SPIKE v4

• Research type

  Research Study

• Full title

  Randomised phase II window study of short-term preoperative treatment with the PI3K inhibitor GDC-0941 plus Anastrozole versus Anastrozole alone in patients with ER-positive primary breast cancer

• IRAS ID

  86689

• Contact name

  Peter Schmid

• Sponsor organisation

  Brighton & Sussex University Hospitals NHS Trust

• Eudract number

  2011-003530-13

• ISRCTN Number

  n/a

• Clinicaltrials.gov Identifier

  n/a

• Research summary

  Estrogen-blocking drugs such as anastrozole (Arimidex) are often prescribed after breast surgery to prevent disease recurrence. Anastrozole is not effective in all women. GDC-0941 is an experimental drug that may help overcome this resistance to anastrozole by inhibiting an enzyme (phosphoinositide-3 kinase) involved in the mechanisms by which cells ??talk?? to each other. Before starting large clinical trials we want to confirm the expected short-term effects on breast tumour cells and signaling pathways using a modified ??window of opportunity?? study. This study will guide the development of GDC-0941, as it helps understand which breast cancers are likely to benefit.Window studies are used at early stages of drug development. A sample of a suspected tumour is stored after the diagnostic biopsy. If surgery is required then an experimental drug can be given in the interval between diagnosis and surgery (typically 2-4 weeks in the NHS). Another sample of the tumour is taken at surgery and compared to the original baseline sample. Window studies allow the initial assessment of a drug with relatively little intrusion into a woman??s progress through the care pathway.We will randomise 141 patients newly-diagnosed with estrogen-responsive tumours to a 2-week course of either 1) GDC-0941 in combination with anastrozole or 2) anastrozole alone. Women receiving anastrozole alone will be operated after 2 weeks. Women on combination therapy have their surgery one week later, during which they stop taking GDC-0941. These women will have an additional breast biopsy at the end of two weeks for comparison to the sample taken at surgery in the anastrozole-alone group. Study outcomes include the impact on breast cancer tumour cells and biomarkers as well as side-effect profiles. We will investigate which particular patients have the best cellular response to the drug combination.

• REC name

  London - City & East Research Ethics Committee

• REC reference

  11/LO/1559

• Date of REC Opinion

  14 Oct 2011

• REC opinion

  Favourable Opinion