دورية أكاديمية
Cancer Precision-Prevention trial of Metformin in adults with Li Fraumeni syndrome (MILI) undergoing yearly MRI surveillance: a randomised controlled trial protocol
| العنوان: | Cancer Precision-Prevention trial of Metformin in adults with Li Fraumeni syndrome (MILI) undergoing yearly MRI surveillance: a randomised controlled trial protocol |
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| المؤلفون: | Dixon-Zegeye, M., Shaw, R., Collins, L., Perez-Smith, K., Ooms, A., Qiao, M., Pantziarka, P., Izatt, L., Tischkowitz, M., Harrison, R. E., George, A., Woodward, E. R., Lord, S., Hawkes, L., Evans, D. G., Franklin, J., Hanson, H., Blagden, S. P. |
| بيانات النشر: | BioMed Central |
| سنة النشر: | 2024 |
| المجموعة: | RD&E Research Repository (Royal Devon and Exeter NHS Foundation Trust) |
| مصطلحات موضوعية: | Adult, Humans, Mice, Animals, Li-Fraumeni Syndrome/diagnostic imaging/genetics/prevention & control, Metformin/adverse effects, Quality of Life, Germ-Line Mutation, Magnetic Resonance Imaging, Genetic Predisposition to Disease, Randomized Controlled Trials as Topic, Clinical Trials, Phase II as Topic, Cancer, Chemoprevention, Lfs, Li-Fraumeni syndrome, Metformin, Precision-Prevention |
| الوصف: | BACKGROUND: Li-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. METHODS: Metformin 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 ... |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| العلاقة: | https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/38308321Test/; Dixon-Zegeye M, Shaw R, Collins L, Perez-Smith K, Ooms A, Qiao M, et al. Cancer Precision-Prevention trial of Metformin in adults with Li Fraumeni syndrome (MILI) undergoing yearly MRI surveillance: a randomised controlled trial protocol. Trials. 2024;25(1):103.; Trials; PMC10837926; https://hdl.handle.net/11287/623225Test |
| DOI: | 10.1186/s13063-024-07929-w |
| الإتاحة: | https://doi.org/10.1186/s13063-024-07929-wTest https://hdl.handle.net/11287/623225Test |
| حقوق: | © 2024. The Author(s). |
| رقم الانضمام: | edsbas.823C006F |
| قاعدة البيانات: | BASE |
| DOI: | 10.1186/s13063-024-07929-w |
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