Clinical and Histopathologic Characteristics of BAP1 Mutations

This study is currently recruiting participants. (see Contacts and Locations)
Verified July 2014 by Memorial Sloan-Kettering Cancer Center
Sponsor:
Information provided by (Responsible Party):
Memorial Sloan-Kettering Cancer Center
ClinicalTrials.gov Identifier:
NCT01773655
First received: January 18, 2013
Last updated: July 3, 2014
Last verified: July 2014
  Purpose

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.


Condition Intervention
Malignant Pleural Mesothelioma (MPM)
Choroidal Nevus
Primary Uveal Melanoma (UM)
Metastatic Uveal Melanoma (UM)
Renal Cell Carcinoma
Cholangiocarcinoma
Other: tumor specimens

Study Type: Observational
Study Design: Observational Model: Cohort
Time Perspective: Prospective
Official Title: Clinical and Histopathologic Characteristics of BAP1 Mutations

Resource links provided by NLM:


Further study details as provided by Memorial Sloan-Kettering Cancer Center:

Primary Outcome Measures:
  • determine the prevalence of germline BAP1 mutations [ Time Frame: 2 years ] [ Designated as safety issue: No ]
    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.


Secondary Outcome Measures:
  • prevalence of somatic BAP1 mutations in disease mesothelioma and metastatic uveal melanoma. [ Time Frame: 2 years ] [ Designated as safety issue: No ]

    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)


Biospecimen Retention:   Samples With DNA

tissue specimens blood or saliva sample


Estimated Enrollment: 460
Study Start Date: January 2013
Estimated Study Completion Date: January 2015
Estimated Primary Completion Date: January 2015 (Final data collection date for primary outcome measure)
Groups/Cohorts Assigned Interventions
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.


  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population

MSKCC's clinics

Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01773655

Contacts
Contact: Marjorie Zauderer, MD 646-888-4656
Contact: David Abramson, M.D. 212-639-7232

Locations
United States, New York
Memorial Sloan Kettering Cancer Center Recruiting
New York, New York, United States, 10065
Contact: Marjorie Zauderer, MD    646-888-4656      
Contact: David Abramson, MD    212-639-7232      
Principal Investigator: Marjorie Zauderer, MD         
Sponsors and Collaborators
Memorial Sloan-Kettering Cancer Center
Investigators
Principal Investigator: Marjorie Zauderer, MD Memorial Sloan-Kettering Cancer Center
  More Information

Additional Information:
No publications provided

Responsible Party: Memorial Sloan-Kettering Cancer Center
ClinicalTrials.gov Identifier: NCT01773655     History of Changes
Other Study ID Numbers: 12-235
Study First Received: January 18, 2013
Last Updated: July 3, 2014
Health Authority: United States: Institutional Review Board

Keywords provided by Memorial Sloan-Kettering Cancer Center:
somatic
germline
mutations
BAP1 (BRCA associated protein-1)
12-235

Additional relevant MeSH terms:
Nevi and Melanomas
Carcinoma
Carcinoma, Renal Cell
Melanoma
Mesothelioma
Cholangiocarcinoma
Uveal Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Adenocarcinoma
Kidney Neoplasms
Urologic Neoplasms
Urogenital Neoplasms
Neoplasms by Site
Kidney Diseases
Urologic Diseases
Neuroendocrine Tumors
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms, Nerve Tissue
Adenoma
Neoplasms, Mesothelial
Eye Neoplasms
Eye Diseases
Uveal Diseases

ClinicalTrials.gov processed this record on July 26, 2014