Prospective Evaluation of High Resolution Dual Energy Computed Tomographic Imaging, Noninvasive (Liquid) Biopsies, and Minimally Invasive Surgical Surveillance for Early Detection of Mesotheliomas in Patients With BAP1 Tumor Predisposition Syndrome

Mesothelioma Clinical Trial

Official title:

Prospective Evaluation of High Resolution Dual Energy Computed Tomographic Imaging, Noninvasive (Liquid) Biopsies, and Minimally Invasive Surgical Surveillance for Early Detection of Mesotheliomas in Patients With BAP1 Tumor Predisposition Syndrome

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04431024
• Other study ID #: 200106
• Secondary ID: 20-C-0106
• Status: Recruiting
• Start date: March 30, 2021
• Est. completion date: June 30, 2038

Study information

• Verified date: June 11, 2024
• Source: National Institutes of Health Clinical Center (CC)
• Contact: Deneise Francis, R.N.
• Phone: (240) 858-3974
• Email: deneise.francis[@]nih.gov
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

Background:

A germline mutation is a change to a person s genes that is carried through their DNA. These mutations can be passed on from parents to their offspring. Germline mutations in a gene called BAP1 are linked to the development of mesothelioma and other cancers. Researchers want to follow people with these mutations to learn more.

Objective:

To see if researchers can improve how people who have or are suspected to have a BAP1 mutation are monitored over time.

Eligibility:

People age 30 and older who are suspected to have a BAP1 germline mutation.

Design:

Participants will be screened with a personal and family medical history. Their medical records may be reviewed. They will give a blood or saliva sample to test for a BAP1 mutation. They will get genetic counseling.

To take part in this study, participants will enroll on 2 to 3 other protocols.

Participants will have a physical exam. They may have a tumor biopsy. They will give blood and urine samples. They will have skin and eye exams.

Some participants will have video-assisted thoracoscopy to examine the chest and lungs and diagnose suspicious areas. For this, a small camera is inserted into the chest through a small incision.

Some participants will have laparoscopy to examine the organs inside the abdomen. For this, a small camera is inserted into the abdomen through a small incision.

Participants will have imaging scans of the chest, abdomen, and pelvis. They may have brain scans.

Participants will visit the NIH once a year for follow-up exams.

Participation lasts indefinitely.

Description:

Background:

• Mutations involving BRCA1-Associated Protein-1 (BAP1), a nuclear deubiquitinase involved in epigenetic regulation of gene expression, DNA repair, and cellular energetics, have emerged as one of the most common somatic mutations in malignant mesotheliomas.

• Germline mutations involving BAP1 predispose individuals to mesothelioma as well as a variety of other malignancies including melanoma and lung, renal, gastric, breast, and biliary tract cancers.

• The cancer penetrance of germline BAP1 mutations is nearly 100%, with most patients developing multiple neoplasms.

• Presently there are no established guidelines for surveillance of cancer patients with germline BAP1 mutations or of cancer-free individuals with germline BAP1 mutations.

Objectives:

To prospectively gather information related to the use of dual energy computed tomographic imaging (DECT), together with minimally invasive surgical surveillance for early detection of pleural or peritoneal mesothelioma in patients with BAP1 tumor predisposition syndrome (TPDS)

Eligibility:

• Individuals with a history of any malignancy with known or suspected germline mutation involving BAP1.

• First- or second-degree relatives of patients with documented germline BAP1 mutations, who are also found to carry similar germline mutations.

• Age greater than or equal to 30

Design:

• Individuals with suspected hereditary tumor predisposition syndromes will undergo germline evaluation using CLIA-certified next-gen sequencing (NGS).

• First- and second-degree relatives of patients with germline BAP1 mutations will be offered similar NGS evaluation.

• Subjects with germline mutations in BAP1, will undergo periodic dual energy CT (DECT) scans of the chest, abdomen, and pelvis. Plasma cell-free DNA (cfDNA) will be assessed at similar intervals, and minimally invasive surveillance procedures (i.e., video- assisted thoracoscopy and laparoscopy) will be performed periodically to detect early, subclinical malignancies that may be amenable to potentially curative local interventions.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 800
• Est. completion date: June 30, 2038
• Est. primary completion date: June 30, 2038
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 30 Years and older

Eligibility

• ELIGIBILITY CRITERIA:

Inclusion Criteria for Genetic Testing

-Eligible individuals include:

--Individuals with a history of any malignancy with known or suspected germline mutations involving BAP1

OR

--First- or second-degree relatives of patients (with or without cancer) with documented BAP1 tumor predisposition syndrome (TPDS).

• Age greater than or equal to 30 years.

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

Inclusion Criteria for Surveillance

-Eligible individuals include those who completed step 1 genetic testing with study-confirmed BAP1 or other germline

TPDS mutation.

-Completed co-enrollment on protocol 06C0014, "Prospective Evaluation of Genetic and Epigenetic Alterations in Patients with Thoracic Malignancies."

Related Conditions & MeSH terms

• Disease Susceptibility
• Familial Cancer
• Mesothelioma
• Mesothelioma, Malignant
• Syndrome
• Tumor Predisposition Syndrome (TPDS)

Locations

Country	Name	City	State
United States	National Institutes of Health Clinical Center	Bethesda	Maryland

Sponsors (1)

Lead Sponsor	Collaborator
National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Prospectively gather information related to the use of dual energy computed tomographic imaging (DECT) together with minimally invasive surveillance for early detection of mesotheliomas in patients with BAP1 TPDS	Documentation of the counts, incidence, and frequencies of cancers from dual energy computed tomographic imaging and minimally invasive surveillance results will be analyzed for statistical analysis for the early detection of mesotheliomas in patients with BAP1 TPDS.	annual or biennial follow-up, 5 years interim analysis
Secondary	To characterize the epigenetic features of mesotheliomas associated with germline mutations in BAP1	Characterization of the epigenetic features of mesotheliomas associated with germline mutations in BAP1.	at clinical visits, annual or bi-annual follow-up
Secondary	To investigate the biological mechanisms associated with prolonged survival in participants with mesothelioma that carry germline BAP1 mutations	Tumor tissue, blood, saliva, or buccal swab specimen for genetic analyses including WES, FACS, Western blots, and RNA sequencing.	once during follow-up per participant agreement

External Links

•   NIH Clinical Center Detailed Web Page