Fulvestrant +/- Akt Inhibition in Advanced Aromatase Inhibitor Resistant Breast Cancer

This study is looking for women who have gone through menopause and have breast cancer that has spread in the body (advanced or metastatic). Your cancer must be Estrogen Receptor Positive, meaning it often responds to hormone treatments, but it should also have continued to grow even after you've been on a hormone treatment called an aromatase inhibitor.

You should generally be well enough to receive further hormone treatment and have decent organ function (like your kidneys, liver, and blood). You might have had some previous hormone treatments (up to three lines) and, for advanced cancer, up to one course of chemotherapy. Importantly, you shouldn't have been treated with Fulvestrant or similar new drugs in the past.

However, you wouldn't be able to join if you have very rapidly progressing cancer, known brain or spine metastases, or other serious health problems, especially heart conditions, that would make taking part unsafe. You also shouldn't be on other medications that could negatively interact with the study drugs.

If you decide to take part, the study starts with a small group of patients to find the safest dose of the new drug, AZD5363, when used with Fulvestrant. This involves taking Fulvestrant injections and AZD5363 (or a dummy pill) as capsules or tablets daily for four days, then having three days off, in a repeating 28-day cycle. You'll have regular checks, including blood tests and scans, especially in the first month, to monitor how you're doing and if there are any side effects.

Once a safe dose is found, more people will join the main part of the study. You'll be randomly assigned to one of two groups: either Fulvestrant plus AZD5363, or Fulvestrant plus a dummy pill. You won't know which group you're in, and neither will your doctors. You’ll receive continuous 28-day treatment cycles, taking Fulvestrant on day 1 of each cycle and the capsules/tablets daily (4 days on, 3 days off) throughout. You'll continue treatment for as long as it's helping and you're not experiencing severe side effects. Even after your regular study visits end, you might be able to continue taking the treatment if it's still beneficial. You will also be asked to provide some stored tissue from previous biopsies and a blood sample at the start.