A Phase 2 Single Arm Study to Examine the Effects of Metformin on Cancer Metabolism in Patients With Early Stage Breast Cancer Receiving Neoadjuvant Chemotherapy
18 Years
N/A
Both
Breast Cancer
Trial Information
A Phase 2 Single Arm Study to Examine the Effects of Metformin on Cancer Metabolism in Patients With Early Stage Breast Cancer Receiving Neoadjuvant Chemotherapy
Metformin is a safe and well tolerated drug that has been widely used in the treatment of
diabetes for over 50 years. There is now growing evidence from in vitro laboratory and
animal work that metformin has anticancer properties. In addition a retrospective clinical
study in a diabetic population has demonstrated evidence of markedly increased pathological
response rates (a typically robust surrogate clinical endpoint of efficacy) to pre-surgical
chemotherapy in early breast cancer for patients that were also taking metformin as part of
their diabetes treatment.
There are several studies of metformin in cancer patients ongoing or being developed
worldwide These are predominantly in relatively unselected cancer populations and with
clinical outcomes as endpoints. However this study is the only study currently planned which
will carry out a substantial assessment of pharmacodynamic endpoints. It is important that
this study is carried out at an early stage in the development of metformin as a potential
cancer therapy in order to ensure that future large scale studies are properly informed.
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.
Type of Study:
Interventional
Study Design:
Endpoint Classification: Pharmacodynamics Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Basic Science
Outcome Measure:
Measure Metformin Induced effects in phosphorylation of S6K, 4E-BP-1 and AMPK via immunohistochemical analysis
Outcome Time Frame:
after 14-21 days of daily metforming dosing
Safety Issue:
No
Principal Investigator
Adrian Harris
Investigator Role:
Principal Investigator
Investigator Affiliation:
The University of Oxford
Authority:
United Kingdom: Research Ethics Committee
Study ID:
EP-TSC-647
NCT ID:
NCT01266486
Start Date:
May 2011
Completion Date:
March 2014
Related Keywords:
- Breast Cancer
- Breast cancer
- Pharmacodynamics
- AMPK
- PET Scan
- Breast Neoplasms
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