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

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

Primary Outcome

Incidence and frequencies of Cancers

Condition

Mesothelioma

Study Arms / Comparison Groups

 1/Germline positive mesothelioma

Description:  Individuals with mesothelioma who have a BAPl or other DNA repair/cancer predispositionmutation regardless of CLIA confirmation

Publications

* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.

Estimated Enrollment

1000

Start Date

March 13, 2019

Completion Date

July 5, 2027

Primary Completion Date

July 6, 2026

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
      

Gender

All

Ages

2 Years - N/A

Accepts Healthy Volunteers

No

Contacts

Raffit Hassan, M.D., (240) 858-3152, [email protected]

Location Countries

United States

Location Countries

United States

NCT ID

NCT03830229

Organization ID

190049

Secondary IDs

19-C-0049

Responsible Party

Sponsor

Study Sponsor

National Cancer Institute (NCI)

Study Sponsor

Raffit Hassan, M.D., Principal Investigator, National Cancer Institute (NCI)

Verification Date

January 12, 2021