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RecruitingNCT04431024Updated Sep 23, 2026

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

An observational study in Familial Cancer, BRCA1-Associated Protein-1 (BAP1) Mutations and Tumor Predisposition Syndrome (TPDS), sponsored by National Cancer Institute (NCI). Recruiting at 1 site in United States. Open to participants aged 30 Years to 120 Years, including healthy volunteers. Per ClinicalTrials.gov, last updated 2026-09-23.

Sponsored by National Cancer Institute (NCI) · Observational

Study type
Observational
Model
Case-only
Time perspective
Prospective
Enrollment
300
Ages
30 Years to 120 Years
Sex
All
01

Study 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....

Read the detailed 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 participants 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 >= 30

Design:

  • Participants 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 who become protocol participants will be offered similar NGS evaluation.
  • Participants 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.
02

Conditions studied

  • Familial Cancer
  • BRCA1-Associated Protein-1 (BAP1) Mutations
  • Tumor Predisposition Syndrome (TPDS)
  • Mesothelioma

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Keywords

  • Germline Mutation in the BAP1 Gene
  • BRCA1-Associated Protein-1
  • Genetics
  • Familial Background
  • Natural History
  • DECT
03

Who can participate

Ages eligible
30 Years to 120 Years
Sexes eligible
All
Accepts healthy volunteers
Yes
Sampling method
Non-probability sample

Study population

Individuals, and family members of the individual, who fulfill clinical criteria of a history of cancer and detected or suspected germline mutation in BAP1 TPDS.

Eligibility criteria

  • ELIGIBILITY CRITERIA:

Inclusion Criteria for Genetic Testing

-Eligible participants 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 >= 30 years.
  • All participants must understand and be willing to sign a written informed consent document.

Inclusion Criteria for Surveillance

  • Eligible participants 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."
04

Study design

Observational model
Case-only
Time perspective
Prospective
Enrollment
300 participants (estimated)

Groups and cohorts

  • Cancer patients

    Individuals with history of cancer and detected or suspected germline mutation in BAP1 TPDS

  • Relatives of cancer patients

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

05

What researchers measure

Primary outcomes

  1. 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.

    Time frame: annual or biennial follow-up, 5 years interim analysis

Secondary outcomes

  1. 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.

    Time frame: at clinical visits, annual or bi-annual follow-up

  2. 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.

    Time frame: once during follow-up per participant agreement

06

Study locations

1 of 1 sites recruiting
  • National Institutes of Health Clinical Center
    Bethesda, Maryland 20892, United States
    • For more information at the NIH Clinical Center contact National Cancer Institute Referral Office · Contact · 888-624-1937
    Recruiting
07

References and documents

Publications

  • Wu X, Hernandez FV, Wang H, Wang R, Shiffka S, Shah N, Carr SR, Hoang CD, Blakely AM, Lebensohn A, Mishra K, Xi S, Zhang MR, Tolunay T, Gara S, Absher A, Francis D, Rowland A, Connolly M, Jacobs S, Orfgen S, Driscoll K, Ghafoor A, Lu X, Malouf GG, Yang H, Carbone M, Hassan R, Jones E, Miettinen M, Schrump DS. Prospective Analysis of Mesotheliomas in Subjects With BAP1 Cancer Syndrome: Clinical Characteristics and Epigenetic Correlates of Disease. J Thorac Oncol. 2025 Nov;20(11):1699-1715. doi: 10.1016/j.jtho.2025.07.132. Epub 2025 Aug 6. PubMed 40774608 ↗

Individual participant data

Plan to share: Yes — All IPD recorded in the medical record will be shared with intramural investigators upon request. @@@@@@In addition, all large scale genomic sequencing data will be shared with subscribers to dbGaP.

Supporting information: Study protocol, Sap, Icf

08

Registry details

Key details

Study ID
NCT04431024
Lead sponsor
National Cancer Institute (NCI)
Responsible party
Sponsor
First posted
Jun 16, 2020
Start date
Mar 30, 2021
Primary completion
Jun 30, 2038 (estimated)
Completion
Jun 30, 2038 (estimated)
Last update
Sep 23, 2026

Study contacts

Rebecca B Alexander
Contact
rebecca.alexander@nih.gov
(240) 781-4037
David S Schrump, M.D.
Contact
david_schrump@nih.gov
(240) 760-6239
David S Schrump, M.D.
principal investigator · National Cancer Institute (NCI)

Oversight

FDA-regulated drug
No
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

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