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

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ClinicalTrials.gov Identifier: NCT04431024
Recruitment Status : Recruiting
First Posted : June 16, 2020
Last Update Posted : April 23, 2021
Sponsor:
Information provided by (Responsible Party):
National Institutes of Health Clinical Center (CC) ( National Cancer Institute (NCI) )

Brief 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.


Condition or disease
Familial Cancer BRCA1-Associate Protein-1 (BAP1) Mutations Tumor Predisposition Syndrome (TPDS) Mesothelioma

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 lung, melanoma, renal, gastric, and breast cholangiocarcinoma.
  • The cancer penetrance of BAP1 is nearly 100%.
  • 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 photon counting computed tomographic imaging (PCCT), 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 photon counting CT (PCCT) 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.

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Study Type : Observational
Estimated Enrollment : 800 participants
Observational Model: Case-Only
Time Perspective: Prospective
Official Title: Prospective Evaluation of Photon Counting Computed Tomographic Imaging, Noninvasive (Liquid) Biopsies, and Minimally Invasive Surgical Surveillance for Early Detection of Mesotheliomas in Patients With BAP1 Tumor Predisposition Syndrome
Actual Study Start Date : March 30, 2021
Estimated Primary Completion Date : June 30, 2038
Estimated Study Completion Date : June 30, 2038


Group/Cohort
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)



Primary Outcome Measures :
  1. Prospectively gather information related to the use of photon counting computed tomographic imaging (PCCT) together with minimally invasive surveillance for early detection of mesotheliomas in patients with BAP1 TPDS [ Time Frame: annual or biennial followup, 5 years interim analysis ]
    Documentation of the counts, incidence, and frequencies of cancers from photon counting 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.


Secondary Outcome Measures :
  1. To characterize the epigenetic features of mesotheliomas associated with germline mutations in BAP1 [ Time Frame: at clinical visits, annual or biannual follow-up ]
    Characterization of the epigenetic features of mesotheliomas associated with germline mutations in BAP1.



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Ages Eligible for Study:   30 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   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.
Criteria
  • 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.
  • Meet the eligibility criteria and are willing to co-enroll on Dr. Elizabeth Jones protocol, 19CC0070, "Translational Development of Photon-Counting CT Imaging."

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 19CC0070, "Translational Development of Photon-Counting CT Imaging" and on protocol 06C0014, "Prospective Evaluation of Genetic and Epigenetic Alterations in Patients with Thoracic Malignancies."


Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04431024


Contacts
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Contact: Tricia Kunst, R.N. (240) 760-6234 tricia.kunst@nih.gov

Locations
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United States, Maryland
National Institutes of Health Clinical Center Recruiting
Bethesda, Maryland, United States, 20892
Contact: For more information at the NIH Clinical Center contact National Cancer Institute Referral Office    888-624-1937      
Sponsors and Collaborators
National Cancer Institute (NCI)
Investigators
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Principal Investigator: David S Schrump, M.D. National Cancer Institute (NCI)
Additional Information:
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Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT04431024    
Other Study ID Numbers: 200106
20-C-0106
First Posted: June 16, 2020    Key Record Dates
Last Update Posted: April 23, 2021
Last Verified: April 21, 2021
Keywords provided by National Institutes of Health Clinical Center (CC) ( National Cancer Institute (NCI) ):
Germline Mutation in the BAP1 Gene
BRCA1-Associated Protein-1
Genetics
Familial Background
Additional relevant MeSH terms:
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Mesothelioma
Syndrome
Disease Susceptibility
Disease
Pathologic Processes
Adenoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Mesothelial
Disease Attributes