<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/NCT03030404</url>
  </required_header>
  <id_info>
    <org_study_id>170043</org_study_id>
    <secondary_id>17-C-0043</secondary_id>
    <nct_id>NCT03030404</nct_id>
  </id_info>
  <brief_title>Hereditary Gastric Cancer Syndromes: An Integrated Genomic and Clinicopathologic Study of the Predisposition to Gastric Cancer</brief_title>
  <official_title>Hereditary Gastric Cancer Syndromes: An Integrated Genomic and Clinicopathologic Study of the Predisposition to Gastric Cancer</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;
      Gastric cancers are cancers of the stomach. Hereditary ones are passed from parent to child.&#xD;
      Researchers want to gather data about hereditary gastric cancers. They want to learn about&#xD;
      changes these cause in the body and about the genes involved.&#xD;
&#xD;
      Objective:&#xD;
&#xD;
      -To gather data about hereditary gastric cancer.&#xD;
&#xD;
      Eligibility:&#xD;
&#xD;
        -  People at least 2 years old with personal or family history with a hereditary gastric&#xD;
           cancer.&#xD;
&#xD;
        -  People at least 2 years old with gene changes that lead to such cancer or a lesion that&#xD;
           may be hereditary.&#xD;
&#xD;
      Design:&#xD;
&#xD;
        -  Participants will be screened in a separate protocol.&#xD;
&#xD;
        -  Participants will have:&#xD;
&#xD;
             -  Physical exam&#xD;
&#xD;
             -  Medical history&#xD;
&#xD;
             -  Blood tests&#xD;
&#xD;
             -  Scans&#xD;
&#xD;
             -  Photos of skin lesions and other findings&#xD;
&#xD;
             -  Gynecology consultation for women&#xD;
&#xD;
             -  Cheek swab (some participants)&#xD;
&#xD;
        -  For some participants, their relatives will be asked to join the study.&#xD;
&#xD;
        -  Some participants will be asked to allow the study to get stored tissue samples for&#xD;
           relatives who have died.&#xD;
&#xD;
        -  Some samples will be sent to outside labs. All personal data will be protected. Samples&#xD;
           will be destroyed when the study ends.&#xD;
&#xD;
        -  Participants will get the results of genetic testing.&#xD;
&#xD;
        -  Participants who cannot come to the NIH clinic may just give a cheek swab and have&#xD;
           genetic testing done.&#xD;
&#xD;
        -  Some participants will be contacted for more testing.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Background:&#xD;
&#xD;
      An estimated 1-3% of gastric cancer cases occur within a familial background as part of an&#xD;
      inherited cancer syndrome.&#xD;
&#xD;
      Hereditary Diffuse Gastric Cancer (HDGC) is the most frequent form of familial gastric cancer&#xD;
      and has been linked to a germline mutation in the CDH1 gene.&#xD;
&#xD;
      Gastric Adenocarcinoma and Proximal Polyposis of the Stomach (GAPPS) is a more recently&#xD;
      described autosomal dominant syndrome characterized by fundic gland polyposis with antral&#xD;
      sparing.&#xD;
&#xD;
      Other germline mutations that predispose to gastric cancer such as SDH (succinate&#xD;
      dehydrogenase protein subunits) gene and CTNNA1 (alpha catenin).&#xD;
&#xD;
      Objectives:&#xD;
&#xD;
      Characterize the natural and clinical histories of hereditary gastric cancer syndromes.&#xD;
&#xD;
      Eligibility:&#xD;
&#xD;
      Individuals, and family members, who fulfill clinical criteria for a hereditary gastric&#xD;
      cancer syndrome irrespective of previous genetic testing or treatment.&#xD;
&#xD;
      Design:&#xD;
&#xD;
      These rare families will be recruited to genetically confirm diagnosis and study the natural&#xD;
      history of hereditary gastric cancers.&#xD;
&#xD;
      Genetic testing will be offered to gain appreciation of the effect of mutations on the&#xD;
      relative activity of various germline and somatic mutations.&#xD;
&#xD;
      We will determine if there is a relationship between mutation and disease phenotype.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">January 27, 2017</start_date>
  <completion_date type="Anticipated">December 31, 2026</completion_date>
  <primary_completion_date type="Anticipated">December 31, 2026</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>Characterization of the natural and clinical histories of hereditary gastric cancer syndromes</measure>
    <time_frame>10 years</time_frame>
    <description>Characterization of the natural and clinical histories of hereditary gastric cancer syndromes</description>
  </primary_outcome>
  <number_of_groups>1</number_of_groups>
  <enrollment type="Anticipated">1150</enrollment>
  <condition>Stomach Neoplasms</condition>
  <condition>Stomach Cancer</condition>
  <condition>Gastric Adenocarcinoma and Proximal Polyposis of the Stomach (GAPPS)</condition>
  <condition>Hereditary Diffuse Gastric Cancer (HDGC)</condition>
  <condition>Familial Diffuse Gastric Cancer</condition>
  <arm_group>
    <arm_group_label>Cohort 1</arm_group_label>
    <description>Subjects with suspicious personal or family medical history of gastric cancer or gastric cancer syndrome.</description>
  </arm_group>
  <eligibility>
    <study_pop>
      <textblock>
        Individuals, and family members, who fulfill clinical criteria for a hereditary gastric&#xD;
        cancer syndrome irrespective of previous genetic testing or treatment&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Non-Probability Sample</sampling_method>
    <criteria>
      <textblock>
        -INCLUSION CRITERIA:&#xD;
&#xD;
          1. An individual, or their family members, with any of the following:&#xD;
&#xD;
               -  Fulfills clinical criteria for Hereditary Diffuse Gastric Cancer (HGDC) syndrome&#xD;
                  or Gastric Adenocarcinoma and Proximal Polyposis of the Stomach (GAPPS) syndrome.&#xD;
&#xD;
               -  Clinically suspicious personal or family medical history of gastric cancer or&#xD;
                  gastric cancer syndrome that warrants genetics evaluation.&#xD;
&#xD;
               -  Current diagnosis of gastric cancer and a germline mutation associated with a&#xD;
                  known cancer syndrome or an associated family history of gastric cancer.&#xD;
&#xD;
               -  Harbors a pathogenic germline mutation known to predispose to gastric cancer.&#xD;
&#xD;
               -  First-degree relatives, regardless of family history or personal history of&#xD;
                  cancer, with a documented deleterious germline mutation (including but not&#xD;
                  limited to CDH1, CTNNA1, SDH) known to predispose to gastric tumors.&#xD;
&#xD;
               -  Diagnosis or suspicion of a premalignant or malignant stomach lesion of suspected&#xD;
                  hereditary etiology.&#xD;
&#xD;
          2. Age &gt;= 2 years and older. Note: Patients under 18 years of age may only participate in&#xD;
             research sample collection if the tissue acquisition is performed during a clinically&#xD;
             indicated surgical procedure, and the sampling of tissue, blood, saliva or urine&#xD;
             collection does not add risk to the clinically indicated procedures.&#xD;
&#xD;
          3. Ability of subject or legally authorized representative (LAR) to understand and the&#xD;
             willingness to sign a written informed consent document.&#xD;
&#xD;
        EXCLUSION CRITERIA:&#xD;
&#xD;
        None.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>2 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Jeremy L Davis, M.D.</last_name>
    <role>Principal Investigator</role>
    <affiliation>National Cancer Institute (NCI)</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Jamie Kirkpatrick, R.N.</last_name>
    <phone>(240) 760-7533</phone>
    <email>foregut@mail.nih.gov</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Jeremy L Davis, M.D.</last_name>
    <phone>(240) 858-3731</phone>
    <email>jeremy.davis@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_2017-C-0043.html</url>
    <description>NIH Clinical Center Detailed Web Page</description>
  </link>
  <reference>
    <citation>Hansford S, Kaurah P, Li-Chang H, Woo M, Senz J, Pinheiro H, Schrader KA, Schaeffer DF, Shumansky K, Zogopoulos G, Santos TA, Claro I, Carvalho J, Nielsen C, Padilla S, Lum A, Talhouk A, Baker-Lange K, Richardson S, Lewis I, Lindor NM, Pennell E, MacMillan A, Fernandez B, Keller G, Lynch H, Shah SP, Guilford P, Gallinger S, Corso G, Roviello F, Caldas C, Oliveira C, Pharoah PD, Huntsman DG. Hereditary Diffuse Gastric Cancer Syndrome: CDH1 Mutations and Beyond. JAMA Oncol. 2015 Apr;1(1):23-32. doi: 10.1001/jamaoncol.2014.168. Erratum In: JAMA Oncol. 2015 Apr;1(1):110.</citation>
    <PMID>26182300</PMID>
  </reference>
  <reference>
    <citation>Fitzgerald RC, Hardwick R, Huntsman D, Carneiro F, Guilford P, Blair V, Chung DC, Norton J, Ragunath K, Van Krieken JH, Dwerryhouse S, Caldas C; International Gastric Cancer Linkage Consortium. Hereditary diffuse gastric cancer: updated consensus guidelines for clinical management and directions for future research. J Med Genet. 2010 Jul;47(7):436-44. doi: 10.1136/jmg.2009.074237. Erratum In: J Med Genet. 2011 Mar;48(3):216. Van Krieken, Nicola [corrected to Van Grieken, Nicola C].</citation>
    <PMID>20591882</PMID>
  </reference>
  <reference>
    <citation>van der Post RS, Vogelaar IP, Carneiro F, Guilford P, Huntsman D, Hoogerbrugge N, Caldas C, Schreiber KE, Hardwick RH, Ausems MG, Bardram L, Benusiglio PR, Bisseling TM, Blair V, Bleiker E, Boussioutas A, Cats A, Coit D, DeGregorio L, Figueiredo J, Ford JM, Heijkoop E, Hermens R, Humar B, Kaurah P, Keller G, Lai J, Ligtenberg MJ, O'Donovan M, Oliveira C, Pinheiro H, Ragunath K, Rasenberg E, Richardson S, Roviello F, Schackert H, Seruca R, Taylor A, Ter Huurne A, Tischkowitz M, Joe ST, van Dijck B, van Grieken NC, van Hillegersberg R, van Sandick JW, Vehof R, van Krieken JH, Fitzgerald RC. Hereditary diffuse gastric cancer: updated clinical guidelines with an emphasis on germline CDH1 mutation carriers. J Med Genet. 2015 Jun;52(6):361-74. doi: 10.1136/jmedgenet-2015-103094. Epub 2015 May 15.</citation>
    <PMID>25979631</PMID>
  </reference>
  <verification_date>September 13, 2023</verification_date>
  <study_first_submitted>January 24, 2017</study_first_submitted>
  <study_first_submitted_qc>January 24, 2017</study_first_submitted_qc>
  <study_first_posted type="Estimate">January 25, 2017</study_first_posted>
  <last_update_submitted>September 14, 2023</last_update_submitted>
  <last_update_submitted_qc>September 14, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">September 15, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Genetics and Germline Mutations</keyword>
  <keyword>Familial Background</keyword>
  <keyword>Inherited Cancer Syndrome</keyword>
  <keyword>Germline Mutation in the CDH1 Gene</keyword>
  <keyword>Lobular Breast Cancer</keyword>
  <keyword>Natural History</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Stomach Neoplasms</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/NCT03030404
org study id: 170043
secondary id: 17-C-0043
nct id: NCT03030404
lead sponsor: 
is fda regulated drug: No
is fda regulated device: No
Background:

      Gastric cancers are cancers of the stomach. Hereditary ones are passed from parent to child.
      Researchers want to gather data about hereditary gastric cancers. They want to learn about
      changes these cause in the body and about the genes involved.

      Objective:

      -To gather data about hereditary gastric cancer.

      Eligibility:

        -  People at least 2 years old with personal or family history with a hereditary gastric
           cancer.

        -  People at least 2 years old with gene changes that lead to such cancer or a lesion that
           may be hereditary.

      Design:

        -  Participants will be screened in a separate protocol.

        -  Participants will have:

             -  Physical exam

             -  Medical history

             -  Blood tests

             -  Scans

             -  Photos of skin lesions and other findings

             -  Gynecology consultation for women

             -  Cheek swab (some participants)

        -  For some participants, their relatives will be asked to join the study.

        -  Some participants will be asked to allow the study to get stored tissue samples for
           relatives who have died.

        -  Some samples will be sent to outside labs. All personal data will be protected. Samples
           will be destroyed when the study ends.

        -  Participants will get the results of genetic testing.

        -  Participants who cannot come to the NIH clinic may just give a cheek swab and have
           genetic testing done.

        -  Some participants will be contacted for more testing.
Background:

      An estimated 1-3% of gastric cancer cases occur within a familial background as part of an
      inherited cancer syndrome.

      Hereditary Diffuse Gastric Cancer (HDGC) is the most frequent form of familial gastric cancer
      and has been linked to a germline mutation in the CDH1 gene.

      Gastric Adenocarcinoma and Proximal Polyposis of the Stomach (GAPPS) is a more recently
      described autosomal dominant syndrome characterized by fundic gland polyposis with antral
      sparing.

      Other germline mutations that predispose to gastric cancer such as SDH (succinate
      dehydrogenase protein subunits) gene and CTNNA1 (alpha catenin).

      Objectives:

      Characterize the natural and clinical histories of hereditary gastric cancer syndromes.

      Eligibility:

      Individuals, and family members, who fulfill clinical criteria for a hereditary gastric
      cancer syndrome irrespective of previous genetic testing or treatment.

      Design:

      These rare families will be recruited to genetically confirm diagnosis and study the natural
      history of hereditary gastric cancers.

      Genetic testing will be offered to gain appreciation of the effect of mutations on the
      relative activity of various germline and somatic mutations.

      We will determine if there is a relationship between mutation and disease phenotype.
observational model: Case-Only
time perspective: Prospective
measure: Characterization of the natural and clinical histories of hereditary gastric cancer syndromes
time frame: 10 years
description: Characterization of the natural and clinical histories of hereditary gastric cancer syndromes
arm group label: Cohort 1
description: Subjects with suspicious personal or family medical history of gastric cancer or gastric cancer syndrome.
study pop: 
sampling method: Non-Probability Sample
criteria: 
gender: All
minimum age: 2 Years
maximum age: N/A
healthy volunteers: Accepts Healthy Volunteers
last name: Jeremy L Davis, M.D.
role: Principal Investigator
affiliation: National Cancer Institute (NCI)
last name: Jamie Kirkpatrick, R.N.
phone: (240) 760-7533
email: foregut@mail.nih.gov
last name: Jeremy L Davis, M.D.
phone: (240) 858-3731
email: jeremy.davis@nih.gov
facility: 
status: Recruiting
contact: 
country: United States
url: https://clinicalstudies.info.nih.gov/cgi/detail.cgi?A_2017-C-0043.html
description: NIH Clinical Center Detailed Web Page
citation: Hansford S, Kaurah P, Li-Chang H, Woo M, Senz J, Pinheiro H, Schrader KA, Schaeffer DF, Shumansky K, Zogopoulos G, Santos TA, Claro I, Carvalho J, Nielsen C, Padilla S, Lum A, Talhouk A, Baker-Lange K, Richardson S, Lewis I, Lindor NM, Pennell E, MacMillan A, Fernandez B, Keller G, Lynch H, Shah SP, Guilford P, Gallinger S, Corso G, Roviello F, Caldas C, Oliveira C, Pharoah PD, Huntsman DG. Hereditary Diffuse Gastric Cancer Syndrome: CDH1 Mutations and Beyond. JAMA Oncol. 2015 Apr;1(1):23-32. doi: 10.1001/jamaoncol.2014.168. Erratum In: JAMA Oncol. 2015 Apr;1(1):110.
PMID: 26182300
citation: Fitzgerald RC, Hardwick R, Huntsman D, Carneiro F, Guilford P, Blair V, Chung DC, Norton J, Ragunath K, Van Krieken JH, Dwerryhouse S, Caldas C; International Gastric Cancer Linkage Consortium. Hereditary diffuse gastric cancer: updated consensus guidelines for clinical management and directions for future research. J Med Genet. 2010 Jul;47(7):436-44. doi: 10.1136/jmg.2009.074237. Erratum In: J Med Genet. 2011 Mar;48(3):216. Van Krieken, Nicola [corrected to Van Grieken, Nicola C].
PMID: 20591882
citation: van der Post RS, Vogelaar IP, Carneiro F, Guilford P, Huntsman D, Hoogerbrugge N, Caldas C, Schreiber KE, Hardwick RH, Ausems MG, Bardram L, Benusiglio PR, Bisseling TM, Blair V, Bleiker E, Boussioutas A, Cats A, Coit D, DeGregorio L, Figueiredo J, Ford JM, Heijkoop E, Hermens R, Humar B, Kaurah P, Keller G, Lai J, Ligtenberg MJ, O'Donovan M, Oliveira C, Pinheiro H, Ragunath K, Rasenberg E, Richardson S, Roviello F, Schackert H, Seruca R, Taylor A, Ter Huurne A, Tischkowitz M, Joe ST, van Dijck B, van Grieken NC, van Hillegersberg R, van Sandick JW, Vehof R, van Krieken JH, Fitzgerald RC. Hereditary diffuse gastric cancer: updated clinical guidelines with an emphasis on germline CDH1 mutation carriers. J Med Genet. 2015 Jun;52(6):361-74. doi: 10.1136/jmedgenet-2015-103094. Epub 2015 May 15.
PMID: 25979631
responsible party type: Sponsor
mesh term: Stomach Neoplasms
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.