Effect of Metformin on Breast Cancer Metabolism

July 1, 2014 updated by: Linda Ward, Oxford University Hospitals NHS Trust

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, 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).

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Actual)

41

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United Kingdom
    • Middlesex
      • Northwood, Middlesex, United Kingdom, HA6 2RN
        • Mount Vernon Centre for Cancer Treatment, Rickmansworth Road
    • Oxfordshire
      • Oxford, Oxfordshire, United Kingdom, OX3 7LJ
        • Dept Oncology, Churchill Hospital, Old Road, Headington
    • Scotland
      • Dundee, Scotland, United Kingdom, DD1 9SY
        • Surgery and Molecular Oncology Ninewells Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Basic Science
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Metformin
Drug: Metformin
Extended release Metformin 1500mg once daily for 14-21 days
Other Names:
  • Glucophage XR

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
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
after 14-21 days of daily metforming dosing

Secondary Outcome Measures

Outcome Measure
Time Frame
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
Day 14-21 after starting metformin dosing
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
14-21 days after start daily metformin dosing

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Oxford University Hospitals NHS Trust

Collaborators

Cancer Research UK

Investigators

  • Principal Investigator: Adrian Harris, The University of Oxford

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

May 1, 2011

Primary Completion (Actual)

May 1, 2014

Study Completion (Actual)

May 1, 2014

Study Registration Dates

First Submitted

December 23, 2010

First Submitted That Met QC Criteria

December 23, 2010

First Posted (Estimate)

December 24, 2010

Study Record Updates

Last Update Posted (Estimate)

July 2, 2014

Last Update Submitted That Met QC Criteria

July 1, 2014

Last Verified

July 1, 2014

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • EP-TSC-647

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Breast Cancer

Clinical Trials on Metformin

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in China

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

3
Subscribe