Condition category
Cancer
Date applied
20/12/2011
Date assigned
22/05/2012
Last edited
17/04/2014
Prospective/Retrospective
Retrospectively registered
Overall trial status
Completed
Recruitment status
No longer recruiting

Plain English Summary

Background and study aims
Endometrial cancer, or cancer of the lining of the womb, has become the most common cancer of the reproductive tract in British women. Obese women are at increased risk of the disease and are also more likely to die from it. The recent obesity epidemic means that more women than ever before are developing the disease. Endometrial cancer can usually be cured by surgery but for obese or elderly women, surgery may be dangerous. It also leaves a woman infertile. There is an urgent need to prevent this cancer and to develop effective non-surgical treatments.
Metformin is one of the drugs used to treat diabetes. Recently, its role in the treatment of cancer has been explored. Diabetics who take metformin for many years are less likely to develop and die from cancer than those who do not. They are also more likely to respond well to chemotherapy if cancer does develop. Metformin has been shown to slow down the growth of breast, prostate, colon and endometrial cancers in the laboratory. Early studies in breast cancer patients have had promising results but metformin has never been tested in patients with endometrial cancer before.
This study will test metformin in patients with atypical endometrial hyperplasia (pre-cancer) and endometrial cancer. Women with atypical endometrial hyperplasia or endometrial cancer will receive metformin for one to four weeks while they wait for their surgery. The effects of metformin will then be assessed by comparing the characteristics of the endometrial tumour, taken at diagnosis, with those of the tumour removed at surgery. We will look at how fast the cells are multiplying and the proportion of cells undergoing cell death, and try to determine whether metformin affects key cancer pathways. It is hoped that the results of this small study will inform the design of a larger one.

Who can participate?
Non-diabetic women, aged 18 years or more who have recently been diagnosed with atypical endometrial hyperplasia or type I endometrial cancer.

What does the study involve?
Women taking part in the study will take metformin tablets twice a day for one to four weeks while they wait for their hysterectomy (Metformin Group). Other women taking part in the study will receive no treatment with metformin (Control Group). Both groups of women will have blood samples and a sample of the lining of the womb (endometrial biopsy) taken at recruitment and at hysterectomy. Those women who took metformin will be asked to report their experiences of taking the tablets by filling out a questionnaire.

What are the possible risks and benefits of participating?
There will be no direct benefit to those taking part. But there should be benefits in future for women with endometrial cancer because this study will help us decide whether metformin is useful in the treatment of this disease.
The main risk of taking metformin is mild tummy upset, nausea or diarrhoea, but this is usually short-lived. Women can not drink alcohol while they are on metformin tablets. Rarely, patients taking metformin have become very unwell because of and allergic reaction (anaphylaxis) or kidney failure (lactic acidosis). Participants will be closely monitored to prevent this happening and tablets will be stopped immediately and appropriate medical treatment started if there are any concerns.

Where is the study run from?
St Mary’s Hospital, Tameside Hospital and the Royal Oldham Hospital in Greater Manchester (UK).

When is the study starting and how long is it expected to run for?
The study will start mid 2012 and is likely to run for two to three years.

Who is funding the study?
1. Central Manchester University Hospitals NHS Foundation Trust - Experimental Medicine Scheme Grant (2011)
2. Wellbeing of Women Research Training Fellowship (2012)

Who is the main contact?
Dr Emma Crosbie
emma.crosbie@manchester.ac.uk
Dr Vanitha Sivalingam
Vanitha.sivalingam@manchester.ac.uk

Trial website

Contact information

Type

Scientific

Primary contact

Dr Emma Crosbie

ORCID ID

Contact details

NIHR Clinical Lecturer in Gynaecological Oncology
University of Manchester
St Mary's Hospital
Hathersage Road
Manchester
M13 9WL
United Kingdom
+44 (0)161 701 6912
emma.crosbie@manchester.ac.uk

Additional identifiers

EudraCT number

ClinicalTrials.gov number

Protocol/serial number

METFORM01

Study information

Scientific title

Proof of mechanism pre-surgical window trial of metformin in non-diabetic women with endometrial carcinoma: a feasibility study

Acronym

Study hypothesis

Metformin reduces cellular proliferation in type 1 endometrial cancer.

Updated 17/04/2014: the trial has completed recruitment.

Ethics approval

North West – Haydock Research Ethics Committee, 19/08/2011, ref: 11/NW/0442

Study design

Non-randomised controlled pre-surgical ‘window’ study

Primary study design

Interventional

Secondary study design

Non randomised controlled trial

Trial setting

Hospitals

Trial type

Treatment

Patient information sheet

Not available in web format, please use the contact details below to request a patient information sheet

Condition

Type 1 or endometrioid adenocarcinoma of the endometrium

Intervention

Current interventions as of 06/09/2013:

Metformin Group
Participants in the Metformin group will receive 850 mg metformin hydrochloride twice daily by mouth for one to four weeks between recruitment into the trial and surgery for endometrial cancer. They will discontinue their metformin the night before surgery. They will be asked to complete a ‘tolerability of metformin treatment’ questionnaire two weeks after surgery. They do not require any other follow up as a result of participation in this study.

Control Group
Participants in the Control group will NOT receive Metformin during the one to four week period between recruitment and surgery. They do not require any follow up after their surgery.


Previous interventions:

Metformin Group
Participants in the Metformin group will receive 850mg metformin hydrochloride twice daily by mouth for two to four weeks between recruitment into the trial and surgery for endometrial cancer. They will discontinue their metformin the night before surgery. They will be asked to complete a ‘tolerability of metformin treatment’ questionnaire two weeks after surgery. They do not require any other follow up as a result of participation in this study.

Control Group
Participants in the Control group will NOT receive Metformin during the two to four week period between recruitment and surgery. They do not require any follow up after their surgery.

Intervention type

Other

Phase

Not Applicable

Drug names

Primary outcome measures

Test for Ki-67

Secondary outcome measures

Test for:
1. Phospho-H3
2. Cleaved caspase-3 and cleaved PARP
3. AKT, phosphorylated AKT
4. ERK1,2, phosphorylated ERK 1,2
5. PTEN, strathmin
6. Phosphorylation status of key signal transduction molecules (mTOR pathway)
7. Insulin receptor/phosphorylated insulin receptor
8. Fasting serum glucose, insulin, IGFBP-1 and C-peptide levels
9. Tolerability of metformin treatment

Overall trial start date

03/01/2012

Overall trial end date

02/01/2015

Reason abandoned

Eligibility

Participant inclusion criteria

Current inclusion criteria as of 06/09/2013:
1. Biopsy-proven atypical endometrial hyperplasia or type 1 endometrial carcinoma
2. Scheduled for surgical treatment in 1 or more weeks’ time
3. Written informed consent to participate in the trial
4. Females aged 18 years or older

Previous inclusion criteria:
1. Biopsy-proven type 1 endometrial carcinoma
2. Scheduled for surgical treatment in 2 or more weeks’ time
3. Written informed consent to participate in the trial
4. Females aged 18 years or older

Participant type

Patient

Age group

Adult

Gender

Female

Target number of participants

30

Participant exclusion criteria

Current exclusion criteria as of 06/09/2013:
1. Already receiving metformin treatment
2. Type 1 or 2 diabetes mellitus on drug treatment
3. Renal or hepatic impairment
4. Unable to comply with treatment protocol

Previous exclusion criteria:
1. Already receiving metformin treatment
2. Type 1 or 2 diabetes mellitus
3. Renal or hepatic impairment
4. Unable to comply with treatment protocol

Recruitment start date

03/01/2012

Recruitment end date

02/01/2015

Locations

Countries of recruitment

United Kingdom

Trial participating centre

NIHR Clinical Lecturer in Gynaecological Oncology
Manchester
M13 9WL
United Kingdom

Sponsor information

Organisation

Central Manchester University Hospitals NHS Foundation Trust (UK)

Sponsor details

c/o Dr Lynne Webster
Head of Research Office
Research and Innovation Division
Postgraduate Medical Centre
Oxford Road
Manchester
M13 9WL
United Kingdom

Sponsor type

Hospital/treatment centre

Website

http://www.cmft.nhs.uk/

Funders

Funder type

University/education

Funder name

University of Manchester (UK)

Alternative name(s)

Funding Body Type

private sector organisation

Funding Body Subtype

academic

Location

United Kingdom

Funder name

Central Manchester University Hospitals NHS Foundation Trust, Experimental Medicine Scheme Grant (UK)

Alternative name(s)

Funding Body Type

Funding Body Subtype

Location

Results and Publications

Publication and dissemination plan

Not provided at time of registration

Intention to publish date

Participant level data

Not provided at time of registration

Results - basic reporting

Publication summary

Publication citations

Additional files

Editorial Notes