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, Miriam, Shaw, Rachel, Collins, Linda, Perez-Smith, Kendra, Ooms, Alexander, Qiao, Maggie, Pantziarka, Pan, Izatt, Louise, Tischkowitz, Marc, Harrison, Rachel E, George, Angela, Woodward, Emma R, Lord, Simon, Hawkes, Lara, Evans, D Gareth, Franklin, James, Hanson, Helen, Blagden, Sarah P |
| بيانات النشر: | Springer Science and Business Media LLC Department of Medical Genetics //dx.doi.org/10.1186/s13063-024-07929-w Trials |
| سنة النشر: | 2024 |
| المجموعة: | Apollo - University of Cambridge Repository |
| مصطلحات موضوعية: | Cancer, Chemoprevention, LFS, Li-Fraumeni syndrome, Metformin, Precision-Prevention, TP53, p53, Adult, Humans, Mice, Animals, Quality of Life, Germ-Line Mutation, Magnetic Resonance Imaging, Genetic Predisposition to Disease, Randomized Controlled Trials as Topic, Clinical Trials, Phase II as Topic |
| 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 |
| وصف الملف: | application/pdf |
| اللغة: | English |
| العلاقة: | https://www.repository.cam.ac.uk/handle/1810/366650Test |
| الإتاحة: | https://www.repository.cam.ac.uk/handle/1810/366650Test |
| حقوق: | Attribution 4.0 International ; https://creativecommons.org/licenses/by/4.0Test/ |
| رقم الانضمام: | edsbas.8E89BE2 |
| قاعدة البيانات: | BASE |
| الوصف غير متاح. |