RecruitingPhase IIInterventional

A clinical trial investigating the use of a drug called metformin as a way of reducing the cancer risk in people with Li Fraumeni Syndrome (LFS)

Li Fraumeni Syndrome (LFS) is a rare genetic condition that greatly increases the lifetime risk of developing cancer. This UK-wide study, called the MILI trial, is investigating whether a well-known diabetes tablet called metformin can help prevent or delay cancer in people with LFS. Researchers are looking for participants aged 16 and over with a confirmed LFS diagnosis. A computer will randomly decide whether you take metformin daily for up to five years or remain on regular health checks without medication. All participants receive the same close medical attention, including yearly whole-body MRI scans, blood tests, physical examinations, and regular check-in phone calls from a specialist research nurse. The trial aims to find out if metformin can offer a safe, life-changing way to lower cancer risks for people and families living with LFS.

At a glance

Status

Recruiting

Phase

Phase II

Sponsor

University of Oxford

Enrolment target

224

Start

20 Dec 2023

Estimated completion

31 Dec 2026

Li Fraumeni Syndrome

What is this study about?

Li Fraumeni Syndrome (LFS) is an inherited condition caused by an alteration in a gene called TP53. In healthy cells, this gene works like an emergency brake, stopping damaged cells from multiplying and turning into cancer. In people with LFS, this gene does not work properly in any of their body's cells. Because of this, people with LFS have a very high chance of developing cancer during their lifetime.

Metformin is a low-cost, widely used medicine that has safely treated type 2 diabetes for decades. Laboratory research found that metformin can change how cells use energy, encouraging cells with altered TP53 genes to behave more like healthy cells. In animal studies, this helped stop tumours from growing. A small study in humans also showed encouraging cell changes, prompting researchers to run this larger clinical trial.

Led by the University of Oxford and supported by Cancer Research UK and the NHS, the MILI trial tests whether taking metformin every day can truly protect people with LFS. Half of the participants take the tablet and half do not, allowing doctors to compare cancer rates accurately. If successful, it could provide the first preventative medicine for people living with LFS.

Key takeaways

The MILI trial tests whether the diabetes drug metformin can lower cancer risk in people with Li Fraumeni Syndrome.
Half of the participants take daily metformin for up to five years, while the other half have regular monitoring without the drug.
Every participant receives yearly whole-body MRI scans and comprehensive blood tests at a specialist hospital.
The study is open to UK residents aged 16 and older who have a confirmed TP53 gene alteration.
Joining is completely voluntary, and you can withdraw from the study at any point without losing any standard NHS care.

Who may be eligible?

This trial is open to people aged 16 and older who have a confirmed genetic diagnosis of Li Fraumeni Syndrome (a known alteration in their TP53 gene). You must be able to attend yearly hospital check-ups and give blood samples.

You cannot join the study if you currently have active cancer or are receiving cancer treatment, although some long-term hormone therapies are permitted. You are also not eligible if you have diabetes, are currently taking metformin, or have taken metformin for more than three months in the past two years.

Because the body processes metformin through the kidneys and liver, people with significant kidney, liver, or heart problems cannot take part. The trial is also not suitable for anyone who is pregnant, breastfeeding, or unable to have an MRI scan due to certain metal implants or pacemakers.

Could this study suit you?

Answer these quick questions to see if you may be eligible. This is a guide only — the research team makes the final call.

I am aged 16 or older.
I have a confirmed genetic diagnosis of Li Fraumeni Syndrome (TP53 alteration).
I do not currently have active cancer or diabetes.
I have not taken metformin for more than three months in the past two years.
I am not pregnant or breastfeeding.
I am safe to have an MRI scan (no incompatible metal implants or pacemakers).

Answer every question to see your result.

What does participation involve?

Taking part in the study lasts for up to five years. A computer randomly places you into one of two groups: one group takes metformin tablets once a day, and the other group has regular check-ups without the medication. Both groups receive the same high standard of care. Once a year, you will visit a specialist trial hospital for a thorough health check, blood tests, and a whole-body MRI scan to look for any early changes in your body. Every six months, a research nurse will phone you to check on your health and discuss any symptoms. You will also be asked to answer occasional questionnaires about your wellbeing.

Potential risks and benefits

A major benefit of taking part is receiving regular, expert health checks and yearly whole-body MRI scans, which can detect health problems very early. If metformin works, it might also help lower your future cancer risk, though this cannot be guaranteed. Metformin is considered very safe, but it can cause mild side effects like nausea, loose stools, or stomach cramps, especially at first. Having regular blood tests may also cause minor bruising or brief discomfort. Taking part is entirely your choice, and you can leave the study at any time without it affecting your standard NHS care.

Locations (10)

Oxford University Hospitals NHS Foundation Trust
City only
Oxford, England
Guys and St Thomas' NHS Foundation Trust
City only
London, England
Addenbrookes Hospital
City only
Cambridge, England
Nottingham University Hospitals NHS Trust - City Campus
City only
Nottingham, England
Aberdeen Royal Infirmary
Approximate
Aberdeen, Scotland
University Hospital Southampton NHS Foundation Trust
Unverified
Southampton, England
University Hospitals of Leicester NHS Trust
Unverified
Leicester, England
Western General Hospital
Unverified
Lothian, Scotland
Manchester University Hospital NHS Ft (hq)
Unverified
Manchester, England
The Royal Marsden NHS Foundation Trust
Unverified
London, England

Common questions

Can I choose whether I take metformin or not?

No. A computer randomly decides whether you take metformin or join the monitoring-only group. This ensures the study results are fair and reliable.

Do I have to pay for the MRI scans or trial medicine?

No. All study medication, specialised hospital visits, and whole-body MRI scans are provided free of charge as part of the clinical trial.

What happens if the metformin upsets my stomach?

Mild digestive upset is common when starting metformin. Your research team will help manage this by starting you on a low dose and adjusting it slowly to keep you comfortable.

Will taking part cure my Li Fraumeni Syndrome?

No. LFS is a permanent genetic condition. The goal of this study is not to cure the gene change, but to find out if metformin can help stop cancer from developing.

What does a whole-body MRI scan feel like?

An MRI scan is painless and uses magnets rather than radiation. You will lie flat inside a tunnel-like scanner, which can be noisy, so you will be given earplugs or headphones.

How to find out more

Imogen North

octo-mili@oncology.ox.ac.uk - Official trial record

Always speak to your GP or specialist before deciding to take part in a study.