Familial CancerNCT04431024
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 of Familial Cancer and BRCA1-Associated Protein-1 (BAP1) Mutations, run by National Cancer Institute (NCI) at 1 site in United States.
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. Read more about this study
- Who is it for?
- Ages 30 to 120 yearsHealthy volunteers can take part
- Conditions the study is for
- Familial Cancer, BRCA1-Associated Protein-1 (BAP1) Mutations, Tumor Predisposition Syndrome (TPDS)
- How many people
- 300 participants
- Where
- 1 siteUnited States
- Study dates
- 30 Mar 2021to 30 Jun 2038
- Phase
- Observational
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 30 to 120 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
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.
Who may be able to join
- -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.
- 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."
Who cannot join
None listed.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United States1 site, 1 recruiting
- Recruiting
National Institutes of Health Clinical Center
Bethesda, Maryland, 20892
For more information at the NIH Clinical Center contact National Cancer Institute Referral Office, 888-624-1937
About this study
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.
Read 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.
- Conditions
- Familial Cancer, BRCA1-Associated Protein-1 (BAP1) Mutations, Tumor Predisposition Syndrome (TPDS), Mesothelioma
- Keywords
- Germline Mutation in the BAP1 Gene, BRCA1-Associated Protein-1, Genetics, Familial Background, Natural History, DECT
- Medical subject headings
- Mesothelioma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
| Study group | Role | What they receive |
|---|---|---|
| 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) |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: annual or biennial follow-up, 5 years interim analysis
Secondary outcomes (2)
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.
Measured: at clinical visits, annual or bi-annual follow-up
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.
Measured: once during follow-up per participant agreement
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 Jun 2020
- Study start30 Mar 2021
- Primary completion30 Jun 2038 (estimated)
- Study completion30 Jun 2038 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Familial CancerStudies of the same condition, open and under way.
- More trials run by National Cancer Institute (NCI)The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Case only
- Time perspective
- Prospective
- Enrolment
- 300 participants (estimated)
Sponsor and investigators
- Lead sponsor
- National Cancer Institute (NCI)
- Sponsor type
- US National Institutes of Health
- Responsible party
- Sponsor
- Investigators
- David S Schrump, M.D., Principal investigator, National Cancer Institute (NCI)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04431024
- Sponsor's protocol ID
- 200106
- Other IDs
- 20-C-0106
- Status last verified
- 19 Oct 2026
- First submitted
- 12 Jun 2020
- Last updated
- 23 Oct 2026
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- 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.
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