Everolimus or Placebo plus Exemestane in Advanced Breast Cancer

• Research type

  Research Study

• Full title

  A Randomized Placebo-controlled Double-Blind Study of Everolimus in Combination with Exemestane in the Treatment of Post-menopausal Women with Estrogen Receptor Positive Locally Advanced or Metastatic Breast Cancer

• IRAS ID

  22223

• Contact name

  Robert Coleman

• Sponsor organisation

  GSK

• Eudract number

  2008-008698-69

• ISRCTN Number

  n/a

• Clinicaltrials.gov Identifier

  n/a

• Research summary

  Everolimus (RAD001) inhibits the activity of a multi-functional signal transduction protein (mTOR) which regulates messenger RNA translation and, through this, cell proliferation. This pathway has been shown to be highly activated in several different types of cancer and is associated with a poor prognosis and resistance to therapy. As well as a direct anti-tumour effect, everolimus also acts indirectly by inhibiting the development of blood vessels that supply blood to the developing tumour. In-vitro studies also indicate that everolimus suppresses osteoclast activity. This is elevated in patients with bone metastases and so everolimus could potentially provide some protection against bone resorption in these patients. Post-menopausal women with oestrogen receptor (ER) positive breast cancer are treated with non-steroidal aromatase inhibitors (letrozole, anastrozole). There is however, no specifically approved treatment when these patients who go on to develop a local recurrence or progression. In current clinical practice, they are treated with steroidal aromatase inhbitors (exemestane or fulvestrant). Everolimus has demonstrated efficacy in the Phase II trials in post-menopausal women with early breast cancer, when given in combination with letozole. In this study, the trial patients (post-menopausal, ER-positive and refractory to letrozole or anastrozole) will all receive exemestane and will be randomised to receive additional treatment with everolimus (10 mg/day) or placebo once-a-day orally. The primary objective of the study is to compare progression free survival in the two groups: exemestane plus everolimus and exemestane plus placebo.

• REC name

  South Central - Hampshire A Research Ethics Committee

• REC reference

  09/H0502/84

• Date of REC Opinion

  6 Aug 2009

• REC opinion

  Further Information Favourable Opinion