MANTA

• Research type

  Research Study

• Full title

  A Randomized Phase II Study of Fulvestrant in Combination with the dual mTOR Inhibitor AZD2014 or Everolimus or Fulvestrant alone in Estrogen Receptor-Positive Advanced or Metastatic Breast Cancer.

• IRAS ID

  133741

• Contact name

  Peter Schmid

• Contact email

  p.schmid@qmul.ac.uk

• Sponsor organisation

  Queen Mary, University of London

• Eudract number

  2013-002403-34

• ISRCTN Number

  n/a

• Clinicaltrials.gov Identifier

  n/a

• Research summary

  Approximately 70-80% of breast cancer diagnosed in postmenopausal women are hormone receptor (HR)-positive and advances in endocrine therapy are therefore of enormous clinical relevance. Resistance to endocrine therapy remains a major therapeutic challenge in HR-positive advanced or metastatic breast cancer. There is increasing evidence that increased signaling through a protein called mTOR plays a critical role in endocrine resistance.
  mTOR that is involved in the growth and spread of some cancers and has been implicated in resistance to endocrine treatment of breast cancer. AZD2014 is an experimental drug that inhibits mTOR. In animal studies and laboratory experiments, AZD2014 has been shown to prevent or slow the growth of HR-positive breast cancer cells, showing superior activity to everolimus both in hormone-sensitive and resistant models.
  The purpose of the study is to find out whether taking AZD2014 benefits participants when given together with the standard endocrine treatment fulvestrant, and how this compares to another mTOR inhibitor, everolimus, that has already shown a benefit when added to different types of endocrine therapy. The study will also examine biomarkers to find out if patients whose tumours have a certain mutation may derive more benefit from this treatment.
  This study will recruit 240 patients, aged 18 and over, with HR-positive breast cancer that has returned after previous treatment or that has already spread to other parts of the body at diagnosis. Consenting patients will be randomised into one of three treatment groups. One group will receive fulvestrant in combination with AZD2014, the second group will receive fulvestrant in combination with everolimus and the third group will receive fulvestrant alone. Patients will be treated until their disease worsens, treatment-limiting toxicity, or death due to any cause.

• REC name

  East Midlands - Leicester South Research Ethics Committee

• REC reference

  13/EM/0349

• Date of REC Opinion

  5 Nov 2013

• REC opinion

  Further Information Favourable Opinion