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Long Term Follow-up of Mesothelioma Patients and Their Family Members With Germline Mutations in BAP1 and Other Genes

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ClinicalTrials.gov Identifier: NCT03830229
Recruitment Status : Recruiting
First Posted : February 5, 2019
Last Update Posted : April 28, 2021
Sponsor:
Information provided by (Responsible Party):
National Institutes of Health Clinical Center (CC) ( National Cancer Institute (NCI) )

Tracking Information
First Submitted Date February 2, 2019
First Posted Date February 5, 2019
Last Update Posted Date April 28, 2021
Actual Study Start Date March 13, 2019
Estimated Primary Completion Date July 6, 2026   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures
 (submitted: February 2, 2019)
Incidence and frequencies of Cancers [ Time Frame: ongoing ]
Standard exploratory and descriptive measures will be used. Counts, incidence, and frequencies of cancers identified via screening procedures on this trial will be reported, all in the context of an exploratory study with appropriate caveats.
Original Primary Outcome Measures Same as current
Change History
Current Secondary Outcome Measures Not Provided
Original Secondary Outcome Measures Not Provided
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title Long Term Follow-up of Mesothelioma Patients and Their Family Members With Germline Mutations in BAP1 and Other Genes
Official Title Long Term Follow-up of Mesothelioma Patients and Their Family Members With Germline Mutations in BAP1 and Other Genes
Brief Summary

Background:

-A gene provides instructions to the body. Mutated genes can sometimes cause cancer. Germline mutations are those people are born with. These mutations in the BAP1 gene can cause mesothelioma and other cancers. Researchers want to study people with germline mutations of BAP1 and other genes known to cause cancer.

Objective:

-To learn how cancer might develop in people with certain gene mutations.

Eligibility:

-People ages 2 and older with a germline mutation in BAP1 or another gene that might cause cancer

Design:

  • Participants will be screened with:

    • Medical and family history
    • Saliva test
  • Participants with mesothelioma will be in the NIH Group. Participants without mesothelioma can choose to be in either the NIH Group or the Remote Group.
  • Remote Group participants will have a medical and family history by phone. If they have tumor tissue from a previous surgery, it will be tested. They will be contacted once a year by phone.
  • NIH Group participants will have a baseline visit. This can take up to 4 days. They may have to stay in the area overnight. The visit will include:

    • Physical exam
    • Evaluation of tumor tissue if available
    • Optional tumor biopsy
    • Blood tests
    • Scans: A machine will take pictures of the body.
    • Photographs of skin lesions or other issues
    • Skin exam
    • Eye exam
  • NIH Group participants will have visits once or twice a year. These will include a physical exam, lab tests, scans, and other tests as needed.
  • Participants who have a confirmed mutation will be asked to contact any relatives who may be at risk and ask them about joining the study.
Detailed Description

Background:

  • BRCA1-Associated Protein-1 (BAP1), a deubiquitinase involved in regulating DNA repair enzymes, is believed to be a prominent mutation in malignant mesothelioma
  • Germline mutations involving BAP1 have been reported in familial studies. These have been associated with a higher likelihood of mesothelioma as well as several other malignancies, including uveal melanoma, cutaneous melanomas, renal cell carcinoma and cholangiocarcinoma
  • BAP1 mutations, if found, have a high probability of detecting multiple malignancies in family members.

Objectives:

-To characterize the natural and clinical history of malignant mesothelioma patients and their family members who have germline mutations in BAP1 and other DNA repair/cancer predisposition genes

Eligibility for Genetic Testing:

Cohort 1

-Individual with mesothelioma with deleterious germline mutations in BAP1 or another DNA-repair/cancer predisposition gene(s) (previous testing may have been research or clinical)

OR

  • Individual with a diagnosis of mesothelioma who is otherwise eligible for testing on Cohort 2
  • Age greater than or equal to 2

Cohort 2

-Individual with a germline BAP1 mutation who does not have a history of mesothelioma (previous testing may have been research or clinical)

OR

-Individual with no personal history of mesothelioma with:

--a first degree biological relative (living or deceased) with a history of mesothelioma

OR

--a first degree biological relative with a CLIA confirmed germline mutation in BAP1

OR

--a first degree biological relative with mesothelioma and a CLIA confirmed germline mutation in another DNA-repair/cancer predisposition genes

OR

--a second degree biological relative with mesothelioma and a CLIA confirmed germline mutation in BAP1

-Age greater than or equal to 16 unless participant has a BAP1 mutation or a first degree biological relative with a confirmed TP53 or BAP1 germline mutation; in such cases, will begin screening at age greater than or equal to 2

Eligibility for Surveillance:

Cohort 1

-No additional criteria

Cohort 2

-Testing performed on study must confirm presence of germline mutation in BAP1 or another DNA repair/cancer predisposition gene(s)

Design:

  • Individuals with suspected hereditary predisposition to mesothelioma and their families will be recruited to assess for genetic mutations, and to study the natural history of malignancies occurring in germline BAP1 mutations as well as other mutations involved in DNA repair.
  • Screening examinations will be offered to those with germline BAP1 mutations as well as other mutations involved in DNA repair/cancer predisposition.
  • We will determine if there is a relationship between germline mutation and disease phenotype.
Study Type Observational
Study Design Observational Model: Cohort
Time Perspective: Prospective
Target Follow-Up Duration Not Provided
Biospecimen Not Provided
Sampling Method Non-Probability Sample
Study Population Persons with mesothelioma and family members as well as individuals with CLIA documented germline BAP-1 and other DNA repair/cancer predisposition mutations
Condition
  • Mesothelioma
  • Families
Intervention Not Provided
Study Groups/Cohorts
  • 1/Germline positive mesothelioma
    Individuals with mesothelioma who have a BAPl or other DNA repair/cancer predispositionmutation regardless of CLIA confirmation
  • 2/CLIA confirmed germline mutation without mesothelioma
    Individuals with a CLIA confirmed BAP1 or other DNA repair/cancer predisposition mutation who do not have a diagnosis of mesothelioma
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status Recruiting
Estimated Enrollment
 (submitted: February 2, 2019)
1000
Original Estimated Enrollment Same as current
Estimated Study Completion Date July 5, 2027
Estimated Primary Completion Date July 6, 2026   (Final data collection date for primary outcome measure)
Eligibility Criteria
  • Inclusion Criteria:

Inclusion Criteria for Genetic Testing:

Cohort 1:

  • Subject with pathology confirming a diagnosis of mesothelioma.
  • Subject must have a deleterious germline BAP1 mutation. Results from either research or clinical analyses are sufficient for this criterion.

OR

-Subject with mesothelioma otherwise eligible for genetic testing in Cohort 2

OR

  • Subject must have deleterious germline mutation in another DNA repair/cancer predisposition gene(s) that is listed on a commercially available, cancer-associated common or customized gene panel. Results from either research or clinical analyses are sufficient for this criterion.
  • Age greater than or equal to 2 years

Cohort 2:

-Individual with a germline BAP1 mutation who does not have a history of mesothelioma (other cancers are allowed). Results from either research or clinical analyses are sufficient for this criterion.

OR

-Individual with no history of mesothelioma with either:

--A biological first degree relative (living or deceased) with a history of mesothelioma

OR

--A first degree biological relative with a CLIA confirmed germline mutation in BAP1

OR

--A first degree biological relative with mesothelioma and a CLIA confirmed germline mutation in another DNA-repair/cancer predisposition gene that is listed on a commercially available, cancer-associated common or customized gene panel

OR

  • A second degree biological relative with mesothelioma and a CLIA confirmed germline mutation in BAP1

    -Age:

  • greater than or equal to 2 years for subjects with a BAP1 or TP53 mutation or with a first degree relative relative that has a germline mutation in TP53 or BAP1
  • greater than or equal to 16 years for all other eligible potential mutations

All participants must understand and be willing to sign a written informed consent

Exclusion Criteria for Genetic Testing

None

Inclusion Criteria for Surveillance:

  • Genetic testing criteria including age restrictions for respective cohorts must be met
  • Subjects in Cohort 1 may be enrolled with positive results for germline BAP1 mutation or another DNA repair/cancer predisposition gene(s) that is listed on a commercially available, cancer-associated common or customized gene panel regardless of CLIA confirmation
  • Subjects in Cohort 2 must have CLIA confirmed germline BAP1 mutation or another DNA repair/cancer predisposition gene(s) that is listed on a commercially available, cancer-associated common or customized gene panel

Exclusion Criteria for Surveillance:

None

Sex/Gender
Sexes Eligible for Study: All
Ages 2 Years and older   (Child, Adult, Older Adult)
Accepts Healthy Volunteers No
Contacts
Contact: Maria G Agra, R.N. (240) 858-3152 mariagracia.agra@nih.gov
Listed Location Countries United States
Removed Location Countries  
 
Administrative Information
NCT Number NCT03830229
Other Study ID Numbers 190049
19-C-0049
Has Data Monitoring Committee Not Provided
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement Not Provided
Responsible Party National Institutes of Health Clinical Center (CC) ( National Cancer Institute (NCI) )
Study Sponsor National Cancer Institute (NCI)
Collaborators Not Provided
Investigators
Principal Investigator: Raffit Hassan, M.D. National Cancer Institute (NCI)
PRS Account National Institutes of Health Clinical Center (CC)
Verification Date April 22, 2021