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Biomarker Monitoring for a Young Individual Carrying a TP53 Gene Mutation in a Familial High-Cancer Predisposition Setting
Sponsor study identifier
observational
6
1 country
1
Study Start
July 2014
Date type not reportedThis date has not been verified as actual or estimated.
Primary Completion
July 2016
Actual (reported)Study Completion
July 2016
Actual (reported)Purpose This study is an 'N-of-one' observational study focusing on individuals with a hereditary predisposition to cancer due to a genetic mutation in the TP53 gene. An individual with this mutation has a \>90% chance of developing many different forms of cancer in their lifetime. Since germline TP53 gene mutation carriers are highly susceptible to cancer, cancer prevention strategies and early cancer detection strategies are crucial. Unfortunately, the current standard of care for monitoring germline TP53 gene mutation carriers for early signs of cancer is yearly MRI scans and intermittent blood draws. Villani et al. showed that standard monitoring is inadequate and introduced a more sophisticated protocol for early cancer detection. We extended the Villani et al. protocol to include a number of markers for early detection and are currently vetting their utility, in terms of their inherent variability, patient tolerability of frequent interrogation, and ability to show changes that might indicate a need for further examination. In addition to the markers being collected, important covariate information, such as diet, sleep, and activities are being collected (via, e.g., wearable wireless devices) in order to take them into account in assessing the levels of the markers at a single data collection time or over time. One important aspect of the protocol is to identify changes, rather than specific levels, in marker status over time for an individual that might be indicative of tumor formation, essentially exploiting the concept of 'personalized thresholds' discussed by Drescher et al. If any indication of the presence of a cancer, tumorigenic process, or general sign of ill-health is observed, the protocol calls for a discussion of the findings among the research team, followed by a discussion between the clinical lead on the research team and the primary care provider and/or specialists overseeing a participating patient's care, possible validation of the assay(s) motivating the discussions, and a decision on how to intervene on the part of the primary care provider and/or specialists.
Registry-reported information. Elapsed time and enrollment totals alone do not measure study progress or recruitment pace.
July 2016
Actual (reported)Click on a node to explore related trials.
Dates and qualifiers reported by the registry. Estimated dates do not confirm that a milestone has occurred.
July 2014
Date type not reportedThis date has not been verified as actual or estimated.
November 10, 2014
Actual (reported)November 13, 2014
Actual (reported)July 2016
Actual (reported)July 2016
Actual (reported)Development of cancer
12 months
Individuals with functionally significant germline TP53 gene mutations who are susceptible to Li-Fraumeni Syndrome.
Scripps Clinic Medical Group
La Jolla, California, 92037, United States
Villani A, Tabori U, Schiffman J, Shlien A, Beyene J, Druker H, Novokmet A, Finlay J, Malkin D. Biochemical and imaging surveillance in germline TP53 mutation carriers with Li-Fraumeni syndrome: a prospective observational study. Lancet Oncol. 2011 Jun;12(6):559-67. doi: 10.1016/S1470-2045(11)70119-X. Epub 2011 May 19.
Chompret A, Brugieres L, Ronsin M, Gardes M, Dessarps-Freichey F, Abel A, Hua D, Ligot L, Dondon MG, Bressac-de Paillerets B, Frebourg T, Lemerle J, Bonaiti-Pellie C, Feunteun J. P53 germline mutations in childhood cancers and cancer risk for carrier individuals. Br J Cancer. 2000 Jun;82(12):1932-7. doi: 10.1054/bjoc.2000.1167.
* DNA and RNA from blood * Stool samples for microbiome analysis * Urine samples for microbiome and general biomarker analysis * Saliva samples for microbiome and general biomarker analysis * Blood for general biomarker and metabolite profiling
Nicholas J Schork, PhD
J. Craig Venter Institute
Victoria Magnuson, PhD
J. Craig Venter Institute
6 participants (actual enrollment reported by the registry).
First Submitted
November 10, 2014
First Posted
November 13, 2014
Study Start
July 2014
Date type not reportedThis date has not been verified as actual or estimated.
Contact the study team to confirm eligibility.
Ruijs MW, Verhoef S, Rookus MA, Pruntel R, van der Hout AH, Hogervorst FB, Kluijt I, Sijmons RH, Aalfs CM, Wagner A, Ausems MG, Hoogerbrugge N, van Asperen CJ, Gomez Garcia EB, Meijers-Heijboer H, Ten Kate LP, Menko FH, van 't Veer LJ. TP53 germline mutation testing in 180 families suspected of Li-Fraumeni syndrome: mutation detection rate and relative frequency of cancers in different familial phenotypes. J Med Genet. 2010 Jun;47(6):421-8. doi: 10.1136/jmg.2009.073429.
Sagne C, Marcel V, Bota M, Martel-Planche G, Nobrega A, Palmero EI, Perriaud L, Boniol M, Vagner S, Cox DG, Chan CS, Mergny JL, Olivier M, Ashton-Prolla P, Hall J, Hainaut P, Achatz MI. Age at cancer onset in germline TP53 mutation carriers: association with polymorphisms in predicted G-quadruplex structures. Carcinogenesis. 2014 Apr;35(4):807-15. doi: 10.1093/carcin/bgt381. Epub 2013 Dec 11.
Petitjean A, Achatz MI, Borresen-Dale AL, Hainaut P, Olivier M. TP53 mutations in human cancers: functional selection and impact on cancer prognosis and outcomes. Oncogene. 2007 Apr 2;26(15):2157-65. doi: 10.1038/sj.onc.1210302.
Hwang SJ, Lozano G, Amos CI, Strong LC. Germline p53 mutations in a cohort with childhood sarcoma: sex differences in cancer risk. Am J Hum Genet. 2003 Apr;72(4):975-83. doi: 10.1086/374567. Epub 2003 Feb 27.
Nichols KE, Malkin D, Garber JE, Fraumeni JF Jr, Li FP. Germ-line p53 mutations predispose to a wide spectrum of early-onset cancers. Cancer Epidemiol Biomarkers Prev. 2001 Feb;10(2):83-7.
Trkova M, Hladikova M, Kasal P, Goetz P, Sedlacek Z. Is there anticipation in the age at onset of cancer in families with Li-Fraumeni syndrome? J Hum Genet. 2002;47(8):381-6. doi: 10.1007/s100380200055.
McBride KA, Ballinger ML, Killick E, Kirk J, Tattersall MH, Eeles RA, Thomas DM, Mitchell G. Li-Fraumeni syndrome: cancer risk assessment and clinical management. Nat Rev Clin Oncol. 2014 May;11(5):260-71. doi: 10.1038/nrclinonc.2014.41. Epub 2014 Mar 18.
Drescher CW, Shah C, Thorpe J, O'Briant K, Anderson GL, Berg CD, Urban N, McIntosh MW. Longitudinal screening algorithm that incorporates change over time in CA125 levels identifies ovarian cancer earlier than a single-threshold rule. J Clin Oncol. 2013 Jan 20;31(3):387-92. doi: 10.1200/JCO.2012.43.6691. Epub 2012 Dec 17.
Ariffin H, Hainaut P, Puzio-Kuter A, Choong SS, Chan AS, Tolkunov D, Rajagopal G, Kang W, Lim LL, Krishnan S, Chen KS, Achatz MI, Karsa M, Shamsani J, Levine AJ, Chan CS. Whole-genome sequencing analysis of phenotypic heterogeneity and anticipation in Li-Fraumeni cancer predisposition syndrome. Proc Natl Acad Sci U S A. 2014 Oct 28;111(43):15497-501. doi: 10.1073/pnas.1417322111. Epub 2014 Oct 13.
Primary Completion
July 2016
Actual (reported)Study Completion
July 2016
Actual (reported)Last Updated
September 19, 2019
Record last verified: 2019-09
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