<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/NCT02221245</url>
  </required_header>
  <id_info>
    <org_study_id>20120959</org_study_id>
    <nct_id>NCT02221245</nct_id>
  </id_info>
  <brief_title>Wnt, Notch and Hedgehog Activity in Chemo-Naive Tumors Collected During Staging of Esophageal Cancer Patients</brief_title>
  <official_title>Interrogation of Wnt, Notch, and Hedgehog Activity in Chemonaive Tumors Collected During the Staging Ultrasound Endoscopies of Patients Diagnosed With Esophageal Cancer</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of Miami</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>University of Miami</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>
      Cancer results when undifferentiated cells grow in an uncontrolled manner, crowding out&#xD;
      normal cells, causing morbidity and ultimately mortality. the cancer stem cell theory&#xD;
      suggests that most tumors undergo a process of differentiation through which a relatively&#xD;
      rare cancer stem or progenitor cell (CSC) gives rise to more differentiated populations of&#xD;
      cells (including transiently amplifying cells) comprising the bulk of the tumor. As a result&#xD;
      of this cellular diversity, one or more cells within the tumor are likely to be resistant to&#xD;
      therapy. Among cells resistant to a given therapy, only CSCs can repopulate the tumor. A key&#xD;
      feature of this resistant subset of CSCs is that they repopulate a tumor resistant to the&#xD;
      original intervention. The cellular programs driving the uncontrolled proliferation of many&#xD;
      solid tumors result from aberrant activity of Wnt, Shh, and/or Notch signaling pathways in&#xD;
      esc. Thus, therapies that down-regulate the activity of these fundamental pathways in CSCs&#xD;
      will be effective in the treatment of cancer. The investigator's research program focuses on&#xD;
      the elucidation of signaling mechanisms, control of cellular processes and discovery of small&#xD;
      molecules that selectively target Wnt, Shh, and Notch signaling pathways that are fundamental&#xD;
      to CSCs. Our preliminary results identified a novel Notch associated protein NACK that&#xD;
      functions as a transcriptional co-activator of Notch. Moreover, Nack is expressed in human&#xD;
      solid tumors and is required for cell survival and tumor growth in notch -dependent tumor&#xD;
      cells.&#xD;
&#xD;
      The investigator's aim is to further interrogate the link between Notch and Nack.&#xD;
&#xD;
      Specific Aims:&#xD;
&#xD;
        -  Identify and isolate the cancer stem cell populations from primary chemo naive&#xD;
           esophageal tumor samples.&#xD;
&#xD;
        -  Interrogate the status of the Notch,( the link between Notch and Nack), Wnt and Hedghog&#xD;
           pathways in the chemo naive esophageal tumor as well as in specific cell populations,&#xD;
           such as the CSC.&#xD;
&#xD;
        -  Determine the degree of cross-talk between these pathways and which of these pathways is&#xD;
           essential for the self renewal properties and tumorigenic properties of the esc&#xD;
           population.&#xD;
&#xD;
        -  Identify critical targets for therapeutic intervention in CSC populations.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Terminated</overall_status>
  <why_stopped>
    Study terminated due to low accrual.&#xD;
  </why_stopped>
  <start_date type="Actual">April 5, 2013</start_date>
  <completion_date type="Actual">November 7, 2018</completion_date>
  <primary_completion_date type="Actual">November 7, 2018</primary_completion_date>
  <study_type>Observational</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <observational_model>Cohort</observational_model>
    <time_perspective>Prospective</time_perspective>
  </study_design_info>
  <primary_outcome>
    <measure>Percentage of samples with identifiable Notch, Wnt and Hedghog pathways in the chemo naive esophageal tumor as well as in cancer stem cell populations (CSC).</measure>
    <time_frame>24 months</time_frame>
  </primary_outcome>
  <number_of_groups>1</number_of_groups>
  <enrollment type="Actual">24</enrollment>
  <condition>Esophageal Cancer</condition>
  <arm_group>
    <arm_group_label>Patients with Esophageal Cancer</arm_group_label>
    <description>Tumor Biopsy via Ultrasound Endoscopy</description>
  </arm_group>
  <intervention>
    <intervention_type>Procedure</intervention_type>
    <intervention_name>Tumor Biopsy via Ultrasound Endoscopy</intervention_name>
    <description>The staging ultrasound endoscopy is performed on patients previously diagnosed with esophageal cancer via diagnostic biopsy. The staging ultrasound identifies affected lymph nodes and depth of tumor to the esophageal wall. The tumor sampling is via a biopsy forcep (one pass to obtain 100 cells).</description>
    <arm_group_label>Patients with Esophageal Cancer</arm_group_label>
  </intervention>
  <biospec_retention>Samples With DNA</biospec_retention>
  <biospec_descr>
    <textblock>
      Esophageal cancer tumor cells&#xD;
    </textblock>
  </biospec_descr>
  <eligibility>
    <study_pop>
      <textblock>
        Patients diagnosed with esophageal cancer&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Non-Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Patients diagnosed with an esophageal cancer and scheduled for a standard of care&#xD;
             endoscopic ultrasound.&#xD;
&#xD;
          -  Patient must sign a consent to be a participant in this protocol.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Patients not diagnosed with an esophageal cancer.&#xD;
&#xD;
          -  Patients that have undergone a previous staging endoscopic ultrasound.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Anthony Capobianco, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>University of Miami</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>University of Miami</name>
      <address>
        <city>Miami</city>
        <state>Florida</state>
        <zip>33136</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>January 2019</verification_date>
  <study_first_submitted>August 18, 2014</study_first_submitted>
  <study_first_submitted_qc>August 18, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">August 20, 2014</study_first_posted>
  <last_update_submitted>January 11, 2019</last_update_submitted>
  <last_update_submitted_qc>January 11, 2019</last_update_submitted_qc>
  <last_update_posted type="Actual">January 15, 2019</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>University of Miami</investigator_affiliation>
    <investigator_full_name>Anthony Capobianco</investigator_full_name>
    <investigator_title>Professor</investigator_title>
  </responsible_party>
  <keyword>Esophageal cancer</keyword>
  <keyword>Cancer Stem Cell</keyword>
  <keyword>CSC</keyword>
  <keyword>Wnt</keyword>
  <keyword>Hegdehog</keyword>
  <keyword>Notch</keyword>
  <keyword>Signaling</keyword>
  <keyword>Pathway</keyword>
  <keyword>Chemo-naive</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Esophageal Neoplasms</mesh_term>
  </condition_browse>
  <!-- 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/NCT02221245
org study id: 20120959
nct id: NCT02221245
lead sponsor: 
is fda regulated drug: No
is fda regulated device: No
Cancer results when undifferentiated cells grow in an uncontrolled manner, crowding out
      normal cells, causing morbidity and ultimately mortality. the cancer stem cell theory
      suggests that most tumors undergo a process of differentiation through which a relatively
      rare cancer stem or progenitor cell (CSC) gives rise to more differentiated populations of
      cells (including transiently amplifying cells) comprising the bulk of the tumor. As a result
      of this cellular diversity, one or more cells within the tumor are likely to be resistant to
      therapy. Among cells resistant to a given therapy, only CSCs can repopulate the tumor. A key
      feature of this resistant subset of CSCs is that they repopulate a tumor resistant to the
      original intervention. The cellular programs driving the uncontrolled proliferation of many
      solid tumors result from aberrant activity of Wnt, Shh, and/or Notch signaling pathways in
      esc. Thus, therapies that down-regulate the activity of these fundamental pathways in CSCs
      will be effective in the treatment of cancer. The investigator's research program focuses on
      the elucidation of signaling mechanisms, control of cellular processes and discovery of small
      molecules that selectively target Wnt, Shh, and Notch signaling pathways that are fundamental
      to CSCs. Our preliminary results identified a novel Notch associated protein NACK that
      functions as a transcriptional co-activator of Notch. Moreover, Nack is expressed in human
      solid tumors and is required for cell survival and tumor growth in notch -dependent tumor
      cells.

      The investigator's aim is to further interrogate the link between Notch and Nack.

      Specific Aims:

        -  Identify and isolate the cancer stem cell populations from primary chemo naive
           esophageal tumor samples.

        -  Interrogate the status of the Notch,( the link between Notch and Nack), Wnt and Hedghog
           pathways in the chemo naive esophageal tumor as well as in specific cell populations,
           such as the CSC.

        -  Determine the degree of cross-talk between these pathways and which of these pathways is
           essential for the self renewal properties and tumorigenic properties of the esc
           population.

        -  Identify critical targets for therapeutic intervention in CSC populations.
observational model: Cohort
time perspective: Prospective
measure: Percentage of samples with identifiable Notch, Wnt and Hedghog pathways in the chemo naive esophageal tumor as well as in cancer stem cell populations (CSC).
time frame: 24 months
arm group label: Patients with Esophageal Cancer
description: Tumor Biopsy via Ultrasound Endoscopy
intervention type: Procedure
intervention name: Tumor Biopsy via Ultrasound Endoscopy
description: The staging ultrasound endoscopy is performed on patients previously diagnosed with esophageal cancer via diagnostic biopsy. The staging ultrasound identifies affected lymph nodes and depth of tumor to the esophageal wall. The tumor sampling is via a biopsy forcep (one pass to obtain 100 cells).
arm group label: Patients with Esophageal Cancer
Esophageal cancer tumor cells
study pop: 
sampling method: Non-Probability Sample
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Anthony Capobianco, MD
role: Principal Investigator
affiliation: University of Miami
facility: 
country: United States
responsible party type: Principal Investigator
investigator affiliation: University of Miami
investigator full name: Anthony Capobianco
investigator title: Professor
mesh term: Esophageal Neoplasms