Frequency and Clinical Phenotype of BAP1 Hereditary Predisposition Syndrome

Hepatocellular Carcinoma Clinical Trial

Official title:

Frequency and Clinical Phenotype of BAP1 Hereditary Predisposition Syndrome

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04792463
• Other study ID #: 2014C0072
• Status: Recruiting
• Start date: March 3, 2015
• Est. completion date: July 1, 2026

Study information

• Verified date: October 2023
• Source: Ohio State University
• Contact: Mohamed H Abdel-Rahman, MD, PhD
• Phone: 614-292-1396
• Email: Mohamed.Abdel-Rahman[@]osumc.edu
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

This research will have a significant impact on the overall management of those cancer patients and their family members who are at risk for hereditary cancer due to germline inactivation of BAP1. Our study will ultimately facilitate the development of novel screening, prevention and treatment strategies for these individuals with the syndrome. Because the vast majority of UM develop in pre-existing nevi, characterization of individuals at high risk for development of UM will allow closer screening and earlier intervention which would improve the treatment outcome not only for retaining vision but also for overall survival. Similarly in patients with germline BAP1 mutation CM develops in premalignant atypical melanocytic lesions and careful follow up of these patients will improve the outcome of their disease. In addition this study could have impact on the management of patients with personal and/or family history of several other cancers reported in patients with germline BAP1 mutation such as mesothelioma, renal cell carcinoma, cholangiocarcinoma, hepatocellular carcinoma, meningioma and basal cell carcinoma.

Description:

BAP1 (BRCA1-associated protein-1), is a deubiquitinating enzyme with a ubiquitin carboxy-terminal hydrolase function that has been suggested to be a tumor suppressor gene with a role in cell proliferation and growth inhibition. Recently germline mutations in BAP1 have been identified by our group and others in families with hereditary cancers. However, the clinical spectrum of cancers in patients with germline BAP1 is still not clear. The association of germline BAP1 mutations with increased risks for uveal melanoma (UM), mesothelioma, cutaneous melanoma (CM), renal cell carcinoma (RCC) and BAP1-inactivated melanocytic tumors is fairly well established. However, several other cancers have been reported in these patients and their family members including cholangiocarcinoma, hepatocellular carcinoma, meningioma, basal cell carcinoma and other internal malignancies. Identification of the clinical phenotype of BAP1-TPDS is important for proper counseling and management of patients.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 500
• Est. completion date: July 1, 2026
• Est. primary completion date: July 1, 2026
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: N/A and older

Eligibility

Inclusion Criteria:

Patients who meet any of the following criteria:

1. Personal history of one cancer reported in BAP1 cancer predisposition syndrome and family history of at least two 1st or 2nd degree relatives with cancer reported in hereditary BAP1 cancer predisposition syndrome such as UM, CM, mesothelioma, RCC, cholangiocarcinoma, meningioma and hepatocellular carcinoma.

2. Any patient with personal history of at least 2 cancers reported in hereditary BAP1 cancer predisposition syndrome.

3. Any subject (affected or unaffected) with a documented BAP1 pathogenic/ likely pathogenic variant.

4. Any patient with a cancer reported in BAP1 and a germline variant of uncertain significance.

5. At risk relatives of a patient with documented BAP1 mutation.

Exclusion Criteria:

• Study material including consent forms are currently only available in English so non-English speaking subjects are excluding

Related Conditions & MeSH terms

• BAP1 Gene Mutation
• Carcinoma
• Carcinoma, Renal Cell
• Cholangiocarcinoma
• Cutaneous Melanoma
• Disease Susceptibility
• Hepatocellular Carcinoma
• Melanoma
• Meningioma
• Meningioma Atypical
• Mesothelioma
• Renal Cell Carcinoma
• Uveal Melanoma

Locations

Country	Name	City	State
United States	The Ohio State University Wexner Medical Center	Columbus	Ohio

Sponsors (1)

Lead Sponsor	Collaborator
Mohamed Abdel-Rahman

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Prevalence of germline BAP1 variants in the unselected general population of cancer patients	Frequency of germline BAP1 pathogenic/likely pathogenic variants in different cancers	5 years
Primary	Clinical phenotypes (this includes premalignant lesions, tumor type and age of onset) in at risk blood-line family members of the patients	Questionnaire and chart review of the clinical phenotype	5 years
Secondary	Questionnaire to assess environmental risk factors modifying cancer risk in patients	Measurement used: questionnaire for various environmental risk factors	10 years
Secondary	Genotyping to assess genetic risk factors modifying risk of cancer	Genotyping for genetic variants that could modify the risk of cancer in subjects.	10 years
Secondary	Disease outcome (response to treatment, prognosis including prognostic markers)	Chart review of disease outcome	10 years
Secondary	Tumor pathology and genomics (including tumor grade, stage, somatic genomic alterations)	Review of pathology and study of genomics alterations in tumors	10 years
Secondary	Assessment of disease penetrance and life time risk estimate	Statistical assessment of disease penetrance and life time risk estimates of various cancers	10 years