A trial looking at metformin to reduce the risk of cancer in people with Li Fraumeni Syndrome (MILI)
Cancer type:
Status:
This trial is looking at whether a drug called metformin might reduce the risk of cancer developing in people with Li Fraumeni Syndrome.
(LFS) is an condition. People who have LFS have an increased risk of developing different types of cancer.
More about this trial
People with LFS have a change (variant or ) in the TP53 gene. A change in the TP53 gene is linked to an increased risk of developing cancer.
The TP53 gene helps control how a cell turns nutrients into energy for the cell. It also controls how often a cell divides. This is called metabolism. Mutations in the TP53 gene can increase the cells’ metabolism and the number of times cells divide and grow. However it is still unclear how cancers form in people with LFS.
Doctors already use metformin to treat people with . Metformin works by improving sugar levels and altering metabolism of cells. There is some evidence that taking metformin in LFS may also lower the risk of developing cancer. The researchers don’t know for sure so this trial will help them to find out.
The aims of the trial are to find out:
- whether metformin reduces the risk of cancer in people with LFS
- the side effects of taking metformin
- how metformin works in people with LFS
- how cancers form in people with LFS
- how safe it is for people with LFS to take metformin
- how taking metformin affects their
quality of life
Who can enter
The following bullet points are a summary of the entry conditions for this trial. Talk to your doctor or the trial team if you are unsure about any of these. They will be able to advise you.
Who can take part
You may be able to join this trial if both of the following apply. You:
- have Li Fraumeni Syndrome and have a confirmed change (mutation) in the TP53 gene
- are at least 16 years old
Who can’t take part
You cannot join this trial if any of these apply. You:
- are taking metformin
- have taken metformin for more than 3 months within the past 2 years
- have type 1 or type 2 diabetes
- have an active cancer
- have had cancer treatment that reaches the whole body such as chemotherapy within the past 6 months
- are pregnant or breastfeeding
- have a
digestive system problem that could affect how well your body absorbs metformin - have a
heart problem that could affect you taking part such as a heart attack within the past 3 months or unstable angina - have high blood pressure that isn’t controlled
- are at risk of a high level of lactic acid in the blood (lactic acidosis). Your doctor will know about this.
- have kidneys that aren’t working well
- have a high level of alkaline phosphate in the blood
- have liver cirrhosis or your liver isn’t working very well
- are allergic or sensitive to metformin or any of its ingredients
- are not able to have an
MRI scan . This could be because you have metal pieces in your body such as a plate or surgical clips, you have a pacemaker, you cannot be in small spaces (claustrophobic).
Trial design
This is a phase 2 trial. The team need 224 people to take part.
A member of your local genetics team can tell you about the trial. They will send some details about you to the trial team if you are interested.
After receiving a referral from your genetics team a member of the trial team will contact you. They will arrange an initial visit to a hospital that is closest to you where the trial is taking place. This would be in either Oxford or Nottingham.
This is a randomised trial. A computer puts you into 1 of 2 groups. Neither you nor your doctor can choose which group you are in. The 2 groups are a:
- hospital appointment for a whole body MRI scan and blood tests once a year and metformin
- hospital appointment for a whole body MRI scan and blood tests once a year and no metformin.
Metformin is a tablet you take once a day for up to 5 years. The hospital pharmacy posts the tablets to you. You will get a phone call from a member of the team to tell you when to start taking the tablets.
You start taking 1 tablet once a day. The team phone you every fortnight during the first 9 weeks. This is to see how you are and to gradually increase the dose of metformin. The maximum dose of metformin is 2 tablets twice a day.
You continue taking metformin for up to 5 years as long as you can tolerate the side effects.
Everyone in the trial will have a clinic appointment at the hospital for a check up and a whole body MRI scan once a year.
Quality of life
You fill in a questionnaire when you join the trial and then once a year for 5 years. The questions ask about:
- your general health
- what you are able to do
- side effects if you are taking metformin
This is a quality of life questionnaire.
Samples for research
You give a blood sample when you join the trial. And then you will have blood tests once a year for 5 years at your hospital appointments.
During the trial if you develop cancer or an abnormal lesion such as a mole or lump you may have a tissue sample () taken. The team will ask the doctor for a piece of the tissue. If you had an operation to remove it then the team will ask for a piece of the tissue removed.
Researchers will use these samples to:
- understand why people with LFS are more likely to get cancer
- understand how metformin works in the cells of people with LFS
- look for substances such as
biomarkers or proteins that could help detect cancer in people with LFS - find out whether certain changes in the TP53 gene are more linked to certain cancers
Hospital visits
You see a member of the trial team to discuss the trial and have some tests. These tests include:
- a fasting blood test. You cannot eat or drink apart from water for a certain number of hours before this test. The team will tell for how long when they contact you to arrange the test.
- a
physical examination - an MRI scan of your body and brain
Everyone sees a member of the trial team at the hospital once a year for the same tests.
Between the hospital appointments a research nurse will phone you to see how you are.
Side effects
The trial team monitor you during the study. Contact your doctor or nurse if any side effects are bad or not getting better.
The most common side effects of metformin are:
- feeling or being sick
- diarrhoea
- tummy (abdominal) ache
- loss of appetite
- changes to taste
- low levels of
vitamin B12 in the blood. Symptoms include tiredness, a sore and red tongue, pins and needles, pale or yellow skin.
A member of the team will talk to you about the possible side effects of metformin and answer any questions before you agree to take part.
Location
Recruitment start:
Recruitment end:
How to join a clinical trial
Please note: In order to join a trial you will need to discuss it with your doctor, unless otherwise specified.
Chief Investigator
Professor Sarah Blagden
Supported by
Cancer Research UK
The George Pantziarka TP53 Trust
Medical Research Council (MRC)
National Institute for Health & Care Research (NIHR)
Oxford Clinical Trials Research Unit (OCTRU)
Oncology Clinical Trials Office (OCTO)
University of Oxford
If you have questions about the trial please contact our cancer information nurses
Freephone 0808 800 4040
