Clinical and Histopathologic Characteristics of BAP1 Mutations

June 30, 2020 updated by: Memorial Sloan Kettering Cancer Center
The goal of this protocol is to determine the prevalence of somatic and germline mutations in BAP1 (BRCA associated protein-1) among patients with mesothelioma , choroidal nevus, primary uveal melanoma (UM), or metastatic UM seen at our institution.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Study Type

Observational

Enrollment (Actual)

196

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • New York
      • Harrison, New York, United States, 10604
        • Memorial Sloan Kettering Westchester
      • New York, New York, United States, 10065
        • Memorial Sloan Kettering Cancer Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Sampling Method

Non-Probability Sample

Study Population

MSKCC's clinics

Description

Inclusion Criteria:

All consents:

  • > or = to 18 years of age
  • Ability to provide informed consent

Consent 1:

Mesothelioma

  • Histologically proven diagnosis of Mesothelioma OR Choroidal nevus
  • Diagnosis of choroidal nevus by direct examination and/or ultrasound/optical coherence tomography and possibly fluorescein angiography OR Primary uveal melanoma
  • Diagnosis of uveal melanoma by direct examination and/or ultrasound/optical coherence tomography and possibly fluorescein angiography

Consent 2:

Mesothelioma

  • Histologically proven diagnosis of Mesothelioma AND
  • BAP1 mutation or loss of expression identified in tumor sample

OR one of the following:

  • Age<50 at diagnosis
  • No history of asbestos exposure
  • Personal history of choroidal nevus, uveal melanoma, melanoma, renal cell carcinoma, or cholangiocarcinoma
  • Family history of choroidal nevus, uveal melanoma, mesothelioma, renal cell carcinoma, or cholangiocarcinoma
  • History of malignancy in more than two first-degree relatives OR Choroidal nevus
  • Diagnosis of choroidal nevus by direct examination and/or ultrasound/optical coherence tomography and possibly fluorescein angiography AND one of the following:
  • More than one clinical risk factor, which may include: orange pigment, thickness > 1 < 2.5mm
  • Personal history of uveal melanoma, skin melanoma, mesothelioma renal cell carcinoma, or cholangiocarcinoma
  • Family history of choroidal nevus, uveal melanoma, mesothelioma renal cell carcinoma, or cholangiocarcinoma OR Primary uveal melanoma
  • Diagnosis of uveal melanoma by direct examination and/or ultrasound/optical coherence tomography and possibly fluorescein angiography

AND one of the following:

  • Personal history of uveal melanoma, skin melanoma, mesothelioma, renal cell carcinoma, or cholangiocarcinoma
  • Family history of choroidal nevus, uveal melanoma, mesothelioma, renal cell carcinoma, or cholangiocarcinoma
  • History of malignancy in more than two first-degree relatives OR Metastatic uveal melanoma
  • Histologically proven diagnosis of metastatic uveal melanoma AND
  • BAP1 mutation or loss of expression identified in tumor sample

OR one of the following:

  • Personal history of uveal melanoma, skin melanoma, mesothelioma renal cell carcinoma, or cholangiocarcinoma
  • Family history of choroidal nevus, uveal melanoma, mesothelioma renal cell carcinoma, or cholangiocarcinoma
  • History of malignancy in more than two first-degree relatives

Consent 3:

  • Relative of patient with germline BAP1 mutation identified through identified testing

Exclusion Criteria:

  • none

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Observational Models: Cohort
  • Time Perspectives: Prospective

Cohorts and Interventions

Group / Cohort
Intervention / Treatment
tissue
This is a protocol to obtain and/or analyze tumor and germline DNA specimens of patients with MPM, choroidal nevus, and UM.
Other: tumor specimens

All consenting patients (Consent 1) will participate in an anonymized assessment of the prevalence of germline BAP1 mutations. Available tumor specimens from patients with MPM and metastatic uveal melanoma will be tested for BAP1 mutation. Patients whose tumors harbor BAP1 mutations and/or meet the criteria for germline mutation specified in 2.2.2 will be approached for identified germline BAP1 testing after appropriate pre-test counseling (Consent 2).

Patients who, through identified testing, are found to have germline BAP1 mutations will be asked to invite their relatives to participate in germline testing (Consent 3). First-degree relatives and any relatives with a malignancy will be prioritized. Expanding testing to family members of patients with BAP1 germline mutations is essential to delineate the penetrance and describe the various manifestations of this new cancer predisposition syndrome.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
determine the prevalence of germline BAP1 mutations
Time Frame: 2 years
Prevalence will be estimated as the proportion of all specimens who tested positive for mutation, and reported along with the corresponding exact 95% confidence intervals.
2 years

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
prevalence of somatic BAP1 mutations in disease mesothelioma and metastatic uveal melanoma.
Time Frame: 2 years

The frequency of somatic mutations will be tabulated by factors of interest such as:

  • personal and familial risk factors: age, smoking, and asbestos mesothelioma, personal and family history of cancer or of related diseases (mesothelioma and metastatic uveal melanoma)
  • disease characteristics: histology, stage, location, site of metastasis (if present) (for mesothelioma and metastatic uveal melanoma); COMS criteria, GEP class, number of clinical risk factors (for metastatic uveal melanoma)
2 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Memorial Sloan Kettering Cancer Center

Collaborators

United States Department of Defense

Investigators

  • Principal Investigator: Marjorie Zauderer, MD, Memorial Sloan Kettering Cancer Center

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

January 1, 2013

Primary Completion (Actual)

June 30, 2020

Study Completion (Actual)

June 30, 2020

Study Registration Dates

First Submitted

January 18, 2013

First Submitted That Met QC Criteria

January 18, 2013

First Posted (Estimate)

January 23, 2013

Study Record Updates

Last Update Posted (Actual)

July 1, 2020

Last Update Submitted That Met QC Criteria

June 30, 2020

Last Verified

June 1, 2020

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 12-235

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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