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
- Are there results?
- Not yet: the study is under way
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
Study at a glance
From the registry record, last updated by the sponsor on 16 Oct 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Frequency and Clinical Phenotype of BAP1 Hereditary Predisposition Syndrome
- ClinicalTrials.gov ID
- NCT04792463
- Acronym / sponsor ID
- 2014C0072
- Conditions
- Uveal Melanoma, Cutaneous Melanoma, BAP1 Gene Mutation, Renal Cell Carcinoma, Mesothelioma, Hepatocellular Carcinoma
- Study type
- Observational
- Recruitment status
- Recruiting
- Enrolment
- 500 participants (estimated)
- Lead sponsor
- Mohamed Abdel-RahmanUniversity, hospital or other
- Study start
- 3 Mar 2015 (actual)
- Primary completion
- 1 Jul 2027 (estimated)
- Study completion
- 1 Jul 2027 (estimated)
- First posted
- 11 Mar 2021 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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.
Study design
- Observational model
- Family based
- Time perspective
- Prospective
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| 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 |
Who may qualify
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- 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.
Key inclusion criteria (6 listed)
- 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.
Key exclusion criteria (1 listed)
- Study material including consent forms are currently only available in English so non-English speaking subjects are excluding
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
Prevalence of germline BAP1 variants in the unselected general population of cancer patients
Time frame: 5 years
Frequency of germline BAP1 pathogenic/likely pathogenic variants in different cancers
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
Questionnaire and chart review of the clinical phenotype
5 secondary outcomes
Questionnaire to assess environmental risk factors modifying cancer risk in patients
Time frame: 10 years
Genotyping to assess genetic risk factors modifying risk of cancer
Time frame: 10 years
Disease outcome (response to treatment, prognosis including prognostic markers)
Time frame: 10 years
Tumor pathology and genomics (including tumor grade, stage, somatic genomic alterations)
Time frame: 10 years
Assessment of disease penetrance and life time risk estimate
Time frame: 10 years
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 16 Oct 2026.
- Derived from this study: PubMed 41843333Godwin 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.
- Individual participant dataSharing planned: No
Related trials for Uveal Melanoma
RecruitingObservational study
High-precision Radiosurgery Followed by Minimally Invasive Surgical Approach in Patients With High-prominence Uveal Melanoma: Modern Radiation Techniques and Outcomes
Uveal Melanoma, High-risk Uveal Melanoma
RecruitingPhase 1/2
A Phase 1 and 2 Study of VMD-102 in Hepatocellular Carcinoma and Other Solid Tumors
Hepatocellular Carcinoma (HCC), Metastatic Uveal Melanoma
RecruitingPhase 2
HS-IT101 Injection Versus Chemotherapy in the Treatment of Advanced Melanoma（FASTIL-Mela02）
Melanoma (Excluding Uveal Melanoma)
Recruiting
Immune Response to Percutaneous Hepatic Perfusion With Melphalan for Ocular Melanoma Metastatic to the Liver
Uveal Melanoma
Active, not recruitingObservational study
Choroidal Melanoma Patient-Reported Outcome Study (CM-PRO) in a Subset of AU-011-301 (CoMpass) Subjects
Choroidal Melanoma, Indeterminate Lesions
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Mohamed H Abdel-Rahman, MD, PhD principal investigator
Ohio State University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Uveal Melanoma and Cutaneous Melanoma, run by Mohamed Abdel-Rahman at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 1 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 16 Oct 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Mohamed H Abdel-Rahman, MD, PhD (614-292-1396, Mohamed.Abdel-Rahman@osumc.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Prevalence of germline BAP1 variants in the unselected general population of cancer patients (time frame: 5 years). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04792463, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 16 Oct 2026.