Evidence map›Paper›PMID 38308321›Full record

ArticleTrials2024

Cancer Precision-Prevention trial of Metformin in adults with Li Fraumeni syndrome (MILI) undergoing yearly MRI surveillance: a randomised controlled trial protocol.

Miriam Dixon-Zegeye, Rachel Shaw, Linda Collins, Kendra Perez-Smith, Alexander Ooms, Maggie Qiao, Pan Pantziarka, Louise Izatt, Marc Tischkowitz, Rachel E Harrison and 8 more

Open access · goldAbstract readClinical Trial Protocol
In one paragraph

Article in Trials, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.

0numbers the graph read from it
0cells of the map it votes in
12citing papers in PubMed
3.7field-weighted citation impact, top 6% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

12 citing papers in PubMed, 13 citations in OpenAlex.

  1. Review
  2. Review
  3. Targeted therapy in patients with genetic tumor syndromes.Medizinische Genetik : Mitteilungsblatt des Berufsverbandes Medizinische Genetik e.V · 2025
    Article
  4. Article
  5. Review
  6. Review
  7. Review
  8. Li-Fraumeni Syndrome : Current Strategies and Future Perspectives.Journal of Korean Neurosurgical Society · 2025
    Article
  9. Review
  10. Article
  11. Review
  12. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

18 authors at 10 institutions in 1 country.

Miriam Dixon-ZegeyeDepartment of Oncology, University of Oxford, Old Road Campus Research Building, Oxford, OX3 7DQ, UK.
Rachel ShawOncology Clinical Trials Office, University of Oxford, Old Road Campus Research Building, Oxford, UK.
Linda CollinsOncology Clinical Trials Office, University of Oxford, Old Road Campus Research Building, Oxford, UK.
Kendra Perez-SmithTrial Support Unit, Department of Oncology, University of Oxford, Old Road Campus Research Building, Oxford, UK.
Alexander OomsCentre for Statistics in Medicine and Oxford Clinical Trials Research Unit (OCTRU), Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, Headington, Oxford, UK.
Maggie QiaoCentre for Statistics in Medicine and Oxford Clinical Trials Research Unit (OCTRU), Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, Headington, Oxford, UK.
Pan PantziarkaGeorge Pantziarka TP53 Trust, 7 Surbiton Cres, Kingston upon Thames, UK.
Louise IzattGuy's and St Thomas' NHS Foundation Trust, Great Maze Pond, London, UK.
Marc TischkowitzDepartment of Medical Genetics, National Institute for Health Research Cambridge Biomedical Research Centre, Cambridge, UK.
Rachel E HarrisonDepartment of Clinical Genetics, Nottingham University Hospitals NHS Trust, Hucknall Rd, Nottingham, UK.
Angela GeorgeRoyal Marsden Hospital, Fulham Road, London, UK.
Emma R WoodwardDivision of Evolution, Infection and Genomics, School of Biological Sciences, Faculty of Biology, Medicine and Health, The University of Manchester, Manchester, UK.
Simon LordDepartment of Oncology, University of Oxford, Old Road Campus Research Building, Oxford, OX3 7DQ, UK.
Lara HawkesOxford Centre for Genomic Medicine, ACE building, Nuffield Orthopaedic Centre, Windmill Road, Headington, Oxford, UK.
D Gareth EvansDivision of Evolution, Infection and Genomics, School of Biological Sciences, Faculty of Biology, Medicine and Health, The University of Manchester, Manchester, UK.
James FranklinInstitute of Medical Imaging and Visualisation, Bournemouth University, St Pauls Lane, Bournemouth, UK.
Helen HansonPeninsula Clinical Genetics Service, Royal Devon University Healthcare NHS Foundation Trust, Exeter, UK.
Sarah P BlagdenDepartment of Oncology, University of Oxford, Old Road Campus Research Building, Oxford, OX3 7DQ, UK. sarah.blagden@oncology.ox.ac.uk.ORCID http://orcid.org/0000-0001-8783-3491
University of Oxford · GBNuffield Orthopaedic Centre · GBUniversity of Manchester · GBBournemouth University · GBGuy's and St Thomas' NHS Foundation Trust · GBNational Institute for Health Research · GBNottingham University Hospitals NHS Trust · GBOxford Research Group · GBRoyal Marsden NHS Foundation Trust · GBUniversity of Exeter · GB

Funding

Cancer Research UK PRCPJTPRCPJT-May22\100018
6 · The paper itself

Abstract

backgroundLi-Fraumeni syndrome (LFS) is a rare autosomal dominant disease caused by inherited or de novo germline pathogenic variants in TP53. Individuals with LFS have a 70-100% lifetime risk of developing cancer. The current standard of care involves annual surveillance with whole-body and brain MRI (WB-MRI) and clinical review; however, there are no chemoprevention agents licensed for individuals with LFS. Preclinical studies in LFS murine models show that the anti-diabetic drug metformin is chemopreventive and, in a pilot intervention trial, short-term use of metformin was well-tolerated in adults with LFS. However, metformin's mechanism of anticancer activity in this context is unclear.

methodsMetformin in adults with Li-Fraumeni syndrome (MILI) is a Precision-Prevention phase II open-labelled unblinded randomised clinical trial in which 224 adults aged ≥ 16 years with LFS are randomised 1:1 to oral metformin (up to 2 mg daily) plus annual MRI surveillance or annual MRI surveillance alone for up to 5 years. The primary endpoint is to compare cumulative cancer-free survival up to 5 years (60 months) from randomisation between the intervention (metformin) and control (no metformin) arms. Secondary endpoints include a comparison of cumulative tumour-free survival at 5 years, overall survival at 5 years and clinical characteristics of emerging cancers between trial arms. Safety, toxicity and acceptability of metformin; impact of metformin on quality of life; and impact of baseline lifestyle risk factors on cancer incidence will be assessed. Exploratory end-points will evaluate the mechanism of action of metformin as a cancer preventative, identify biomarkers of response or carcinogenesis and assess WB-MRI performance as a diagnostic tool for detecting cancers in participants with LFS by assessing yield and diagnostic accuracy of WB-MRI. DISCUSSION: Alongside a parallel MILI study being conducted by collaborators at the National Cancer Institute (NCI), MILI is the first prevention trial to be conducted in this high-risk group. The MILI study provides a unique opportunity to evaluate the efficacy of metformin as a chemopreventive alongside exploring its mechanism of anticancer action and the biological process of mutated P53-driven tumourigenesis.

trial registrationISRCTN16699730. Registered on 28 November 2022. URL: https://www.isrctn.com/ EudraCT/CTIS number 2022-000165-41.

Indexed as

Li-Fraumeni SyndromeMetforminAdultAnimalsClinical Trials, Phase II as TopicGenetic Predisposition to DiseaseGerm-Line MutationHumansMagnetic Resonance ImagingMiceQuality of LifeRandomized Controlled Trials as TopicMetforminCancerChemopreventionLFSLi-Fraumeni syndromeMetforminp53Precision-PreventionTP53

Identifiers

PMID38308321
PMCPMC10837926
OpenAlexW4391513639

What Socratic holds

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LicenceCC BY
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Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.