<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT04431024</url>
  </required_header>
  <id_info>
    <org_study_id>200106</org_study_id>
    <secondary_id>20-C-0106</secondary_id>
    <nct_id>NCT04431024</nct_id>
  </id_info>
  <brief_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</brief_title>
  <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</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>National Cancer Institute (NCI)</agency>
      <agency_class>NIH</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>National Institutes of Health Clinical Center (CC)</source>
  <oversight_info>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      Background:&#xD;
&#xD;
      A germline mutation is a change to a person s genes that is carried through their DNA. These&#xD;
      mutations can be passed on from parents to their offspring. Germline mutations in a gene&#xD;
      called BAP1 are linked to the development of mesothelioma and other cancers. Researchers want&#xD;
      to follow people with these mutations to learn more.&#xD;
&#xD;
      Objective:&#xD;
&#xD;
      To see if researchers can improve how people who have or are suspected to have a BAP1&#xD;
      mutation are monitored over time.&#xD;
&#xD;
      Eligibility:&#xD;
&#xD;
      People age 30 and older who are suspected to have a BAP1 germline mutation.&#xD;
&#xD;
      Design:&#xD;
&#xD;
      Participants will be screened with a personal and family medical history. Their medical&#xD;
      records may be reviewed. They will give a blood or saliva sample to test for a BAP1 mutation.&#xD;
      They will get genetic counseling.&#xD;
&#xD;
      To take part in this study, participants will enroll on 2 to 3 other protocols.&#xD;
&#xD;
      Participants will have a physical exam. They may have a tumor biopsy. They will give blood&#xD;
      and urine samples. They will have skin and eye exams.&#xD;
&#xD;
      Some participants will have video-assisted thoracoscopy to examine the chest and lungs and&#xD;
      diagnose suspicious areas. For this, a small camera is inserted into the chest through a&#xD;
      small incision.&#xD;
&#xD;
      Some participants will have laparoscopy to examine the organs inside the abdomen. For this, a&#xD;
      small camera is inserted into the abdomen through a small incision.&#xD;
&#xD;
      Participants will have imaging scans of the chest, abdomen, and pelvis. They may have brain&#xD;
      scans.&#xD;
&#xD;
      Participants will visit the NIH once a year for follow-up exams.&#xD;
&#xD;
      Participation lasts indefinitely.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Background:&#xD;
&#xD;
        -  Mutations involving BRCA1-Associated Protein-1 (BAP1), a nuclear deubiquitinase involved&#xD;
           in epigenetic regulation of gene expression, DNA repair, and cellular energetics, have&#xD;
           emerged as one of the most common somatic mutations in malignant mesotheliomas.&#xD;
&#xD;
        -  Germline mutations involving BAP1 predispose individuals to mesothelioma as well as a&#xD;
           variety of other malignancies including melanoma and lung, renal, gastric, breast, and&#xD;
           biliary tract cancers.&#xD;
&#xD;
        -  The cancer penetrance of germline BAP1 mutations is nearly 100%, with most patients&#xD;
           developing multiple neoplasms.&#xD;
&#xD;
        -  Presently there are no established guidelines for surveillance of cancer patients with&#xD;
           germline BAP1 mutations or of cancer-free individuals with germline BAP1 mutations.&#xD;
&#xD;
      Objectives:&#xD;
&#xD;
      To prospectively gather information related to the use of dual energy computed tomographic&#xD;
      imaging (DECT), together with minimally invasive surgical surveillance for early detection of&#xD;
      pleural or peritoneal mesothelioma in patients with BAP1 tumor predisposition syndrome (TPDS)&#xD;
&#xD;
      Eligibility:&#xD;
&#xD;
        -  Individuals with a history of any malignancy with known or suspected germline mutation&#xD;
           involving BAP1.&#xD;
&#xD;
        -  First- or second-degree relatives of patients with documented germline BAP1 mutations,&#xD;
           who are also found to carry similar germline mutations.&#xD;
&#xD;
        -  Age greater than or equal to 30&#xD;
&#xD;
      Design:&#xD;
&#xD;
        -  Individuals with suspected hereditary tumor predisposition syndromes will undergo&#xD;
           germline evaluation using CLIA-certified next-gen sequencing (NGS).&#xD;
&#xD;
        -  First- and second-degree relatives of patients with germline BAP1 mutations will be&#xD;
           offered similar NGS evaluation.&#xD;
&#xD;
        -  Subjects with germline mutations in BAP1, will undergo periodic dual energy CT (DECT)&#xD;
           scans of the chest, abdomen, and pelvis. Plasma cell-free DNA (cfDNA) will be assessed&#xD;
           at similar intervals, and minimally invasive surveillance procedures (i.e., video-&#xD;
           assisted thoracoscopy and laparoscopy) will be performed periodically to detect early,&#xD;
           subclinical malignancies that may be amenable to potentially curative local&#xD;
           interventions.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">March 30, 2021</start_date>
  <completion_date type="Anticipated">June 30, 2038</completion_date>
  <primary_completion_date type="Anticipated">June 30, 2038</primary_completion_date>
  <study_type>Observational</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <observational_model>Case-Only</observational_model>
    <time_perspective>Prospective</time_perspective>
  </study_design_info>
  <primary_outcome>
    <measure>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</measure>
    <time_frame>annual or biennial follow-up, 5 years interim analysis</time_frame>
    <description>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.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>To characterize the epigenetic features of mesotheliomas associated with germline mutations in BAP1</measure>
    <time_frame>at clinical visits, annual or bi-annual follow-up</time_frame>
    <description>Characterization of the epigenetic features of mesotheliomas associated with germline mutations in BAP1.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>To investigate the biological mechanisms associated with prolonged survival in participants with mesothelioma that carry germline BAP1 mutations</measure>
    <time_frame>once during follow-up per participant agreement</time_frame>
    <description>Tumor tissue, blood, saliva, or buccal swab specimen for genetic analyses including WES, FACS, Western blots, and RNA sequencing.</description>
  </secondary_outcome>
  <number_of_groups>2</number_of_groups>
  <enrollment type="Anticipated">800</enrollment>
  <condition>Familial Cancer</condition>
  <condition>BRCA1-Associated Protein-1 (BAP1) Mutations</condition>
  <condition>Tumor Predisposition Syndrome (TPDS)</condition>
  <condition>Mesothelioma</condition>
  <arm_group>
    <arm_group_label>Cancer patients</arm_group_label>
    <description>Individuals with history of cancer and detected or suspected germline mutation in BAP1 TPDS</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Relatives of cancer patients</arm_group_label>
    <description>First- or second-degree relatives of a cancer patient (with or without cancer) with documented BAP1 tumor predisposition syndrome (TPDS)</description>
  </arm_group>
  <eligibility>
    <study_pop>
      <textblock>
        Individuals, and family members of the individual, who fulfill clinical criteria of a&#xD;
        history of cancer and detected or suspected germline mutation in BAP1 TPDS.&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Non-Probability Sample</sampling_method>
    <criteria>
      <textblock>
        -  ELIGIBILITY CRITERIA:&#xD;
&#xD;
        Inclusion Criteria for Genetic Testing&#xD;
&#xD;
        -Eligible individuals include:&#xD;
&#xD;
        --Individuals with a history of any malignancy with known or suspected germline mutations&#xD;
        involving BAP1&#xD;
&#xD;
        OR&#xD;
&#xD;
        --First- or second-degree relatives of patients (with or without cancer) with documented&#xD;
        BAP1 tumor predisposition syndrome (TPDS).&#xD;
&#xD;
          -  Age greater than or equal to 30 years.&#xD;
&#xD;
          -  All participants must understand and be willing to sign a written informed consent&#xD;
             document.&#xD;
&#xD;
        Inclusion Criteria for Surveillance&#xD;
&#xD;
        -Eligible individuals include those who completed step 1 genetic testing with&#xD;
        study-confirmed BAP1 or other germline&#xD;
&#xD;
        TPDS mutation.&#xD;
&#xD;
        -Completed co-enrollment on protocol 06C0014, &quot;Prospective Evaluation of Genetic and&#xD;
        Epigenetic Alterations in Patients with Thoracic Malignancies.&quot;&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>30 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>David S Schrump, M.D.</last_name>
    <role>Principal Investigator</role>
    <affiliation>National Cancer Institute (NCI)</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Lydiah Mutumbi</last_name>
    <phone>(240) 858-7562</phone>
    <email>lydiah.mutumbi@nih.gov</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>David S Schrump, M.D.</last_name>
    <phone>(240) 760-6239</phone>
    <email>david_schrump@nih.gov</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>National Institutes of Health Clinical Center</name>
      <address>
        <city>Bethesda</city>
        <state>Maryland</state>
        <zip>20892</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>For more information at the NIH Clinical Center contact National Cancer Institute Referral Office</last_name>
      <phone>888-624-1937</phone>
    </contact>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <link>
    <url>https://clinicalstudies.info.nih.gov/cgi/detail.cgi?A_2020-C-0106.html</url>
    <description>NIH Clinical Center Detailed Web Page</description>
  </link>
  <verification_date>September 14, 2023</verification_date>
  <study_first_submitted>June 12, 2020</study_first_submitted>
  <study_first_submitted_qc>June 13, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">June 16, 2020</study_first_posted>
  <last_update_submitted>September 15, 2023</last_update_submitted>
  <last_update_submitted_qc>September 15, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">September 18, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Germline Mutation in the BAP1 Gene</keyword>
  <keyword>BRCA1-Associated Protein-1</keyword>
  <keyword>Genetics</keyword>
  <keyword>Familial Background</keyword>
  <keyword>Natural History</keyword>
  <keyword>DECT</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Mesothelioma</mesh_term>
    <mesh_term>Mesothelioma, Malignant</mesh_term>
    <mesh_term>Syndrome</mesh_term>
    <mesh_term>Disease Susceptibility</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>Yes</sharing_ipd>
    <ipd_description>.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.</ipd_description>
    <ipd_info_type>Study Protocol</ipd_info_type>
    <ipd_info_type>Statistical Analysis Plan (SAP)</ipd_info_type>
    <ipd_info_type>Informed Consent Form (ICF)</ipd_info_type>
    <ipd_time_frame>Clinical data available during the study and indefinitely.@@@@@@Genomic data are available once genomic data are uploaded per protocol GDS plan for as long as database is active.</ipd_time_frame>
    <ipd_access_criteria>Clinical data will be made available via subscription to BTRIS and with the permission of the study PI. @@@@@@Genomic data are made available via dbGaP through requests to the data custodians.</ipd_access_criteria>
  </patient_data>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT04431024
org study id: 200106
secondary id: 20-C-0106
nct id: NCT04431024
lead sponsor: 
is fda regulated drug: No
is fda regulated device: No
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.
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.
observational model: Case-Only
time perspective: Prospective
measure: 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
time frame: annual or biennial follow-up, 5 years interim analysis
description: 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.
measure: To characterize the epigenetic features of mesotheliomas associated with germline mutations in BAP1
time frame: at clinical visits, annual or bi-annual follow-up
description: Characterization of the epigenetic features of mesotheliomas associated with germline mutations in BAP1.
measure: To investigate the biological mechanisms associated with prolonged survival in participants with mesothelioma that carry germline BAP1 mutations
time frame: once during follow-up per participant agreement
description: Tumor tissue, blood, saliva, or buccal swab specimen for genetic analyses including WES, FACS, Western blots, and RNA sequencing.
arm group label: Cancer patients
description: Individuals with history of cancer and detected or suspected germline mutation in BAP1 TPDS
arm group label: Relatives of cancer patients
description: First- or second-degree relatives of a cancer patient (with or without cancer) with documented BAP1 tumor predisposition syndrome (TPDS)
study pop: 
sampling method: Non-Probability Sample
criteria: 
gender: All
minimum age: 30 Years
maximum age: N/A
healthy volunteers: Accepts Healthy Volunteers
last name: David S Schrump, M.D.
role: Principal Investigator
affiliation: National Cancer Institute (NCI)
last name: Lydiah Mutumbi
phone: (240) 858-7562
email: lydiah.mutumbi@nih.gov
last name: David S Schrump, M.D.
phone: (240) 760-6239
email: david_schrump@nih.gov
facility: 
status: Recruiting
contact: 
country: United States
url: https://clinicalstudies.info.nih.gov/cgi/detail.cgi?A_2020-C-0106.html
description: NIH Clinical Center Detailed Web Page
responsible party type: Sponsor
mesh term: Mesothelioma
mesh term: Mesothelioma, Malignant
mesh term: Syndrome
mesh term: Disease Susceptibility
sharing ipd: Yes
ipd description: .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.
ipd info type: Study Protocol
ipd info type: Statistical Analysis Plan (SAP)
ipd info type: Informed Consent Form (ICF)
ipd time frame: Clinical data available during the study and indefinitely.@@@@@@Genomic data are available once genomic data are uploaded per protocol GDS plan for as long as database is active.
ipd access criteria: Clinical data will be made available via subscription to BTRIS and with the permission of the study PI. @@@@@@Genomic data are made available via dbGaP through requests to the data custodians.