4EVERUK

• Research type

  Research Study

• Full title

  A Phase IV multicentre, open label study of postmenopausal women with oestrogen receptor positive locally advanced or metastatic breast cancer treated with everolimus (RAD001) in combination with exemestane, with exploratory epigenetic marker analysis

• IRAS ID

  111825

• Contact name

  Stephen Johnston

• Sponsor organisation

  Novartis Pharmaceuticals UK Ltd

• Eudract number

  2012-003689-41

• ISRCTN Number

  xx

• Research summary

  Recent scientific discoveries indicate that whilst the genetic sequence of cancer cells and non-cancer cells may be the same, there are non-structural modifications to the genetic material of cancer cells that may be important in how the disease develops and to its responsiveness to treatment. These non-structural modifications are referred to as epigenetic changes. In this exploratory study, we will explore the response of patients with locally advanced or metastatic breast cancer to treatment with everolimus (RAD001) and exemestane and the association of their response to various epigenetic markers in archival tissue and blood samples. Following informed consent, fifty women with post-menopausal oestrogen-receptor positive locally advanced or metastatic breast cancer, who have experienced progression or recurrence on prior non-steroidal aromatase inhibitor therapy, will undergo screening & baseline evaluations; medical history, physical examination, vital signs, performance assessment, blood tests, urinalysis, electrocardiogram and tumour assessment and complete two quality of life questionnaires. They will then commence oral treatment with 10 mg everolimus (RAD001) once-day in combination with 25 mg exemestane once-a-day. Dose modifications will be permitted to manage side-effects as detailed in the protocol. During the treatment phase, patients will return to the clinic at 4, 12, 24, 36 and 48 weeks for tumour evaluations and safety assessments. Patients whose disease progresses, who develop unacceptable toxicity or withdraw or are withdrawn for any other reason will discontinue study medication. Patients who are still responding to treatment at Week 48 will be able to continue to receive everolimus and exemestane treatment after the study. Blood samples for epigenetic analyses will be collected at baseline, week 12 and at week 48/End of Trial. Archival tissue will also be analysed for epigenetic markers.

• REC name

  London - Chelsea Research Ethics Committee

• REC reference

  12/LO/1538

• Date of REC Opinion

  19 Nov 2012

• REC opinion

  Further Information Favourable Opinion