FAKTION
Research type
Research Study
Full title
A phase 1b/2 randomised placebo controlled trial of fulvestrant +/- AZD5363 in postmenopausal women with advanced breast cancer previously treated with a third generation aromatase inhibitor.
IRAS ID
137245
Contact name
Sacha Howell
Contact email
Sponsor organisation
Velindre NHS Trust
Eudract number
2013-000898-68
Research summary
Breast cancer cells which have the estrogen receptor (ER positive or ER+) are stimulated to grow by estrogen. Anti-estrogens such as tamoxifen,fulvestrant and the aromatase inhibitors (anastrozole, letrozole and exemestane) work in such cancers by blocking the action of estrogen or reducing the amount of estrogen in the body. Although these drugs are often effective in controlling advanced breast cancer for a period of time, cancers always become resistant to the drugs which stop working. Patients then require treatment with chemotherapy.
We are looking to conduct a trial of a new drug from AstraZeneca called AZD5363. This drug blocks the activity of a cell protein called Akt which, when active, has been shown to lead to resistance to anti-estrogen treatments such as fulvestrant.
The study is divided into two phases. In phase I all patients will receive fulvestrant and AZD5363. We will test whether there are any unexpected interactions between fulvestrant and AZD5363 and work out the best dose for phase 2. In phase 2 patients will be randomised such that half will receive fulvestrant alone (plus a dummy drug - placebo) and half will receive a combination of the fulvestrant and AZD5363. This will involve a larger number of patients and will allow us to compare the anticancer activity and safety of fulvestrant combined with AZD5363 versus fulvestrant alone.
We will also investigate whether DNA mutations in the AKT gene and the genes of other proteins that Akt interacts with influence the response to AZD5363. This may enable us to identify patients who would benefit from AZD5363 treatment in the future. This will be done by examining the original cancer specimen from a previous biopsy or operation, and a blood test when patients enter the trial.REC name
North West - Haydock Research Ethics Committee
REC reference
13/NW/0842
Date of REC Opinion
24 Jan 2014
REC opinion
Further Information Favourable Opinion