Clinical and Histopathologic Characteristics of BAP1 Mutations

Renal Cell Carcinoma Clinical Trial

Official title:

Clinical and Histopathologic Characteristics of BAP1 Mutations

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01773655
• Other study ID #: 12-235
• Status: Completed
• Start date: January 2013
• Est. completion date: June 30, 2020

Study information

• Verified date: June 2020
• Source: Memorial Sloan Kettering Cancer Center
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 196
• Est. completion date: June 30, 2020
• Est. primary completion date: June 30, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Carcinoma, Renal Cell
• Cholangiocarcinoma
• Choroidal Nevus
• Malignant Pleural Mesothelioma (MPM)
• Melanoma
• Mesothelioma
• Metastatic Uveal Melanoma (UM)
• Primary Uveal Melanoma (UM)
• Renal Cell Carcinoma
• Uveal Neoplasms

Intervention

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.

Locations

Country	Name	City	State
United States	Memorial Sloan Kettering Westchester	Harrison	New York
United States	Memorial Sloan Kettering Cancer Center	New York	New York

Sponsors (2)

Lead Sponsor	Collaborator
Memorial Sloan Kettering Cancer Center	United States Department of Defense

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	determine the prevalence of germline BAP1 mutations	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	prevalence of somatic BAP1 mutations in disease mesothelioma and metastatic uveal melanoma.	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

External Links

•   Memorial Sloan Kettering Cancer Center