Everolimus or Placebo + Trastuzumab and Vinorelbine in Breast Cancer

• Research type

  Research Study

• Full title

  A Randomized Placebo-controlled Double-Blind Study of Everolimus in Combination with Trastuzumab and Vinorelbine in Pre-treated Women with HER2/neu Over-expressing Locally Advanced or Metastatic Breast Cancer

• IRAS ID

  33595

• Contact name

  Timothy Perren

• Sponsor organisation

  Novartis Pharma Services AG

• Eudract number

  2008-008697-31

• 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. This study is being conducted in advanced breast cancer patients that over-express the HER2 receptor. Such patients account for approximately 20-25% of all cases of breast cancer and HER2 over-expression is associated with a short disease-free survival and an aggressive course. Patients with HER2 over-expressing tumours are treated with trastuzumab, alone initially and later on in combination with other chemotherapy agents, such as vinorelbine. Some patients appear to acquire resistance to trastuzumab within a year. mTOR inhibition with everolimus may counter the mechanisms associated with trastuzumab resistance, thereby restoring or enhancing trastuzumab activity. The purpose of this study is to compare the effect of treatment with everolimus plus trastuzumab plus vinorelbine with that of placebo plus trastuzumab plus vinorelbine in patients with HER2/neu over-expressing advanced breast cancer who have previously been treated with taxanes and are resistant to trastuzumab alone.

• REC name

  South Central - Hampshire A Research Ethics Committee

• REC reference

  09/H0502/115

• Date of REC Opinion

  13 Nov 2009

• REC opinion

  Further Information Favourable Opinion