Study to compare the effects of AZD9496 vs Fulvestrant in breast cancer. - D6090C00002

Exclusion Criteria

• 1. Pre-treatment biopsy sample not likely to provide adequate tissue sections for the biomarker assays
• 2. Previous systemic or local treatment for the new primary breast cancer currently under investigation (including surgery, radiotherapy, cytotoxic and endocrine treatments)
• 3. Inflammatory breast cancer
• 4. Evidence of metastases
• 5. Patients currently receiving medications or herbal supplements known to be strong inhibitors/inducers of CYP3A4/5 or strong inhibitors of CYP2C8 or that are sensitive substrates of CYP2C8 inhibition
• 6. Concurrent treatment with other experimental drugs within 4 weeks prior to receiving study treatment
• 7. Use of hormone-replacement therapy from <4 weeks of the diagnostic/baseline core biopsy to the start of trial treatment
• 8. Patients with second primary cancer. Any endocrine therapies or other anti-cancer therapies must have been ceased at least 12 months prior to enrollment.
• 9. Any of the following cardiac criteria:
• -Mean resting QT interval corrected for heart rate (QTc) > 470 msec obtained from 3 ECGs using Fridericia’s formula
• -Any clinically important abnormalities in rhythm, conduction or morphology of resting ECG
• -Any factors that increase the risk of QTc prolongation or risk of arrhythmic events
• 10. Experience of any of the following in the preceding 6 months: coronary artery bypass graft (CABG), angioplasty, vascular stent, myocardial infarction (MI), angina pectoris, congestive heart failure New York Heart Association (NYHA) Grade ≥2, cerebrovascular accident (CVA), transient ischaemic attack (TIA), deep venous or arterial thrombosis, pulmonary embolism, bleeding diathesis (i.e., disseminated intravascular coagulation, clotting factor deficiency) or requirement of anticoagulant therapy
• 11. As judged by the Investigator, any evidence of severe or uncontrolled systemic diseases,
• 12. Uncontrolled symptomatic thyroid dysfunction (hyperthyroidism or hypothyroidism).
• 13. Unexplained symptomatic endometrial disorders.
• 14. Refractory nausea and vomiting, uncontrolled chronic GI diseases, inability to swallow the formulated product or previous significant bowel resection that would preclude adequate absorption of AZD9496.
• 15. Inadequate bone marrow reserve or organ function as demonstrated by any of the following laboratory values: absolute neutrophil count < 1.5 x 109/L, Platelet count < 100 x 109/L, Haemoglobin < 90 g/L, alanine aminotransferase (ALT) > 2.5x upper limit of normal (ULN), aspartate aminotransferase (AST) > 2.5 x ULN, Total bilirubin > 1.5 x ULN or > 3 x in case of Gilbert’s Syndrome, glomerular filtration rate < 50 mL/min
• 16. Direct involvement in the planning and conduct of the study
• 17. History of hypersensitivity to AZD9496
• 18. History of hypersensitivity to fulvestrant and/or castor oil
• 19. Judgment by the investigator that the patient should not participate in the study if unlikely to comply with study procedures, restrictions and requirements
• In addition, the following is considered a criterion for exclusion from the exploratory genetic research: Previous allogeneic bone marrow transplant; Non-leukocyte depleted whole blood transfusion within 120 days of the date of the genetic sample collection