Clinical Trial: Biomarker Monitoring in TP53 Mutation Carriers

Study Status: Active, not recruiting
Recruit Status: Active, not recruiting
Study Type: Observational

Official Title: Biomarker Monitoring for a Young Individual Carrying a TP53 Gene Mutation in a Familial High-Cancer Predisposition Setting

Brief Summary:

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, fo

Detailed Summary:

Individuals who carry certain germline TP53 gene mutations are highly susceptible to cancer and are likely to develop any one, or many, cancer types during their lifetimes. Prevention strategies and early tumor detection strategies are crucial for such individuals. It has been shown by Villani et al. that aggressive monitoring of markers of cancer can lead to much better outcomes (e.g., earlier detection of cancer) than standard monitoring protocols. However, the choice of markers for use in early detection that can indicate the presence of cancer and surveillance and monitoring strategies of patients or individuals with specific cancer predispositions, such as inherited cancer syndromes, is complex. This choice is often guided by the observed utility of a set of markers among a broader list of potential markers in large-scale population-level clinical studies. However, the utility of an early detection or surveillance strategy based on a set of markers in the population at large does not necessarily translate to the utility of those markers for a particular individual. This phenomenon is even more problematic for individuals with rare hereditary cancer syndromes and conditions, such as individuals with germline TP53 gene mutations, as these individuals are highly susceptible to different types of cancer over their lifetimes. Even among individuals with TP53 mutations there is variation in the age-of-onset of cancers due to other factors, such as exposures to carcinogenic substances and the presences of other susceptibility mutations (Arrifin et al. 2015). In addition, given that individuals with inherited TP53 mutations are indeed rare, there are no large-scale studies that have been pursued to identify sets of markers that might be useful for monitoring TP53 mutation carriers going forward for signs of cancer and or disease generally.

Specifically, individuals who inher
Sponsor: Scripps Health

Current Primary Outcome: Development of cancer [ Time Frame: 12 months ]

Original Primary Outcome: Same as current

Current Secondary Outcome:

Original Secondary Outcome:

Information By: Scripps Health

Dates:
Date Received: November 10, 2014
Date Started: July 2014
Date Completion: July 2017
Last Updated: April 26, 2015
Last Verified: April 2015