Researchers from the University of Oxford will undertake the world’s first cancer prevention trial in adults with Li Fraumeni Syndrome (LFS). The “Metformin in Li Fraumeni” (MILI) trial is a randomised open-label Phase II trial jointly funded by the National Institute for Health Research and the Medical Research Council that will evaluate whether the existing type 2 diabetes drug metformin can prevent or delay the emergence of cancer in people with LFS.
LFS is a rare inherited disorder that currently impacts around 600 people in the UK but, with increasing use of self-testing and genetic sequencing in diagnostic practice, this number is expected to rise. LFS is caused by mutations in the TP53 tumour suppressor gene that encodes an important protein that prevents cancer. People with LFS have a 70-90% lifetime risk of developing a wide range of cancers, particularly cancers of the brain, breast, blood and soft tissue.
Currently, the only option for people with LFS is to undergo intensive regular screening in the hope of catching and treating emerging cancers as early as possible. However, this “watch and wait” strategy can create a high level of anxiety among patients with LFS patients and their families.
The George Pantziarka TP53 Trust, the UK patient support group for people with LFS, has also been deeply involved in the initiation and development of the trial.
Many LFS families have to deal with one family member after another becoming ill with cancer. In some cases, families are dealing with multiple cancers at the same time, and there is always the knowledge that another cancer may arise later down the line. For our families, reducing the risk of cancer with a drug like this will make the hugest difference - it is something we are desperately hoping for.
- Pan Pantziarka, whose son George and wife Gina died from LFS-related cancers
Metformin is a well-known and safe oral blood sugar-lowering drug that has been used to treat Type 2 diabetes for over 60 years. Previous experiments in mice with LFS have shown that metformin can alter metabolism to delay cancer occurrence. Led by the University of Oxford, in collaboration with St George’s Hospital, London and the University of Manchester, the MILI study aims to recruit over 200 adults with LFS nationwide, to be randomly assigned to either receive metformin or not.
There is a huge unmet need in the LFS population and, following promising data from studies in mice, we have designed the MILI trial to help meet this need. It will be the world’s largest study into LFS and the first ever cancer prevention study for this community. We hope that the outcomes of the trial will provide the first, and much needed, intervention option for families diagnosed with LFS.
- Sarah Blagden, Chief Investigator for the MILI study
All participants will undergo regular imaging scans, blood tests and other assessments to detect any emerging cancers and monitor any side effects. The study will compare the number of cancer-free patients between those treated with metformin or not after 5 years. If successful, metformin could be the first cancer intervention available for those with LFS, as no dietary, lifestyle or drug interventions have so far been shown to decrease cancer development.
This study is a global collaboration, with parallel studies in Canada, Germany and the USA recruiting to a similar protocol and, upon study completion, data will be pooled. This international approach means that this will be the world’s largest study in LFS to tell us definitively whether or not metformin reduces the risk of cancer in this community.
About the MILI study
The MILI trial is jointly funded by the NIHR and MRC. Further support and patient input will be provided by the George Pantziarka TP53 Trust, the UK's only charity dedicated to supporting families with Li Fraumeni Syndrome, who will be funding the travel costs for participants attending clinics and taking part in the trial. First outcomes from the trial are expected in 2028.
This trial is being led by the University of Oxford by Associate Professor Sarah Blagden through the Oncology Clinical Trials Office, in collaboration with the Universities of Cambridge and Manchester and St George’s Hospital, London.