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Breast CancerPhase 2NCT01266486

Effect of Metformin on Breast Cancer Metabolism

A Phase 2 study testing Metformin in people with Breast Cancer, run by Oxford University Hospitals NHS Trust at 3 sites in United Kingdom.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Breast Cancer
What is being tested?
Metformin
Could I receive a placebo?
No, everyone receives an active treatment
How many people
41 participants
Where
3 sitesUnited Kingdom
Study dates
May 2011to May 2014
Phase
Phase 2
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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.

Who cannot join

  • 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.
Show all 9Show fewer
  • 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.

Trial locations and contacts

3 sites in 1 country.

United Kingdom3 sites

  • Surgery and Molecular Oncology Ninewells Hospital

    Dundee, Scotland, DD1 9SY

  • Mount Vernon Centre for Cancer Treatment, Rickmansworth Road

    Northwood, Middlesex, HA6 2RN

  • Dept Oncology, Churchill Hospital, Old Road, Headington

    Oxford, Oxfordshire, OX3 7LJ

Other trials in United Kingdom

About this study

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

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.

Read more

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).

Read the 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.

Conditions
Breast Cancer
Being tested
Metformin
Keywords
Breast cancer, Pharmacodynamics, AMPK, PET Scan
Medical subject headings
Breast Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • MetforminDrug

    Also called Glucophage XR

    Extended release Metformin 1500mg once daily for 14-21 days

Study groups in NCT01266486
Study groupRoleWhat they receive
MetforminExperimentalNot described
Receives: Drug: Metformin

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Measure Metformin Induced effects in phosphorylation of S6K, 4E-BP-1 and AMPK via immunohistochemical analysis

    Measured: after 14-21 days of daily metforming dosing

Secondary outcomes (2)

  1. Measure fatty acid desaturation and deuterated water uptake into fatty acids at baseline and after 2 weeks of metformin.

    Measured: Day 14-21 after starting metformin dosing

  2. Measure baseline and induced effect of metformin on upstream and downstream members of AMPK family via gene array analysis.

    Measured: 14-21 days after start daily metformin dosing

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted24 Dec 2010 (estimated)
  2. Study startMay 2011
  3. Primary completionMay 2014
  4. Study completionMay 2014

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Basic science
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
41 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01266486
Sponsor's protocol ID
EP-TSC-647
Status last verified
Jul 2014
First submitted
23 Dec 2010
Last updated
2 Jul 2014
Results posted
No
Data monitoring committee
No

Publications

  • Ralli GP, Carter RD, McGowan DR, Cheng WC, Liu D, Teoh EJ, Patel N, Gleeson F, Harris AL, Lord SR, Buffa FM, Fenwick JD. Radiogenomic analysis of primary breast cancer reveals [18F]-fluorodeoxglucose dynamic flux-constants are positively associated with immune pathways and outperform static uptake measures in associating with glucose metabolism. Breast Cancer Res. 2022 May 17;24(1):34. doi: 10.1186/s13058-022-01529-9.

    PubMed 35581637

  • Lord SR, Collins JM, Cheng WC, Haider S, Wigfield S, Gaude E, Fielding BA, Pinnick KE, Harjes U, Segaran A, Jha P, Hoefler G, Pollak MN, Thompson AM, Roy PG, English R, Adams RF, Frezza C, Buffa FM, Karpe F, Harris AL. Transcriptomic analysis of human primary breast cancer identifies fatty acid oxidation as a target for metformin. Br J Cancer. 2020 Jan;122(2):258-265. doi: 10.1038/s41416-019-0665-5. Epub 2019 Dec 10.

    PubMed 31819193

  • Lord SR, Cheng WC, Liu D, Gaude E, Haider S, Metcalf T, Patel N, Teoh EJ, Gleeson F, Bradley K, Wigfield S, Zois C, McGowan DR, Ah-See ML, Thompson AM, Sharma A, Bidaut L, Pollak M, Roy PG, Karpe F, James T, English R, Adams RF, Campo L, Ayers L, Snell C, Roxanis I, Frezza C, Fenwick JD, Buffa FM, Harris AL. Integrated Pharmacodynamic Analysis Identifies Two Metabolic Adaption Pathways to Metformin in Breast Cancer. Cell Metab. 2018 Nov 6;28(5):679-688.e4. doi: 10.1016/j.cmet.2018.08.021. Epub 2018 Sep 20.

    PubMed 30244975

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Metformin in people with Breast Cancer, run by Oxford University Hospitals NHS Trust at 3 sites in United Kingdom.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 6 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 2 Jul 2014. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 3 sites in United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

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). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01266486, which also lists 3 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 2 Jul 2014.

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