Clinical trial NCT05126290: CTNNA1 Familial Expansion Study
Official title: CTNNA1 Familial Expansion (CAFÉ) Study
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Cancer Gene Mutation
Gastric Cancer
Breast Cancer
Keywords: CTNNA1
Hereditary diffuse gastric cancer
Gastric cancer
Breast cancer
Lead sponsor: Abramson Cancer Center at Penn Medicine
Sponsor class: OTHER
First posted: 2021-11-19
Enrollment: 100
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: The CAFÉ Study will recruit individuals who carry a germline CTNNA1 loss-of-function variant as well as first degree relatives of germline CTNNA1 loss-of-function variant carriers.

Brief summary: The goal of the CAFÉ Study is to determine the cancer risks associated with germline CTNNA1 loss-of-function variants.

Detailed description: The CAFÉ Study aims to determine the degree to which loss-of-function variants in the CTNNA1 gene are associated with hereditary cancers, including gastric cancer, breast cancer, as well as other cancers that may be associated with this gene. By obtaining personal and family history information from individuals who carry a CTNNA1 loss-of-function variant and their family members, this study will aim to better define CTNNA1 associated cancer risks and determine whether there is a genotype/phenotype correlation for CTNNA1 loss-of-function variants. This information will be important for the future cancer risk management of individuals who carry a CTNNA1 loss-of-function variant.

Eligibility criteria: Inclusion Criteria:

* 18 years of age and older
* Participants must be carrier, or a first degree relative of a carrier, of a CTNNA1 loss-of-function variant defined as: a variant predicted to lead to protein truncation (nonsense and frameshift variants), a large deletion of one or more exons, or a consensus splice site variant predicted to disrupt splicing in CTNNA1. CTNNA1 loss-of-function variants do not need to be classified as pathogenic or likely pathogenic to be included.
* Participants must be able to understand and read English
* Participants must be able to provide informed verbal or written consent

Exclusion Criteria:

* Less than 18 years of age
* Individuals who do not carry a CTNNA1 loss-of-function variant and are not a first degree relative of a CTNNA1 loss-of-function variant carrier.
* Individuals who cannot speak and read English
* Major psychiatric illness or cognitive impairment that in the judgement of the study investigators or study staff would preclude study participation
* Unable to comply with the study procedures as determined by the study investigators or study staff

Primary outcomes:
measure: Rate of cancer amongst carriers of CTNNA1 loss-of-function variants
timeFrame: Through study completion, which will average 1 year
measure: Number of CTNNA1 genotypes associated with a cancer phenotype
timeFrame: Through study completion, which will average 1 year
Secondary outcomes:
Other outcomes:
Locations:
city: Philadelphia
country: United States
facility: Abramson Cancer Center of the University of Pennsylvania
state: Pennsylvania
Study officials:
affiliation: University of Pennsylvania
name: Bryson W Katona, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Clark DF, Michalski ST, Tondon R, Nehoray B, Ebrahimzadeh J, Hughes SK, Soper ER, Domchek SM, Rustgi AK, Pineda-Alvarez D, Anderson MJ, Katona BW. Loss-of-function variants in CTNNA1 detected on multigene panel testing in individuals with gastric or breast cancer. Genet Med. 2020 May;22(5):840-846. doi: 10.1038/s41436-020-0753-1. Epub 2020 Feb 13.