Women of childbearing potential (WOCBP) is defined as any female who has experienced menarche and who has not undergone surgical sterilization (hysterectomy or bilateral oophorectomy) or who is not postmenopausal; menopause is defined clinically as 12 months of amenorrhea in a woman over 45 in the absence of other biological or physiological causes; in addition, women under the age of 55 must have a documented serum follicle stimulating hormone (FSH) level less than 40 mIU/mL
Women of childbearing potential (WOCBP) not using a medically acceptable means of contraception throughout the study treatment and for at least 23 weeks following the last dose of study treatment (5 half-lives of study drug plus 30 days duration of ovulatory cycle).\r\n* WOCBP are defined as those who have experienced menarche and who have not undergone successful surgical sterilization (hysterectomy, bilateral tubal ligation, or bilateral oophorectomy) or are not postmenopausal. Postmenopausal is defined as:\r\n** Amenorrhea >= 12 consecutive months without another cause, or\r\n** For women with irregular menstrual periods and on hormone replacement therapy (HRT), a documented serum follicle stimulating hormone (FSH) level > 35 mIU/mL.
Women of childbearing potential (WOCBP) must have a negative serum or urine pregnancy test (minimum sensitivity 25 IU/L or equivalent units of human chorionic gonadotropin [hCG]) within 7 days prior to registration; NOTE: women are considered of childbearing potential unless they are surgically sterile (have undergone a hysterectomy, bilateral tubal ligation, or bilateral oophorectomy) or are postmenopausal; menopause is defined clinically as 12 months of amenorrhea in a woman over 45 in the absence of other biological or physiological causes. In addition, women under the age of 62 must have a documented serum follicle stimulating hormone (FSH) level less than 40 mIU/mL
Women of child-bearing potential (WOCBP) comprises women who have experienced menarche and who have not undergone successful surgical sterilization (hysterectomy, bilateral tubal ligation, or bilateral oophorectomy) or who are not post-menopausal (see definition below)\r\n* Post-menopause is defined as:\r\n** Women who have had amenorrhea for >= 12 consecutive months (without another cause) and who have a documented serum follicle stimulating hormone (FSH) level > 35 mIU/mL\r\n** Women who have irregular menstrual periods and a documented serum FSH level > 35 mIU/mL\r\n** Women who are taking hormone replacement therapy (HRT)
Women of reproductive potential must use highly effective contraception methods to avoid pregnancy for 23 weeks after the last dose of study drugs; “women of reproductive potential” is defined as any female who has experienced menarche and who has not undergone surgical sterilization (hysterectomy or bilateral oophorectomy) or who is not postmenopausal; menopause is defined clinically as 12 months of amenorrhea in a woman over 45 in the absence of other biological or physiological causes; in addition, women under the age of 55 must have a documented serum follicle stimulating hormone (FSH) level less than 40 mIU/mL
Patients who are pregnant or nursing; women of child-bearing potential (WOCBP) must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation; WOCBP must have a screening negative serum or urine pregnancy test within 14 days of registration; a second pregnancy test must be done within 24 hours prior to the start of the first cycle of study treatment; women must not be breastfeeding\r\n* Women who are not of childbearing potential (i.e., who are postmenopausal or surgically sterile) do not require contraception\r\n* Women of childbearing potential (WOCBP) is defined as any female who has experienced menarche and who has not undergone surgical sterilization (hysterectomy and/or bilateral oophorectomy) or who is not postmenopausal; menopause is defined clinically as 12 month amenorrhea in a woman over 45 in the absence of other biological or physiological causes; in addition, women under the age of 55 must have a documented serum follicle stimulating hormone (FSH) level greater than 40mIU/mL
Women of childbearing potential (WOCBP) must have a negative serum pregnancy test within 24 hours prior to the start of study drug; a woman of childbearing potential is defined as any female who has experienced menarche and who has not undergone surgical sterilization (hysterectomy or bilateral oophorectomy) or is not postmenopausal; menopause is defined clinically as 12 months of amenorrhea in a woman over age 50 in the absence of other biologic or physiologic causes
Women of childbearing potential (WOCBP) must have a negative serum pregnancy test within 24 hours prior to receiving first dose of protocol-indicated treatment.\r\n* WOCBP is defined as any female who has experienced menarche who has not undergone surgical sterilization (hysterectomy or bilateral oophorectomy) or is not postmenopausal.\r\n* Menopause is defined clinically as 12 months of amenorrhea in a woman over 45 years of age in the absence of other biological or physiological causes.\r\n* If menopausal status is considered for the purpose of evaluating childbearing potential, women < 62 years of age must have a documented serum follicle stimulating hormone (FSH) level within laboratory reference range for postmenopausal women, in order to be considered postmenopausal and not of childbearing potential.
Women of reproductive potential must use highly effective contraception methods to avoid pregnancy for 23 weeks after the last dose of study drugs; “women of reproductive potential” is defined as any female who has experienced menarche and who has not undergone surgical sterilization (hysterectomy or bilateral oophorectomy) or who is not postmenopausal; menopause is defined clinically as 12 months of amenorrhea in a woman over 45 in the absence of other biological or physiological causes; in addition, women under the age of 55 must have a documented serum follicle stimulating hormone (FSH) level less than 40 mIU/mL
Women of reproductive potential must use highly effective contraception methods to avoid pregnancy for 23 weeks after the last dose of study drugs; “women of reproductive potential” is defined as any female who has experienced menarche and who has not undergone surgical sterilization (hysterectomy or bilateral oophorectomy) or who is not postmenopausal; menopause is defined clinically as 12 months of amenorrhea in a woman over 45 in the absence of other biological or physiological causes; in addition, women under the age of 55 must have a documented serum follicle stimulating hormone (FSH) level less than 40 mIU/mL
Women of child-bearing potential who are unwilling or unable to use an acceptable method of birth control to avoid pregnancy for the entire study period and for 30 days after the last dose of GC4419. This includes any woman who has experienced menarche but has not undergone successful surgical sterilization or is not postmenopausal (defined as amenorrhea for at least 12 consecutive months, or women on hormone replacement therapy with serum FSH levels greater than 35 mIU/mL. A negative urine or serum pregnancy test must be obtained within 14 days prior to the start of study therapy in all women of child-bearing potential.
Male and female patients of childbearing potential and at risk for pregnancy must agree to use two highly effective methods of contraception throughout the study and for at least 90 days after the last dose of assigned treatment. Female patients who are not of childbearing potential (permanently sterilized or postmenopausal; i.e., meet at least one of the following criteria):\r\n* Have undergone a documented hysterectomy and/or bilateral oophorectomy; or\r\n* Have medically confirmed ovarian failure; or\r\n* Achieved postmenopausal status, defined as follows: cessation of regular menses for at least 12 consecutive months with no alternative pathological or physiological cause; status may be confirmed by having a serum follicle stimulating hormone (FSH) level within the laboratory’s reference range for postmenopausal women
WOCBP is defined as any female who has experienced menarche and who has not undergone successful surgical sterilization (hysterectomy, bilateral tubal ligation, or bilateral oophorectomy), and who is not postmenopausal; post menopause is defined as:\r\n* Amenorrhea >= 12 consecutive months without another cause, and a documented serum follicle stimulating hormone (FSH) level > 35 mIU/mL or\r\n* Women with irregular menstrual periods and a documented serum follicle stimulating hormone (FSH) level > 35 mIU/mL or NOTE: FSH level testing is not required for women >= 62 years old with amenorrhea of >= 1 year\r\n* Women on hormone replacement therapy (HRT)
WOCBP is defined as any female who has experienced menarche and who has not undergone successful surgical sterilization or who is not postmenopausal
Women of childbearing potential must have a negative serum or urine pregnancy test (minimum sensitivity 25 iu/l or equivalent units of human chorionic gonadotropin [hcg]) within 24 hours of the first dose of the study drug\r\n* \Women of childbearing potential” is defined as any female who has experienced menarche and who has not undergone surgical sterilization (hysterectomy or bilateral oophorectomy) or who is not postmenopausal; menopause is defined clinically as 12 months of amenorrhea in a woman over 45 in the absence of other biological or physiological causes.
Patients who are pregnant or nursing; women of child-bearing potential (WOCBP) must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation; WOCBP must have a negative serum pregnancy test within 7 days of study enrollment, prior to dosing nivolumab, then every 6 weeks; after discontinuation from nivolumab these should be repeated at approximately 30 days and approximately 70 days; women must not be breastfeeding\r\n* Women who are not of childbearing potential (i.e., who are postmenopausal or surgically sterile) do not require contraception\r\n* Women of childbearing potential (WOCBP) is defined as any female who has experienced menarche and who has not undergone surgical sterilization (hysterectomy and/or bilateral oophorectomy) or who is not postmenopausal; menopause is defiled clinically as 12 month amenorrhea in a woman over 45 in the absence of other biological or physiological causes; in addition, women under the age of 55 must have a documented serum follicle stimulating hormone (FSH) level greater than 40 mlU/mL
Pregnant or lactating female: Women of childbearing potential (WOCB) must have a negative serum or urine pregnancy test (minimum sensitivity 25 IU/L or equivalent units of human chorionic gonadotropin [HCG]) within 72 hours prior to the start of nivolumab; Women of childbearing potential is defined as any female who has experienced menarche and who has not undergone surgical sterilization (hysterectomy or bilateral oophorectomy) or who is not postmenopausal. Menopause is defined clinically as 12 months of amenorrhea in a woman over 45 in the absence of other biological or physiological causes
Women of child-bearing potential (WOCBP) must agree to use an approved form of birth control and to have a negative pregnancy test result before registration; WOCBP is defined as any female who has experienced menarche and who has not undergone surgical sterilization (hysterectomy or bilateral oophorectomy) or who is not postmenopausal; menopause is defined clinically as 12 consecutive months of amenorrhea in a woman over 45 in the absence of other biological or physiological causes; approved forms of birth control:\r\n* Combined (estrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation (oral, intravaginal, or transdermal)\r\n* Progestogen only hormonal contraception associated with inhibition of ovulation (oral, injectable, or implantable)\r\n* Intrauterine device, intrauterine hormone-releasing system\r\n* Bilateral tubal occlusion/ligation\r\n* Vasectomized partner\r\n* Barrier contraception\r\n* Sexual abstinence
For women with irregular menstrual periods and on hormone replacement therapy (HRT), a documented serum follicle stimulating hormone (FSH) level > 35 mIU/mL
Women of childbearing potential must have a negative serum pregnancy test within 24 hours prior to the administration of the investigational product; female patients who are not of childbearing potential as defined below, are eligible to be included (ie, meet at least one of the following criteria):\r\n* Have undergone a documented hysterectomy and/or bilateral oophorectomy\r\n* Have medically confirmed ovarian failure; or\r\n* Achieved postmenopausal status, defined as follows: cessation of regular menses for at least 12 consecutive months with no alternative pathological or physiological cause; a serum follicle stimulating hormone (FSH) level within the laboratory’s reference range for postmenopausal women
Pregnancy or lactation period; note: a negative pregnancy test is required for women of childbearing potential; women who are postmenopausal (age-related amenorrhea >= 12 consecutive months or follicle-stimulating hormone [FSH] > 40 milli international units per milliliter [mIU/ml]), or who had undergone hysterectomy or bilateral oophorectomy are exempt from pregnancy testing; if necessary to confirm postmenopausal status a FSH level will be included at screening; pregnant women are excluded from this study; breastfeeding should be discontinued if the mother is treated with avelumab; pregnant women are excluded from this study; breastfeeding should be discontinued if the mother is treated with avelumab
Women of childbearing potential (WOCBP) must have a negative serum or urine pregnancy test at screening; WOCBP must agree to use adequate contraception (barrier method of birth control or abstinence) prior to study entry and for the duration of study participation; WOCBP should use an adequate method to avoid pregnancy for 7 months after the last dose of investigational drug; women must not be breastfeeding; women of childbearing potential (WOCBP) is defined as any female who has experienced menarche and who has not undergone surgical sterilization (hysterectomy or bilateral oophorectomy) or who is not postmenopausal; menopause is defined clinically as 12 months of amenorrhea in a woman over age 45 in the absence of other biological or physiological causes; in addition, women under the age of 55 must have a documented serum follicle stimulating hormone (FSH) level less than 40 mIU/mL; should a woman become pregnant or suspect she is pregnant while she is participating in this study, she should inform her treating physician immediately
Women of childbearing potential (WOCBP) is defined as any female who has experienced menarche and who has not undergone surgical sterilization (hysterectomy or bilateral oophorectomy) or who is not postmenopausal; menopause is defined clinically as 12 months of amenorrhea in a woman over 45 in the absence of other biological or physiological causes
Pregnant and breastfeeding women are excluded; women of childbearing potential who are unwilling or unable to use an acceptable method of birth control to avoid pregnancy for the entire study period and for up to 4 weeks after the study are excluded; this applies to any woman who has experienced menarche and who has not undergone successful surgical sterilization or is not postmenopausal (defined as amenorrhea for at least 12 consecutive months, or women on hormone replacement therapy with serum follicle stimulating hormone [FSH] levels greater than 35 mIU/mL); a negative urine or serum pregnancy test must be obtained within 14 days prior to the start of study therapy in all women of child-bearing potential; male subjects must also agree to use effective contraception for the same period as above
WOCBP is defined as any female who has experienced menarche and has not undergone surgical sterilization (hysterectomy or bilateral oophorectomy) or who is not postmenopausal; menopause is defined clinically as 12 months of amenorrhea in a woman over 45 in the absence of other biological or physiological causes; in addition, women under the age of 55 must have a documented serum follicle stimulating hormone (FSH) level less than 40 mIU/mL
Women of childbearing potential (WOCBP) is defined as any female who has experienced menarche and who has not undergone surgical sterilization (hysterectomy or bilateral oophorectomy) or who is not postmenopausal; menopause is defined clinically as 12 months of amenorrhea in a woman over 45 in the absence of other biological or physiological causes; in addition, women under the age of 55 must have a documented serum follicle stimulating hormone (FSH) level greater than 40 mIU/mL
NOTE: “Women of childbearing potential” is defined as any female who has experienced menarche and who has not undergone surgical sterilization (hysterectomy or bilateral oophorectomy) or who is not postmenopausal; menopause is defined clinically as 12 months of amenorrhea in a woman over 45 in the absence of other biological or physiological causes; in addition, women under the age of 55 must have a documented serum follicle stimulating hormone (FSH) level less than 40 mIU/ml
Women who are pregnant or lactating. NOTE: Women of childbearing potential (WOCBP) must have a \negative\ serum pregnancy test within one week prior to treatment. a) Women not OCBP defined as any of the following: i) Postmenopausal with > 1 year since last menses and: (1) If younger than 65 years old, with a follicle-stimulating hormone (FSH) > 40 mIU/mL (2) If older than 65 years old and not on hormone replacement therapy (HRT), with a FSH > 30 mIU/mL (3) If older than 65 years old and on HRT, the FSH requirement in not applicable. Postmenopausal females on HRT will be allowed if the treatment is stable for at least 6 months prior to dosing of study drug(s) (4) Written medical documentation of being sterilized (e.g. hysterectomy, double oophorectomy, bilateral salpingectomy) with the procedure performed at least 6 months prior to dosing study drug(s). Note: Tubal ligation is not considered a form of permanent sterilization (5) Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately.
Of non-childbearing potential defined as women who have had a hysterectomy, bilateral oophorectomy, medically documented ovarian failure, or are documented postmenopausal (follicle stimulating hormone > 40 mIU/mL); OR, Of childbearing potential defined as including women < 55 years of age, even those who have experienced 2 years of amenorrhea; all women should also meet both of the following criteria:
Negative serum or urine pregnancy test done =< 7 days prior to registration and repeated prior to dosing on day 1 of each cycle, for individuals of childbearing potential only; NOTE: Individuals are considered to be of childbearing potential unless one of the following applies:\r\n* Is postmenopausal, defined as no menses for at least 12 months without an alternative medical cause; a high follicle-stimulating hormone (FSH) level consistently in the postmenopausal range (30 mIU/mL or higher) may be used to confirm a postmenopausal state in women not using hormonal contraception or hormonal replacement therapy; however, in the absence of 12 months of amenorrhea, a single FSH measurement is insufficient to confirm a postmenopausal state: or\r\n* Considered to be permanently sterile; permanent sterilization includes hysterectomy, bilateral salpingectomy, and/or bilateral oophorectomy
Women of reproductive potential must use highly effective contraception methods to avoid pregnancy for 23 weeks after the last dose of study drugs; “women of reproductive potential” is defined as any female who has experienced menarche and who has not undergone surgical sterilization (hysterectomy or bilateral oophorectomy) or who is not postmenopausal; menopause is defined clinically as 12 months of amenorrhea in a woman over 45 in the absence of other biological or physiological causes; in addition, women under the age of 55 must have a documented serum follicle stimulating hormone (FSH) level less than 40 mIU/mL
Women of childbearing potential (WOCBP) must have a negative serum pregnancy test within 14 days prior to registration. These women must also have a negative serum or urine pregnancy test (minimum sensitivity 25 IU/L or equivalent units of human chorionic gonadotropin [HCG]) within 24 hours prior to the start of nivolumab then every 6 weeks thereafter. NOTE: Women are considered of child bearing potential unless they are surgically sterile (have undergone a hysterectomy, bilateral tubal ligation, or bilateral oophorectomy) or are post-menopausal. Menopause is defined clinically as 12 months of amenorrhea in a woman over 45 in the absence of other biological or physiological causes. In addition, women under the age of 62 must have a documented serum follicle stimulating hormone (FSH) level less than 40 mIU/mL.
Women of child-bearing potential (WOCBP) must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation; WOCBP should use an adequate method to avoid pregnancy for 31 weeks after the last dose of investigational drug; women of childbearing potential must have a negative serum or urine pregnancy test (minimum sensitivity 25 IU/L or equivalent units of human chorionic gonadotropin [HCG]) within 24 hours prior to the start of nivolumab; women must not be breastfeeding; women who are not of childbearing potential (i.e., who are postmenopausal or surgically sterile) do not require contraception\r\n* Women of childbearing potential (WOCBP) is defined as any female who has experienced menarche and who has not undergone surgical sterilization (hysterectomy or bilateral oophorectomy) or who is not postmenopausal; menopause is defined clinically as 12 months of amenorrhea in a woman over 45 in the absence of other biological or physiological causes; in addition, women under the age of 55 must have a documented serum follicle stimulating hormone (FSH) level less than 40 mIU/mL\r\n* WOCBP receiving nivolumab will be instructed to adhere to contraception for a period of 31 weeks after the last dose of investigational product; these durations have been calculated using the upper limit of the half-life for nivolumab (25 days) and are based on the protocol requirement that WOCBP use contraception for 5 half-lives plus 30 days\r\n* Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform the treating physician immediately
Female participants of child bearing potential include any female who:\r\n* Has experienced menarche and who has not undergone successful surgical sterilization (hysterectomy, bilateral tubal ligation or bilateral oophorectomy) \r\n* Is not postmenopausal, defined as amenorrhea >= 12 consecutive months\r\n* Is on hormone replacement therapy with documented serum follicle stimulating hormone (FSH) level > 35 IU/mL
Patients who are pregnant or nursing; women of child-bearing potential (WOCBP) must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation; WOCBP should use an adequate method to avoid pregnancy for 23 weeks after the last dose of investigational drug; WOCBP must have a negative serum or urine pregnancy test (minimum sensitivity 25 IV/L or equivalent units of human chorionic gonadotropin [HCG]) within 24 hours prior to the start of nivolumab; women must not be breastfeeding\r\n* Women who are not of childbearing potential (i.e., who are postmenopausal or surgically sterile or have undergone definitive radiation) do not require contraception\r\n* Women of childbearing potential (WOCBP) is defined as any female who has experienced menarche and who has not undergone surgical sterilization (hysterectomy of bilateral oophorectomy) or who is not postmenopausal; menopause is defined clinically as 12 month amenorrhea in a woman over 45 in the absence of other biological or physiological causes; in addition, women under the age of 55 must have a documented serum follicle stimulating hormone (FSH) level greater than 40 mIU/mL\r\n* WOCBP receiving nivolumab will be instructed to adhere to contraception for a period of 23 weeks after the last dose of investigational product\r\n* Should a woman become pregnant or suspect she is pregnant while she is participating in this study, she should inform the treating physician immediately
Patients who are pregnant or nursing are not eligible; women of child bearing potential must have a negative serum or urine pregnancy test within 16 days prior to registration; women of child-bearing potential include: \r\n* Any female who has experienced menarche and who has not undergone surgical sterilization (hysterectomy, bilateral tubal ligation or bilateral oophorectomy) or is not postmenopausal (defined as amenorrhea >= 12 consecutive months) \r\n* Women on hormone replacement therapy (HRT) with documented serum follicle stimulating hormone (FSH) level > 35m IU/mL\r\n* Women who are using oral, implanted or injectable contraceptive hormones or mechanical products such as an intrauterine device or barrier methods (diaphragm, condoms, spermicides) to prevent pregnancy or practicing abstinence or where partner is sterile (e.g., vasectomy)
Patients who are pregnant or nursing; women of child-bearing potential (WOCBP) must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation; WOCBP should use an adequate method to avoid pregnancy for 23 weeks after the last dose of investigational drug; WOCBP must have a negative serum or urine pregnancy test (minimum sensitivity 25 IV/L or equivalent units of human chorionic gonadotropin [HCG]) within 24 hours prior to the start of nivolumab or nivolumab + ipilimumab; women must not be breastfeeding; women who are not of childbearing potential (i.e., who are postmenopausal or surgically sterile) do not require contraception; women of childbearing potential (WOCBP) is defined as any female who has experienced menarche and who has not undergone surgical sterilization (hysterectomy and/or bilateral oophorectomy) or who is not postmenopausal; menopause is defined clinically as 12 month amenorrhea in a woman over 45 in the absence of other biological or physiological causes; in addition, women under the age of 55 must have a documented serum follicle stimulating hormone (FSH) level greater than 40 mIU/mL; if, following initiation of the investigational product(s), it is subsequently discovered that a study subject is pregnant or may have been pregnant at the time of investigational product exposure, including during at least 6 half-lives after product administration, the investigational product will be permanently discontinued in an appropriate manner (e.g., dose tapering if necessary for subject safety); the investigator must report this event and any outcomes by amendment through Cancer Therapy Evaluation Program (CTEP)-Adverse Event Reporting System (AERS); protocol-required procedures for study discontinuation and follow-up must be performed on the subject unless contraindicated by pregnancy (e.g., X-ray studies); other appropriate pregnancy follow-up procedures should be considered if indicated; in addition, the investigator must report and follow-up on information regarding the course of the pregnancy, including perinatal and neonatal outcome; infants should be followed for a minimum of 8 weeks
Women of non-childbearing potential may be included if they are either surgically sterile or considered postmenopausal; women who have documentation of at least 12 months of spontaneous amenorrhea and have an follicle stimulating hormone (FSH) level > 40 mIU/mL will be considered postmenopausal
Women of childbearing potential (WOCBP) is defined as any female who has experienced menarche and who has not undergone surgical sterilization (hysterectomy or bilateral oophorectomy) or who is not postmenopausal; menopause is defined clinically as 12 months of amenorrhea in a woman over 45 in the absence of other biological or physiological causes; additionally, women under the age of 62 who are not surgically sterile must have a documented serum follicle stimulating hormone (FSH) level less than 40 mIU/mL to document postmenopausal status\r\n* WOCBP must agree to use appropriate method(s) of contraception for 6 months after the last dose of study treatment, per Food and Drug Administration (FDA) recommendations on use of contraception following bevacizumab; should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately
For women: Negative pregnancy test during screening (Day 3 to Day 1) before C1D1 and compliant with a medically-approved contraceptive regimen during and for 3 months after the treatment period or documented to be surgically sterile (hysterectomy, bilateral tubal ligation or bilateral oophorectomy) or postmenopausal (defined as amenorrhea for ?12 consecutive months; or receiving hormone replacement therapy [HRT] with documented serum follicle stimulating hormone [FSH] level >35 mIU/mL).
Women of childbearing potential (WOCBP) is defined as any female who has experienced menarche and who has not undergone surgical sterilization (hysterectomy or bilateral oophorectomy) or who is not postmenopausal; menopause is defined clinically as 12 months of amenorrhea in a woman over 45 in the absence of other biological or physiological causes
Both pre- and postmenopausal women will be included in this study; premenopausal will be defined as < 6 months since last menstrual period, no prior bilateral oophorectomy, and no use of hormone replacement therapy; postmenopausal status will be defined as the absence of menses for > 12 months, serum follicle-stimulating hormone (FSH) > 20 mIU/ml, or history of bilateral oophorectomy; perimenopausal women will be excluded, defined as menstrual cycle irregularity (variable cycle length that differs from normal by more than 7 days) and an FSH > 20 mIU/ml
Pregnant and breastfeeding women are excluded. Women of child-bearing potential who are unwilling or unable to use an acceptable method of birth control to avoid pregnancy for the entire study period and for up to 4 weeks after the study are excluded. This applies to any woman who has experienced menarche and who has not undergone successful surgical sterilization or is not postmenopausal defined as amenorrhea for at least 12 consecutive months, or women on hormone replacement therapy with serum follicle stimulating hormone (FSH) levels greater than 35 mIU/mL. A negative serum pregnancy test must be obtained within 14 days prior to the start of study therapy in all women of child-bearing potential. Male subjects must also agree to use effective contraception for the same period as above
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)
Women must not be pregnant or nursing; women of child bearing potential must have a negative serum or urine pregnancy test (minimum sensitivity 25 IU/L or equivalent units of human chorionic gonadotropin [HCG]) within 72 hours prior to registration; women of child-bearing potential include any female who has experienced menarche and who has not undergone surgical sterilization (hysterectomy, bilateral tubal ligation or bilateral oophorectomy) or is not postmenopausal (defined as amenorrhea >= 12 consecutive months; or women on hormone replacement therapy [HRT] with documented serum follicle stimulating hormone [FSH] level > 35 mIU/mL)
Women of childbearing potential must have a negative serum or urine pregnancy test within 24 hours prior to the start of nivolumab\r\n* “Women of childbearing potential” is defined as any female who has experienced menarche and who has not undergone surgical sterilization (hysterectomy or bilateral oophorectomy) or who is not postmenopausal\r\n* Menopause is defined as 12 months of amenorrhea in a woman over 45 in the absence of other biological or physiological causes; if menopausal status is considered for the purpose of evaluating childbearing potential, women under the age of 62 must have a documented serum follicle stimulating hormone (FSH) level > 40 mIU/mL, in order to be considered postmenopausal and not of childbearing potential
Pregnant and breastfeeding women are excluded; women of child-bearing potential who are unwilling or unable to use an acceptable method of birth control to avoid pregnancy for the entire study period and for up to 4 weeks after the study are excluded; this applies to any woman who has experienced menarche and who has not undergone successful surgical sterilization or is not postmenopausal (defined as amenorrhea for at least 12 consecutive months), or women on hormone replacement therapy with serum follicle stimulating hormone (FSH) levels greater than 35 mIU/mL; a negative urine or serum pregnancy test must be obtained within 14 days prior to the start of study therapy in all women of child-bearing potential; male subjects must also agree to use effective contraception for the same period as above
Women of childbearing potential must have a negative pregnancy test at screening; women of childbearing potential include women who have experienced menarche and who have not undergone successful surgical sterilization (hysterectomy, bilateral tubal ligation or bilateral oophorectomy) or are not postmenopausal; postmenopausal is defined as:\r\n* Amenorrhea >= 12 consecutive months without another cause OR\r\n* A documented serum follicle-stimulating hormone (FSH) level > 35 mIU/mL (for women with irregular menstrual periods and on hormone replacement therapy)
Women of child bearing potential (WOCBP) and men who are sexually active with WOCBP must agree to use appropriate method(s) of contraception; women of childbearing potential (WOCBP) receiving nivolumab will be instructed to adhere to contraception for a period of 23 weeks (30 days plus the time required for nivolumab to undergo five half-lives) after the last dose of investigational product; a WOCBP is defined as any female who has experienced menarche and who has not undergone surgical sterilization (hysterectomy or bilateral oophorectomy) or who is not postmenopausal; menopause is defined clinically as 12 consecutive months of amenorrhea in a woman over 45 in the absence of other biological or physiological causes; in addition, women under the age of 55 must have a documented serum follicle stimulating hormone (FSH) level less than 40 mIU/mL
Both pre- and postmenopausal women will be included in this study; postmenopausal status will be defined as the absence of menses for > 12 months, serum follicle-stimulating hormone (FSH) > 20 mIU/ml, or history of bilateral oophorectomy
Negative serum or urine pregnancy test done =< 24 hours prior to randomization, for women of childbearing potential only; note: a women of childbearing potential (WOCBP) is defined as any female who has experienced menarche and who has not undergone surgical sterilization (hysterectomy or bilateral oophorectomy) and is not postmenopausal; menopause is defined as 12 months of amenorrhea in a woman over age 45 years in the absence of other biological or physiological causes
Women of childbearing potential (WOCBP) not using a medically acceptable means of contraception throughout the study treatment and for at least 23 weeks following the last dose of study treatment (5 half-lives of study drug plus 30 days duration of ovulatory cycle)\r\n* WOCBP are defined as those who has experienced menarche and who has not undergone successful surgical sterilization (hysterectomy, bilateral tubal ligation, or bilateral oophorectomy) or is not postmenopausal; post-menopausal is defined as:\r\n** Amenorrhea >= 12 consecutive months without another cause, or\r\n** For women with irregular menstrual periods and on hormone replacement therapy (HRT), a documented serum follicle stimulating hormone (FSH) level > 35 mIU/mL
Women of child-bearing potential (WOCPB) and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation; WOCBP must have a negative serum or urine pregnancy test (minimum sensitivity 25 IU/L or equivalent units of human chorionic gonadotropin [HCG]) at baseline; women must not be breastfeeding; women who are not of childbearing potential (i.e., who are postmenopausal or surgically sterile as well as azoospermic men) do not require contraception; NOTE: a WOCBP is defined as any female who has experienced menarche and who has not undergone surgical sterilization (hysterectomy or bilateral oophorectomy) or who is not postmenopausal; menopause is defined clinically as 12 months of amenorrhea in a woman over 45 in the absence of other biological or physiological causes
Negative serum or urine pregnancy test done =< 7 days prior to registration, for women of childbearing potential only;\r\n* Note: a woman of childbearing potential (WOCBP) is defined as any female who has experienced menarche and who has not undergone surgical sterilization (hysterectomy or bilateral oophorectomy) and is not postmenopausal; menopause is defined as 12 months of amenorrhea in a woman over age 45 years in the absence of other biological or physiological causes
Participants must be premenopausal (defined as < 3 months since last menstrual period OR serum follicle-stimulating hormone [FSH] < 20 mIU/mL)
Pregnancy or nursing; women of child bearing potential must have a negative serum or urine pregnancy test (minimum sensitivity 25 IU/L or equivalent units of human chorionic gonadotropin [HCG]) within 72 hours prior to randomization\r\n* Women of child-bearing potential include any female who has experienced menarche and who has not undergone surgical sterilization (hysterectomy, bilateral tubal ligation or bilateral oophorectomy) or is not postmenopausal (defined as amenorrhea >= 12 consecutive months; or women on hormone replacement therapy [HRT] with documented serum follicle stimulating hormone [FSH] level > 35 mIU/mL); even women who are using oral, implanted or injectable contraceptive hormones or mechanical products such as an intrauterine device or barrier methods (diaphragm, condoms, spermicides) to prevent pregnancy or practicing abstinence or where partner is sterile (e.g., vasectomy), should be considered to be of child bearing potential
Evidence of post-menopausal status or negative urinary or serum pregnancy test for female pre-menopausal patients is required; women will be considered post-menopausal if they have been amenorrheic for 12 months without an alternative medical cause; the following age-specific requirements apply:\r\n* Women < 50 years of age would be considered post-menopausal if they have been amenorrheic for 12 months or more following cessation of exogenous hormonal treatments and if they have luteinizing hormone and follicle stimulating hormone levels in the post-menopausal range for the institution or underwent surgical sterilization (bilateral oophorectomy or hysterectomy)\r\n* Women >= 50 years of age would be considered post-menopausal if they have been amenorrheic for 12 months or more following cessation of all exogenous hormonal treatments, had radiation-induced oophorectomy with last menses > 1 year ago, had chemotherapy-induced menopause with > 1 year interval since last menses, or underwent surgical sterilization (bilateral oophorectomy or hysterectomy)
Postmenopausal or evidence of non-childbearing status for women of childbearing potential a negative urine or serum pregnancy test within 28 days of study treatment and confirmed prior to treatment on day 1; postmenopausal is defined as:\r\n* Amenorrheic for 1 year or more following cessation of exogenous hormonal treatments\r\n* Luteinizing hormone (LH )and follicle stimulating hormone (FSH) levels in the post menopausal range for women under 50\r\n* Radiation-induced oophorectomy with last menses > 1 year ago\r\n* Chemotherapy-induced menopause with > 1 year interval since last menses\r\n* Surgical sterilization (bilateral oophorectomy or hysterectomy)
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
Women who are not postmenopausal or have not undergone hysterectomy must have a documented negative pregnancy test within 14 days prior to study registration\r\n* Note: Postmenopausal is defined as one or more of the following:\r\n** Age >= 60 years\r\n** Age < 60 years and amenorrheic for at least 1 year with follicle-stimulating hormone (FSH) and plasma estradiol levels in the postmenopausal range\r\n** Bilateral oophorectomy
Women of childbearing potential must have a negative urine or serum pregnancy test within 28 days of initial dose of olaparib and temozolomide AND must agree to the use of two highly effective forms of contraception throughout their participation in the study and for at least 3 months after the last dose of olaparib and temozolomide, OR confirmed prior to treatment on day 1 to be postmenopausal or surgically sterile; postmenopausal is defined as:\r\n* Amenorrheic for 1 year or more following cessation of exogenous hormonal treatments\r\n* Luteinizing hormone (LH) and follicle stimulating hormone (FSH) levels in the postmenopausal range for women under 50\r\n* Radiation-induced oophorectomy with last menses > 1 year ago\r\n* Chemotherapy-induced menopause with > 1 year interval since last menses, or surgical sterilization (bilateral oophorectomy or hysterectomy)
Post-menopausal or evidence of non-childbearing status for women of childbearing potential; for women who are not post-menopausal, a negative urine or serum pregnancy test is required within 28 days of study treatment and confirmed prior to treatment on day 1; post-menopausal is defined as one of the following:\r\n* > 60 years old\r\n* Amenorrheic for 1 year or more following cessation of exogenous hormonal treatments\r\n* Luteinizing hormone (LH) and follicle stimulating hormone (FSH) levels in the post-menopausal range for women under 50\r\n* Radiation-induced oophorectomy with last menses > 1 year ago\r\n* Surgical sterilization (bilateral oophorectomy or hysterectomy)
Females should be using adequate contraceptive measures, should not be breast feeding and must have a negative pregnancy test prior to start of dosing if of child-bearing potential or must have evidence of non-child-bearing potential by fulfilling one of the following criteria at screening:\r\n* Post-menopausal defined as:\r\n** Aged more than 50 years and amenorrheic for at least 12 months following cessation of all exogenous hormonal treatments\r\n** Estradiol, follicle stimulating hormone (FSH) and luteinizing hormone (LH) levels in post-menopausal range while receiving gonadotrophin releasing hormone (LHRH) analogues for medical castration in patients with breast cancer\r\n* Documentation of irreversible surgical sterilization by hysterectomy, bilateral oophorectomy or bilateral salpingectomy but not tubal ligation
Women of child-bearing potential must not be pregnant or breastfeeding and must have a negative pregnancy test at screening. Women of non-childbearing potential are those who have had a hysterectomy or bilateral oophorectomy, or who have completed menopause, defined as no menses for at least 1 year AND either age ?65 years or follicle-stimulating hormone levels in the menopausal range.
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 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
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
Women of childbearing potential enrolling on study must have a negative serum pregnancy test prior to registration.\r\n* Childbearing potential is defined as women who are not postmenopausal (defined as amenorrheic for >= 12 months following cessation of any exogenous hormonal treatments; luteinizing hormone (LH) and follicle stimulating hormone (FSH) levels in the postmenopausal range for women under 50; radiation-induced oophorectomy with last menses > 12 months prior; or chemotherapy-induced menopause with last menses > 12 months prior) or surgically sterile (bilateral oophorectomy or hysterectomy).
Male patients: willing to use adequate contraception (barrier or abstinence) while on treatment with study drug and for 3 months after finishing treatment\r\n* Female patients: willing to use adequate contraception (barrier or abstinence) at least 2 weeks before receiving any study medication, while on treatment with study drug, and for 3 months after finishing treatment\r\n* Female patients: must not be pregnant or breast-feeding; women of child-bearing potential must have a negative pregnancy test prior to start of dosing or must have evidence of non-child-bearing potential by fulfilling one of the following criteria at screening: \r\n** Post-menopausal defined as aged more than 50 years and amenorrheic for at least 12 months following cessation of all exogenous hormonal treatments\r\n** Women under 50 years are 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 institution\r\n** Documentation of irreversible surgical sterilization by hysterectomy, bilateral oophorectomy, or bilateral salpingectomy but not tubal ligation
Post-menopausal (>= 60 years of age or with follicle stimulating hormone [FSH] > 30 IU/L if age 50-59)
Female patients: Must not be pregnant or breast-feeding; women of child-bearing potential must have a negative pregnancy test prior to start of dosing or must have evidence of non-child-bearing potential by fulfilling one of the following criteria at screening:\r\n* Post-menopausal defined as aged more than 50 years and amenorrheic for at least 12 months following cessation of all exogenous hormonal treatments\r\n* Women under 50 years are 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 institution\r\n* Documentation of irreversible surgical sterilization by hysterectomy, bilateral oophorectomy, or bilateral salpingectomy but not tubal ligation
Women of childbearing potential enrolling on study must have a negative serum pregnancy test prior to registration\r\n* Childbearing potential is defined as women who are not postmenopausal (defined as amenorrheic for >= 12 months following cessation of any exogenous hormonal treatments; luteinizing hormone [LH] and follicle stimulating hormone [FSH] levels in the postmenopausal range for women under 50; radiation-induced oophorectomy with last menses > 12 months prior; or chemotherapy-induced menopause with last menses > 12 months prior) or surgically sterile (bilateral oophorectomy or hysterectomy)
Women of child-bearing potential and men must agree to use enhanced methods of contraception; all women are considered to be of childbearing potential unless they fulfill one of the following criteria at screening:\r\n* Post-menopausal defined as age >= 50 and amenorrheic for at least 12 months OR\r\n* Women age < 50 if they have been amenorrheic for at least 12 months and have a serum follicle-stimulating hormone (FSH) and luteinizing hormone (LH) level in the postmenopausal range (per institutional standards)\r\n* If women have documentation of irreversible surgical sterilization by hysterectomy, bilateral oophorectomy, or bilateral salpingectomy, or bilateral tubal ligation, they are considered post-menopausal
Post-menopausal defined as age more than 50 years and amenorrheic for at least 12 months following cessation of all exogenous hormonal treatments.
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.
Only postmenopausal women and some premenopausal women (as outlined below) will be eligible; should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her study physician immediately\r\n* Women will be considered postmenopausal if one of the following is met:\r\n** Prior bilateral oophorectomy\r\n** 60 years of age or older\r\n** Age less than 60 years; amenorrheic for 12 or more months; and follicle stimulating hormone (FSH) and plasma estradiol in the postmenopausal range\r\n* Premenopausal women without childbearing potential are eligible to participate if one of the following criteria is met:\r\n** Prior hysterectomy\r\n** Prior fallopian tubal ligation (cut, tied, or sealed)\r\n** Prior placement of permanent intratubal contraceptive devices (e.g. Essure)
Pregnant women are excluded from this study because olaparib has the potential for teratogenic or abortifacient effects. Women must either be post-menopausal or must have a negative pregnancy test (urine or serum) =< 28 days prior to enrollment and confirmed on day 1 of cycle 1 of study therapy\r\nPostmenopausal is defined as:\r\n* Amenorrheic for 1 year or more following cessation of exogenous hormonal treatments\r\n* Luteinizing hormone (LH) and follicle stimulating hormone (FSH) levels in the post-menopausal range for women under 50 years of age\r\n* Radiation-induced oophorectomy with last menses > 1 year ago\r\n* Chemotherapy-induced menopause with > 1-year interval since last menses\r\n* Surgical sterilization (bilateral oophorectomy or hysterectomy)
Evidence of post-menopausal status OR negative urinary or serum pregnancy test for female pre-menopausal patients; women will be considered post-menopausal if they have been amenorrheic for 12 months without an alternative medical cause; the following age-specific requirements apply: \r\n* Women < 50 years of age would be considered post-menopausal if they have been amenorrheic for 12 months or more following cessation of exogenous hormonal treatments and if they have luteinizing hormone and follicle-stimulating hormone levels in the post-menopausal range for the institution or underwent surgical sterilization (bilateral oophorectomy, or hysterectomy)\r\n* Women ? 50 years of age would be considered post-menopausal if they have been amenorrheic for 12 months or more following cessation of all exogenous hormonal treatments, had radiation-induced menopause with last menses > 1 year ago, had chemotherapy-induced menopause with last menses > 1 year ago, or underwent surgical sterilization (bilateral oophorectomy, bilateral salpingectomy or hysterectomy).
Female subjects must be postmenopausal or there must be evidence of non-childbearing status for women of childbearing potential: negative urine or serum pregnancy test within 28 days of study treatment and confirmed prior to treatment on day 1. Postmenopausal is defined as:\r\n* Amenorrheic for 1 year or more following cessation of exogenous hormonal treatments.\r\n* Luteinizing hormone (LH) and Follicle stimulating hormone (FSH) levels in the post-menopausal range for women under 50.\r\n* Radiation-induced oophorectomy with last menses > 1 year ago.\r\n* Chemotherapy-induced menopause with > 1 year interval since last menses.\r\n* Surgical sterilization (bilateral oophorectomy or hysterectomy).
Negative pregnancy test done =< 7 days (or per institutional policy) prior to treatment, for women of childbearing potential only. Female must use highly effective contraceptive measures, and must have a negative pregnancy test or must have evidence of non-child-bearing potential by fulfilling one of the following criteria at screening:\r\n* Post-menopausal defined as aged more than 50 years and amenorrheic for at least 12 months following cessation of all exogenous hormonal treatments\r\n* 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 institution\r\n* Documentation of irreversible surgical sterilization by hysterectomy, bilateral oophorectomy or bilateral salpingectomy but not tubal ligation
Evidence of post-menopausal status or negative urinary or serum pregnancy test for female pre-menopausal subjects. Women will be considered post-menopausal if they have been amenorrheic for 12 months without an alternative medical cause. The following age-specific requirements apply: Women < 50 years of age would be considered post-menopausal if they have been amenorrheic for 12 months or more following cessation of exogenous hormonal treatments and if they have luteinizing hormone and follicle-stimulating hormone levels in the post-menopausal range for the institution or underwent surgical sterilization (bilateral oophorectomy or hysterectomy).
Women >= 50 years of age would be considered post-menopausal if they have been amenorrheic for 12 months or more following cessation of all exogenous hormonal treatments, had radiation-induced menopause with last menses > 1 year ago, had chemotherapy-induced menopause with last menses > 1 year ago, or underwent surgical sterilization (bilateral oophorectomy, bilateral salpingectomy or hysterectomy).
Post-menopausal defined as aged more than 50 years and amenorrhoeic for at least 12 months following cessation of all exogenous hormonal treatments
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
Women will be considered post-menopausal if they have been amenorrheic for the past 12 months without an alternative medical cause. The following age-specific requirements must also apply: \r\n* Women < 50 years old: they would be considered post-menopausal if they have been amenorrheic for the past 12 months or more following cessation of exogenous hormonal treatments. The levels of luteinizing hormone (LH) and follicle-stimulating hormone (FSH) must also be in the post-menopausal range (as per the institution). \r\n* Women >= 50 years old: they would be consider post-menopausal if they have been amenorrheic for the past 12 months or more following cessation of all exogenous hormonal treatments, or have had radiation-induced oophorectomy with the last menses > 1\r\nyear ago, or have had chemotherapy-induced menopause with > 1 year interval since last menses, or have had surgical sterilization by either bilateral oophorectomy or hysterectomy
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
Evidence of post-menopausal status or negative urinary or serum pregnancy test for female pre-menopausal patients; women will be considered post-menopausal if they have been amenorrheic for 12 months without an alternative medical cause; the following age-specific requirements apply:\r\n* Women < 50 years of age would be considered post-menopausal if they have been amenorrhea for 12 months or more following cessation of exogenous hormonal treatments and if they have luteinizing hormone and follicle-stimulating hormone levels in the post-menopausal range for the institution or underwent surgical sterilization (bilateral oophorectomy or hysterectomy)\r\n* Women >= 50 years of age would be considered post-menopausal if they have been amenorrheic for 12 months or more following cessation of all exogenous hormonal treatments, had radiation-induced oophorectomy with last menses > 1 year ago, had chemotherapy-induced menopause with > 1 year interval since last menses, or underwent surgical sterilization (bilateral oophorectomy or hysterectomy)
Female subjects must either be of non-reproductive potential (i.e., post-menopausal as described below) OR history of surgical sterilization (hysterectomy, bilateral tubal ligation, or bilateral oophorectomy) or must have a negative serum pregnancy test upon study entry\r\n* Women < 50 years of age would be considered post-menopausal if they have been amenorrheic for 12 months or more following cessation of exogenous hormonal treatments and if they have luteinizing hormone and follicle-stimulating hormone levels in the post-menopausal range for the institution\r\n* Women >= 50 years of age would be considered post-menopausal if they have been amenorrheic for 12 months or more following cessation of all exogenous hormonal treatments, had radiation-induced menopause with last menses > 1 year ago, or had chemotherapy-induced menopause with last menses > 1 year ago
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
Female subjects will be considered of non-reproductive potential if they are either:\r\n* Postmenopausal (defined as at least 24 months with no menses without an alternative medical cause; in women < 45 years of age a high follicle stimulating hormone (FSH) level in the postmenopausal range may be used to confirm a post-menopausal state in women not using hormonal contraception or hormonal replacement therapy; in the absence of 12 months of amenorrhea, a single FSH measurement is insufficient); OR\r\n* Have had a hysterectomy and/or bilateral oophorectomy, bilateral salpingectomy or bilateral tubal ligation/occlusion, at least 6 weeks prior to screening; OR\r\n* Has a congenital or acquired condition that prevents childbearing
Evidence of post-menopausal status or negative urinary or serum pregnancy test for female pre-menopausal patients; women will be considered post-menopausal if they have been amenorrheic for 12 months without an alternative medical cause; the following age-specific requirements apply:\r\n* Women < 50 years of age would be considered post-menopausal if they have been amenorrheic for 12 months or more following cessation of exogenous hormonal treatments and if they have luteinizing hormone and follicle-stimulating hormone levels in the post-menopausal range for the institution or underwent surgical sterilization (bilateral oophorectomy or hysterectomy)\r\n* Women >= 50 years of age would be considered post-menopausal if they have been amenorrheic for 12 months or more following cessation of all exogenous hormonal treatments, had radiation-induced menopause with last menses > 1 year ago, had chemotherapy-induced menopause with last menses > 1 year ago, or underwent surgical sterilization (bilateral oophorectomy, bilateral salpingectomy or hysterectomy; subject is willing and able to comply with the protocol for the duration of the study including undergoing treatment and scheduled visits and examinations including follow up
Evidence of post-menopausal status or negative urine or serum pregnancy test for female pre-menopausal subjects; women will be considered post-menopausal if they have been amenorrheic for 12 months without an alternative medical cause; the following age-specific requirements apply:\r\n* Women < 50 years of age would be considered post-menopausal if they have been amenorrheic for 12 months or more following cessation of exogenous hormonal treatments and if they have luteinizing hormone and follicle-stimulating hormone levels in the post-menopausal range for the institution or underwent surgical sterilization (bilateral oophorectomy or hysterectomy)\r\n* Women >= 50 years of age would be considered post-menopausal if they have been amenorrheic for 12 months or more following cessation of all exogenous hormonal treatments, had radiation-induced menopause with last menses > 1 year ago, had chemotherapy-induced menopause with last menses > 1 year ago, or underwent surgical sterilization (bilateral oophorectomy, bilateral salpingectomy, or hysterectomy)
Postmenopausal or evidence of non-childbearing status for women of childbearing potential: negative urine or serum pregnancy test within 7 days of study treatment. Postmenopausal is defined as: amenorrheic for 1 year or more following cessation of exogenous hormonal treatments; luteinizing hormone (LH) and follicle stimulating hormone (FSH) levels in the postmenopausal range for women under 50; radiation-induced oophorectomy with last menses > 1 year ago; chemotherapy-induced menopause with > 1 year interval since last menses; OR surgical sterilization (bilateral oophorectomy or hysterectomy)
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
Female subject of childbearing potential who is unwilling to use acceptable method(s) of effective contraception during study treatment and through 3 months after the last dose of talimogene laherparepvec; (note: women not of childbearing potential are defined as: any female who is post-menopausal [age > 55 years with cessation of menses for 12 or more months or less than 55 years but not spontaneous menses for at least 2 years or less than 55 years and spontaneous menses within the past 1 year, but currently amenorrheic (eg, spontaneous or secondary to hysterectomy), and with postmenopausal gonadotropin levels (luteinizing hormone and follicle-stimulating hormone levels > 40 IU/L) or postmenopausal estradiol levels (< 5 ng/dL) or according to the definition of \postmenopausal range\ for the laboratory involved] or who have had a hysterectomy, bilateral salpingectomy, or bilateral oophorectomy)
Male and female subjects of childbearing potential who are unwilling to use acceptable method(s) of effective contraception during study treatment and through 3 months after the last dose of talimogene laherparepvec and 4 months after the last dose of pembrolizumab; (Note: women not of childbearing potential are defined as: any female who is post-menopausal [age >= 55 years with cessation of menses for 12 or more months or less than 55 years but not spontaneous menses for at least 2 years or less than 55 years and spontaneous menses within the past 1 year, but currently amenorrheic (e.g., spontaneous or secondary to hysterectomy), and with postmenopausal gonadotropin levels (luteinizing hormone and follicle-stimulating hormone levels > 40 IU/L) or postmenopausal estradiol levels (< 5 ng/dL) or according to the definition of \postmenopausal range\ for the laboratory involved] or who have had a hysterectomy, bilateral salpingectomy, or bilateral oophorectomy)
The following age-specific requirements must also apply:\r\nWomen < 50 years old: they would be considered post-menopausal if they have been amenorrheic for the past 12 months or more following cessation of exogenous hormonal treatments; the levels of luteinizing hormone (LH) and follicle-stimulating hormone (FSH) must also be in the post-menopausal range (as per the institution); women >= 50 years old: they would be considered post-menopausal if they have been amenorrheic for the past 12 months or more following cessation of all exogenous hormonal treatments, or have had radiation-induced oophorectomy with the last menses > 1 year ago, or have had chemotherapy-induced menopause with > 1 year interval since last menses, or have had surgical sterilization by either bilateral oophorectomy or hysterectomy
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
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
Fertile men or women of childbearing potential unless 1) permanently sterile or 2) using a highly effective measure of contraception such as condoms in males and consistent and correct use of one of the following in females: intrauterine device, tubal sterilization, Essure micro-insert system, vasectomy in the male partner; effective contraception is required for males during treatment with study drug and to continue for 3 months after the last dose of either entospletinib or obinutuzumab, whichever is later; for women, effective contraception is required to continue for >= 12 months after the last dose of obinutuzumab or for 30 days after the last dose of entospletinib, whichever is later; for men, effective contraception is required to continue for 3 months after the last dose of obinutuzumab treatment\r\n* Definition of childbearing potential: for this study, a female subject is considered of childbearing potential until becoming post-menopausal unless permanently sterile or with medically documented ovarian failure; women are considered to be in a postmenopausal state when >= 54 years of age with cessation of previously occurring menses for >= 12 months without an alternative cause; women of any age with amenorrhea of >= 12 months may also be considered post-menopausal if their follicle stimulating hormone (FSH) level is in the post-menopausal range and they are not using hormonal contraception or hormonal replacement therapy; permanent sterilization in females includes hysterectomy, bilateral oophorectomy, or bilateral salpingectomy in a female subject of any age; permanent sterilization in males include bilateral orchiectomy or medical documentation of alternative explanation
Women who are not postmenopausal or have not undergone hysterectomy must have a documented negative serum pregnancy test within 72 hours prior to initiating study treatment; Note: postmenopausal is defined as any of the following:\r\n* Age >= 60 years\r\n* Age < 60 years and amenorrheic for at least 1 year with follicle-stimulating hormone (FSH) and plasma estradiol levels in the postmenopausal range\r\n* Bilateral oophorectomy
Post-menopausal: defined as more than 50 years-of-age and amenorrhoeic for at least 12 months following cessation of all exogenous hormonal treatments
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.
Postmenopausal status is defined either by: I). Prior bilateral oophorectomy OR ii). Age ? 60 OR iii). 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. If patient is taking tamoxifen or toremifene and age < 60, then FSH and plasma estradiol levels should be in post-menopausal range per local normal range. Note: For women with therapy-induced amenorrhea, serial measurements of FSH and/or estradiol are needed to ensure menopausal status.
Post-menopausal defined as\r\n* Age >= 60 and amenorrhea > 12 consecutive months, OR\r\n* Age < 60 and amenorrhea > 12 consecutive months without another cause and documented follicle stimulating hormone (FSH) level within post-menopausal range according to institutional standard, OR\r\n* Previous bilateral oophorectomy
Evidence of post-menopausal status or negative urinary or serum pregnancy test for female pre-menopausal patients; women will be considered post-menopausal if they have been amenorrheic for 12 months without an alternative medical cause; the following age-specific requirements apply:\r\n* Women < 50 years of age would be considered post-menopausal if they have been amenorrheic for 12 months or more following cessation of exogenous hormonal treatments and if they have luteinizing hormone and follicle-stimulating hormone levels in the post-menopausal range for the institution or underwent surgical sterilization (bilateral oophorectomy or hysterectomy)\r\n* Women >= 50 years of age would be considered post-menopausal if they have been amenorrheic for 12 months or more following cessation of all exogenous hormonal treatments, had radiation-induced menopause with last menses > 1 year ago, had chemotherapy-induced menopause with last menses > 1 year ago, or underwent surgical sterilization (bilateral oophorectomy, bilateral salpingectomy or hysterectomy; subject is willing and able to comply with the protocol for the duration of the study including undergoing treatment and scheduled visits and examinations including follow up
PHASE I: Women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry, for the duration of study participation and for 120 days (both male and female) following last dose of study drug; should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately; fertile females of childbearing potential are defined as women physically capable of becoming pregnant unless the female patient cannot have children because of surgery or other medical reasons (effective tubal ligation, ovaries or the uterus removed, or are post-menopausal); post-menopausal is defined as:\r\n* Amenorrheic for 1 year or more following cessation of exogenous hormonal treatments,\r\n* Luteinizing hormone (LH) and follicle stimulating hormone (FSH) levels in the post menopausal range for women under 50,\r\n* Radiation-induced oophorectomy with last menses > 1 year ago,\r\n* Chemotherapy-induced menopause with > 1 year interval since last menses, or\r\n* Surgical sterilization (bilateral oophorectomy or hysterectomy)
PHASE II SCLC: Women of child-bearing potential and men must agree to use highly effective contraception (hormonal or barrier method of birth control; abstinence) prior to study entry, for the duration of study participation and for 120 days (both male and female) following last dose of study drug; should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately; fertile females of childbearing potential are defined as women physically capable of becoming pregnant unless the female patient cannot have children because of surgery or other medical reasons (effective tubal ligation, ovaries or the uterus removed, or are post-menopausal); post-menopausal is defined as:\r\n* Amenorrheic for 1 year or more following cessation of exogenous hormonal treatments,\r\n* LH and FSH levels in the post menopausal range for women under 50,\r\n* Radiation-induced oophorectomy with last menses > 1 year ago,\r\n* Chemotherapy-induced menopause with > 1 year interval since last menses, or\r\n* Surgical sterilization (bilateral oophorectomy or hysterectomy)
UROTHELIAL CARCINOMA EXPANSION COHORT: Women of childbearing potential and men must agree to use highly effective contraception (hormonal or barrier method of birth control; abstinence) prior to study entry, for the duration of study participation and for 120 days (both male and female) following last dose of study drug; should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately; fertile females of childbearing potential are defined as women physically capable of becoming pregnant unless the female patient cannot have children because of surgery or other medical reasons (effective tubal ligation, ovaries or the uterus removed, or are post-menopausal); post-menopausal is defined as:\r\n* Amenorrheic for 1 year or more following cessation of exogenous hormonal treatments,\r\n* LH and FSH levels in the post menopausal range for women under 50,\r\n* Radiation-induced oophorectomy with last menses > 1 year ago,\r\n* Chemotherapy-induced menopause with > 1 year interval since last menses, or\r\n* Surgical sterilization (bilateral oophorectomy or hysterectomy)
Females should not be breast feeding and must have a negative pregnancy test prior to start of dosing if of child-bearing potential or must have evidence of non-child-bearing potential by fulfilling one of the following criteria at screening:\r\n* Post-menopausal defined as aged more than 50 years and amenorrheic for at least 12 months following cessation of all exogenous hormonal treatments \r\n* Women under 50 years old would be consider 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 institution\r\n* Documentation of irreversible surgical sterilization by hysterectomy, bilateral oophorectomy or bilateral salpingectomy but not tubal ligation
Evidence of post-menopausal status or negative urinary or serum pregnancy test for female pre-menopausal patients; women will be considered post-menopausal if they have been amenorrheic for 12 months without an alternative medical cause; the following age-specific requirements apply: \r\n* Women < 50 years of age would be considered post-menopausal if they have been amenorrheic for 12 months or more following cessation of exogenous hormonal treatments and if they have luteinizing hormone and follicle-stimulating hormone levels in the post-menopausal range for the institution or underwent surgical sterilization (bilateral oophorectomy or hysterectomy)\r\n* Women >= 50 years of age would be considered post-menopausal if they have been amenorrheic for 12 months or more following cessation of all exogenous hormonal treatments, had radiation-induced menopause with last menses > 1 year ago, had chemotherapy-induced menopause with last menses > 1 year ago, or underwent surgical sterilization (bilateral oophorectomy, bilateral salpingectomy or hysterectomy)
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
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
Post-menopausal defined as\r\n* Age >= 55 years and 1 year or more of amenorrhea\r\n* Age < 55 years and 1 year or more of amenorrhea with an estradiol assay < 20 pg/mL\r\n* Surgical menopause with bilateral oophorectomy
Women who are not postmenopausal or have not undergone hysterectomy must have a documented negative serum pregnancy test within 7 days prior to initiating study treatment; Note: Postmenopausal is defined as one or more of the following:\r\n* Age >= 60 years\r\n* Age < 60 years and amenorrheic for at least 1 year with follicle-stimulating hormone (FSH) and plasma estradiol levels in the postmenopausal range\r\n* Bilateral oophorectomy
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)
Female subjects must either be of non-reproductive potential or must have a negative serum pregnancy test within 7 days prior to registration on study; evidence of post-menopausal status or negative urinary or serum pregnancy test for female pre-menopausal patients; women will be considered post-menopausal if they have been amenorrheic for 12 months without an alternative medical cause; the following age-specific requirements apply:\r\n* Women < 50 years of age would be considered post-menopausal if they have been amenorrheic for 12 months or more following cessation of exogenous hormonal treatments and if they have luteinizing hormone and follicle-stimulating hormone levels in the post-menopausal range for the institution or underwent surgical sterilization (bilateral oophorectomy or hysterectomy)\r\n* Women >= 50 years of age would be considered post-menopausal if they have been amenorrheic for 12 months or more following cessation of all exogenous hormonal treatments, had radiation induced menopause with last menses > 1 year ago, had chemotherapy-induced menopause with last menses > 1 year ago, or underwent surgical sterilization (bilateral oophorectomy, bilateral salpingectomy or hysterectomy)
Postmenopausal status, as defined by the National Comprehensive Cancer Network\r\n* Age > 60 years old OR\r\n* Prior bilateral oophorectomy regardless of age\r\n* If patient < 60 years old and amenorrheic for > 12 months or in the absence of ovarian suppression, follicle-stimulating hormone (FSH) and estradiol have to be in the postmenopausal range
Female patients are considered to be of childbearing potential unless:\r\n* They are post-menopausal (defined as older than 50 years and amenorrheic for at least 12 months following cessation of all exogenous hormonal treatments)\r\n* There is documentation of irreversible surgical sterilization by hysterectomy, bilateral oophorectomy or bilateral salpingectomy (but not tubal ligation), or\r\n* They are 50 years or younger but have been amenorrheic for at least 12 months following the cessation of exogenous hormonal treatments, and have serum follicle-stimulating hormone (FSH) and luteinizing hormone (LH) levels in the postmenopausal range for the institution\r\n** Female patients who are of childbearing potential must agree to use adequate contraceptive measures (as defined below) for the duration of study participation, and for 90 days after the final dose of study drug; cessation of birth control after this point should be discussed with a responsible physician; they also may not be breast feeding and must have a negative serum or urine pregnancy test within 72 hours prior to start of study treatment\r\n** Male patients who are sexually active with a female partner of childbearing potential must be either surgically sterilized or agree to use barrier contraception (i.e., condoms) for the duration of study participation, and for 90 days after the final dose of study drug; cessation of birth control after this point should be discussed with a responsible physician
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
Evidence of non-childbearing status for women of childbearing potential: negative urine or serum pregnancy test within 28 days of study treatment, confirmed prior to treatment on day 1; postmenopausal is define as:\r\n* Amenorrheic for 1 year or more following cessation of exogenous hormonal treatments\r\n* Luteinizing hormone (LH) and follicle stimulating hormone (FSH) levels in the post-menopausal range for women under 50\r\n* Radiation-induced oophorectomy with last menses > 1 year ago\r\n* Chemotherapy-induced menopause with > 1 year interval since last menses\r\n* Surgical sterilization (bilateral oophorectomy or hysterectomy)
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
Post-menopausal status defined by any of the following:\r\n* Age > 55 years\r\n* History of bilateral oophorectomy\r\n* Spontaneous amenorrhea for 1 year with intact uterus and ovaries\r\n* Serum estradiol and follicle-stimulating hormone (FSH) concentrations in the post-menopausal range, along with either amenorrhea for 6 months or previous hysterectomy
Female subjects should be using highly effective contraceptive measures, and must have a negative pregnancy test and not be breast-feeding prior to start of dosing if of child- bearing potential or must have evidence of non-child-bearing potential by fulfilling one of the following criteria at screening:\r\n* Post-menopausal defined as aged more than 50 years and amenorrheic for at least 12 months following cessation of all exogenous hormonal treatments\r\n* Women under 50 years old would be consider 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 institution\r\n* Documentation of irreversible surgical sterilization by hysterectomy, bilateral oophorectomy or bilateral salpingectomy but not tubal ligation
Evidence of post-menopausal status or negative urinary or serum pregnancy test for pre-menopausal patients is required; women will be considered post-menopausal if they have been amenorrheic for 12 months without an alternative medical cause; the following age-specific requirements apply:\r\n* Women < 50 years of age would be considered post-menopausal if they have been amenorrheic for 12 months or more following cessation of exogenous hormonal treatments and if they have luteinizing hormone and follicle stimulating hormone levels in the post-menopausal range for the institution or underwent surgical sterilization (bilateral oophorectomy or hysterectomy)\r\n* Women >= 50 years of age would be considered post-menopausal if they have been amenorrheic for 12 months or more following cessation of all exogenous hormonal treatments, had radiation-induced oophorectomy with last menses > 1 year ago, had chemotherapy-induced menopause with > 1-year interval since last menses, or underwent surgical sterilization (bilateral oophorectomy, bilateral salpingectomy or hysterectomy)
Age 55 years and 1 year or more of amenorrhea with LH and/or FSH levels in the postmenopausal range
Age 55 with prior hysterectomy but intact ovaries with LH and/or FSH levels in the postmenopausal range
Prior to the discovery of the breast cancer, clinically post?menopausal as defined as: i) one or more years from last menses; or ii) history of oophorectomy; or iii) follicle stimulating hormone (FSH) test result in the post-menopause reference range
Evidence of post-menopausal status or negative urinary or serum pregnancy test for female pre-menopausal patients; women will be considered post-menopausal if they have been amenorrheic for 12 months without an alternative medical cause; the following age-specific requirements apply:\r\n* Women < 50 years of age would be considered post-menopausal if they have been amenorrheic for 12 months or more following cessation of exogenous hormonal treatments and if they have luteinizing hormone and follicle-stimulating hormone levels in the post-menopausal range for the institution or underwent surgical sterilization (bilateral oophorectomy or hysterectomy)\r\n* Women >= 50 years of age would be considered post-menopausal if they have been amenorrheic for 12 months or more following cessation of all exogenous hormonal treatments, had radiation-induced menopause with last menses > 1 year ago, had chemotherapy-induced menopause with last menses > 1 year ago, or underwent surgical sterilization (bilateral oophorectomy, bilateral salpingectomy or hysterectomy)
Subjects must either be of non-reproductive potential (ie, post-menopausal by history; OR history of hysterectomy, OR history of bilateral tubal ligation, OR history of bilateral oophorectomy) or must have a negative serum or urine pregnancy test upon study entry; women will be considered post-menopausal if they have been amenorrheic for 12 months without an alternative medical cause; the following age-specific requirements apply:\r\n* Women < 50 years of age would be considered post-menopausal if they have been amenorrheic for 12 months or more following cessation of exogenous hormonal treatments and if they have luteinizing hormone and follicle-stimulating hormone levels in the post-menopausal range for the institution or underwent surgical sterilization (bilateral oophorectomy or hysterectomy)\r\n* Women >/= 50 years of age would be considered post-menopausal if they have been amenorrheic for 12 months or more following cessation of all exogenous hormonal treatments, had radiation-induced menopause with last menses > 1 year ago, had chemotherapy-induced menopause with last menses > 1 year ago, or underwent surgical sterilization (bilateral oophorectomy, bilateral salpingectomy or hysterectomy)
Postmenopausal or evidence of non-childbearing status for women of childbearing potential: negative urine or serum pregnancy test within 28 days and within 72 hours of study treatment and confirmed prior to receiving treatment on this study. Patients with positive results will be removed from the study. Postmenopausal is defined as: 1. amenorrheic for 1 year or more following cessation of exogenous hormonal treatments. 2. luteinizing hormone (LH) and follicle stimulating hormone (FSH) levels in the postmenopausal range for women under 50. 3. radiation-induced oophorectomy with last menses > 1 year ago. 4. chemotherapy-induced menopause with >1 year interval since last menses. 5. surgical sterilization (bilateral oophorectomy or hysterectomy). 6. female patients must agree to use a highly effective birth control method while on study and for at least 1 month after your last dose of study drug(s).
Female patients of childbearing potential are not willing to use highly effective contraception to prevent pregnancy or agree to abstain from heterosexual activity throughout the study. Highly effective contraception is defined as:\r\n* Surgical birth control/sterilization (such as male vasectomy or female sterilization.\r\n* Birth control pills, injections, implants, or patches.\r\n* Intrauterine devices (IUDs).\r\n* Two barrier methods (male condom and female diaphragm, cervical cap, or sponge) in combination with a spermicide.\r\n* Highly effective contraception must be used by both sexes during the study and must be continued for 3 months after the last dose of study treatment. (Women of not childbearing potential: post-menopausal [age > 55 years with cessation of menses > 12 months or < 55 years but not spontaneous menses for at least 2 years or < 55 years and spontaneous menses within the past 1 year, but currently amenorrheic (e.g., spontaneous or secondary to hysterectomy), and with postmenopausal gonadotropin levels (luteinizing hormone and follicle-stimulating hormone levels > 40 IU/L) or postmenopausal estradiol levels (< 5 ng/dL) or according to the definition of \postmenopausal range\ for the laboratory involved] or who have had a hysterectomy, bilateral salpingectomy, or bilateral oophorectomy).
Non pregnant: negative serum test for pregnancy, unless male, prior hysterectomy, tubal ligation, or postmenopausal; (Note: postmenopausal is defined as age > 55 with amenorrhea for > 1 year or age < 55 years with amenorrhea for 2 years and follicle stimulating hormone (FSH) level within postmenopausal range of institutional parameters; patients requiring FSH level to determine menopausal status need not have this performed and may choose to proceed with serum pregnancy testing)
Age <60 and amenorrhea for 12 or more months (in the absence of chemotherapy, tamoxifen, toremifene, or ovarian suppression) and FSH and/or estradiol in the postmenopausal range per local normal range. If patient is taking tamoxifen or toremifene and age <60, then FSH and plasma estradiol levels should be in post-menopausal range per local normal range. Note: For women using therapy-induced amenorrhea other than ovarian radiation, goserelin or leuprolide, etc., serial measurements of FSH and/or estradiol are needed to ensure menopausal status
For women of childbearing potential, a negative serum or urine pregnancy test within 14 days prior to step 1 registration; Note: women will be considered post-menopausal if they have been amenorrheic for 12 months without an alternative medical cause; the following age-specific requirements apply: \r\n* Women < 50 years of age would be considered post-menopausal if they have been amenorrheic for 12 months or more following cessation of exogenous hormonal treatments and if they have luteinizing hormone and follicle-stimulating hormone levels in the post-menopausal range for the institution or underwent surgical sterilization (bilateral oophorectomy or hysterectomy)\r\n* Women >= 50 years of age would be considered post-menopausal if they have been amenorrheic for 12 months or more following cessation of all exogenous hormonal treatments, had radiation-induced menopause with last menses > 1 year ago, had chemotherapy-induced menopause with last menses > 1 year ago, or underwent surgical sterilization (bilateral oophorectomy, bilateral salpingectomy or hysterectomy)
Post-menopausal subjects as defined by any of the following:\r\n* Subjects at least 55 years of age\r\n* Subjects under 55 years of age and amenorrheic for at least 12 months or follicle-stimulating hormone (FSH) values >= 40 IU/L and estradiol levels =< 20 IU/L\r\n* Prior bilateral oophorectomy or prior radiation castration with amenorrhea for at least 6 months
Women of child-bearing potential are expected to use highly effective contraception during the study and for 1 month after the last dose of study drug; postmenopausal or evidence of non-childbearing status for women of childbearing potential: negative urine or serum pregnancy test within 28 days of study treatment and confirmed prior to treatment on day 1; postmenopausal is defined as:\r\n* Amenorrheic for 1 year or more following cessation of exogenous hormonal treatments\r\n* Luteinizing hormone (LH) and follicle stimulating hormone (FSH) levels in the post-menopausal range for women under 50\r\n* Radiation-induced oophorectomy with last menses > 1 year ago\r\n* Chemotherapy-induced menopause with > 1 year interval since last menses\r\n* Surgical sterilization (bilateral oophorectomy or hysterectomy)
Postmenopausal or evidence of non-pregnant status for women of childbearing potential as confirmed by a negative urine or serum pregnancy test within 7 days prior to the start of therapy; postmenopausal status is defined as:\r\n* Age >= 60 years, or\r\n* Age < 60 with any one or more of the conditions below:\r\n** Amenorrheic for >= 1 year in the absence of chemotherapy and/or hormonal treatments,\r\n** Luteinizing hormone and/or follicle stimulating hormone and/or estradiol levels in the post-menopausal range,\r\n** Radiation-induced oophorectomy with last menses > 1 year ago,\r\n** Chemotherapy-induced menopause with > 1 year interval since last menses,\r\n** Surgical sterilization (bilateral oophorectomy or hysterectomy)
Women of child-bearing potential (WOCBP) must have a negative serum pregnancy test within 28 days of registration; the patient and her sexual partner(s) must agree to use adequate contraception when sexually active for the duration of the study and for 6 months after finishing study drug; a woman is considered of childbearing potential following menarche and until becoming post-menopausal unless permanently sterile; permanent sterilization methods include hysterectomy, bilateral salpingectomy and bilateral oophorectomy; a postmenopausal state is defined as no menses for 12 months without an alternative medical cause; a high follicle stimulating hormone (FSH) level in the postmenopausal range maybe used to confirm a post-menopausal state in women not using hormonal contraception or hormonal replacement therapy
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
Evidence of non-childbearing status for women of childbearing potential, or postmenopausal status: negative urine or serum pregnancy test within 28 days of study treatment, confirmed prior to treatment on day 1; postmenopausal is defined as:\r\n* Amenorrheic for 1 year or more following cessation of exogenous hormonal treatments\r\n* Luteinizing hormone (LH) and follicle-stimulating hormone (FSH) levels in the post-menopausal range for women under 50\r\n* Radiation-induced oophorectomy with last menses > 1 year ago\r\n* Chemotherapy-induced menopause with > 1 year interval since last menses\r\n* Or surgical sterilization (bilateral oophorectomy or hysterectomy)
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
Follicle stimulating hormone measurement elevated into the menopausal range
Negative pregnancy test (serum or urine) for women of childbearing potential (WOCBP) • Women considered not of childbearing potential include any of the following: no menses for at least 2 years or menses within 2 years but amenorrheic for at least 2 months and luteinizing hormone (LH) and follicular stimulating hormone (FSH) values within normal range (according to definition of postmenopausal for laboratory used) or bilateral oophorectomy or radiation castration and amenorrheic for at least 3 months or with bilateral tubal ligation
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
Women must be postmenopausal\r\n* Postmenopausal status is verified by:\r\n** Prior bilateral surgical oophorectomy, or\r\n** Age >= 60 years, or\r\n** Age < 60 with no menses for > 1 year with follicle-stimulating hormone (FSH) and estradiol levels within post menopausal range, according to institutional standard
Amenorrheic for > 2 years without a hysterectomy and oophorectomy and a Follicle Stimulating Hormone (FSH) value in the postmenopausal range upon pretrial (screening) evaluation
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
Female subject of childbearing potential who is unwilling to use acceptable method(s) of effective contraception during study treatment and through 3 months after the last dose of talimogene laherparepvec; (women of not childbearing potential: post-menopausal [age > 55 years with cessation of menses > 12 months or < 55 years but not spontaneous menses for at least 2 years or < 55 years and spontaneous menses within the past 1 year, but currently amenorrheic (eg, spontaneous or secondary to hysterectomy), and with postmenopausal gonadotropin levels (luteinizing hormone and follicle-stimulating hormone levels > 40 IU/L) or postmenopausal estradiol levels (< 5 ng/dL) or according to the definition of \postmenopausal range\ for the laboratory involved] or who have had a hysterectomy, bilateral salpingectomy, or bilateral oophorectomy)
Postmenopausal status, defined as any one of the following criteria:\r\n* Documented history of bilateral oophorectomy\r\n* Age 60 years or more\r\n* Age 45 to 59 and satisfying one or more of the following criteria:\r\n** Amenorrhea for at least 12 months and intact uterus\r\n** Amenorrhea for less than 12 months and a follicle stimulating hormone (FSH) and estradiol concentration within postmenopausal range including:\r\n*** Patients who have had a hysterectomy\r\n*** Patients who have received hormone replacement
Female patients must be willing to use 2 forms of highly effective contraception (per institution standards) from the time of screening until 4 weeks after discontinuing study, must not be breast feeding and must have a negative pregnancy test prior to start of dosing if of child bearing potential or must have evidence of non-childbearing potential by fulfilling one of the following criteria at screening: (1) post-menopausal women, defined as either women aged more than 50 years and amenorrheic for at least 12 months following cessation of all exogenous hormonal treatments, or, (2) women under 50 years old who have been amenorrheic for at least 12 months following the cessation of exogenous hormonal treatments, and have serum follicle-stimulating hormone (FSH) and luteinizing hormone (LH) levels in the postmenopausal range for the institution; alternatively, women must have documentation of irreversible surgical sterilization by hysterectomy, bilateral oophorectomy or bilateral salpingectomy but not tubal ligation; male patients should either be surgically sterile or willing to use an effective barrier method of contraception during the study and for 16 weeks following the last dose of study treatment if sexually active with a female of childbearing potential; if not done previously, storage of sperm prior to receiving AZD2014 will be advised to male patients with a desire to have children
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
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
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.
Postmenopausal or evidence of non-childbearing status for women of childbearing potential: negative serum pregnancy test within 28 days of study treatment and confirmed prior to treatment on day 1.\r\n* Postmenopausal is defined as any one or more of the following:\r\n** Age >= 60 years.\r\n** Age < 60 and amenorrheic for 1 year or more in the absence of chemotherapy and/or hormonal treatment.\r\n** Luteinizing hormone (LH) and Follicle stimulating hormone (FSH) levels in the post menopausal range for women under 60.\r\n** Radiation-induced oophorectomy with last menses > 1 year ago.\r\n** Chemotherapy-induced menopause with > 1 year interval since last menses.\r\n** Surgical sterilisation (bilateral oophorectomy or hysterectomy).
Women who are breast feeding or pregnant\r\n* Men or women of reproductive potential who are not willing to employ effective birth control from screening to 30 days after the last dose of study drugs; the definition of adequate contraception will be based on the judgment of the principal investigator or a designated associate\r\nFor a female patient to be considered as not of child bearing potential, she should fulfill one of the following:\r\n* Post-menopausal women, defined as either women aged more than 50 years and amenorrhoeic for at least 12 months following cessation of all exogenous hormonal treatments, or, women under 50 years old who have been amenorrhoeic for at least 12 months following the cessation of exogenous hormonal treatments, and have serum follicle-stimulating hormone (FSH) and luteinizing hormone (LH) levels in the postmenopausal range for the institution Or\r\n* Have documentation of irreversible surgical sterilization by hysterectomy, bilateral oophorectomy or bilateral salpingectomy (but not tubal ligation)
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 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
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
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
Postmenopausal women defined by one of the criteria:\r\n* No spontaneous menses for at least 12 months if the subject is >= 50 years old\r\n* Amenorrheic for at least 12 months if the subject is < 50 years old, with serum estradiol within the institutional postmenopausal range\r\n* Bilateral oophorectomy\r\n* If prior hysterectomy but intact ovaries, must be >= 55 years old, or have serum estradiol within the postmenopausal range\r\n* If premenopausal, must be on a gonadotropin-releasing hormone (GnRH) agonist (leuprolide or goserelin) with serum estradiol levels within the institutional postmenopausal range
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
Evidence of post-menopausal status or negative urinary or serum pregnancy test for female pre-menopausal patients; women will be considered post-menopausal if they have been amenorrheic for 12 months without an alternative medical cause; the following age-specific requirements apply:\r\n* Women < 50 years of age would be considered post-menopausal if they have been amenorrheic for 12 months or more following cessation of exogenous hormonal treatments and if they have luteinizing hormone and follicle-stimulating hormone levels in the post-menopausal range for the institution or underwent surgical sterilization (bilateral oophorectomy or hysterectomy)\r\n* Women >= 50 years of age would be considered post-menopausal if they have been amenorrheic for 12 months or more following cessation of all exogenous hormonal treatments, had radiation-induced menopause with last menses > 1 year ago, had chemotherapy-induced menopause with last menses > 1 year ago, or underwent surgical sterilization (bilateral oophorectomy, bilateral salpingectomy or hysterectomy)\r\n* A positive serum pregnancy test must be confirmed by a pelvic ultrasound (US) since some non-seminomatous germ cell tumors (NSGCT) may secrete beta-hCG and cause a false positive pregnancy; a pelvic US does not need to be repeated with each cycle unless the treating physician thinks it is necessary to do so
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
Reproductive status for cohort 2: HR+ stage IV post-menopausal breast cancer; post-menopausal is defined by at least one of the following criteria:\r\n* Prior bilateral oophorectomy OR amenorrheic for >= 12 months (if =< 55 years of age and prior chemotherapy or on medical ovarian ablative therapy or received ovarian radiation for ablation in the past 5 years and/or tamoxifen or an aromatase inhibitor [AI] within the past year, then follicle-stimulating hormone [FSH] and estradiol must be in the post-menopausal range and obtained within 28 days prior to registration) OR \r\n* Previous hysterectomy with one or both ovaries left in place (or previous hysterectomy in which documentation of bilateral oophorectomy is unavailable AND FSH values consistent with the institutional normal values for the post-menopausal state; FSH levels must be obtained within 28 days prior to registration
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 be postmenopausal women; for the purposes of this trial, postmenopausal will be defined as:\r\n* Age greater than or equal to 55 years and amenorrheic for 12 or more months; OR\r\n* Age less than 55 years and amenorrheic for 12 or more months in the ABSCENCE of treatment with an intervening agent expected to cause menstrual dysregulation (including but not limited to chemotherapy, tamoxifen, toremifene or ovarian suppression); a documented serum follicular stimulating hormone (FSH) level and serum estradiol level consistent with postmenopausal status as per the institutional normal limits is also required' OR\r\n* Documented bilateral salpingo-oophorectomy regardless of age
Baseline serum FSH, luteinizing hormone LH, and estradiol levels should be drawn
Patients must be post-menopausal; post-menopausal will be defined as women meeting any of the following criteria:\r\n* >= 60 years of age; or\r\n* < 60 years of age and amenorrheic for >= 12 months prior to day 1 if uterus/ovaries are intact; or\r\n* < 60 years of age, and the last menstrual period 6-12 months prior to day 1, if intact uterus/ovaries and meets biochemical criteria for menopause (follicle-stimulating hormone [FSH] and estradiol within institutional standard for postmenopausal status); or\r\n* < 60 years of age, without a uterus, and meets biochemical criteria for menopause (FSH and estradiol within institutional standards for postmenopausal status); or\r\n* < 60 years of age and history of bilateral oophorectomy; surgery must have been completed at least 4 weeks prior to day 1; or\r\n* Prior radiation castration with amenorrhea for at least 6 months
Post-menopausal as defined by at least ONE of the following:\r\n* 12 months (365 days) without a period;\r\n* Bilateral oophorectomy;\r\n* Chemically induced menopause as long as there are no plans to stop during the study;\r\n* For women 57 and under, if at least one ovary and woman has had hysterectomy, must have follicle stimulating hormone (FSH) (> 30 mIU/mL) and estradiol in menopausal range per institution’s laboratory (< 10 for ultra sensitive assay: < 25-30 otherwise); (Note: women 58 and older do not have to have hormonal tests)\r\n* At least one ovary intact, with a uterus, and 180 days without a period with FSH (> 30 mIU/mL) and estradiol in menopausal range per institution’s laboratory (generally that is < 10 for ultra sensitive assay: < 25-30 otherwise) (Note: women 58 and older do not have to have hormonal tests)
Please note, pre-menopausal will be defined as women meeting the following criteria:\r\n* Patients not currently on hormonal contraception with the presence of menses in the past 6 months\r\n* If no menstruation in the past 6 months, without hormonal manipulation, then confirmed follicle-stimulating hormone (FSH) < 23 mlU/mL\r\n* If age < 47 years and on hormonal contraception then patient will be eligible regardless of menstrual history\r\n* If age >= 47 years and on hormonal contraception then FSH confirmed < 23 mIU/mL
Post-menopausal (defined as [A] amenorrhea persisting for an entire year, [B] oophorectomy, or [C] hysterectomy and age greater than 51 years)
Be post-menopausal as defined by any of the following: age > 55 years, history of bilateral oophorectomy, amenorrhea for 1 year with intact uterus and ovaries, or serum estradiol and follicle-stimulating hormone (FSH) concentrations in the post-menopausal range along with either amenorrhea for 6 months or previous hysterectomy
Ovarian insufficiency defined as an elevated follicle-stimulating hormone (FSH) over 10
Women of non-child bearing potential must be:\r\n* Women more than 50 years must be post-menopausal for at least 12 months following the end of all exogenous hormonal treatments OR\r\n* Women under 50 years must be postmenopausal for at least 12 months following the end of exogenous hormonal treatments and with LH and FSH levels in the post-menopausal range for the institution OR\r\n* Documentation of irreversible surgical sterilization by hysterectomy, bilateral oophorectomy or bilateral salpingectomy but not tubal ligation
Postmenopausal (confirmed by self-report on the Health History Questionnaire; menopausal status could also be confirmed by a recent [< 6 months from enrollment] laboratory report documenting serum follicle-stimulating hormone [FSH] > 30 mIU/ml and/or serum estradiol < 30 pg/ml)
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)
Postmenopausal women (postmenopausal: age >= 60 years, or amenorrhea >= 12 months, or bilateral oophorectomy, or - in women with hysterectomy only - follicle stimulating hormone [FSH] in the menopausal levels as per local institutional guidelines if < 60 years old) with histologically-confirmed estrogen receptor (ER)-positive (>= 10%) primary breast cancer stage cT0-2, cN0-1, Mx; women with larger tumors who refuse chemotherapy (chemo) and/or endocrine neoadjuvant therapy can be eligible
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
Women with vasomotor symptoms with a uterus who are postmenopausal (no menstrual period for 12 months) or in late menopause transition (no period for 3 months and elevated follicle stimulating hormone [FSH])
Postmenopausal women defined as:\r\n* Prior bilateral oophorectomy \r\n* Age >= 60\r\n* Age < 60 and amenorrhea for 12 or more months (in the absence of chemotherapy, tamoxifen, toremifen, or ovarian suppression) and follicle-stimulating hormone (FSH) and estradiol in the postmenopausal range for the local laboratory
Postmenopausal, defined as meeting any of the following criteria: \r\n* Periods stopped more than 6 months ago \r\n* Bilateral oophorectomy \r\n* Not already classified as pre- or peri-menopausal \r\n* Started using hormone therapy for menopausal symptoms before periods stopped, and/or \r\n* Hysterectomy before age 56 years but aged 56 years or more at baseline
Subjects must fit into ONE of the following menopausal categories:\r\n* Premenopausal (n = 40) – defined as meeting all the following criteria:\r\n** Have had at least 8 menstrual cycles in the past 12 months\r\n** Have had no hormonal contraception in the past 3 months prior to registration\r\n** Have serum hormone parameters (estradiol [E2], progesterone, follicle stimulating hormone [FSH]) in premenopausal range on the day of random fine needle aspiration (rFNA); NOTE: subjects will self-report menopausal status at registration, and confirmation of hormonal parameters will occur after registration as part of pre-intervention procedures; if there is mis-assignment of status, the recruitment of future subjects will be adjusted accordingly\r\n* Postmenopausal (n = 40) – defined as meeting all of the following criteria:\r\n** Last menstrual period (LMP) > 1 year previously\r\n** Have had no hormone use in the past 3 months prior to registration\r\n** Serum E2, progesterone, FSH in postmenopausal range on the day of rFNA; NOTE: subjects will self-report menopausal status at registration, and confirmation of hormonal parameters will occur after registration as part of pre-intervention procedures; if there is mis-assignment of status, the recruitment of future subjects will be adjusted accordingly
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
Women of childbearing potential must have a negative urine or serum pregnancy test within 28 days of initial dose of olaparib and temozolomide, confirmed prior to treatment on day 1; postmenopausal is defined as:\r\n* Amenorrheic for 1 year or more following cessation of exogenous hormonal treatments\r\n* Luteinizing hormone (LH) and follicle-stimulating hormone (FSH) levels in the postmenopausal range for women under 50\r\n* Radiation-induced oophorectomy with last menses > 1 year ago\r\n* Chemotherapy-induced menopause with > 1 year interval since last menses, or surgical sterilization (bilateral oophorectomy or hysterectomy)
Evidence of post-menopausal status or negative urinary or serum pregnancy test for female pre-menopausal patients; women will be considered post-menopausal if they have been amenorrheic for 12 months without an alternative medical cause; the following age-specific requirements apply: \r\n* Women < 50 years of age would be considered post-menopausal if they have been amenorrheic for 12 months or more following cessation of exogenous hormonal treatments and if they have luteinizing hormone and follicle-stimulating hormone levels in the post-menopausal range for the institution or underwent surgical sterilization (bilateral oophorectomy or hysterectomy)\r\n* Women >= 50 years of age would be considered post-menopausal if they have been amenorrheic for 12 months or more following cessation of all exogenous hormonal treatments, had radiation-induced menopause with last menses > 1 year ago, had chemotherapy-induced menopause with last menses > 1 year ago, or underwent surgical sterilization (bilateral oophorectomy, bilateral salpingectomy or hysterectomy)
Pre- and postmenopausal women are eligible; premenopausal women must have a negative serum or urine pregnancy test; pregnancy testing does not need to be pursued in female patients who are: age >= 60 years; or age < 60 with intact uterus and amenorrhea for 12 consecutive months or more AND estrogen (estradiol) levels within postmenopausal range; or status-post bilateral oophorectomy, total hysterectomy, or bilateral tubal ligation
Patients must be post-menopausal women; post-menopausal women are defined as: (1) those >= 50 years of age who had not menstruated during the preceding 12 months or who had castrate follicle-stimulating hormone levels (> 40IU/L), (2) those who had undergone a bilateral oophorectomy
Patient must be postmenopausal defined as meeting one or more of the following:\r\n* Age >= 60 years\r\n* Amenorrheic for at least 12 months\r\n* Surgically sterile - having undergone bilateral oophorectomy\r\n* Follicle stimulating hormone (FSH) laboratory test level in postmenopausal range according to institutional standards (Note: FSH lab test must be ordered as standard of care to determine best treatment option and should not be ordered simply to confirm eligibility to this study)\r\n* OR pre-menopausal for whom standard ET is planned with ovarian suppression (imaging on study should be completed prior to start of ovarian suppression)
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
Female patients must be willing to use 2 forms of highly effective contraception (per institution standards) from the time of screening until four weeks after discontinuing study, must not be breast feeding, and must have a negative pregnancy test prior to start of dosing if of child bearing potential or must have evidence of non-childbearing potential by fulfilling one of the following criteria at screening: (1) post-menopausal women, defined as either women aged more than 50 years and amenorrheic for at least 12 months following cessation of all exogenous hormonal treatments, or (2) women under 50 years old who have been amenorrheic for at least 12 months following the cessation of exogenous hormonal treatments, and have serum follicle-stimulating hormone (FSH) and luteinizing hormone (LH) levels in the postmenopausal range for the institution; alternatively, women must have documentation of irreversible surgical sterilization by hysterectomy, bilateral oophorectomy or bilateral salpingectomy but not tubal ligation; male patients should either be surgically sterile or willing to use an effective barrier method of contraception during the study and for 16 weeks following the last dose of study treatment if sexually active with a female of childbearing potential; if not done previously, storage of sperm prior to receiving AZD2014 will be advised to male patients with a desire to have children
Have menopausal status determined prior to study enrollment; for study purposes, postmenopausal is defined as\r\n* A prior documented bilateral oophorectomy, or\r\n* A history of at least 12 months without spontaneous menstrual bleeding, or\r\n* Age 60 or older with a prior hysterectomy without oophorectomy, or \r\n* Age less than 60 with a prior hysterectomy without oophorectomy (or in whom the status of the ovaries is unknown) with a documented follicle-stimulating hormone (FSH) level demonstrating confirmatory elevation in the postmenopausal range for the lab
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.