The Phase IIa clinical trial will be run through the Cancer Research UK and NIHR Experimental Cancer Medicine Centre (ECMC) in conjunction with the Imperial Clinical Trials Unit Section on cancer (ICTU-Ca), Imperial College London. It will recruit post-menopausal women with oestrogen positive breast cancer* who are no longer responding to either anastrozole or letrozole – standard treatments for this patient group.
The trial will be divided into two groups. In one group, patients will receive AstraZeneca’s experimental treatment AZD4547 alongside either anastrozole or letrozole. In the second group, patients will be treated with exemestane alone. The trial will evaluate whether the combination of this experimental drug with an existing therapy that has begun to fail may halt the progression of the disease, and make the tumour respond again to the original therapy.
AstraZeneca is the first pharmaceutical industry partner to join the ECMC Combinations Alliance, which launched in 2011. The alliance aims to increase patient access to trials of potential new cancer treatments by combining molecularly-targeted experimental drugs developed and owned by the company – with standard chemotherapy, radiotherapy and other new drugs.
This study is the third launched by the Alliance, and AstraZeneca is providing both supply of AZD4547 and additional funding, with Cancer Research UK’s DDO also providing support. Imperial College London is sponsoring the trial.
Chief investigator, Professor Michael Seckl, at Imperial College London, said: “The opening of this trial is great news. It’s an incredibly tough part of my job telling breast cancer patients that they are no longer responding to the drugs they are taking. We hope that this trial will be a step forward in finding new and better ways to treat advanced breast cancer, to increase survival from this disease.
“More women are surviving breast cancer than ever before. But while we’re making great progress in developing new targeted treatments there’s still an urgent need for medicine that will treat the disease once it has spread.”
Andrew Foxley, clinical programme director for AZD4547 at AstraZeneca, said: “AstraZeneca has a long-standing commitment to cancer research and has developed medicines that are making a meaningful difference for people with breast cancer. We believe that collaboration is crucial to finding solutions in the fight against cancer and are pleased to partner with others in the UK who share our dedication to bringing new medicines to patients.”
Dr Ian Walker, head of alliance management at Cancer Research UK’s DDO, said: “This is the third trial we’ve launched through collaboration with AstraZeneca – with others in the pipeline. This unique alliance is powering UK research to bring together combinations of new and existing drugs in early clinical trials to find better ways to treat patients and increase survival from a range of cancers.
“Without this important alliance these trials might not be possible. We want to build on the foundations established with AstraZeneca to add additional partners to collaborate with us in the future. Our aim is to set up cross-company agreements to provide access to a larger number of potential treatment combinations.”
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Notes to editors
Patient selection will be focused on patients whose cancer shows signs of being dependent on a particular growth factor receptor protein that is involved in tumour cell growth.
Breast cancer is now the most common cancer in the UK with almost 47,700 women diagnosed with the disease each year – around 130 women a day. Eight in 10 breast cancer cases are diagnosed in women aged 50 and over.
Many breast cancers are stimulated to grow by the female sex hormones oestrogen and progesterone – called hormone sensitive or hormone receptor positive – and can be treated with drugs that block the effects of these hormones. Women who have had their menopause do not produce oestrogen from their ovaries. But they still produce a small amount by turning other sex hormones called androgens into oestrogen. Androgens need an enzyme called aromatase to turn them into oestrogen. Aromatase inhibitors stop aromatase, so it cannot change the androgen into oestrogen.
Anastrozole, letrozole and exemestane are types of aromatase inhibitors and are currently used to treat post menopausal women with hormone receptor positive breast cancer.
Some patients with breast cancer have higher than usual amounts of a gene called fibroblast growth factor receptor-1 (FGFR1). Faulty FGFR1 signalling found in cancer cells causes them to grow and spread uncontrollably. AZD4547 blocks these faulty cell signals. Pre-clinical studies also indicate that FGFR1 signalling in breast cancer cells interferes with the cancer cells’ ability to respond to drugs that block the effects of female sex hormones, and that by blocking the signals from the FGFR1, the cancer cells may then become more responsive to drugs that block the production or the effects of female sex hormones.