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
Condition: Advanced ER-Positive HER2-Negative Breast Cancer
MeSH terms: Breast Neoplasms
Intervention: AZD9833; Fulvestrant
Intervention description: Dosage formulation: AZD9833 tablets will be administered orally.; Dosage formulation: Fulvestrant will be administered via intramuscular (IM) injection.
Intervention MeSH terms: Fulvestrant
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 240.0
Sex: Female
Minimum age: 18 Years
Maximum age: 130 Years
Healthy volunteers: No
Keywords: Open-Label; Parallel-Group; Fulvestrant; ER-Positive HER2-Negative Breast Cancer; Metastatic; AZD9833; Oral SERD; Camizestrant

Summary:

      This study is randomized, open-label, parallel-group, multicentre Phase 2 study aimed to
      compare the efficacy and safety of oral AZD9833 versus intramuscular (IM) fulvestrant in
      women with advanced breast cancer.
    

Eligibility criteria:

        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.