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Frequency and Clinical Phenotype of BAP1 Hereditary Predisposition Syndrome

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ClinicalTrials.gov Identifier: NCT04792463
Recruitment Status : Recruiting
First Posted : March 11, 2021
Last Update Posted : March 11, 2021
Sponsor:
Information provided by (Responsible Party):
Mohamed Abdel-Rahman, Ohio State University

Brief 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.

Condition or disease
Uveal Melanoma Cutaneous Melanoma BAP1 Gene Mutation Renal Cell Carcinoma Mesothelioma Hepatocellular Carcinoma Cholangiocarcinoma Meningioma Atypical

Detailed 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.

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Study Type : Observational
Estimated Enrollment : 500 participants
Observational Model: Family-Based
Time Perspective: Prospective
Official Title: Frequency and Clinical Phenotype of BAP1 Hereditary Predisposition Syndrome
Actual Study Start Date : March 3, 2015
Estimated Primary Completion Date : July 1, 2026
Estimated Study Completion Date : July 1, 2026


Group/Cohort
Patients with personal and/or family history suggestive of hereditary BAP1
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, hepatocellular carcinoma and meningioma
Pathogenic, likely pathogenic variants in BAP1 and variants of uncertain significance

Affected and unaffected individuals with pathogenic or likely pathogenic variant in BAP1 and their family members

Patients with personal family history of any of the BAP1 associated cancer and a variant of uncertain significance of BAP1




Primary Outcome Measures :
  1. Prevalence of germline BAP1 variants in the unselected general population of cancer patients [ Time Frame: 5 years ]
  2. Clinical phenotypes (this includes premalignant lesions, tumor type and age of onset) in at risk blood-line family members of the patients [ Time Frame: 5 years ]

Secondary Outcome Measures :
  1. Environmental risk factors modifying cancer risk [ Time Frame: 10 years ]
  2. Genetic risk factors modifying risk of cancer [ Time Frame: 10 years ]
  3. Disease outcome (response to treatment, prognosis including prognostic markers) [ Time Frame: 10 years ]
  4. Tumor pathology and genomics (including tumor grade, stage, somatic genomic alterations) [ Time Frame: 10 years ]
  5. Disease penetrance [ Time Frame: 10 years ]


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Ages Eligible for Study:   Child, Adult, Older Adult
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Sampling Method:   Non-Probability Sample
Study Population
Providers at OSU will identify eligible participants through clinical practice. Providers at other institutions who become aware of our research through presentations at conferences, publications, etc. may identify one of their patients as eligible or potentially eligible for the study and introduce the study to their patient.
Criteria

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04792463


Contacts
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Contact: Mohamed H Abdel-Rahman, MD, PhD 614-292-1396 Mohamed.Abdel-Rahman@osumc.edu

Locations
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United States, Ohio
The Ohio State University Wexner Medical Center Recruiting
Columbus, Ohio, United States, 43210
Contact: Mohamed H Abdel-Rahman, MD, PhD    614-292-1396    Mohamed.Abdel-Rahman@osumc.edu   
Contact: Lindsey Byrne, MS, CGC    614-293-3159    lindsey.byrne@osumc.edu   
Sponsors and Collaborators
Mohamed Abdel-Rahman
Investigators
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Principal Investigator: Mohamed H Abdel-Rahman, MD, PhD Ohio State University
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Responsible Party: Mohamed Abdel-Rahman, Associate Professor, Ohio State University
ClinicalTrials.gov Identifier: NCT04792463    
Other Study ID Numbers: 2014C0072
First Posted: March 11, 2021    Key Record Dates
Last Update Posted: March 11, 2021
Last Verified: March 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Carcinoma
Melanoma
Mesothelioma
Cholangiocarcinoma
Meningioma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Neuroendocrine Tumors
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms, Nerve Tissue
Nevi and Melanomas
Adenocarcinoma
Neoplasms by Site
Adenoma
Neoplasms, Mesothelial
Neoplasms, Vascular Tissue
Meningeal Neoplasms
Central Nervous System Neoplasms
Nervous System Neoplasms
Nervous System Diseases