Metformin in Li Fraumeni Syndrome (MILI) Trial: A phase II randomised open-label cancer prevention study of metformin in adults with Li Fraumeni Syndrome
Recipient organisationNIHR Leicester Clinical Research Facility
NIHR supportRecorded as supported by this research centre
PeriodMar 2025 — Ongoing
In plain English
AI plain-English summary
People with Li Fraumeni Syndrome face a 90% cancer risk for women and 70% for men, yet no drug exists to lower that risk—the MILI trial is testing whether the diabetes drug metformin can change that. This matters because Li Fraumeni Syndrome is caused by a lifelong mutation in the TP53 gene, the body’s most important anticancer defence. Current care relies on regular whole-body MRI scans to catch cancers early, but there is no preventive treatment. Laboratory experiments in mice with LFS have shown that metformin alters the metabolism of cells carrying the mutated TP53, making them behave more like normal cells and reducing cancer development. That evidence is not enough to justify clinical use without a proper trial. The MILI study will recruit 224 people with LFS across the UK. Half will take metformin daily for five years; the other half will not. All participants will receive regular check-ups and whole-body MRI scans. If metformin proves effective, it could become the first drug to reduce cancer risk in people with this devastating inherited condition, transforming their long-term outlook without requiring invasive interventions.
View original technical description
This clinical study is investigating the use of a drug called metformin as a way of reducing the cancer risk in people with Li Fraumeni Syndrome (LFS). LFS is a rare genetic condition that predisposes people to develop one or more cancers. It is caused by an inherited mutation in a gene called TP53. TP53 is the most important anticancer gene in the body. For most people with cancer the gene is only mutated in their cancer cells but for people with LFS it is mutated in all the cells in the body. This means there is a very high risk of developing cancer for people with LFS – a 90% risk for women and about 70% for men. Currently there are no treatments to reduce this high risk of cancer. People with LFS have regular health checks and whole-body MRI imaging to catch any new cancers early. Research shows that for people with LFS, spotting cancer early improves survival. Many LFS people are still not getting the care and scans they need.Metformin is a well-known and safe drug used to treat diabetes. Laboratory experiments have shown that in mice with LFS, metformin can reduce the risk of them developing cancer. Metformin alters the metabolism of cells with mutated TP53 and makes them act more like normal cells. This is not enough evidence to conclude that metformin will reduce the risks of cancer in people with LFS. A larger clinical trial is needed. The MILI study aims to enroll 224 people with LFS in the UK. Half the participants will take metformin everyday for 5 years, the other half will not. All participants will have regular check-ups including whole body MRI scans at selected NHS hospitals. The sample collection will help researchers understand more how the cells increase the risk of cancer in people with LFS. The study has been designed with members from the George Pantziarka TP53 Trust (GPTT) the charity for LFS. Fore more information please go to the GPTT charity website http://www.tp53.co.uk or contact the MILI trial office: octo-MILI@oncology.ox.ac.uk
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