Uveal MelanomaNCT04792463
Frequency and Clinical Phenotype of BAP1 Hereditary Predisposition Syndrome
An observational study of Uveal Melanoma and Cutaneous Melanoma, run by Mohamed Abdel-Rahman at 1 site in United States.
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. Read more about this study
- Who is it for?
- Any ageHealthy volunteers can take part
- Conditions the study is for
- Uveal Melanoma, Cutaneous Melanoma, BAP1 Gene Mutation
- How many people
- 500 participants
- Where
- 1 siteUnited States
- Study dates
- 3 Mar 2015to 1 Jul 2027
- Phase
- Observational
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages Any age
- All sexes
- Healthy volunteers accepted
- Child, Adult, Older adult
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.
Who may be able to join
- Patients who meet any of the following criteria:
- 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.
- Any patient with personal history of at least 2 cancers reported in hereditary BAP1 cancer predisposition syndrome.
- Any subject (affected or unaffected) with a documented BAP1 pathogenic/ likely pathogenic variant.
- Any patient with a cancer reported in BAP1 and a germline variant of uncertain significance.
- At risk relatives of a patient with documented BAP1 mutation.
Who cannot join
- Study material including consent forms are currently only available in English so non-English speaking subjects are excluding
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United States1 site, 1 recruiting
- Recruiting
The Ohio State University Wexner Medical Center
Columbus, Ohio, 43210
Mohamed H Abdel-Rahman, MD, PhD, 614-292-1396, Mohamed.Abdel-Rahman@osumc.edu
Lindsey Byrne, MS, CGC, 614-293-3159, lindsey.byrne@osumc.edu
About this study
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.
Read the 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.
- Conditions
- Uveal Melanoma, Cutaneous Melanoma, BAP1 Gene Mutation, Renal Cell Carcinoma, Mesothelioma, Hepatocellular Carcinoma
- Medical subject headings
- Uveal Melanoma, Melanoma, Carcinoma, Renal Cell, Mesothelioma, Carcinoma, Hepatocellular, Cholangiocarcinoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
| Study group | Role | What they receive |
|---|---|---|
| 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 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Prevalence of germline BAP1 variants in the unselected general population of cancer patients
Frequency of germline BAP1 pathogenic/likely pathogenic variants in different cancers
Measured: 5 years
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
Measured: 5 years
Secondary outcomes (5)
Questionnaire to assess environmental risk factors modifying cancer risk in patients
Measurement used: questionnaire for various environmental risk factors
Measured: 10 years
Genotyping to assess genetic risk factors modifying risk of cancer
Genotyping for genetic variants that could modify the risk of cancer in subjects.
Measured: 10 years
Disease outcome (response to treatment, prognosis including prognostic markers)
Chart review of disease outcome
Measured: 10 years
Tumor pathology and genomics (including tumor grade, stage, somatic genomic alterations)
Review of pathology and study of genomics alterations in tumors
Measured: 10 years
Assessment of disease penetrance and life time risk estimate
Statistical assessment of disease penetrance and life time risk estimates of various cancers
Measured: 10 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Mar 2021
- Study start3 Mar 2015
- Primary completion1 Jul 2027 (estimated)
- Study completion1 Jul 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Uveal MelanomaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Family based
- Time perspective
- Prospective
- Enrolment
- 500 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Mohamed Abdel-Rahman
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor-investigator, Mohamed Abdel-Rahman, Ohio State University
- Investigators
- Mohamed H Abdel-Rahman, MD, PhD, Principal investigator, Ohio State University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04792463
- Sponsor's protocol ID
- 2014C0072
- Status last verified
- Oct 2026
- First submitted
- 7 Mar 2021
- Last updated
- 16 Oct 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Godwin K, McElroy J, Senter L, Byrne L, Abdel-Rahman MH. Patient-derived outcome assessment of knowledge, communication, and management in those diagnosed with BAP1-tumor predisposition syndrome. Fam Cancer. 2026 Mar 17;25(2):28. doi: 10.1007/s10689-026-00541-8.
PubMed 41843333