A study to assess the effects of enobosarm on early breast cancer

INTERVENTION: Current interventions as of 24/09/2018: Patients are screened, consented and then randomised onto the trial using the LCTUs TARDIS (Treatment Allocation RanDomIsation System) which for EMERALD uses randomly permuted blocks based on stratified lists to a ratio of 3:1 (treatment : standard of care). Treatment arm: Patients will take 9 mg of enobosarm capsules orally every day for 14 (+4) days, before pre‐scheduled surgery/research core biopsy (within 24 hours of last dose). Patients will be followed up for 14 days after surgery/research core biopsy for adverse events. Blood (20 ml or about 4 teaspoons) will be taken at the Baseline Visit (Day 1) and the Tissue Collection Visit (Day 14). The sample from the core biopsy (FFPE block) will be requested to measure Ki67 at baseline and a sample (FFPE block) will be taken from the surgical specimen/research core biopsy specimen. Standard care arm: Patients will have their pre‐scheduled surgery/research core biopsy as planned after 14 (+4) days. Blood (20 ml or about 4 teaspoons) will be taken at the Baseline Visit (Day 1) and the Tissue Collection Visit (Day 14). The sample from the core biopsy (FFPE block) will be requested to measure Ki67 at baseline and a sample (FFPE block) will be taken from the surgical specimen/research core biopsy specimen. Previous interventions: Patients are screened, consented and then randomised onto the trial using the LCTUs TARDIS (Treatment Allocation RanDomIsation System) which for EMERALD uses randomly permuted blocks based on stratified lists to a ratio of 3:1 (treatment : standard of care). Treatment arm: Patients will take 9mg of enobosarm capsules orally every day for 14(+4) days, before pre‐scheduled surgery (within 24 hours of last dose). Patients will be followed up for 14 days after surgery for adverse events. Blood (20ml or about 4 teaspoons) will be taken at the baseline visit (Day 1), the mid‐treatment visit (Day 7) and the surgery visit (Day 14). The sample from the core biop CONDITION: Specialty: Cancer, Primary sub‐specialty: Breast Cancer; UKCRC code/ Disease: Cancer/ Malignant neoplasm of breast ; Cancer ; Breast Cancer PRIMARY OUTCOME: Current primary outcome measure as of 24/09/2018:; Change in the proliferation marker Ki67 (% positive tumour cells) determined by tissue immunohistochemistry at baseline and 2 weeks.; ; Previous primary outcome measure:; Reduction in the proliferation marker Ki67 (% positive tumour cells) determined by tissue immunohistochemistry at baseline and 2 weeks. SECONDARY OUTCOME: Current secondary outcome measures as of 24/09/2018:; 1. Amount of cleaved caspase 3 determined by tissue immunohistochemistry at baseline and two weeks; 2. Expression of PSA, Gross Cystic Disease Fluid Proteins (GCDFP)‐24 &‐15; PgR, GREB1 by tissue immunohistochemistry at baseline and two weeks; 3. Amount in serum levels of circulating steroidogenic hormones oestradiol, oestrone, oestrone sulfate, androstenedione, follicle stimulating hormone, luteinizing hormone, DHT, progesterone, sex hormone binding globulin (SHBG) and total testosterone in blood determined by blood assay at baseline and two weeks; free testosterone to be derived from SHBG and total testosterone; 4. Amount in serum levels of PSA and steroidogenic hormones determined by blood assay at baseline and two weeks; ; Previous secondary outcome measures:; 1. Amount of cleaved caspase 3 determined by tissue immunohistochemistry at baseline and two weeks; 2. Expression of PSA, Gross Cystic Disease Fluid Proteins (GCDFP)‐24 &‐15; PgR, GREB1 by tissue immunohistochemistry at baseline and two weeks ; 3. Amount in plasma levels of circulating steroidogenic hormones oestradiol, oestrone, oestrone sulfate, androstenedione, follicle stimulating hormone, luteinizing hormone, DHT, progesterone, sex hormone binding globulin (SHBG) and total testosterone in blood determined by blood assay at baseline and two weeks; free testosterone to be derived from SHBG and total testosterone; 4. Amount in plasma levels of PSA and steroidogenic hormones determined by blood assay at baseline and two weeks INCLUSION CRITERIA: Current inclusion criteria as of 24/09/2018: 1. Females 16 years of age or older 2. Histologically confirmed ER positive breast cancer (Allred =3) 3. AnR positive breast cancer (defined as =10% nuclear AnR staining by immunohistochemistry) 4. Any HER2 status 5. Tumour measuring =14 mm in longest diameter by ultrasound (US) examination, MRI or mammogram 6. Postmenopausal as defined by one of the following criteria: 6.1. Women =55 years of age with an intact uterus and amenorrhoea =12 months at the time of diagnosis (or documented or current FSH and oestradiol levels within the postmenopausal range (as per local institutional/laboratory standard)) 6.2. Prior bilateral oophorectomy 6.3. Documented or current FSH and oestradiol levels within the postmenopausal range (as per local institutional/laboratory standard) in women aged <55 years or in women who have had a hysterectomy with intact ovaries 7. Eastern Cooperative Oncology Group (ECOG)