<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/NCT02198092</url>
  </required_header>
  <id_info>
    <org_study_id>816593</org_study_id>
    <nct_id>NCT02198092</nct_id>
  </id_info>
  <brief_title>Preliminary Evaluation of Septin9 in Patients With Hereditary Colon Cancer Syndromes</brief_title>
  <acronym>Septin9</acronym>
  <official_title>Preliminary Evaluation of Septin9 in Patients With Hereditary Colon Cancer Syndromes</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of Pennsylvania</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Epigenomics, Inc</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>University of Pennsylvania</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      This is an observational, case-control study evaluating the quantitative level of Septin9 in&#xD;
      plasma pre- and post-colectomy in hereditary colorectal cancer (CRC) syndrome patients&#xD;
      (Familial Adenomatous Polyposis (FAP), Lynch syndrome (also known as HNPCC), and Multiple&#xD;
      Adenomatous Polyposis (MAP, also known as MYK/MYH) cases) and genetically related FAP-family&#xD;
      members as controls and references.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date>July 2014</start_date>
  <completion_date type="Actual">August 2019</completion_date>
  <primary_completion_date type="Actual">August 2019</primary_completion_date>
  <study_type>Observational</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <observational_model>Case-Control</observational_model>
    <time_perspective>Prospective</time_perspective>
  </study_design_info>
  <primary_outcome>
    <measure>Septin9 Plasma Levels</measure>
    <time_frame>Up to 2 years</time_frame>
    <description>The primary objective of the study is the observational analysis of quantitative Septin9 plasma levels over time in hereditary CRC syndrome patients pre- and post-colectomy.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Septin9 Plasma Levels Versus Polyps</measure>
    <time_frame>Up to 2 years</time_frame>
    <description>• Correlation of quantitative Septin9 plasma levels with the approx. number of polyps</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Pre- and Post-Colectomy Colonic Epithelial Cell Numbers</measure>
    <time_frame>Up to 2 years</time_frame>
    <description>• Correlation of circulating colonic epithelial cell number pre- and post-colectomy</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Septin9 Levels Versus Circulating Colonic Epithelial Cell Numbers</measure>
    <time_frame>Up to 2 years</time_frame>
    <description>• Correlation of circulating colonic epithelial cell number with Septin9 levels</description>
  </secondary_outcome>
  <other_outcome>
    <measure>Septin9 Monitoring in Individual Groups</measure>
    <time_frame>Up to 2 years</time_frame>
    <description>The primary endpoint of the study is the completion of Septin9 monitoring in the individual patient disease groups (or family controls) over a period of two years or in case of colectomy within 28 days after colectomy. The endpoint is defined as the documented receipt of blood draws at least every six months on the scheduled healthcare visit at the institute after enrollment over the two years participation period. If any patient needs to undergo colectomy within the two years of study participation, the endpoint is defined as documented receipt of both blood draws occured prior to any surgical bowel preparation and 28 days at the latest after surgery.</description>
  </other_outcome>
  <other_outcome>
    <measure>Circulating Colonic Epithelial Cells at Blood Draws</measure>
    <time_frame>Up to 2 years</time_frame>
    <description>The secondary endpoints of the study are the documented results of the circulating colonic epithelial cell numbers for each blood draw performed.</description>
  </other_outcome>
  <number_of_groups>4</number_of_groups>
  <enrollment type="Actual">24</enrollment>
  <condition>Familial Adenomatous Polyposis</condition>
  <condition>Map Syndrome</condition>
  <condition>Lynch Syndrome</condition>
  <condition>Hnpcc</condition>
  <condition>Colorectal Cancer</condition>
  <arm_group>
    <arm_group_label>Patient Group FAP</arm_group_label>
    <description>Clinical diagnosis of familial adenomatous polyposis (FAP).&#xD;
The patients of the disease and control groups participating in the study are followed up clinically and with blood draws at least every 6 months for the duration of 2 years. These follow-ups might be more frequent, if warranted by the clinical course of the individual disease in the participating patients. Blood draws in FAP patients should always be accompanied by blood draws in their family member controls.&#xD;
If colectomy is performed in a patient of any disease group within the study participation period, additional blood draws will occur prior to any surgical bowel preparation and within a 28-day window after surgery.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Patient Group Lynch Syndrome</arm_group_label>
    <description>Clinical diagnosis of Lynch Syndrome, also known as HNPCC.&#xD;
The patients of the disease and control groups participating in the study are followed up clinically and with blood draws at least every 6 months for the duration of 2 years. These follow-ups might be more frequent, if warranted by the clinical course of the individual disease in the participating patients.&#xD;
If colectomy is performed in a patient of any disease group within the study participation period, additional blood draws will occur prior to any surgical bowel preparation and within a 28-day window after surgery.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Patient Group MAP / MYH</arm_group_label>
    <description>Clinical diagnosis of MYH-associated polyposis and presence of more than 20 colon polyps.&#xD;
The patients of the disease and control groups participating in the study are followed up clinically and with blood draws at least every 6 months for the duration of 2 years. The follow-ups might be more frequent, if warranted by the clinical course of the individual disease in the participating patients.&#xD;
If colectomy is performed in a patient of any disease group within the study participation period, additional blood draws will occur prior to any surgical bowel preparation and within a 28-day window after surgery.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Control Group (FAP Genetically-Related)</arm_group_label>
    <description>Genetically related family member of enrolled FAP patient.&#xD;
Controls, i.e. relatives of patients: Willingness to give blood at each routine follow-up as advised for the diseased relative.&#xD;
The patients of the control group participating in the study are followed up clinically and with blood draws at least every 6 months for the duration of 2 years. These follow-ups might be more frequent, if warranted by the clinical course of the individual disease in the participating FAP patients.&#xD;
If colectomy is performed in a FAP patient of any disease group within the study participation period, additional blood draws will occur prior to any surgical bowel preparation and within a 28-day window after surgery.&#xD;
Blood draws in FAP patients should always be accompanied by blood draws in their family member controls.</description>
  </arm_group>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Epi proColon Testing</intervention_name>
    <description>Plasma specimens will be collected and processed according to the Instructions for Use of the Epi proColon investigational device.&#xD;
For circulating colonic epithelial cell analysis, at least one ml whole blood will be required for analysis. Samples will be analyzed for circulating epithelial cells using the geometrically enhanced immunocapture device (GEDI; Gleghorn et al., 2009). Circulating epithelial cells will be captured using EpCAM antibodies and quantified by immunofluorescence microscopy as defined as cells that are DAPI+, CK+, CD45-. Captured cells will be fixed and stored at -20˚C.</description>
    <arm_group_label>Control Group (FAP Genetically-Related)</arm_group_label>
    <arm_group_label>Patient Group FAP</arm_group_label>
    <arm_group_label>Patient Group Lynch Syndrome</arm_group_label>
    <arm_group_label>Patient Group MAP / MYH</arm_group_label>
  </intervention>
  <biospec_retention>Samples With DNA</biospec_retention>
  <biospec_descr>
    <textblock>
      Blood samples will be used as per the study protocol. Consented subjects will provide at&#xD;
      least 10 ml but not more than 20 ml (for repeating testing) of blood at each time point for&#xD;
      Epi proColon testing. An additional volume of up to 10 ml anticoagulated blood will be drawn&#xD;
      for circulating colonic epithelial cell analysis at each time point. Blood samples will be&#xD;
      stored and will only be used in future research with the express written permission of study&#xD;
      subjects. Subjects may withdraw consent from the study or for future use of blood samples at&#xD;
      any time.&#xD;
    </textblock>
  </biospec_descr>
  <eligibility>
    <study_pop>
      <textblock>
        Age &gt; or = to 18 years of age Clinical diagnosis of familial adenomatous polyposis Clinical&#xD;
        diagnosis of Lynch syndrome Clinical diagnosis of MYH-associated polyposis and presence of&#xD;
        more than 20 colon polyps Genetically related family member of patients with clinical&#xD;
        diagnosis of FAP for Control group&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Non-Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Informed consent provided&#xD;
&#xD;
          -  Age &gt; or = to 18 years of age&#xD;
&#xD;
          -  Patient group FAP&#xD;
&#xD;
             - Clinical diagnosis of familial adenomatous polyposis&#xD;
&#xD;
          -  Patient group Lynch syndrome Clinical diagnosis of Lynch syndrome&#xD;
&#xD;
          -  Patient group MAP&#xD;
&#xD;
             - Clinical diagnosis of MYH-associated polyposis and presence of more than 20 colon&#xD;
             polyps&#xD;
&#xD;
          -  Control group (FAP)&#xD;
&#xD;
             - Genetically related family member of patient&#xD;
&#xD;
          -  Patients: Able and willing to attend routine follow-up as advised&#xD;
&#xD;
          -  Controls, i.e. relatives of patients: Willingness to give blood at each routine&#xD;
             follow-up as advised for the diseased relative&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Known infection with Human Immunodeficiency Virus (HIV), Hepatitis B Virus (HBV), or&#xD;
             Hepatitis C Virus (HCV)&#xD;
&#xD;
          -  Current diagnosis of colorectal cancer&#xD;
&#xD;
          -  Pregnancy&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Bryson Katona, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>University of Pennsylvania</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>University of Pennsylvania</name>
      <address>
        <city>Philadelphia</city>
        <state>Pennsylvania</state>
        <zip>19104</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <reference>
    <citation>Rustgi AK. The genetics of hereditary colon cancer. Genes Dev. 2007 Oct 15;21(20):2525-38. doi: 10.1101/gad.1593107.</citation>
    <PMID>17938238</PMID>
  </reference>
  <reference>
    <citation>Galiatsatos P, Foulkes WD. Familial adenomatous polyposis. Am J Gastroenterol. 2006 Feb;101(2):385-98. doi: 10.1111/j.1572-0241.2006.00375.x.</citation>
    <PMID>16454848</PMID>
  </reference>
  <reference>
    <citation>Lofton-Day C, Model F, Devos T, Tetzner R, Distler J, Schuster M, Song X, Lesche R, Liebenberg V, Ebert M, Molnar B, Grutzmann R, Pilarsky C, Sledziewski A. DNA methylation biomarkers for blood-based colorectal cancer screening. Clin Chem. 2008 Feb;54(2):414-23. doi: 10.1373/clinchem.2007.095992. Epub 2007 Dec 18.</citation>
    <PMID>18089654</PMID>
  </reference>
  <verification_date>August 2019</verification_date>
  <study_first_submitted>July 15, 2014</study_first_submitted>
  <study_first_submitted_qc>July 22, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">July 23, 2014</study_first_posted>
  <last_update_submitted>August 27, 2019</last_update_submitted>
  <last_update_submitted_qc>August 27, 2019</last_update_submitted_qc>
  <last_update_posted type="Actual">August 28, 2019</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>familial adenomatous polyposis</keyword>
  <keyword>multiple adenomatous polyposis</keyword>
  <keyword>lynch syndrome</keyword>
  <keyword>hnpcc</keyword>
  <keyword>colorectal cancer</keyword>
  <keyword>genetic syndrome</keyword>
  <keyword>epigenomics</keyword>
  <keyword>septin9</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Colorectal Neoplasms</mesh_term>
    <mesh_term>Colorectal Neoplasms, Hereditary Nonpolyposis</mesh_term>
    <mesh_term>Adenomatous Polyposis Coli</mesh_term>
    <mesh_term>Syndrome</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/NCT02198092
org study id: 816593
nct id: NCT02198092
lead sponsor: 
collaborator: 
has dmc: No
This is an observational, case-control study evaluating the quantitative level of Septin9 in
      plasma pre- and post-colectomy in hereditary colorectal cancer (CRC) syndrome patients
      (Familial Adenomatous Polyposis (FAP), Lynch syndrome (also known as HNPCC), and Multiple
      Adenomatous Polyposis (MAP, also known as MYK/MYH) cases) and genetically related FAP-family
      members as controls and references.
observational model: Case-Control
time perspective: Prospective
measure: Septin9 Plasma Levels
time frame: Up to 2 years
description: The primary objective of the study is the observational analysis of quantitative Septin9 plasma levels over time in hereditary CRC syndrome patients pre- and post-colectomy.
measure: Septin9 Plasma Levels Versus Polyps
time frame: Up to 2 years
description: • Correlation of quantitative Septin9 plasma levels with the approx. number of polyps
measure: Pre- and Post-Colectomy Colonic Epithelial Cell Numbers
time frame: Up to 2 years
description: • Correlation of circulating colonic epithelial cell number pre- and post-colectomy
measure: Septin9 Levels Versus Circulating Colonic Epithelial Cell Numbers
time frame: Up to 2 years
description: • Correlation of circulating colonic epithelial cell number with Septin9 levels
measure: Septin9 Monitoring in Individual Groups
time frame: Up to 2 years
description: The primary endpoint of the study is the completion of Septin9 monitoring in the individual patient disease groups (or family controls) over a period of two years or in case of colectomy within 28 days after colectomy. The endpoint is defined as the documented receipt of blood draws at least every six months on the scheduled healthcare visit at the institute after enrollment over the two years participation period. If any patient needs to undergo colectomy within the two years of study participation, the endpoint is defined as documented receipt of both blood draws occured prior to any surgical bowel preparation and 28 days at the latest after surgery.
measure: Circulating Colonic Epithelial Cells at Blood Draws
time frame: Up to 2 years
description: The secondary endpoints of the study are the documented results of the circulating colonic epithelial cell numbers for each blood draw performed.
arm group label: Patient Group FAP
description: Clinical diagnosis of familial adenomatous polyposis (FAP).
The patients of the disease and control groups participating in the study are followed up clinically and with blood draws at least every 6 months for the duration of 2 years. These follow-ups might be more frequent, if warranted by the clinical course of the individual disease in the participating patients. Blood draws in FAP patients should always be accompanied by blood draws in their family member controls.
If colectomy is performed in a patient of any disease group within the study participation period, additional blood draws will occur prior to any surgical bowel preparation and within a 28-day window after surgery.
arm group label: Patient Group Lynch Syndrome
description: Clinical diagnosis of Lynch Syndrome, also known as HNPCC.
The patients of the disease and control groups participating in the study are followed up clinically and with blood draws at least every 6 months for the duration of 2 years. These follow-ups might be more frequent, if warranted by the clinical course of the individual disease in the participating patients.
If colectomy is performed in a patient of any disease group within the study participation period, additional blood draws will occur prior to any surgical bowel preparation and within a 28-day window after surgery.
arm group label: Patient Group MAP / MYH
description: Clinical diagnosis of MYH-associated polyposis and presence of more than 20 colon polyps.
The patients of the disease and control groups participating in the study are followed up clinically and with blood draws at least every 6 months for the duration of 2 years. The follow-ups might be more frequent, if warranted by the clinical course of the individual disease in the participating patients.
If colectomy is performed in a patient of any disease group within the study participation period, additional blood draws will occur prior to any surgical bowel preparation and within a 28-day window after surgery.
arm group label: Control Group (FAP Genetically-Related)
description: Genetically related family member of enrolled FAP patient.
Controls, i.e. relatives of patients: Willingness to give blood at each routine follow-up as advised for the diseased relative.
The patients of the control group participating in the study are followed up clinically and with blood draws at least every 6 months for the duration of 2 years. These follow-ups might be more frequent, if warranted by the clinical course of the individual disease in the participating FAP patients.
If colectomy is performed in a FAP patient of any disease group within the study participation period, additional blood draws will occur prior to any surgical bowel preparation and within a 28-day window after surgery.
Blood draws in FAP patients should always be accompanied by blood draws in their family member controls.
intervention type: Other
intervention name: Epi proColon Testing
description: Plasma specimens will be collected and processed according to the Instructions for Use of the Epi proColon investigational device.
For circulating colonic epithelial cell analysis, at least one ml whole blood will be required for analysis. Samples will be analyzed for circulating epithelial cells using the geometrically enhanced immunocapture device (GEDI; Gleghorn et al., 2009). Circulating epithelial cells will be captured using EpCAM antibodies and quantified by immunofluorescence microscopy as defined as cells that are DAPI+, CK+, CD45-. Captured cells will be fixed and stored at -20˚C.
arm group label: Control Group (FAP Genetically-Related)
arm group label: Patient Group FAP
arm group label: Patient Group Lynch Syndrome
arm group label: Patient Group MAP / MYH
Blood samples will be used as per the study protocol. Consented subjects will provide at
      least 10 ml but not more than 20 ml (for repeating testing) of blood at each time point for
      Epi proColon testing. An additional volume of up to 10 ml anticoagulated blood will be drawn
      for circulating colonic epithelial cell analysis at each time point. Blood samples will be
      stored and will only be used in future research with the express written permission of study
      subjects. Subjects may withdraw consent from the study or for future use of blood samples at
      any time.
study pop: 
sampling method: Non-Probability Sample
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: Accepts Healthy Volunteers
last name: Bryson Katona, MD
role: Principal Investigator
affiliation: University of Pennsylvania
facility: 
country: United States
citation: Rustgi AK. The genetics of hereditary colon cancer. Genes Dev. 2007 Oct 15;21(20):2525-38. doi: 10.1101/gad.1593107.
PMID: 17938238
citation: Galiatsatos P, Foulkes WD. Familial adenomatous polyposis. Am J Gastroenterol. 2006 Feb;101(2):385-98. doi: 10.1111/j.1572-0241.2006.00375.x.
PMID: 16454848
citation: Lofton-Day C, Model F, Devos T, Tetzner R, Distler J, Schuster M, Song X, Lesche R, Liebenberg V, Ebert M, Molnar B, Grutzmann R, Pilarsky C, Sledziewski A. DNA methylation biomarkers for blood-based colorectal cancer screening. Clin Chem. 2008 Feb;54(2):414-23. doi: 10.1373/clinchem.2007.095992. Epub 2007 Dec 18.
PMID: 18089654
responsible party type: Sponsor
mesh term: Colorectal Neoplasms
mesh term: Colorectal Neoplasms, Hereditary Nonpolyposis
mesh term: Adenomatous Polyposis Coli
mesh term: Syndrome