NCI Registry Tracks 1,000 Mesothelioma Patients and Families With BAP1 Mutations (NCT03830229)

The National Cancer Institute is enrolling 1,000 people into a long-term study of mesothelioma that does not test a drug. The study, NCT03830229, follows mesothelioma patients and their biological family members who carry inherited mutations in the BAP1 gene, or in other genes linked to cancer risk. The principal investigator is Raffit Hassan, M.D., of the NCI Center for Cancer Research. The single enrollment site is the NIH Clinical Center in Bethesda, Maryland.

What the study is, and what it is not

This is a natural-history registry, not an interventional treatment trial. Participants do not receive an investigational therapy. They receive long-term clinical evaluation, imaging, and biospecimen collection so the NCI can characterize who develops mesothelioma in families that carry inherited cancer-predisposition mutations, what those cancers look like, and which biomarkers may eventually allow earlier detection.

The published primary outcome is incidence and frequencies of cancers across enrolled mesothelioma patients and their relatives, captured as the cohort is followed. Secondary measures include surveillance for malignancy beyond mesothelioma, quality of life, and the participant’s environmental and occupational exposures over the follow-up window. The full protocol design lives at ClinicalTrials.gov.

Why BAP1 matters for mesothelioma

Germline mutations in the BAP1 tumor-suppressor gene define a hereditary cancer-predisposition syndrome. People who inherit a damaged copy of BAP1 face increased lifetime risk of mesothelioma, uveal melanoma, and several other cancers. A 2022 Journal of Thoracic Oncology paper from the NCI group covering the medical and surgical care of these carriers documents the clinical implications, and a 2025 Journal of Thoracic Oncology analysis describes germline-BAP1-associated mesothelioma as a biologically and clinically distinct entity from sporadic disease.

Carriers tend to develop mesothelioma at younger ages and may have longer survival than non-carrier patients. MesoWatch covered the Memorial Sloan Kettering analysis of 273 patients under age 50 that found BAP1 mutations in more than half of the tumors studied. The mechanism question, why BAP1 carriers respond differently to asbestos and to treatment, is the subject of Michele Carbone’s discovery work on BAP1 and LBAM.

What NCT03830229 adds is prospective, longitudinal data. Most BAP1 mesothelioma research has historically been retrospective. A 2025 prospective analysis in Journal of Thoracic Oncology of mesotheliomas in subjects with BAP1 cancer syndrome reports clinical characteristics and epigenetic correlates of disease in the cohort, the kind of structured readout that retrospective series cannot produce. Following 1,000 people across years, including unaffected family members, lets investigators measure cancer incidence as it happens and lets them bank serial biospecimens before any second cancer develops.

Who can enroll

The protocol opens two cohorts. Both require age 2 or older. The full eligibility text is on ClinicalTrials.gov.

Cohort 1: people with mesothelioma. Eligible if they have a pathology-confirmed mesothelioma diagnosis and either a confirmed deleterious germline BAP1 mutation or a deleterious germline mutation in another DNA-repair or cancer-predisposition gene on a commercially available panel. Genetic-test results from either research or clinical labs are accepted.

Cohort 2: biological relatives. Eligible if they carry a confirmed germline BAP1 mutation (with no history of mesothelioma themselves), or if they have a first-degree relative living or deceased with mesothelioma, or a first-degree relative with a CLIA-confirmed germline BAP1 mutation. Second-degree relatives qualify if the relevant first-degree relative is deceased or unavailable for testing.

How this fits the treatment landscape

Because NCT03830229 is observational, it does not compete with current first-line standards of care. Two phase-3 trials anchor those standards for pleural mesothelioma. CheckMate 743, reported by Baas and colleagues in The Lancet in 2021, established nivolumab plus ipilimumab as a first-line option for unresectable disease. The CCTG IND.227 study, reported by Chu and colleagues in The Lancet in 2023, added pembrolizumab plus platinum-pemetrexed to the first-line conversation. NCT03830229 sits alongside those regimens, asking different questions: not which therapy works, but who develops the disease in the first place and why.

For peritoneal mesothelioma, cytoreductive surgery with HIPEC plus systemic pemetrexed-cisplatin remains the working standard for appropriate candidates. A registry like this one will not change that algorithm in the short term, but it may eventually inform screening recommendations for relatives of peritoneal patients with germline mutations.

What enrollment actually looks like

Participants travel to the NIH Clinical Center in Bethesda, Maryland, the only enrolling site. NIH covers the cost of study-related visits at its hospital, including travel reimbursement for many participants, under standard NCI intramural-protocol policy. Enrollees consent to genetic testing if they have not already been tested, contribute blood, buccal, saliva, skin-biopsy, and where clinically appropriate solid-tumor and body-fluid specimens, and return for clinical evaluation across the study window. The published summary does not specify imaging modality or visit cadence, and we are not extrapolating one.

The estimated completion date is July 5, 2027, with long-term follow-up data flowing for years after enrollment closes. Recruitment as of May 19, 2026 remains open.

The bigger picture

Dr. Hedy Kindler, Director of the Multidisciplinary Mesothelioma Program at the University of Chicago, who reviewed this piece, has previously stated that “these genes, particularly BAP1, will make patients more sensitive to the carcinogenic effects of asbestos, rather than serving as a direct cause of mesothelioma.” That framing matters for families weighing whether to enroll. A germline BAP1 mutation is not a verdict. It is a risk modifier that, paired with exposure history and long-term follow-up, may eventually yield a screening protocol that does not exist today.

For families whose history points to inherited risk, the path forward is two-fold: confirm germline status through a certified clinical lab if not already documented, and ask the treating oncologist or a genetic counselor about referral to NCT03830229 or to comparable NCI natural-history work. For broader context, our BAP1 mesothelioma mechanisms guide covers the underlying biology.