause or who have had a hysterectomy without bilateral oophorectomy must have postmenopausal luteinizing hormone (LH) and follicle stimulating hormone (FSH) levels; patients on hormone replacement therapy (HRT) must agree to withdrawal of hormone therapy before letrozole is started
Subjects with hypothyroidism (eg, following Hashimoto syndrome) stable on hormone replacement; or
Castration 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.
Anti-tumor therapy (chemotherapy, antibody therapy, molecular targeted therapy) within 21 days or 5 half-lives, whichever is longer, of study drug dosing (6 weeks for nitrosoureas, mitomycin C, or molecular agents with t1/2 > 10 days); concurrent use of an luteinizing hormone releasing hormone (LHRH) agonist is permitted for all individuals and ongoing enzalutamide is required in Group 3.
Age < 55 years and surgical menopause with bilateral oophorectomy a. Note: Ovarian radiation or treatment with a luteinizing hormone-releasing hormone (LH-RH) agonist (goserelin acetate or leuprolide acetate) is not permitted for induction of ovarian suppression at the time of screening. Long term use (>6 months prior to screening) is permitted
Currently receiving hormone replacement therapy, unless discontinued prior to screening
Subjects with hypothyroidism (eg, following Hashimoto syndrome) stable on hormone replacement for ? 3 months prior to signing the ICF; or
Once randomized at day 1, subject must maintain ADT with an LHRH agonist or antagonist during study treatment or have a history of bilateral orchiectomy (i.e., medical or surgical castration).
Ongoing androgen deprivation therapy with a gonadotropin-releasing hormone (GnRH) agonist/antagonist or prior bilateral orchiectomy (medical or surgical castration);
Prior therapy for prostate cancer (exceptions: luteinizing hormone-releasing hormone [LHRH] agonist or antagonist may have been initiated within 30 days prior to enrollment; bicalutamide may have been given within 60 days of enrollment as long as it has been stopped at least 7 days before enrollment and total duration was no longer than 30 days; previous alpha-reductase inhibitor use allowed IF patient has not been taking for at least 30 days prior to abiraterone acetate initiation, OR if alpha reductase inhibitor was not used as a primary treatment of prostate cancer and the PSA on alpha-reductase inhibitor remains within eligibility when doubled
Patients must not receive any other anti-cancer therapy (cytotoxic, biologic, radiation, or hormonal other than for replacement) while on this study except for medications that are prescribed for supportive care but may potentially have an anti-cancer effect (i.e. megestrol acetate, bisphosphonates); these medications must have been started 1 month prior to enrollment on this study; in addition, men receiving treatment for prostate cancer will be maintained at castrate levels of testosterone by continuation of luteinizing-releasing hormone agonists
Age <60 years with amenorrhea for at least 12 months and both follicle-stimulating hormone (FSH) and estradiol levels are in postmenopausal range (according to the local laboratory)
Age < 60 years and cessation of regular menses for at least 12 consecutive months in the absence of chemotherapy, tamoxifen, toremifene, or ovarian suppression and serum estradiol and follicle-stimulating hormone (FSH) level within the post-menopausal range
Pre-/peri-menopausal women can be enrolled if amenable to be treated with the luteinizing-hormone releasing hormone (LHRH) agonist, goserelin. Individuals must have commenced treatment with goserelin or an alternative LHRH agonist at least 4 weeks prior to first dose of study drug. If individuals have received an alternative LHRH agonist prior to study entry, they must switch to goserelin on or before Cycle 1 Day 1 (C1D1) for the duration of the study
EARLY INDUCTION GROUP: Subjects who have started androgen deprivation therapy (luteinizing hormone-releasing hormone (LHRH) agonist or antagonist therapy with or without an anti-androgen agent) a maximum of 28 days before registration and who otherwise meet all the eligibility criteria.
LATE INDUCTION GROUP: Subjects who have NOT started any androgen deprivation therapy (luteinizing hormone-releasing hormone (LHRH) agonist or antagonist therapy with or without an antiandrogen agent).
Adequate thyroid function within 28 days prior to registration defined as serum thyroid-stimulating hormone (TSH) in normal range
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 (4 weeks) prior to enrollment and no more than six months (24 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 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.
Have a history of uncontrolled pituitary hormone diseases that currently require varying doses of supplemental hormonal administration (thyroid hormones, adrenocorticotropic hormone [ACTH], growth hormone) or other endocrine disorders requiring varying doses of hormone administration with the exception of diabetes and osteoporosis
Castrate 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-androgen
Prior hormonal therapy, such as LHRH agonists (e.g., goserelin, leuprolide), antiandrogens (e.g., flutamide, bicalutamide), estrogens (e.g., diethylstilbestrol [DES]), or bilateral orchiectomy
Thyroid-stimulating hormone (TSH) (0.3-5.0) and free thyroxine (0.8-1.87) within Mayo normal range
Androgen deprivation therapy (if applicable) initiated > 3 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 with a history of autoimmune hypothyroidism on a stable dose of thyroid replacement hormone may be eligible.
Hormone replacement therapy of any type, megestrol acetate, or raloxifene within four weeks prior to first study treatment
Uncompensated hypothyroidism (defined as thyroid-stimulating hormone [TSH] greater than 2 x upper limit of normal not treated with replacement hormone)
Ongoing androgen depletion therapy with a Gonadotropin Releasing Hormone analog or inhibitor, or orchiectomy (surgical or medical castration)
Previous hormonal therapy such as luteinizing hormone releasing hormone (LHRH) agonists (e.g. goserelin, leuprolide), anti-androgens (e.g. flutamide, bicalutamide), estrogens (e.g. diethylstilbestrol [DES]), or surgical castration (orchiectomy)
Postmenopausal women are eligible; postmenopausal is defined as any of the following:\r\n* Age >= 60 years\r\n* Age < 60 and amenorrhea for 12 or more months (in the absence of chemotherapy, tamoxifen, toremifene, or ovarian suppression) and follicle-stimulating hormone (FSH) and estradiol in the postmenopausal range per local normal range\r\n* Premenopausal women who have been on a gonadotropin-releasing hormone (GnRH) agonist for at least 3 consecutive months prior to study entry are eligible; women in this group MUST remain on the GnRH agonist for the duration of protocol treatment\r\n* Status-post bilateral oophorectomy-after adequate healing post surgery
Throughout the study, ongoing androgen deprivation therapy with a luteinizing hormone-releasing hormone (LHRH) analogue or prior bilateral orchiectomy (medical or surgical castration);
Patients must have undergone orchiectomy, or have been on LHRH agonists or antagonists, for at least 3 months prior to study entry. Patients on LHRH agonists/antagonists must remain on these agents for the duration of the study.
Adequately controlled thyroid function, with no symptoms of thyroid dysfunction and thyroid stimulating hormone (TSH) within normal limits
Subjects who are currently taking or have received hormones (eg, estrogen or progesterone) within 7 days the first dose of study drug. Note: Luteinizing hormone-releasing hormone (LHRH) analogs are permissible.
Patients must have a normal baseline thyroid stimulating hormone (TSH); a history of hypothyroidism and/or hyperthyroidism is allowed
Have 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 study
Receiving hormone replacement therapy, tamoxifen, or raloxifene within 6 months of trial entry; patients on non-systemic hormone replacement therapy are eligible
Prior hormone therapy for prostate cancer including orchiectomy, antiandrogens (including first-generation antiandrogens, enzalutamide, ARN-509 and others), cytochrome P450, family 17 (CYP17) inhibitors (including abiraterone, TAK-700, galeterone, ketoconazole, and others), estrogens, luteinizing hormone-releasing hormone (LHRH) agonist/antagonists; topical ketoconazole and other topical antifungal agents are allowed; prior therapy with 5alpha-reductase inhibitors is allowed; LHRH therapy allowed if begun within 4 weeks of day 1\r\n* Prior androgens are allowed if the patient had a testosterone within the normal range prior to starting androgens and the androgens have been stopped for at least 7 days
Postmenopausal women (women are considered post-menopausal and not of child-bearing potential if they are > 18 years of age and have had 12 months of natural [spontaneous] amenorrhea with an appropriate clinical profile [e.g. age appropriate, history of vasomotor symptoms or biochemically postmenopausal by estradiol and follicle stimulating hormone (FSH) levels]) prior to enrollment or have had surgical bilateral oophorectomy (with or without hysterectomy) at least six weeks prior to registration; medical ovarian suppression with luteinizing hormone-releasing hormone (LHRH) agonists to render a patient postmenopausal will not be acceptable
The 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 intolerant
Castration 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 therapy
Have postmenopausal status due to either surgical/natural menopause or ovarian suppression (initiated at least 28 days prior to Day 1 of Cycle 1) with a gonadotropin-releasing hormone (GnRH) agonist such as goserelin
Ongoing androgen depletion therapy with a gonadotropin releasing hormone (GnRH) analogue or inhibitor, or orchiectomy (i.e., surgical or medical castration); for patients who have not had an orchiectomy, there must be a plan to maintain effective GnRH-analogue therapy for the duration of the trial
Carcinoid with hormone related symptoms
All 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 registration
Patients who are being treated with a GNRH antagonist should be willing to switch to a LHRH analogue after registration
Patients 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 enrollment
PSA 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.
Currently on androgen ablation hormone therapy (a luteinizing hormone-releasing hormone [LHRH] agonist/antagonist or orchiectomy) with testosterone level < 50 ng/dL)
Metastatic breast cancer patients who are hormone receptor positive at baseline must be hormone refractory or have indications for emergent treatment with chemotherapy (e.g., visceral crisis)
Patients must have a one week washout period from prior hormonal therapy (e.g. testosterone, estrogen, progestin, gonadotropin-releasing hormone antagonist)
Participants without orchiectomy must be maintained on luteinizing-hormone-releasing hormone (LHRH) agonist/antagonist therapy
Bilateral orchiectomy or maintenance on androgen ablation therapy with luteinizing-hormone-releasing hormone (LHRH) agonist or antagonist, or polyestradiol phosphate
COHORT A: More than 5 months of prior hormonal therapy (e.g., gonadotropin hormone releasing analogs, megestrol acetate, or Casodex); there is no washout period required for gonadotropin hormone releasing (GnRH) analogs; a two week washout period is required for megestrol or anti-androgen
Patients must agree to continue androgen deprivation therapy with a GnRH agonist/antagonist throughout the study or have had a prior bilateral orchiectomy
Subject has ongoing androgen deprivation therapy with a Gonadotropin-releasing hormone (GnRH) analogue (agonist or antagonist) or bilateral orchiectomy (i.e., surgical or medical castration).
Uncontrolled hypothyroidism; patients must have a normal thyroid-stimulating hormone (TSH) per institutional standards at baseline
Surgically 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 study
Age <60 and amenorrhea for 12 or more months (in the absence of chemotherapy, tamoxifen, toremifen, or ovarian suppression) and FSH and estradiol in the postmenopausal range per local normal range Note: For women with therapy-induced amenorrhea, serial measurements of FSH and/or estradiol are needed to ensure postmenopausal status. Ovarian radiation or treatment with a luteinizing hormone-releasing hormone agonist (LH-RHa) (goserelin acetate or leuprolide acetate) is not permitted for induction of ovarian suppression in this trial.
Patients must not have previously received hormonal therapy (luteinizing hormone-releasing hormone [LHRH] agonist, antiandrogen, or both), with the exception of neoadjuvant or adjuvant hormones given in conjunction with prostatectomy; in such cases, hormone therapy must have been administered for =< 6 months, discontinued >= 6 months ago, and serum testosterone must be >= 150 ng/dL
Is a surgically sterile male or female, or is postmenopausal for at least 1 year, at least 50 years of age, with a follicle-stimulating hormone level > 40 milli-International units per mL (mIU/mL)
Patients must maintain ongoing androgen deprivation therapy with a GnRH analogue, antagonist, or bilateral orchiectomy (i.e., surgical or medical castration)
Participants without orchiectomy must be maintained on luteinizing hormone-releasing hormone (LHRH) agonist/antagonist therapy
Ongoing 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/dl
Prior androgen deprivation with luteinizing hormone-releasing hormone (LHRH) is permitted provided that testosterone levels prior to study entry have recovered to normal limits per reference laboratory
Postmenopausal women, as defined by one of the following (estradiol assay cutoff takes into account that the patient is on aromatase inhibitor therapy):\r\n* Age >= 55 years and one year or more of amenorrhea\r\n* Age < 55 years and one year or more of amenorrhea, with an estradiol assay within the post-menopausal range\r\n* Age < 55 years with prior hysterectomy but intact ovaries, with an estradiol assay within the post-menopausal range\r\n* Surgical menopause with bilateral oophorectomy\r\n* Ovarian suppression with a luteinizing hormone-releasing hormone (LH-RH) agonist, with an estradiol assay within the post-menopausal range at baseline and periodically on-study
Patients must agree to continue to continuation of androgen deprivation therapy (ADT) with a gonadotropin-releasing hormone analogue/antagonist or bilateral orchiectomy
Thyroid stimulating hormone (TSH) within normal limits (WNL); medications for thyroid dysfunction are allowed as long as TSH is normal at registration; in patients with abnormal TSH, if the free thyroxine (free T4) and free thyroxine index (FTI) are normal and patient is clinically euthyroid, patient is eligible
Patients must be post-menopausal; post-menopausal female subjects should be defined prior to protocol enrollment by any of the following:\r\n* Subjects at least 55 years of age; OR\r\n* Subjects under 55 years of age and naturally (spontaneous) amenorrhea for at least 12 months or follicle-stimulating hormone (FSH) values >= 40 IU/L and estradiol levels =< 20 IU/L; OR\r\n* Prior bilateral oophorectomy; OR\r\n* Prior radiation castration with amenorrhea for at least 6 months\r\n* NOTE: Treatment with a luteinizing hormone-releasing hormone (LH-RH) agonist (such as goserelin acetate or leuprolide acetate) is not permitted for induction of ovarian suppression
Known hormone-receptor status
More than 8 months of prior hormonal therapy (e.g., gonadotropin-releasing hormone analogs, megestrol acetate, or Casodex)\r\n* Note: patients who have been on prior hormonal therapy must wait at least 1 year after the drug is fully metabolized to start treatment on protocol
Menopausal at study entry as described by: \r\n* Surgical menopause (TAH/BSO), or\r\n* Age >= 50 years and cessation of menstruation for at least 1 year, or\r\n* Age < 50 years and cessation of menstruation for at least 1 year with estradiol level in post-menopausal range, or\r\n* Rendered post-menopausal with the use of luteinizing hormone-releasing hormone (LHRH) agonist
Currently taking hormone replacement therapy (local or systemic) (patients must discontinue for 2 weeks in order to be eligible prior to study enrollment)
Castrate-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 registration
Ongoing androgen deprivation therapy with a gonadotropin-releasing hormone (GnRH) analogue or bilateral orchiectomy (i.e., surgical or medical castration)
The subject has received prior treatment with a small molecule kinase inhibitor or a hormonal therapy (including investigational kinase inhibitors or hormones) within 14 days or five half-lives of the compound or active metabolites, whichever is longer, before the first dose of study treatment with the exception of patients receiving prior abiraterone or ketoconazole; for patients receiving prior abiraterone or ketoconazole, they must discontinue the medication within 5 half-lives of the compound before the first dose of study treatment in order to participate in this study; Note: subjects with prostate cancer currently receiving luteinizing-hormone-releasing hormone (LHRH) or gonadotropin-releasing hormone (GnRH) agonists must be maintained on these agents
Newly diagnosed androgen-dependent prostate cancer; patients already on androgen-dependent therapy (ADT) are eligible as long as the time from initiation of luteinizing-hormone-releasing hormone (LHRH) analog or antagonist is not greater than 3 months
Have testosterone < 50 ng/dL; patients must continue primary androgen-deprivation with a luteinizing hormone-releasing hormone (LHRH) analogue if they have not undergone orchiectomy
Patients on bisphosphonates for any cancer or on hormone therapy for prostate cancer will not need to discontinue this therapy to be eligible; however, patients with prostate cancer will need to have metastatic prostate cancer that has progressed despite hormonal therapy; castrate testosterone levels occur within hours after castration and within 2 to 3 weeks of a luteinizing hormone-releasing hormone agonist; the current standard is to continue androgen suppression despite progressive disease
Postmenopausal women are eligible; postmenopausal is defined as any of the following:\r\n* Age > 60 years\r\n* Age > 45 with intact uterus and amenorrhea for 12 months or more\r\n* Follicle stimulating hormone (FSH) levels within postmenopausal range according the ranges established by the testing facility\r\n* Premenopausal women who have been on a gonadotropin-releasing hormone (GnRH) agonist for at least 3 consecutive months prior to study entry are eligible; women in this group MUST remain on the GnRH agonist for the duration of protocol treatment\r\n* Status-post bilateral oophorectomy after adequate healing post-surgery
For cohorts 1, 2, and 4 only: current or prior hormonal therapy (e.g., gonadotropin hormone releasing analogs, megestrol acetate, or antiandrogens) are exclusionary
A 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 interruption
Clinically euthyroid; Note: Patients are permitted to receive thyroid hormone supplements to treat underlying hypothyroidism
Patients currently being treated with a gonadotropin-releasing hormone (GnRH agonist), bicalutamide or with bisphosphonates may continue treatment while on clinical trial PU-H71 as long as the treatment has been initiated before the study start; GnRH agonist must have been well tolerated for at least three months
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 24 months of androgen deprivation treatment, and must not have been treated within 12 months prior to screening; other treatment with androgen deprivation therapy is prohibited
I 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.
Clinically euthyroid; Note: patients are permitted to receive thyroid hormone supplements to treat underlying hypothyroidism
Serum 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 orchiectomy
Ongoing androgen deprivation therapy with a GnRH analogue or bilateral orchiectomy
Is willing to maintain androgen deprivation therapy with a gonadotropin-releasing hormone (GnRH) agonist/antagonist or has had a bilateral orchiectomy; The exclusion criteria apply only to patients starting new treatment with enzalutamide after receiving placebo as randomized treatment. Each patient must not meet any of the following criteria:
Female patients must either be: post-menopausal women as defined by a. age >= 60 years of age; b. prior bilateral oophorectomy; c. age < 60 with at least 12 months of spontaneous amenorrhea or post-menopausal range follicle-stimulating hormone (FSH) and estradiol levels OR premenopausal women receiving a gonadotropin-releasing hormone agonist
Any ongoing toxicity from prior anti-cancer therapy that is > grade 1 and/or that is progressing in severity; hypothyroidism treated with medication is not excluded if thyroid-stimulating hormone (TSH) is within normal limits
Ongoing androgen depletion therapy with a Gonadotropin Releasing Hormone (GnRH) analogue or inhibitor, or orchiectomy (i.e., surgical or medical castration)
The participant is receiving concurrent exogenous reproductive hormone therapy (for example, birth control pills, hormone replacement therapy, or megestrol acetate).
Ongoing monthly gonadotrophin releasing hormone (GNRH) agonist is required in pre-menopausal women or male participants for at least 4 weeks prior to study entry
Patients with a history of autoimmune hypothyroidism AND without normal thyroid hormone levels on a stable dose of thyroid replacement hormone
Ongoing androgen depletion therapy with a gonadotropin-releasing hormone (GnRH) analog or inhibitor, or orchiectomy (i.e., surgical or medical castration). Note: patients who have not undergone orchiectomy must continue GnRH analog therapy for the duration of this protocol.
intrauterine hormone-releasing system ( IUS)
Endocrinopathies, unless on stable hormone replacement therapy;
No therapy modulating testosterone levels (such as luteinizing-hormone releasing-hormone agonists/antagonists and antiandrogens) is permitted within 12 months prior to enrollment; agents such as 5alpha-reductase inhibitors, ketoconazole, megestrol acetate, systemic steroids (replacement doses of steroids are allowed), PC-SPES, Saw Palmetto are not permitted at any time during the period that the PSA values are being collected
>90 days post hormone therapy usages, subjects who have or are currently undergoing hormone therapy (GnRH agonist/antagonist) must discontinue hormone therapy and go through a 90 day washout period prior to consideration for study participation, and must remain off hormone therapy throughout the duration of the follow-up period (5 years);
No prior treatment for prostate cancer including prior surgery (excluding TURP), pelvic lymph node dissection, radiation therapy, or chemotherapy; patients may have received up to 4 months of androgen deprivation therapy (luteinizing hormone releasing hormone [LHRH] agonists, antiandrogens, or both) prior to being enrolled on the study
Ongoing 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 screening
Castrate testosterone levels at screening with continued Luteinizing hormone-releasing hormone (LHRH) therapy
Patients with a history of autoimmune hypothyroidism on a stable dose of thyroid replacement hormone may be eligible.
CRPC 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)
Ongoing androgen deprivation therapy with an gonadotropin releasing hormone (GnRH) analogue or prior bilateral orchiectomy (medical or surgical castration). For patients who have not had bilateral orchiectomy, there must be a plan to maintain effective GnRH-analogue for the duration of the trial.
Receiving any other therapies for cancer treatment (with the exception of gonadotropin-releasing hormone [GnRH] agonists for prostate cancer); Note: hydroxyurea is allowed before initiation of study treatment and for the first 5 days of study treatment
Ongoing gonadal androgen deprivation therapy with LHRH analogues or orchiectomy. Patients, who have not had an orchiectomy, must be maintained on standard dosing of LHRH analogue therapy at appropriate frequency for the duration of the study
Participants with hormone-receptor positive tumors must have failed available lines of hormonal therapy unless hormone therapy was not tolerated or not clinically appropriate
Unknown hormone-receptor status
Concurrent chronic immunosuppressive or hormone anticancer therapy (except other physiologic hormone replacement)
Patients on active treatment for hypo- or hyperthyroidism that is uncontrolled, requiring new medication, treatment intervention (such as thyroid ablation or surgery), or a > 30% medication dose adjustment within the previous 3 months; patients on stable doses of thyroid hormone replacement for hypothyroidism or thyroid suppression for hyperthyroidism can participate
The patient has normal thyroid function tests (thyroid-stimulating hormone [TSH], free T4) as defined by the testing laboratory, a test abnormality that is asymptomatic and does not warrant medical intervention, or a pre-existing thyroid disorder that is controlled on medical treatment
Has not received systemic therapy for prostate cancer (i.e. luteinizing-hormone-releasing hormone [LHRH] agonist/antagonist therapy)
Subjects who are currently on gonadotropin-releasing hormone (GnRH) agonists or antagonist therapy must continue androgen suppression
Women of child-bearing potential (i.e. =< 50 years of age or has had menstrual cycle within the past 12 months, if > 50 years of age; if in doubt, check follicle-stimulating hormone [FSH], luteinizing hormone [LH], and estradiol level) must have a negative urine or serum pregnancy test at screening
Postmenopausal; use of luteinizing hormone-releasing hormone (LHRH) agonist permitted
Concurrent use of other anticancer agents or treatments except luteinizing hormone-releasing hormone (LHRH) antagonists, LHRH agonists, zoledronic acid and other bone targeting agents
Thyroid-stimulating hormone (TSH) >= LLN and free T4 within normal limits; patients are permitted to receive thyroid hormone supplements to treat underlying hypothyroidism; the thyroid supplement dose must be a stable dose for at least one month prior to study enrollment
=< 2 regimens of cytotoxic chemotherapy prior to study entry; retinoids, vitamin D analogues, peroxisome proliferator-activated receptor (PPAR) gamma agonists or antagonists, antiandrogens, progestational agents, estrogens, prostate cancer (PC)-SPES, luteinizing hormone-releasing hormone (LHRH)-analogues, vaccines, cytokines will not be considered \cytotoxics\; patients who have previously received ketoconazole + glucocorticoids will be eligible for this trial
Progressive metastatic prostate cancer (positive bone scan or measurable disease) despite castrate levels of testosterone (either from orchiectomy or luteinizing hormone-releasing hormone [LHRH] agonist therapy)
Hormonal anticancer therapies except for LHRH antagonists or LHRH agonists in hormone-refractory prostate cancer
Ongoing systemic therapy (other than a gonadotropin releasing hormone [GnRH] agonist/antagonist) for prostate cancer including, but not limited to:\r\n* Cytochrome P450, family 17 (CYP-17) inhibitors (e.g. ketoconazole, abiraterone)\r\n* Antiandrogens (e.g. bicalutamide, nilutamide)\r\n* Second generation antiandrogens (e.g. ARN-509)\r\n** Note: patients receiving ongoing treatment with enzalutamide will be allowed to join the study\r\n* Immunotherapy (e.g. sipuleucel-T, ipilimumab)\r\n* Chemotherapy (e.g. docetaxel, cabazitaxel)\r\n* Radiopharmaceutical therapy (e.g. radium-223, strontium-89, samarium-153)
Post-menopausal at enrollment (age >= 60, age =< 60 and amenorrhea for >= 12 months in the absence of chemotherapy, tamoxifen, ovarian suppression and follicle stimulating hormone [FSH]/estradiol in the post-menopausal range)
Patients 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 study
Patients with prostate cancer must continue to receive gonadotropin-releasing hormone (GnRH) agonist therapy (unless orchiectomy has been done); if a patient has refused GnRH therapy, they may be enrolled on a dose level for which the safety has already been determined
Received anti-cancer therapy, including antibody, retinoid, or hormonal treatment (except megestrol acetate as supportive care), and radiation, within 3 weeks before dosing. Prior and concurrent use of hormone replacement therapy, the use of gonadotropin-releasing hormone modulators for prostate cancer, and the use of somatostatin and analogs for neuroendocrine tumors are permitted
Uncontrolled hypothyroidism defined as serum thyroid stimulating hormone (TSH) higher than 5 mIU/mL while receiving appropriate thyroid hormone therapy
Patients must have had evidence of disease progression while receiving primary androgen suppression therapy by orchiectomy or other primary hormonal therapy and abiraterone (specifically, patients can have received multiple prior additional androgen axis targeting agents including enzalutamide, and prior chemotherapy, but must have had progression while receiving abiraterone either currently or in the past)\r\n* Patients currently on abiraterone may continue with the start of the study drug(s)\r\n* Patients may continue luteinizing hormone-releasing hormone (LHRH) agonist therapy (e.g., leuprolide or goserelin) or LHRH antagonist (e.g. aberelix); patients who have not undergone bilateral orchiectomy may continue LHRH therapy while on protocol
Baseline serum FSH, luteinizing hormone LH, and estradiol levels should be drawn
a GnRH analog is permitted if the patient had progressive disease on a GnRH (Gonadotropin-Releasing Hormone) analog plus a SERM (Selective Estrogen Receptor Modulators) or an AI; the GnRH analog may continue but the SERM or AI must be discontinued.
Prior androgen deprivation therapy (ADT) with luteinizing hormone-releasing hormone (LHRH) agonist and/or antagonist allowed for either (neo)adjuvant treatment with local therapy or for biochemical relapse
Hormonal therapy with gonadotropin-releasing hormone (GnRH) agonists, GnRH antagonists or high dose bicalutamide within 1 month of enrollment unless serum testosterone is within normal limits
Adequate thyroid-stimulating hormone (TSH) suppression (< 0.5 mIU/L)
Normal thyroid function (thyroid stimulating hormone [TSH] and free thyroxine [T4]) (clinically euthyroid patients are acceptable)
Ongoing androgen deprivation therapy with a gonadotropin releasing hormone (GnRH) analogue or orchiectomy (i.e., surgical or medical castration)
Any type of systemic anticancer agent (including investigational) within 3 weeks of first dose of study treatment, or within 5 half-lives of the agent whichever is shorter; subjects on luteinizing-hormone-releasing hormone (LHRH) or gonadotropin-releasing hormone (GnRH) agonists may be maintained on these agents
Thyroid stimulating hormone (TSH) within normal limits (WNL) (patients may be on thyroid hormone replacement)
Surgical castration or ongoing use of gonadotropin-releasing hormone agonists with confirmed castrate levels of testosterone
Metastatic progressive CRPC defined as progressive disease despite surgical castration or ongoing use of gonadotropin-releasing hormone agonists with confirmed castrate levels of testosterone
Patients with hormone receptor-positive disease must have progressed on or following hormone therapy
Have discontinued previous treatments for cancer and recovered from the acute effects of therapy (for example, at least 42 days for mitomycin-C or nitrosoureas, 28 days for other chemotherapy and biologics. At the discretion of the investigator, hormone refractory prostate cancer patients who are stable on gonadotropin-releasing hormone (GnRH) agonist therapy and breast cancer patients who are stable on antiestrogen therapy (for example, an aromatase inhibitor) may continue treatment
Clinically euthyroid; Note: patients are permitted to receive thyroid hormone supplements to treat underlying hypothyroidism
Subjects should be willing to abstain from use of hormonal therapies (e.g. hormone replacement therapy, oral contraceptive pills, hormone-containing IUDs, and E-string) and chronic NSAID's for the duration of the study (chronic use of NSAID's is defined as a frequency >3 times/week for more than two weeks per year and includes low dose aspirin).
Ongoing androgen deprivation therapy with a gonadotropin releasing hormone (GnRH) analogue or inhibitor, or orchiectomy (i.e., surgical or medical castration);
Thyroid-stimulating hormone (TSH) within normal limits (WNL) \r\n* Supplementation is acceptable to achieve a TSH WNL; in patients with abnormal TSH if free T4 is normal and patient is clinically euthyroid, patient is eligible
Prior hormone therapy for prostate cancer including orchiectomy, antiandrogens, ketoconazole, or estrogens (5-alpha reductase inhibitors allowed), or luteinizing hormone-releasing hormone (LHRH) agonists/antagonists
Ongoing systemic therapy (other than a luteinizing hormone-releasing hormone agonists [LHRH] agonist/antagonist) for prostate cancer including, but not limited to:\r\n* CYP-17 inhibitors (e.g. ketoconazole, abiraterone)\r\n* Antiandrogens (e.g. bicalutamide, nilutamide)\r\n* Second generation antiandrogens (e.g. ARN-509)\r\n* Immunotherapy (e.g. sipuleucel-T)\r\n* Chemotherapy (e.g. docetaxel, cabazitaxel)\r\n* Radiopharmaceutical therapy (e.g. radium-223, strontium-89, samarium- 153)
Patients must have normal baseline thyroid function tests (thyroid stimulating hormone [TSH], triiodothyronine [T3], thyroxine [T4]); a history of hypothyroidism and/or hyperthyroidism is allowed, as long as the patient has stable well-controlled thyroid function for a minimum of 2 months
Women are considered post-menopausal and not of child-bearing potential if they have had 12 months of natural (spontaneous) amenorrhea with an appropriate clinical profile (e.g. age appropriate, history of vasomotor symptoms) or have had surgical bilateral oophorectomy (with or without hysterectomy) at least six weeks ago; for women with therapy-induced amenorrhea, oophorectomy or serial measurements of follicle-stimulating hormone (FSH) and/or estradiol are needed to ensure postmenopausal status; NOTE: ovarian radiation or treatment with a luteinizing hormone-releasing hormone (LH-RH) agonist (goserelin acetate or leuprolide acetate) is not permitted for induction of ovarian suppression
NOTE: use of luteinizing hormone-releasing hormone (LHRH) agonists (e.g., leuprolide or goserelin) is not allowed
Use of any of the following medications within the past 6 months: testosterone, dehydroepiandrosterone (DHEA), estrogens, gonadotropin-releasing hormone (GnRH) analogs, antiandrogens, spironolactone, ketoconazole, recombinant human growth hormone (rhGH), megestrol acetate, prednisone 20 mg daily or equivalent doses of other glucocorticoids for more than two weeks
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
Planned treatment with castration therapy (gonadotropin-releasing hormone [GnRH] agonist/antagonist) for >= 8 months
Patients who are not biochemically euthyroid; patients with known history of hypothyroidism are eligible if they are on adequate and stable replacement thyroid hormone therapy for at least 3 months
Known diagnosis of pituitary hormone deficiency
Prior hormone therapy for prostate cancer including orchiectomy, antiandrogens (including first-generation antiandrogens, enzalutamide, apalutamide and others), CYP17 inhibitors (including abiraterone, TAK-700, galeterone, ketoconazole, and others), estrogens, luteinizing hormone releasing hormone (LHRH) agonist/antagonists; prior therapy with 5-alpha-reductase inhibitors is allowed; LHRH therapy allowed if begun within 4 weeks of day 1; up to 30 days of bicalutamide is allowed if it is stopped two weeks prior to day 1
Men > 18 diagnosed with prostate cancer for which antiandrogen therapy (ADT) (castration therapy) is being prescribed for at least 16 weeks; castration may be achieved surgically or using gonadotrophin releasing hormone (LHRH) agonists (i.e. leuprolide, goserelin, etc.) or LHRH antagonists (i.e. degarelix)
Hormone replacement therapy in the last three months
Post-menopausal status, as defined by institutional guidelines; concurrent gonadotropin-releasing hormone (GnRH) agonist therapy is allowed
Medical indication for androgen deprivation therapy (ADT) via luteinizing hormone-releasing hormone (LHRH) analog +/- oral anti-androgen
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
Be on androgen deprivation therapy (ADT) with a gonadotropin-releasing hormone (GnRH) agonist/antagonist or prior bilateral orchiectomy; all patients will be required to be on ADT during the study period
Unwilling or unable to stop supplemental sex hormone therapy (estrogen, progesterone, and/or testosterone preparations)
PROSTATE CANCER: Patients who are initiating any chemotherapy (examples are docetaxel, cabazitaxel, etc.) and/or hormone directed treatment for prostate cancer; examples of hormone directed therapy include gonadotropin releasing hormone (GnRH) agonist or antagonists (such as leuprolide, goserelin, triptorelin, histrelin and degarelix), androgen receptor blockers (such as bicalutamide or enzalutamide), or androgen biosynthesis inhibitors (such as abiraterone)
Steroid hormone use (antiandrogen therapy [ADT]) within the past 12 months
Second malignancies are allowed as long as the disease does not require active treatment with concomitant systemic cytotoxic chemotherapy, investigational or biologic therapy (e.g., anti-cytotoxic T-lymphocyte-associated protein 4 [CTLA4] or human epidermal growth factor receptor 2 [HER2] monoclonal antibodies); hormone-related therapies (e.g., gonadotrophin releasing hormone (LHRH) agonists, tamoxifen, etc.) are allowed
All women will be postmenopausal, defined as having follicle-stimulating hormone (FSH) and estradiol within the institutional postmenopausal range at the time of study entry and no menstrual cycle in the last 12 months
Diagnosed with prostate cancer\r\n* Treatment with ADT (gonadotropin-releasing hormone [GnRH] agonist/antagonist with or without anti-androgen) for prostate cancer\r\n* Receiving ADT for a minimum of 12 weeks before enrollment into the study\r\n* Planned ADT for the duration of the 12-week study period
Ovarian insufficiency defined as an elevated follicle-stimulating hormone (FSH) over 10
Abnormal thyroid-stimulating hormone (TSH)
Receiving or planning to receive androgen deprivation therapy (ADT) with luteinizing hormone-releasing hormone (LHRH) agonist or antagonist
History of using any of the following medications, regardless of dose, for at least 1 month, within 3 months of enrollment: anabolic agents, glucocorticoids (does not include inhaled glucocorticoids), growth hormone, parathyroid hormone (PTH)
Untreated endocrine abnormality, such as hypothyroidism, parathyroid hormone disorder
Thyroid stimulating hormone (TSH) < 10 mIU/L
History of uncontrolled hypothyroidism as evidenced by thyroid test (thyroid-stimulating hormone [TSH]) within the last month, hypercalcemia or hyperglycemia (within the last 15 days)
Hormone receptor status not specified
Subjects may be currently prescribed hormone treatment or Herceptin therapy
Men ? 30 years of age with non-metastatic prostate cancer, having undergone bilateral orchiectomy or initiated androgen deprivation therapy (ADT) with gonadotropin-releasing hormone (GnRH) agonists and is expected to continue on ADT for at least 12 months
Arm 1 patients may not have received any prior luteinizing-hormone-releasing hormone (LHRH) agonists/antagonists, antiandrogens, or chemotherapy for their prostate cancer; treatment with 5-alpha reductase inhibitors (finasteride, dutasteride) are allowed
Pre-menopausal women as defined as four menstrual cycles within the last six months prior to pre-registration; women with less than 4 menses within 6 months prior to pre-registration, or women who have had a hysterectomy with ovaries intact will be considered premenopausal if follicle-stimulating hormone (FSH) level is < 20; women who are using hormonal contraceptives that cause amenorrhea (e.g. injectable and extended oral contraceptives, hormone containing contraceptive ring, or hormone containing intrauterine device) will be considered eligible if they had a minimum of 4 menstrual cycles within the last six months prior to starting on the contraceptive
Premenopausal women with a documented deleterious mutation in one of the following ovarian cancer genes: BRCA1, BRCA2, BRIP1, PALB2, RAD51C, RAD51D, BARD1, MSH2, MSH6, MLH1, or PMS2, or EPCAM; (please note: menopause is defined as >= 12 months of amenorrhea; however, for those patients with >= 12 months of amenorrhea who may be pre-menopausal, levels of follicle-stimulating hormone [FSH], luteinizing hormone [LH], and estradiol in the pre-menopausal range will be acceptable)
Women must be pre-menopausal as defined as having intact ovaries with regular menses or if not menstruating, have a premenopausal status confirmed by serum follicle-stimulating hormone (FSH) and estradiol
Thyroid-stimulating hormone (TSH) within normal institutional limits
Have been previously diagnosed with a malignant solid tumor, completed their required surgical, and/or chemotherapy and/or radiation curative intent therapy at least three months prior to enrollment, and have an anticipated treatment-free life span of 12 months or longer; chemoprophylaxis with tamoxifen or aromatase inhibitors for breast cancer in women and anti-luteinizing hormone releasing hormone (LHRH) therapy for prostate cancer in men will be permitted
Must agree to use effective consistent contraception. Hormone-based birth control (pills, patches, or shots) is allowed. Hormone replacement therapy is not allowed for postmenopausal participants.
Participants must be premenopausal (defined as < 3 months since last menstrual period OR serum follicle-stimulating hormone [FSH] < 20 mIU/mL)
Use of endocrine therapy (selective estrogen receptor modulator, aromatase inhibitor, gonadotrophin releasing hormone [GnRH] agonist) within 6 months of start of study
Taking luteinizing hormone-releasing hormone (LHRH) agonists, androgen receptor blocking agents, finasteride, or has undergone bilateral orchiectomy
Thyroid stimulating hormone (TSH) =< 1.5 times ULN, within 30 days prior to enrollment
Currently taking postmenopausal hormone replacement therapy
Subjects who have received hormonal contraception and/or hormone therapy in the past 3 months are not eligible
Subjects with hypothyroidism (eg, following Hashimoto syndrome) stable on hormone replacement for ? 3 months; or
Documentation of menopausal status: postmenopausal subjects or pre-menopausal subjects with ovarian radiation or concomitant therapy with a luteinizing hormone-releasing hormone (LH-RH) agonist/antagonist are eligible.
Have 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 orchiectomy
Female patients must either be: post-menopausal women as defined by a) age >= 60 years of age; b) prior bilateral oophorectomy; c) age < 60 with at least 12 months of spontaneous amenorrhea or post-menopausal range follicle stimulating hormone (FSH) and estradiol levels or premenopausal women receiving a gonadotropin-releasing hormone agonist
Receiving hormone replacement therapy that cannot be discontinued
Currently on therapy aimed at lowering testosterone levels (includes gonadotropin-releasing hormone [GnRH] agonist/antagonist, prior bilateral orchiectomy, oral anti-androgens, or 5-alpha reductase inhibitors); testosterone replacement is allowed but treatment should be stable during the entire study
Patients must not receive any other anti-cancer therapy (cytotoxic, biologic, radiation, or hormonal other than for replacement) while on this study except for medications that are prescribed for supportive care but may potentially have an anti-cancer effect (i.e. megestrol acetate, bisphosphonates); in addition, men receiving treatment for prostate cancer will be maintained at castrate levels of testosterone by continuation of luteinizing-releasing hormone agonists
Treatment with chemotherapy, hormone therapy, or other investigational therapy within 3 weeks of first study doses; patients with non-adenocarcinoma of the prostate who may be on luteinizing hormone-releasing hormone agonist/antagonist therapy may continue use
Participants must have been on adjuvant endocrine therapy, either tamoxifen or aromatase inhibitor (AI), for at least 6 months without any significant adverse events leading to drug interruption for more than 1 month, and must not have had any change in endocrine therapy in the past 6 months; ongoing use of any AI, including letrozole, anastrozole or exemestane, or tamoxifen is allowed; concurrent gonadotrophin releasing hormone (GNRH) agonist is allowed
Thyroid stimulating hormone (TSH) 0.27 - 4.20 ulU/mL
Menopause as defined as no menses for 1 year and/or follicle-stimulating hormone (FSH) >= 25.8 mIU/ml
Use of aromatase inhibitors, gonadotropin-releasing hormone (GNRH)-agonists i.e. Lupron, Zoladex within the last 6 months
Hormone replacement therapy within the last 6 months
Hormone therapy, including vaginal estrogen creams
DISEASE CHARACTERISTICS:\n\n          -  Confirmed diagnosis of prior operable, noninflammatory breast cancer meeting the\n             following criteria:\n\n               -  Steroid hormone receptor-positive tumors (estrogen receptor and/or progesterone\n                  receptor), determined by immunohistochemistry, after primary surgery and before\n                  commencement of prior endocrine therapy\n\n               -  Prior local treatment including surgery with or without radiotherapy for primary\n                  breast cancer with no known clinical residual loco-regional disease\n\n               -  Following primary surgery, eligible patients must have had evidence of lymph node\n                  involvement either in the axillary or internal mammary nodes, but not\n                  supraclavicular nodes\n\n               -  Clinically disease-free\n\n          -  Must have completed 4-6 years of prior adjuvant selective estrogen receptor modulators\n             (SERMs), aromatase inhibitors (AIs), or a sequential combination of both\n\n               -  When calculating 4-6 years, neoadjuvant endocrine therapy should not be included\n\n          -  No evidence of recurrent disease or distant metastatic disease\n\n          -  No prior bilateral breast cancer\n\n        PATIENT CHARACTERISTICS:\n\n          -  Female\n\n          -  Must be postmenopausal by any of the following criteria:\n\n               -  Patients of any age who have had a bilateral oophorectomy (including radiation\n                  castration AND amenorrheic for > 3 months)\n\n               -  Patients 56 years old or older with any evidence of ovarian function must have\n                  biochemical evidence of definite postmenopausal status (defined as estradiol,\n                  luteinizing hormone [LH], and follicle-stimulating hormone [FSH] in the\n                  postmenopausal range)\n\n               -  Patients 55 years old or younger must have biochemical evidence of definite\n                  postmenopausal status (defined as estradiol, LH, and FSH in the postmenopausal\n                  range)\n\n                    -  Patients who have received prior luteinizing-hormone releasing-hormone\n                       (LHRH) analogues within the last year are eligible if they have definite\n                       evidence of postmenopausal status as defined above\n\n          -  Clinically adequate hepatic function\n\n          -  No bone fracture due to osteoporosis at any time during the 4-6 years of prior therapy\n\n          -  No prior or current malignancy except adequately treated basal cell or squamous cell\n             carcinoma of the skin, in situ carcinoma of the cervix or bladder, or contra- or\n             ipsilateral in situ breast carcinoma\n\n          -  No other nonmalignant systemic diseases (cardiovascular, renal, lung, etc.) that would\n             prevent prolonged follow-up\n\n          -  No psychiatric, addictive, or any other disorder that compromises compliance with\n             protocol requirements\n\n        PRIOR CONCURRENT THERAPY:\n\n          -  See Disease Characteristics\n\n          -  More than 12 months since prior and no other concurrent endocrine SERM/AI therapy\n\n          -  Any type of prior adjuvant therapy allowed including, but not limited to, any of the\n             following:\n\n               -  Neoadjuvant chemotherapy\n\n               -  Neoadjuvant endocrine therapy\n\n               -  Adjuvant chemotherapy\n\n               -  Trastuzumab (Herceptin®)\n\n               -  Ovarian ablation\n\n               -  Gonadotropin releasing hormone analogues\n\n               -  Lapatinib ditosylate\n\n          -  No concurrent hormone-replacement therapy, bisphosphonates (except for treatment of\n             bone loss), or any other investigational agent
Note: Ovarian radiation or treatment with a luteinizing hormone-releasing hormone (LH-RH) agonist (goserelin acetate or leuprolide acetate) is not permitted for induction of ovarian suppression
Hyperthyroidism (thyroid-stimulating hormone [TSH] < 0.4 mIU/L and free T4 > 1.6 ng/dL)
Hyperparathyroidism (parathyroid hormone [PTH] > 80 pg/mL)
Patients 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) criteria
Thyroid-stimulating hormone (TSH) ? 13 micro international units/mL
Thyroid-stimulating hormone (TSH) < 13 micro international units/mL
Patients must have prior bilateral orchiectomy or be on continuous LHRH analogue therapy for the duration of study
Primary or recurrent castration resistant prostate carcinoma with skeletal and/or nodal involvement not currently undergoing systemic chemotherapy who are about to commence therapy with docetaxel/prednisone; (note that systemic hormonal targeted therapy including luteinizing hormone-releasing hormone [LHRH] agonists [Lupron or Trelstar], other anti-androgens, and/or abiraterone or enzalutamide may be in use)
Be planning to begin a course of at least 4 months of ADT; the ADT is defined as: (a) surgical castration; (b) gonadotropin-releasing hormone (GNRH) antagonist alone; (c) GNRH antagonist with oral androgen receptor blockade, and (d) GNRH antagonist, oral androgen receptor blockade, and 5-alpha reductase inhibitors; we will not include men with only oral anti-androgen therapy such as 5-alpha reductase inhibitors alone or oral anti-androgens alone
Hormone deprivation therapy
Prior bovine thyroid stimulating hormone (TSH) use
Androgen ablation (hormone treatment) within the last 3 months
Thyroid-stimulating hormone (TSH) < 13 micro International units/mL
Men who have received any hormonal manipulation (antiandrogens; luteinizing hormone releasing hormone [LHRH] agonist; 5-alpha-reductase inhibitors) within the previous 12 months
Thyroid-stimulating hormone (TSH) =< 10 micro international units/mL
For patients who are not postmenopausal (women) or surgically sterile (absence of ovaries and/or uterus or vasectomy), agreement to remain abstinent or to use two adequate methods of contraception (e.g., condoms, diaphragm, vasectomy/vasectomized partner, tubal ligation), during the treatment period and for at least 30 days after the last dose of study treatment; hormone based oral contraceptives are not allowed on study; postmenopausal is defined as:\r\n* Age >= 60 years\r\n* Age =< 60 years and amenorrheic for 12 months in the absence of chemotherapy, tamoxifen, toremifene, or ovarian suppression; or follicle stimulating hormone and estradiol in the postmenopausal range
Thyroid-stimulating hormone (TSH) < 13 micro international units/mL
For part 2 of the study: plans to initiate castrating therapy (with a gonadotropin-releasing hormone [GnRH] antagonist, GnRH agonist, or orchiectomy); an antiandrogen may be started after initial imaging but cannot be used prior to baseline imaging; an antiandrogen is allowed but not required
- Must remain on androgen deprivation therapy for duration of trial if no prior bilateral orchiectomy
Patient must have surgical resection followed by systemic adjuvant therapy with an aromatase inhibitor (AIs) as part of planned treatment; any approved AI at standard clinical dosing may be used; in pre-menopausal patients, ovarian suppression with a gonadotropin-releasing hormone (GnRH) agonist will be started prior to initiation of the AI on a separate clinical trial in parallel with the imaging study
Patients may receive no other concurrent anticancer treatments such as chemotherapy, hormone therapy (except for prostate cancer patients on luteinizing hormone-releasing hormone ((LHRH)) agonists), immunotherapy, biological agents, investigational agents, or radiation therapy during this trial, and should be off these treatments for at least 2 weeks, or until they have completely recovered from the side effects of these treatments, whichever is longest, except for persistent grade 1 neuropathy in patients who received prior platinum or taxanes.
Must be willing to continue androgen deprivation therapy while on study, if no prior orchiectomy
Replacement hormone therapy initiated before study entry is permitted
Replacement hormone therapy initiated before study entry is permitted
Medically confirmed post-menopausal status defined as spontaneous cessation of regular menses for at least 12 consecutive months or follicle-stimulating hormone (FSH), luteinizing hormone (LH) and estradiol blood levels in their respective postmenopausal ranges.
Premenopausal women will be considered eligible for study participation if they are receiving medical ovarian suppression with luteinizing hormone-releasing hormone (LHRH) agonists with documented estradiol blood levels in their respective postmenopausal ranges.
Hormonal therapy (luteinizing hormone-releasing hormone [LHRH] agonist or oral anti-androgen) exceeding 4 months prior to registration
Participants must be receiving thyroxine suppression therapy and thyroid stimulating hormone (TSH) should not be elevated (TSH should be ?5.50 mcIU/ML). When tolerated by the participant, thyroxine dose should be changed to achieve TSH suppression (TSH <0.50 mcIU/ML) and this dose may be changed concurrently upon starting study drug treatment.
Progressive disease post-surgical castration or during androgen suppression therapy (pre-secondary hormone CRPC) OR
Failed prior therapy with a secondary hormone (e.g. enzalutamide, abiraterone) with documented progressive disease (post-secondary hormone CRPC)
For pre-secondary hormone patients, no prior or concurrent treatment with a secondary hormone (e.g. enzalutamide, abiraterone)
For post-secondary hormone patients, no concurrent treatment with a secondary hormone (e.g. enzalutamide, abiraterone), no metastasis to the liver or brain