Anyone On Clinical Trial with Metforman+Avastin

Metformin, a drug that has been used since the 1950's in the treatment of diabetes, has recently generated great interest in its anticancer effects based on in vitro, in vivo and clinical studies. This study assesses the pharmacodynamic effects of metformin on breast cancer metabolism.

The trial design is based on a 2 centre study 'Early Antiangiogenic Response to Bevacizumab in Primary Breast Cancer' that is about to successfully complete recruitment in Oxford and Mount Vernon hospitals. The study takes advantage of the 2 week window between the first clinic visit and commencement of neoadjuvant chemotherapy. Metformin will be given to patients for at least 2 weeks prior to neoadjuvant chemotherapy with a set of 3 breast core biopsies, a PET-CT scan and blood tests carried out before and after this 2 week period of treatment. Patients will also receive a drink of heavy (deuterated) water, a safe and stable isotope commonly used in clinical lipid metabolism studies, the evening prior to both sets of core biopsies. Having completed the first 2 weeks of metformin patients will have the option of continuing metformin until completion of chemotherapy, at the discretion of the trial physician.

The core biopsies will then be used to assess for changes in:

• immunohistochemical staining;
• gene profiles;
• uptake of heavy water into tumour fatty acids using mass spectrometry techniques.

The aim is to identify potential biomarkers of response to metformin (and other future cancer metabolism drugs).

Inclusion Criteria:

• Women with histology proven locally advanced breast cancer (LABC) or tumours >3 cm in diameter.
• ECOG performance status 0-1.
• Age ≥18 years.
• No prior treatment for breast cancer and scheduled to commence neoadjuvant chemotherapy in <3 weeks time.
• Have given written informed consent and are capable of cooperating with protocol.
• Adequate bone marrow, renal and liver function.

Exclusion Criteria:

• Radiotherapy, major surgery, significant traumatic injury, endocrine therapy, immunotherapy, chemotherapy or experimental therapy during four weeks prior to starting or during trial.
• Pregnancy or breast feeding
• History of type 1 or type 2 diabetes.
• Serum glucose greater than 7.0 mMol/L.
• Treatment with metformin in the past year.
• Estimated glomerular filtration rate (eGFR) <45ml/min.
• Acute or chronic metabolic acidosis
• Known hypersensitivity to metformin
• Other psychological, social or medical condition, physical examination finding or a laboratory abnormality that the Investigator considers would make the patient a poor trial candidate or could interfere with protocol compliance or the interpretation of trial results.