<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/NCT03039595</url>
  </required_header>
  <id_info>
    <org_study_id>11846</org_study_id>
    <nct_id>NCT03039595</nct_id>
  </id_info>
  <brief_title>Ploidy and Stroma in Early Rectal Cancer</brief_title>
  <official_title>An Observational Study to Correlate the Results of Ploidy and Stroma Analysis With Prognosis in Early Rectal Cancer</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Oxford University Hospitals NHS Trust</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Oslo University Hospital</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Oxford University Hospitals NHS Trust</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      Early rectal cancer can be removed by minimally-invasive surgery, and the standard&#xD;
      pathological assessment of the removed tumour gives valuable information about how advanced&#xD;
      the tumour is. This gives an indication of how likely the cancer is to recur, so doctors and&#xD;
      patient can decide on the most appropriate further treatment and follow-up. However there is&#xD;
      still much uncertainty in these predictions about recurrence. This study will assess two&#xD;
      further pathology tests, ploidy and stroma ratio in the tumour, by correlating the results&#xD;
      with outcome. This will determine whether these two tests provide additional value in&#xD;
      predicting outcome. If so, clinicians would be better able to advise patients with early&#xD;
      rectal cancer about their prognosis and further management.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Early rectal cancer can be removed by minimally-invasive surgery, and the standard&#xD;
      pathological assessment of the removed tumour gives valuable information about how advanced&#xD;
      the tumour is. This information is very important in indicating whether the cancer is likely&#xD;
      to recur, and therefore in advising the patient after surgery whether further treatment is&#xD;
      advisable, and if not, what is the most appropriate follow-up regime. However there is still&#xD;
      a lot of uncertainty in these predictions about recurrence of the cancer, and better tests&#xD;
      are being sought. This study aims to look at two further pathology tests, ploidy and stroma&#xD;
      ratio in the tumour, and correlate these test results with outcome in patients who have had&#xD;
      an early rectal cancer removed. This will allow the investigators to assess whether these two&#xD;
      tests provide additional value in predicting outcome. If so, clinicians would be better able&#xD;
      to advise patients with early rectal cancer about their prognosis and further management.&#xD;
&#xD;
      Routine histopathology analysis of a rectal cancer specimen removed at surgery includes&#xD;
      assessment of tumour size, depth of invasion, vascular, lymphatic and perineural invasion,&#xD;
      tumour involvement of resection margins and nodal involvement. This information is valuable&#xD;
      in predicting outcome. For example, predicted rates of local recurrence at 36 months&#xD;
      following local excision of rectal cancer by transanal endoscopic microsurgery (TEM) based on&#xD;
      tumour size, depth of invasion and lymphatic invasion have been tabulated. However such&#xD;
      models are not perfect, and leave room for improvement. Ploidy and stroma ratio are two&#xD;
      further tests which have shown some promise in predicting outcome.&#xD;
&#xD;
      Ploidy refers to the number of sets of chromosomes in a cell nucleus. Most human cells are&#xD;
      normally diploid, with two sets of 23 chromosomes. Abnormal tumour cells may have a different&#xD;
      number of sets of chromosomes, or be aneuploid, having some replicated or deleted&#xD;
      chromosomes. In general, aneuploidy in cancer cells is associated with a worse prognosis. An&#xD;
      early study of DNA ploidy in rectal cancer using flow cytometry showed an independent but&#xD;
      small predictive effective of aneuploidy on survival. Technological advances now allow more&#xD;
      accurate and detailed assessment of ploidy. The DNA ploidy status of tumour cells in early&#xD;
      ovarian cancer has been found to predict which patients will benefit from adjuvant&#xD;
      chemotherapy after surgery to remove the ovarian tumour and is used routinely in some centres&#xD;
      to aid in decision-making.&#xD;
&#xD;
      Stroma ratio refers to the tumour: stroma ratio. A lower proportion of tumour cells or,&#xD;
      conversely, a higher percentage of stroma, in a cancer tends to be associated with a poorer&#xD;
      prognosis. This ratio has been found to be strongly associated with tumour growth and&#xD;
      invasion in colorectal cancers, and to independently predict survival in patients undergoing&#xD;
      surgery to removal colorectal tumours. However previous studies have looked mainly at more&#xD;
      advanced colon cancers, rather than early rectal cancers, and have used only cancer-related&#xD;
      death as the endpoint, rather than looking at local recurrence and response to adjuvant&#xD;
      treatments.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">March 29, 2017</start_date>
  <completion_date type="Actual">July 31, 2019</completion_date>
  <primary_completion_date type="Actual">May 31, 2019</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>Other</time_perspective>
  </study_design_info>
  <primary_outcome>
    <measure>Correlation Between Ploidy Status With Local Recurrence of Cancer</measure>
    <time_frame>a minimum of 6 months after surgery</time_frame>
    <description>Results of ploidy status will be correlated with patient follow-up information for between 6 months and 9 years following surgery, to look for any correlation with local recurrence of the rectal cancer</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Correlation Between Tumour: Stroma Ratio With Local Recurrence of Cancer</measure>
    <time_frame>a minimum of 6 months after surgery</time_frame>
    <description>Results of tumour:stromal ratio (TSR) will be correlated with patient follow-up information for between 6 months and 9 years following surgery, to look for any correlation with local recurrence of the rectal cancer. A 50% cut-off is used to define high TSR.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Correlation Between Ploidy Status and Overall Survival After TEM Surgery to Remove Rectal Cancer</measure>
    <time_frame>a minimum of 6 months after surgery</time_frame>
    <description>Results of ploidy status will be correlated with patient follow-up information for between 6 months and 9 years following surgery, to look for any correlation between the test results and overall survival</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Correlation Between Tumour:Stroma Ratio and Overall Survival After TEM Surgery to Remove Rectal Cancer</measure>
    <time_frame>a minimum of 6 months after surgery</time_frame>
    <description>Results of tumour:stromal ratio (TSR) will be correlated with patient follow-up information for between 6 months and 9 years following surgery, to look for any correlation between the test results and overall survival. High TSR is defined using a 50% cut-off.</description>
  </secondary_outcome>
  <enrollment type="Actual">150</enrollment>
  <condition>Rectal Cancer</condition>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Ploidy and tumour:stromal ratio measurements</intervention_name>
    <description>Ploidy and tumour:stromal ratio measurements will be made on specimens of early rectal cancer removed by transanal endoscopic microsurgery (TEM)</description>
  </intervention>
  <biospec_retention>Samples Without DNA</biospec_retention>
  <biospec_descr>
    <textblock>
      Specimens of early rectal cancer removed by transanal endoscopic microsurgery, which are&#xD;
      routinely retained, will be further analysed.&#xD;
    </textblock>
  </biospec_descr>
  <eligibility>
    <study_pop>
      <textblock>
        Participants diagnosed with rectal cancer that is operable and patients who have already&#xD;
        had rectal cancer removed by transanal endoscopic microsurgery (TEM) in Oxford since 2007.&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Non-Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Participant is willing and able to give informed consent (in English) for&#xD;
             participation in the study, or gave informed consent for donation of tissue for&#xD;
             research at the time of surgery&#xD;
&#xD;
          -  Male or Female, aged 18 years or above&#xD;
&#xD;
          -  Diagnosed with operable rectal cancer&#xD;
&#xD;
          -  Due to undergo, or has already undergone, TEM surgery to remove rectal cancer&#xD;
&#xD;
          -  A useable tissue sample has already been, or will be, taken as part of routine surgery&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Age less than 18&#xD;
&#xD;
          -  Adults who are not able to give consent or who are deemed vulnerable&#xD;
&#xD;
          -  Participants who do not have a useable tissue sample will be excluded&#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>Chris Cunningham, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Employee</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Churchill Hospital</name>
      <address>
        <city>Oxford</city>
        <zip>OX3 7LE</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United Kingdom</country>
  </location_countries>
  <reference>
    <citation>Bach SP, Hill J, Monson JR, Simson JN, Lane L, Merrie A, Warren B, Mortensen NJ; Association of Coloproctology of Great Britain and Ireland Transanal Endoscopic Microsurgery (TEM) Collaboration. A predictive model for local recurrence after transanal endoscopic microsurgery for rectal cancer. Br J Surg. 2009 Mar;96(3):280-90. doi: 10.1002/bjs.6456.</citation>
    <PMID>19224520</PMID>
  </reference>
  <reference>
    <citation>Goh HS, Jass JR, Atkin WS, Cuzick J, Northover JM. Value of flow cytometric determination of ploidy as a guide to prognosis in operable rectal cancer: a multivariate analysis. Int J Colorectal Dis. 1987 Feb;2(1):17-21. doi: 10.1007/BF01648992.</citation>
    <PMID>3598327</PMID>
  </reference>
  <reference>
    <citation>Kristensen GB, Kildal W, Abeler VM, Kaern J, Vergote I, Trope CG, Danielsen HE. Large-scale genomic instability predicts long-term outcome for women with invasive stage I ovarian cancer. Ann Oncol. 2003 Oct;14(10):1494-500. doi: 10.1093/annonc/mdg403.</citation>
    <PMID>14504048</PMID>
  </reference>
  <reference>
    <citation>Park JH, Richards CH, McMillan DC, Horgan PG, Roxburgh CSD. The relationship between tumour stroma percentage, the tumour microenvironment and survival in patients with primary operable colorectal cancer. Ann Oncol. 2014 Mar;25(3):644-651. doi: 10.1093/annonc/mdt593. Epub 2014 Jan 23.</citation>
    <PMID>24458470</PMID>
  </reference>
  <reference>
    <citation>Downey CL, Simpkins SA, White J, Holliday DL, Jones JL, Jordan LB, Kulka J, Pollock S, Rajan SS, Thygesen HH, Hanby AM, Speirs V. The prognostic significance of tumour-stroma ratio in oestrogen receptor-positive breast cancer. Br J Cancer. 2014 Apr 2;110(7):1744-7. doi: 10.1038/bjc.2014.69. Epub 2014 Feb 18.</citation>
    <PMID>24548861</PMID>
  </reference>
  <reference>
    <citation>West NP, Dattani M, McShane P, Hutchins G, Grabsch J, Mueller W, Treanor D, Quirke P, Grabsch H. The proportion of tumour cells is an independent predictor for survival in colorectal cancer patients. Br J Cancer. 2010 May 11;102(10):1519-23. doi: 10.1038/sj.bjc.6605674. Epub 2010 Apr 20.</citation>
    <PMID>20407439</PMID>
  </reference>
  <verification_date>March 2022</verification_date>
  <study_first_submitted>January 30, 2017</study_first_submitted>
  <study_first_submitted_qc>January 30, 2017</study_first_submitted_qc>
  <study_first_posted type="Estimate">February 1, 2017</study_first_posted>
  <results_first_submitted>January 10, 2022</results_first_submitted>
  <results_first_submitted_qc>March 9, 2022</results_first_submitted_qc>
  <results_first_posted type="Actual">June 9, 2022</results_first_posted>
  <last_update_submitted>March 9, 2022</last_update_submitted>
  <last_update_submitted_qc>March 9, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">June 9, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Oxford University Hospitals NHS Trust</investigator_affiliation>
    <investigator_full_name>Chris Cunningham</investigator_full_name>
    <investigator_title>Consultant colorectal surgeon</investigator_title>
  </responsible_party>
  <keyword>Early rectal cancer</keyword>
  <keyword>Ploidy</keyword>
  <keyword>Tumour:stroma ratio</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Rectal Neoplasms</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
    <ipd_description>No individual data will be made available</ipd_description>
  </patient_data>
  <provided_document_section>
    <provided_document>
      <document_type>Study Protocol and Statistical Analysis Plan</document_type>
      <document_has_protocol>Yes</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>Yes</document_has_sap>
      <document_date>October 21, 2016</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/95/NCT03039595/Prot_SAP_000.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <group_list>
        <group group_id="P1">
          <title>Patients</title>
          <description>All patients. This is an observational study; no interventions were used.</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="150"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="143"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="7"/>
              </participants_list>
            </milestone>
          </milestone_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>Patients</title>
          <description>All patients</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="143"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>years</units>
          <param>Median</param>
          <dispersion>Full Range</dispersion>
          <class_list>
            <class>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="143"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="69" lower_limit="38" upper_limit="94"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Sex: Female, Male</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="143"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <title>Female</title>
                  <measurement_list>
                    <measurement group_id="B1" value="56"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="87"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Race and Ethnicity Not Collected</title>
          <population>Race and Ethnicity were not collected from any participant.</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="0"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Region of Enrollment</title>
          <units>participants</units>
          <param>Number</param>
          <class_list>
            <class>
              <title>United Kingdom</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="143"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="143"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Tumour stage</title>
          <description>Tumour component of the TNM (Tumour, Node, Metastasis) staging system determined by histopathological analysis of the resected tumour.</description>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="143"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <title>pT1 (tumour confined to the inner layer of the bowel)</title>
                  <measurement_list>
                    <measurement group_id="B1" value="76"/>
                  </measurement_list>
                </category>
                <category>
                  <title>pT2 (tumour extends into the muscle layer of the bowel wall)</title>
                  <measurement_list>
                    <measurement group_id="B1" value="58"/>
                  </measurement_list>
                </category>
                <category>
                  <title>pT3 (tumour has reached the outer lining of the bowel wall)</title>
                  <measurement_list>
                    <measurement group_id="B1" value="9"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Post-TEM management</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="143"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <title>Surveillance</title>
                  <measurement_list>
                    <measurement group_id="B1" value="88"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Completion radical surgery</title>
                  <measurement_list>
                    <measurement group_id="B1" value="13"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Adjuvant radiotherapy</title>
                  <measurement_list>
                    <measurement group_id="B1" value="42"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Correlation Between Ploidy Status With Local Recurrence of Cancer</title>
        <description>Results of ploidy status will be correlated with patient follow-up information for between 6 months and 9 years following surgery, to look for any correlation with local recurrence of the rectal cancer</description>
        <time_frame>a minimum of 6 months after surgery</time_frame>
        <population>Only patients for whom ploidy status was available were included in the analysis (ploidy assessment failed in 3 patients for technical reasons)</population>
        <group_list>
          <group group_id="O1">
            <title>Patients</title>
            <description>All patients</description>
          </group>
        </group_list>
        <measure>
          <title>Correlation Between Ploidy Status With Local Recurrence of Cancer</title>
          <description>Results of ploidy status will be correlated with patient follow-up information for between 6 months and 9 years following surgery, to look for any correlation with local recurrence of the rectal cancer</description>
          <population>Only patients for whom ploidy status was available were included in the analysis (ploidy assessment failed in 3 patients for technical reasons)</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="140"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Diploid - Local recurrence</title>
                  <measurement_list>
                    <measurement group_id="O1" value="3"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Diploid - No local recurrence</title>
                  <measurement_list>
                    <measurement group_id="O1" value="31"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Non-diploid - Local recurrence</title>
                  <measurement_list>
                    <measurement group_id="O1" value="14"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Non-diploid - No local recurrence</title>
                  <measurement_list>
                    <measurement group_id="O1" value="92"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Correlation Between Tumour: Stroma Ratio With Local Recurrence of Cancer</title>
        <description>Results of tumour:stromal ratio (TSR) will be correlated with patient follow-up information for between 6 months and 9 years following surgery, to look for any correlation with local recurrence of the rectal cancer. A 50% cut-off is used to define high TSR.</description>
        <time_frame>a minimum of 6 months after surgery</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Patients</title>
            <description>All patients</description>
          </group>
        </group_list>
        <measure>
          <title>Correlation Between Tumour: Stroma Ratio With Local Recurrence of Cancer</title>
          <description>Results of tumour:stromal ratio (TSR) will be correlated with patient follow-up information for between 6 months and 9 years following surgery, to look for any correlation with local recurrence of the rectal cancer. A 50% cut-off is used to define high TSR.</description>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="143"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>High TSR - Local recurrence</title>
                  <measurement_list>
                    <measurement group_id="O1" value="2"/>
                  </measurement_list>
                </category>
                <category>
                  <title>High TSR - No local recurrence</title>
                  <measurement_list>
                    <measurement group_id="O1" value="9"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Low TSR - Local recurrence</title>
                  <measurement_list>
                    <measurement group_id="O1" value="17"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Low TSR - No local recurrence</title>
                  <measurement_list>
                    <measurement group_id="O1" value="115"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Correlation Between Ploidy Status and Overall Survival After TEM Surgery to Remove Rectal Cancer</title>
        <description>Results of ploidy status will be correlated with patient follow-up information for between 6 months and 9 years following surgery, to look for any correlation between the test results and overall survival</description>
        <time_frame>a minimum of 6 months after surgery</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Patients</title>
            <description>All patients</description>
          </group>
        </group_list>
        <measure>
          <title>Correlation Between Ploidy Status and Overall Survival After TEM Surgery to Remove Rectal Cancer</title>
          <description>Results of ploidy status will be correlated with patient follow-up information for between 6 months and 9 years following surgery, to look for any correlation between the test results and overall survival</description>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="140"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Diploid - Alive</title>
                  <measurement_list>
                    <measurement group_id="O1" value="27"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Diploid - Deceased</title>
                  <measurement_list>
                    <measurement group_id="O1" value="7"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Non-diploid - Alive</title>
                  <measurement_list>
                    <measurement group_id="O1" value="86"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Non-diploid - Deceased</title>
                  <measurement_list>
                    <measurement group_id="O1" value="20"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Correlation Between Tumour:Stroma Ratio and Overall Survival After TEM Surgery to Remove Rectal Cancer</title>
        <description>Results of tumour:stromal ratio (TSR) will be correlated with patient follow-up information for between 6 months and 9 years following surgery, to look for any correlation between the test results and overall survival. High TSR is defined using a 50% cut-off.</description>
        <time_frame>a minimum of 6 months after surgery</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Patients</title>
            <description>All patients</description>
          </group>
        </group_list>
        <measure>
          <title>Correlation Between Tumour:Stroma Ratio and Overall Survival After TEM Surgery to Remove Rectal Cancer</title>
          <description>Results of tumour:stromal ratio (TSR) will be correlated with patient follow-up information for between 6 months and 9 years following surgery, to look for any correlation between the test results and overall survival. High TSR is defined using a 50% cut-off.</description>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="143"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>High TSR - Alive</title>
                  <measurement_list>
                    <measurement group_id="O1" value="6"/>
                  </measurement_list>
                </category>
                <category>
                  <title>High TSR - Deceased</title>
                  <measurement_list>
                    <measurement group_id="O1" value="5"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Low TSR - Alive</title>
                  <measurement_list>
                    <measurement group_id="O1" value="110"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Low TSR - Deceased</title>
                  <measurement_list>
                    <measurement group_id="O1" value="22"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>Up to 12 years following surgery</time_frame>
      <group_list>
        <group group_id="E1">
          <title>Patients</title>
          <description>All patients</description>
        </group>
      </group_list>
      <serious_events>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, all-cause mortality</sub_title>
                <counts group_id="E1" subjects_affected="27" subjects_at_risk="143"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="143"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>0</frequency_threshold>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, other adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="143"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </other_events>
    </reported_events>

    <certain_agreements>
      <pi_employee>All Principal Investigators ARE employed by the organization sponsoring the study.</pi_employee>
      <restrictive_agreement>There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed. </restrictive_agreement>
    </certain_agreements>
    <point_of_contact>
      <name_or_title>Dr Helen Jones</name_or_title>
      <organization>Oxford Univeristy Hospitals NHS Foundation Trust</organization>
      <phone>01865 235657</phone>
      <email>helen.jones3@ouh.nhs.uk</email>
    </point_of_contact>
  </clinical_results>
</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/NCT03039595
org study id: 11846
nct id: NCT03039595
lead sponsor: 
collaborator: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
Early rectal cancer can be removed by minimally-invasive surgery, and the standard
      pathological assessment of the removed tumour gives valuable information about how advanced
      the tumour is. This gives an indication of how likely the cancer is to recur, so doctors and
      patient can decide on the most appropriate further treatment and follow-up. However there is
      still much uncertainty in these predictions about recurrence. This study will assess two
      further pathology tests, ploidy and stroma ratio in the tumour, by correlating the results
      with outcome. This will determine whether these two tests provide additional value in
      predicting outcome. If so, clinicians would be better able to advise patients with early
      rectal cancer about their prognosis and further management.
Early rectal cancer can be removed by minimally-invasive surgery, and the standard
      pathological assessment of the removed tumour gives valuable information about how advanced
      the tumour is. This information is very important in indicating whether the cancer is likely
      to recur, and therefore in advising the patient after surgery whether further treatment is
      advisable, and if not, what is the most appropriate follow-up regime. However there is still
      a lot of uncertainty in these predictions about recurrence of the cancer, and better tests
      are being sought. This study aims to look at two further pathology tests, ploidy and stroma
      ratio in the tumour, and correlate these test results with outcome in patients who have had
      an early rectal cancer removed. This will allow the investigators to assess whether these two
      tests provide additional value in predicting outcome. If so, clinicians would be better able
      to advise patients with early rectal cancer about their prognosis and further management.

      Routine histopathology analysis of a rectal cancer specimen removed at surgery includes
      assessment of tumour size, depth of invasion, vascular, lymphatic and perineural invasion,
      tumour involvement of resection margins and nodal involvement. This information is valuable
      in predicting outcome. For example, predicted rates of local recurrence at 36 months
      following local excision of rectal cancer by transanal endoscopic microsurgery (TEM) based on
      tumour size, depth of invasion and lymphatic invasion have been tabulated. However such
      models are not perfect, and leave room for improvement. Ploidy and stroma ratio are two
      further tests which have shown some promise in predicting outcome.

      Ploidy refers to the number of sets of chromosomes in a cell nucleus. Most human cells are
      normally diploid, with two sets of 23 chromosomes. Abnormal tumour cells may have a different
      number of sets of chromosomes, or be aneuploid, having some replicated or deleted
      chromosomes. In general, aneuploidy in cancer cells is associated with a worse prognosis. An
      early study of DNA ploidy in rectal cancer using flow cytometry showed an independent but
      small predictive effective of aneuploidy on survival. Technological advances now allow more
      accurate and detailed assessment of ploidy. The DNA ploidy status of tumour cells in early
      ovarian cancer has been found to predict which patients will benefit from adjuvant
      chemotherapy after surgery to remove the ovarian tumour and is used routinely in some centres
      to aid in decision-making.

      Stroma ratio refers to the tumour: stroma ratio. A lower proportion of tumour cells or,
      conversely, a higher percentage of stroma, in a cancer tends to be associated with a poorer
      prognosis. This ratio has been found to be strongly associated with tumour growth and
      invasion in colorectal cancers, and to independently predict survival in patients undergoing
      surgery to removal colorectal tumours. However previous studies have looked mainly at more
      advanced colon cancers, rather than early rectal cancers, and have used only cancer-related
      death as the endpoint, rather than looking at local recurrence and response to adjuvant
      treatments.
observational model: Cohort
time perspective: Other
measure: Correlation Between Ploidy Status With Local Recurrence of Cancer
time frame: a minimum of 6 months after surgery
description: Results of ploidy status will be correlated with patient follow-up information for between 6 months and 9 years following surgery, to look for any correlation with local recurrence of the rectal cancer
measure: Correlation Between Tumour: Stroma Ratio With Local Recurrence of Cancer
time frame: a minimum of 6 months after surgery
description: Results of tumour:stromal ratio (TSR) will be correlated with patient follow-up information for between 6 months and 9 years following surgery, to look for any correlation with local recurrence of the rectal cancer. A 50% cut-off is used to define high TSR.
measure: Correlation Between Ploidy Status and Overall Survival After TEM Surgery to Remove Rectal Cancer
time frame: a minimum of 6 months after surgery
description: Results of ploidy status will be correlated with patient follow-up information for between 6 months and 9 years following surgery, to look for any correlation between the test results and overall survival
measure: Correlation Between Tumour:Stroma Ratio and Overall Survival After TEM Surgery to Remove Rectal Cancer
time frame: a minimum of 6 months after surgery
description: Results of tumour:stromal ratio (TSR) will be correlated with patient follow-up information for between 6 months and 9 years following surgery, to look for any correlation between the test results and overall survival. High TSR is defined using a 50% cut-off.
intervention type: Other
intervention name: Ploidy and tumour:stromal ratio measurements
description: Ploidy and tumour:stromal ratio measurements will be made on specimens of early rectal cancer removed by transanal endoscopic microsurgery (TEM)
Specimens of early rectal cancer removed by transanal endoscopic microsurgery, which are
      routinely retained, will be further analysed.
study pop: 
sampling method: Non-Probability Sample
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Chris Cunningham, MD
role: Principal Investigator
affiliation: Employee
facility: 
country: United Kingdom
citation: Bach SP, Hill J, Monson JR, Simson JN, Lane L, Merrie A, Warren B, Mortensen NJ; Association of Coloproctology of Great Britain and Ireland Transanal Endoscopic Microsurgery (TEM) Collaboration. A predictive model for local recurrence after transanal endoscopic microsurgery for rectal cancer. Br J Surg. 2009 Mar;96(3):280-90. doi: 10.1002/bjs.6456.
PMID: 19224520
citation: Goh HS, Jass JR, Atkin WS, Cuzick J, Northover JM. Value of flow cytometric determination of ploidy as a guide to prognosis in operable rectal cancer: a multivariate analysis. Int J Colorectal Dis. 1987 Feb;2(1):17-21. doi: 10.1007/BF01648992.
PMID: 3598327
citation: Kristensen GB, Kildal W, Abeler VM, Kaern J, Vergote I, Trope CG, Danielsen HE. Large-scale genomic instability predicts long-term outcome for women with invasive stage I ovarian cancer. Ann Oncol. 2003 Oct;14(10):1494-500. doi: 10.1093/annonc/mdg403.
PMID: 14504048
citation: Park JH, Richards CH, McMillan DC, Horgan PG, Roxburgh CSD. The relationship between tumour stroma percentage, the tumour microenvironment and survival in patients with primary operable colorectal cancer. Ann Oncol. 2014 Mar;25(3):644-651. doi: 10.1093/annonc/mdt593. Epub 2014 Jan 23.
PMID: 24458470
citation: Downey CL, Simpkins SA, White J, Holliday DL, Jones JL, Jordan LB, Kulka J, Pollock S, Rajan SS, Thygesen HH, Hanby AM, Speirs V. The prognostic significance of tumour-stroma ratio in oestrogen receptor-positive breast cancer. Br J Cancer. 2014 Apr 2;110(7):1744-7. doi: 10.1038/bjc.2014.69. Epub 2014 Feb 18.
PMID: 24548861
citation: West NP, Dattani M, McShane P, Hutchins G, Grabsch J, Mueller W, Treanor D, Quirke P, Grabsch H. The proportion of tumour cells is an independent predictor for survival in colorectal cancer patients. Br J Cancer. 2010 May 11;102(10):1519-23. doi: 10.1038/sj.bjc.6605674. Epub 2010 Apr 20.
PMID: 20407439
responsible party type: Principal Investigator
investigator affiliation: Oxford University Hospitals NHS Trust
investigator full name: Chris Cunningham
investigator title: Consultant colorectal surgeon
mesh term: Rectal Neoplasms
sharing ipd: No
ipd description: No individual data will be made available
provided document: 
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 