A randomised double blind placebo controlled Phase II study of fulvestrant with or without the addition of vandetanib as treatment for patients with metastatic breast cancer resistant to aromatase inhibitor therapy.
For patients with advanced breast cancer that has spread around the body, hormone therapy is often the best treatment. As well as being very effective, this means that patients do not experience the toxicity and inconvenience of chemotherapy. However, eventually the cancer is likely to become resistant to hormone therapy and, although other hormone drugs can be used, they sometimes do not work very well in this situation. So it is important to find ways of getting the cancer to respond to hormone treatment again.
There are many ways in which breast cancer cells become resistant to hormone treatments, including a ‘signalling’ pathway in the cells called RET. Research has shown increased activity of RET in hormone resistant cancer cells. Vandetanib is an oral drug that inhibits RET and has been shown in laboratory studies to prevent the growth of breast cancer cells which have become resistant to hormone therapy. Hormone therapy drugs include tamoxifen, and the aromatase inhibitors (anastrozole, letrozole and exemestane). We therefore believe that giving vandetanib together with hormone therapy may help prevent resistance to treatment in patients with breast cancer.
This Phase 2 trial is looking at using vandetanib alongside a hormone therapy drug called fulvestrant that is known to work and is sometimes used alone in patients who have developed resistance to aromatase inhibitors, or tamoxifen. We will recruit a total of 160 post-menopausal women with breast cancer that has spread into tissue surrounding the breast (is locally advanced) or to another part of the body and has receptors for the hormone oestrogen (is ER positive). Half of the them will be given fulvestrant and vandetanib (experimental drug), and half will be given fulvestrant and inactive placebo, and the treatment a particular patient will get will be chosen at random. The study is ‘double blinded’ so neither the patient nor her doctor will know whether she is getting vandetanib or placebo.
Patients will receive 16 x 4 week cycles of study treatment (64 weeks) and will see their doctor for tests every month to begin with, then every 3 months after the first 7 cycles of treatment. When patients finish the study treatment they will continue to see their doctor for tests every 3 months for up to 12 months.
The most important measure of effect will be the time until the cancer grows again (disease progression), but the study will also look closely at the side effects of the drugs. We will also conduct laboratory studies on the RET pathways using previously stored tumour samples to look whether the way in which an individual responds relates to the results. This will mean that patients will not need to have additional biopsy samples taken.
|End date||30 Sep 2017|