A Study to Investigate Efficacy and Safety With Oral AZD9833 Compared With Intramuscular Fulvestrant in Post-menopausal Women at Least 18 Years of Age With Advanced ER-positive HER2 Negative Breast Cancer

Inclusion Criteria:

* Post-menopausal female patients aged at least 18 years.
* Metastatic or loco-regionally recurrent ER-positive HER2-negative adenocarcinoma of the breast.
* Radiological or other objective evidence of progression on or after the last systemic therapy prior to starting study treatment.
* Patients must have at least 1 lesion, not previously irradiated, that can be measured accurately at baseline as ≥10 mm in the longest diameter or in absence of measurable disease as defined above, at least 1 lytic or mixed (lytic+sclerotic) bone lesion.
* Eastern Cooperative Oncology Group (ECOG)/World Health Organisation (WHO) performance status 0 to 1.
* Prior endocrine therapy as follows:

  1. Recurrence or progression on at least one line of endocrine therapy
  2. No more than 1 line of endocrine therapy for advanced disease
  3. No more than 1 line of chemotherapy for advanced disease
  4. Prior treatment with CDK4/6 inhibitors is permitted
  5. No prior treatment with fulvestrant, oral selective oestrogen receptor degrader (SERD), or related therapies
* Inclusion criterion for the paired tumour biopsy research subgroup:

Washout from prior tamoxifen: 4 months to elapse from last tamoxifen dose to pre-dose on-study biopsy.

Exclusion Criteria:

Intervention with any of the following:

* Any cytotoxic chemotherapy, investigational agents or other anti-cancer drugs for the treatment of breast cancer from a previous treatment regimen or clinical study within 14 days of the first dose of study treatment.
* Use of systemic oestrogen-containing hormone replacement therapy within 6 months prior to the first dose of study treatment.
* Medications or herbal supplements known to be strong inhibitors/inducers of cytochrome P450 3A4/5 and sensitive CYP2B6 substrates, and drugs which are substrates of CYP2C9 and/or CYP2C19 which have a narrow therapeutic index or inability to stop use within the washout period prior to receiving the first dose of study treatment.
* Drugs that are known to prolong QT and have a known risk of torsades de pointes.
* The following cardiovascular criteria: QTcF \>470 ms, resting heart rate \<45 bpm, clinically significant abnormalities of resting electrocardiogram, uncontrolled hypertension, symptomatic hypotension, factors that increase the risk for QTc prolongation, left ventricular ejection fraction \<50%.
* Radiotherapy with a limited field of radiation for palliation within 1 week of dosing, or to \> 30% of bone marrow or a wide field within 4 weeks of dosing.
* Major surgical procedure or significant traumatic injury.
* Presence of life-threatening metastatic visceral disease or uncontrolled central nervous system metastatic disease.
* Inadequate bone marrow reserve or organ function.
* Refractory nausea and vomiting, uncontrolled chronic gastrointestinal diseases, inability to swallow the formulated product, or previous significant bowel resection that would preclude adequate absorption of AZD9833.
* History of hypersensitivity to active or inactive excipients of AZD9833 or fulvestrant.
* Previous randomisation in the present study.
* Women of childbearing potential.