Long-term follow-up of mesothelioma patients with specific gene mutations

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

This study is looking to see how mesothelioma and certain gene mutations affect patients and their families over time, and it includes people aged 2 and older who have these mutations.

Quick facts

• Study type: Observational
• Enrollment: 1000 (estimated)
• Ages: 2 Years and up
• Sex: All
• Sponsor: National Institutes of Health Clinical Center (CC) (NIH)
• Locations: 1 site (Bethesda, Maryland)
• Trial ID: NCT03830229 on ClinicalTrials.gov

What this trial studies

This observational study aims to investigate the natural and clinical history of patients with mesothelioma and their family members who have germline mutations in the BAP1 gene and other cancer predisposition genes. Participants, aged 2 and older, will be screened through medical and family history assessments and saliva tests. Those with mesothelioma will be part of the NIH Group, while others can choose to participate in either the NIH Group or a Remote Group, which involves annual phone contact and potential tumor tissue testing. The study seeks to understand how cancer develops in individuals with these genetic mutations.

Who should consider this trial

Good fit: Ideal candidates include individuals aged 2 and older with a germline mutation in BAP1 or other cancer predisposition genes, as well as their family members.

Not a fit: Patients without a germline mutation in BAP1 or other relevant cancer predisposition genes may not benefit from this study.

Why it matters

Potential benefit: If successful, this study could provide insights into cancer development in patients with specific genetic mutations, potentially leading to improved screening and prevention strategies.

How similar studies have performed: Other studies have shown success in understanding the implications of germline mutations in cancer predisposition, making this approach both relevant and potentially impactful.

Eligibility criteria

* Inclusion Criteria:

Inclusion Criteria for Genetic Testing:

Cohort 1:

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

OR

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

OR

* Participant 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:

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

OR

--A first degree biological relative with a CLIA (or equivalent) confirmed germline mutation in BAP1

OR

--A second degree biological relative with a CLIA (or equivalent) confirmed germline mutation in BAP1 if relevant first degree relative is deceased or unavailable for testing,

OR

--A first degree biological relative with mesothelioma and a CLIA (or equivalent) 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 (or equivalent) confirmed germline mutation in BAP1

  -Age:
* greater than or equal to 2 years for participants with a BAP1 or TP53 mutation or with a first degree 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
* Participants 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 (or equivalent) confirmation
* Participants in Cohort 2 must have CLIA (or equivalent) 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

OR

-if germline status negative, have a biological relative that is enrolled for surveillance

Exclusion Criteria for Surveillance:

None

Where this trial is running

Bethesda, Maryland

• National Institutes of Health Clinical Center — Bethesda, Maryland, United States (Recruiting)

Study contacts

• Principal investigator: Raffit Hassan, M.D. — National Cancer Institute (NCI)
• Study coordinator: Maria Gracia L Agra, R.N.

Conditions Mesothelioma; Families; DNA Repair Genes; Natural History