A Phase III Double-blind Randomised Study Assessing the Efficacy and Safety of Capivasertib + Fulvestrant Versus Placebo + Fulvestrant as Treatment for Locally Advanced (Inoperable) or Metastatic Hormone Receptor Positive, Human Epidermal Growth Factor Receptor 2 Negative (HR+/HER2−) Breast Cancer Following Recurrence or Progression On or After Treatment With an Aromatase Inhibitor
To assess the efficacy of capivasertib + fulvestrant vs placebo + fulvestrant for the treatment of patients with locally advanced (inoperable) or metastatic Hormone Receptor Positive, Human Epidermal Growth Factor Receptor 2 Negative (HR+/HER2−) breast cancer following recurrence or progression on or after aromatase inhibitor (AI) therapy.
- Experimental: Capivasertib + fulvestrantPlacebo Comparator: Pertuzumab, Trastuzumab, Paclitaxel, Placebo
- Placebo Comparator: Placebo + fulvestrant
- Adult females, pre- and/or post-menopausal, and adult males. Pre-menopausal (and peri-menopausal) women can be enrolled if amenable to treatment with an LHRH agonist. Patients are to have commenced concomitant treatment with LHRH agonist at least 4 weeks prior to Cycle 1, Day 1 and must be willing to continue on it for the duration of the study
- Histologically confirmed HR+/HER2− breast cancer determined from the most recent tumour sample (primary or metastatic), as per the American Society of Clinical Oncology and College of American Pathologists guideline recommendations. To fulfil the requirement of HR+ disease, a breast cancer must express ER with or without co-expression of progesterone receptor.
- Metastatic or locally advanced disease with radiological or objective evidence of recurrence or progression; locally advanced disease must not be amenable to resection with curative intent (patients who are considered suitable for surgical or ablative techniques following potential down-staging with study treatment are not eligible)
- ECOG/WHO PS: 0-1
- Patients are to have received treatment with an AI containing regimen (single agent or in combination) and have:
- Radiological evidence of breast cancer recurrence or progression while on, or within 12 months of the end of (neo)adjuvant treatment with an AI, OR
- Radiological evidence of progression while on prior AI administered as a treatment line for locally advanced or metastatic breast cancer (this does not need to be the most recent therapy)
- Patients must have measurable disease according to RECIST 1.1 and/or at least 1 lytic or mixed (lytic + sclerotic) bone lesion that can be assessed by CT or MRI; patients with sclerotic/osteoblastic bone lesions only in the absence of measurable disease are not eligible
- FFPE tumour sample from primary/recurrent cancer for central testing