Effect of Metformin on Breast Cancer Metabolism

This study is currently recruiting participants.
Verified March 2013 by Oxford University Hospitals NHS Trust
Sponsor:
Collaborator:
Cancer Research UK
Information provided by (Responsible Party):
Linda Ward, Oxford University Hospitals NHS Trust
ClinicalTrials.gov Identifier:
NCT01266486
First received: December 23, 2010
Last updated: March 28, 2013
Last verified: March 2013
  Purpose

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).


Condition Intervention Phase
Breast Cancer
Drug: Metformin
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Pharmacodynamics Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Basic Science
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

Resource links provided by NLM:


Further study details as provided by Oxford University Hospitals NHS Trust:

Primary Outcome Measures:
  • Measure Metformin Induced effects in phosphorylation of S6K, 4E-BP-1 and AMPK via immunohistochemical analysis [ Time Frame: after 14-21 days of daily metforming dosing ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Measure fatty acid desaturation and deuterated water uptake into fatty acids at baseline and after 2 weeks of metformin. [ Time Frame: Day 14-21 after starting metformin dosing ] [ Designated as safety issue: No ]
  • Measure baseline and induced effect of metformin on upstream and downstream members of AMPK family via gene array analysis. [ Time Frame: 14-21 days after start daily metformin dosing ] [ Designated as safety issue: No ]

Estimated Enrollment: 40
Study Start Date: May 2011
Estimated Study Completion Date: March 2014
Estimated Primary Completion Date: March 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Metformin Drug: Metformin
Extended release Metformin 1500mg once daily for 14-21 days
Other Name: Glucophage XR

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

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01266486

Contacts
Contact: Adrian L Harris, MBChB FRCP +44 (0) 1865 235310 earlyphasehub@oncology.ox.ac.uk

Locations
United Kingdom
Mount Vernon Centre for Cancer Treatment, Rickmansworth Road Recruiting
Northwood, Middlesex, United Kingdom, HA6 2RN
Contact: Andreas Makris    +44 (0) 1923 844723    andreas.makris@hotmail.com   
Principal Investigator: Andreas Makris         
Dept Oncology, Churchill Hospital, Old Road, Headington Recruiting
Oxford, Oxfordshire, United Kingdom, OX3 7LJ
Contact: Simon lord    01865 235302    earlyphasehub@oncology.ox.ac.uk   
Principal Investigator: Adrian L Harris, BSc DPhil         
Surgery and Molecular Oncology Ninewells Hospital Not yet recruiting
Dundee, Scotland, United Kingdom, DD1 9SY
Contact: Alaister Thompson    +44 (0) 1382 632565    a.m.thompson@dundee.ac.uk   
Principal Investigator: Alistair Thompson         
Sponsors and Collaborators
Oxford University Hospitals NHS Trust
Cancer Research UK
Investigators
Principal Investigator: Adrian Harris The University of Oxford
  More Information

No publications provided

Responsible Party: Linda Ward, QA Coordinator, Cancer Centre, Oxford University Hospitals NHS Trust
ClinicalTrials.gov Identifier: NCT01266486     History of Changes
Other Study ID Numbers: EP-TSC-647
Study First Received: December 23, 2010
Last Updated: March 28, 2013
Health Authority: United Kingdom: Research Ethics Committee
United Kingdom: National Health Service

Keywords provided by Oxford University Hospitals NHS Trust:
Breast cancer
Pharmacodynamics
AMPK
PET Scan

Additional relevant MeSH terms:
Breast Neoplasms
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Metformin
Hypoglycemic Agents
Physiological Effects of Drugs
Pharmacologic Actions

ClinicalTrials.gov processed this record on April 15, 2014