A Phase 1 Study of AZD9833 in Japanese Women With ER Positive, HER2 Negative Advanced Breast Cancer

Criteria the registry did not label

• Major Inclusion Criteria:
• Signed written informed consent.
• \>= 20 years.
• Any menopausal status:
  • Pre and Post menopausal defined according to standard criteria in the protocol.
• Histological or cytological confirmation of adenocarcinoma of the breast.
• Documented positive estrogen receptor status of primary or metastatic tumor tissue, according to the local laboratory parameters. HER-2 negative.
• Metastatic or locoregionally recurrent disease and radiological or objective evidence of progression on or after the last systemic therapy prior to starting IMP.
• Prior chemotherapy, endocrine therapy and other therapy in the advanced setting is restricted as follows:
  • No more than 2 lines of chemotherapy for advanced disease.
  • Recurrence or progression on at least one line of endocrine therapy in the advanced/metastatic disease setting.
  • There is no limit on the number of lines of prior endocrine therapies.
  • Prior treatment with CDK4/6 inhibitors is permitted.
• At least one lesion (measurable and/or non-measurable, as per RECIST 1.1) that can be accurately assessed at baseline and is suitable for repeated assessment by computed tomography (CT), magnetic resonance imaging (MRI), or plain X-ray; or clinical examination.
• Eastern Cooperative Oncology Group (ECOG)/World Health Organisation (WHO) performance status 0 to 1
  • Major Exclusion Criteria:
• Intervention with any of the following:
  • Any cytotoxic chemotherapy, investigational agents, or other anti-cancer drugs for the treatment of advanced breast cancer from a previous treatment regimen or clinical study within 14 days of the first dose of study treatment.
  • Medications or herbal supplements known to be strong inhibitors/inducers of cytochrome P450 (CYP) 3A4/5 sensitive CYP2B6 substrates and drugs which are substrates of CYP2C9 and/or CYP2C19.
  • Drugs that are known to prolong QT and have a known risk of Torsades de Pointes.
  • Radiotherapy with a limited field of radiation for palliation within one week of the first dose of IMP, radiotherapy to more than 30% of the bone marrow or a wide field of radiation within 4 weeks of the first dose of IMP.
  • Major surgical procedure or significant traumatic injury.
• Any unresolved toxicities from prior therapy greater than CTCAE Grade 1 at the time of starting IMP.
• Presence of life-threatening metastatic visceral disease.
• Evidence of severe or uncontrolled systemic diseases, including uncontrolled hypertension and active bleeding diatheses.
• 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 another primary malignancy.
• Male subjects are excluded from this study.
• History of hypersensitivity to active or inactive excipients of AZD9833.
• 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%.
• Inadequate bone marrow reserve or organ function
• Involvement in the planning and conduct of the study.
• Judgment by the investigator that the patient should not participate in the study.