Effect of Metformin on Breast Cancer Metabolism
Information source: Oxford University Hospitals NHS Trust
ClinicalTrials.gov processed this data on August 23, 2015 Link to the current ClinicalTrials.gov record.
Condition(s) targeted: Breast Cancer
Intervention: Metformin (Drug)
Phase: Phase 2
Status: Completed
Sponsored by: Oxford University Hospitals NHS Trust Official(s) and/or principal investigator(s): Adrian Harris, Principal Investigator, Affiliation: The University of Oxford
Summary
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).
Clinical Details
Official title: 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
Study design: Endpoint Classification: Pharmacodynamics Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Basic Science
Primary outcome: Measure Metformin Induced effects in phosphorylation of S6K, 4E-BP-1 and AMPK via immunohistochemical analysis
Secondary outcome: Measure fatty acid desaturation and deuterated water uptake into fatty acids at baseline and after 2 weeks of metformin.Measure baseline and induced effect of metformin on upstream and downstream members of AMPK family via gene array analysis.
Detailed description:
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.
Eligibility
Minimum age: 18 Years.
Maximum age: N/A.
Gender(s): Both.
Criteria:
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.
Locations and Contacts
Mount Vernon Centre for Cancer Treatment, Rickmansworth Road, Northwood, Middlesex HA6 2RN, United Kingdom
Dept Oncology, Churchill Hospital, Old Road, Headington, Oxford, Oxfordshire OX3 7LJ, United Kingdom
Surgery and Molecular Oncology Ninewells Hospital, Dundee, Scotland DD1 9SY, United Kingdom
Additional Information
Starting date: May 2011
Last updated: July 1, 2014
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