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 Marys 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.
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 measure
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 (if study stopped)
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
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
Basic results (scientific)
Publication list