<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/NCT03287843</url>
  </required_header>
  <id_info>
    <org_study_id>17-4.1/13</org_study_id>
    <nct_id>NCT03287843</nct_id>
  </id_info>
  <brief_title>Appropriate Timing of Surgery After Neoadjuvant Chemoradiation for Locally Advanced Rectal Cancer</brief_title>
  <official_title>Effect of Timing of Surgery After Neoadjuvant Chemoradiation on Histopathological Results, Complications, Recurrence and Survivals for Locally Advanced Rectal Cancer</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Ege University</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Ege University</source>
  <oversight_info>
    <has_dmc>Yes</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>
      This study aimed to compare the outcomes of early versus late surgical resection in patients&#xD;
      who underwent curative total mesorectal excision after neoadjuvant chemoradiation. Half of&#xD;
      the participants will undergo surgery before 8 weeks, while the other half will undergo&#xD;
      surgery after 8 weeks.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">January 1, 2006</start_date>
  <completion_date type="Actual">January 1, 2022</completion_date>
  <primary_completion_date type="Actual">January 1, 2017</primary_completion_date>
  <phase>N/A</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Pathological Complete Response Rate</measure>
    <time_frame>2 months</time_frame>
    <description>Complete pathological response, defined as the absence of viable tumor cells, may develop after neoadjuvant treatment for rectal cancer. Prognostic factors affecting pathological complete response will be evaluated.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Completeness of the Mesorectal Dissection</measure>
    <time_frame>30 days after surgery</time_frame>
    <description>Examination will be made in a fresh state for completeness of the mesorectal dissection and will be graded according to the criteria of Quirke as follows:&#xD;
Low: (Grade 1) Little bulk of the mesorectum with defects down into the muscularis propria and/or very irregular circumferential resection margin.&#xD;
Moderate: (Grade 2) Moderate bulk of the mesorectum but there is irregularity in the mesorectal surface. Moderate coning of the specimen toward the distal margin. At no site is the muscularis propria visible with exception of the insertion of the levator muscles. Moderate irregularity of the circumferential resection margin.&#xD;
High: (Grade 3) Intact mesorectum with smooth mesorectal surface. No defect deeper than 5 mm. No coning on the specimen. Smooth circumferential resection margins on slicing.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Tumour Regression Grade</measure>
    <time_frame>30 days after surgery</time_frame>
    <description>All pathological examinations were undertaken by two experienced gastrointestinal pathologists. Pathological treatment response to neoadjuvant chemoradiotherapy was evaluated by a five-tiered system described by Mandard.&#xD;
Tumor regression grade groups were identified as:&#xD;
Grade 1: the absence of residual cancer Grade 2: the presence of residual cancer cells scattered throughout the fibrosis Grade 3: an increase in the number of residual cancer cells but fibrosis still predominant Grade 4: residual cancer outgrowing fibrosis Grade 5, the absence of regressive changes&#xD;
Grade 1 considered as complete response. Grade 2-4 considered as partial response and Grade 5 considered as no response.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Surgical Complications</measure>
    <time_frame>90 days after surgery</time_frame>
    <description>Morbidity will be assessed according to the classification of Clavien-Dindo as follows:&#xD;
Grade 1: Any deviation from the normal postoperative course without the need for pharmacological treatment or surgical, endoscopic, and radiological interventions. Allowed therapeutic regimens are: drugs as antiemetics, antipyretics, analgetics, diuretics, electrolytes, and physiotherapy. This grade also includes wound infections opened at the bedside Grade 2: Requiring pharmacological treatment with drugs other than such allowed for grade I complications. Blood transfusions and total parenteral nutrition are also included.&#xD;
Grade 3: Requiring surgical, endoscopic or radiological intervention (Grade 3a: Intervention not under general anesthesia, Grade 3b: Intervention under general anesthesia) Grade 4: Life-threatening complication requiring Intensive Care Unit management (Grade 4a: Single organ dysfunction (including dialysis), Grade 4b: Multiorgan dysfunction) Grade 5 Death</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Recurrence</measure>
    <time_frame>5 years after surgery</time_frame>
    <description>Both pelvic recurrence and distant metastasis will be assessed.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Disease-free Survival</measure>
    <time_frame>5 years after surgery</time_frame>
    <description>Recurrence free survival</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Overall Survival</measure>
    <time_frame>5 years after surgery</time_frame>
    <description>Total survival with or without disease</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">350</enrollment>
  <condition>Neoplasm, Rectum</condition>
  <arm_group>
    <arm_group_label>Early surgery group</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>İn this arm patients will go under surgery before eight weeks, after neoadjuvant chemoradiation therapy.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Late surgery group</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>İn this arm patients will go under surgery after eight weeks, after neoadjuvant chemoradiation therapy.</description>
  </arm_group>
  <intervention>
    <intervention_type>Procedure</intervention_type>
    <intervention_name>Total mesorectal excision before 56 days (4-8 weeks)</intervention_name>
    <description>Low anterior resection or abdominoperineal resection</description>
    <arm_group_label>Early surgery group</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Procedure</intervention_type>
    <intervention_name>Total mesorectal excision after 56 days (8-12 weeks)</intervention_name>
    <description>Low anterior resection or abdominoperineal resection</description>
    <arm_group_label>Late surgery group</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Clinic stage II-III cancer ( T3- T4 tm or/and N(+) disease )&#xD;
&#xD;
          2. Patients with histologically confirmed adenocarcinoma of the rectum&#xD;
&#xD;
          3. Tumor distal border located within 15 cm. from anal verge (as measured by rigid&#xD;
             rectoscopy)&#xD;
&#xD;
          4. Standardized total mesorectal excision surgery&#xD;
&#xD;
          5. Tumor must be clinically resectable with curative intent (R0 resection must be most&#xD;
             likely)&#xD;
&#xD;
          6. Elective operation&#xD;
&#xD;
          7. The patient must consent to be in the study and the informed consent must be signed&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Clinic stage I and IV cancer disease&#xD;
&#xD;
          2. Patients with malignant disease of the rectum other than adenocarcinoma&#xD;
&#xD;
          3. Recurrent rectal cancer&#xD;
&#xD;
          4. Emergency cases (Mechanical bowel obstruction, perforation)&#xD;
&#xD;
          5. Other previous or concurrent malignancies&#xD;
&#xD;
          6. Any contraindication for radiochemotherapy&#xD;
&#xD;
          7. Previous chemotherapy or radiotherapy to the pelvis&#xD;
&#xD;
          8. Tumor has arisen from chronic inflammatory bowel disease or hereditary polyposis&#xD;
             disease&#xD;
&#xD;
          9. American Society of Anesthesiologists Score &gt;3 patients&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>85 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Z.Erhan Akgun, Proffesor</last_name>
    <role>Principal Investigator</role>
    <affiliation>Ege University</affiliation>
  </overall_official>
  <verification_date>March 2022</verification_date>
  <study_first_submitted>September 13, 2017</study_first_submitted>
  <study_first_submitted_qc>September 17, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">September 19, 2017</study_first_posted>
  <results_first_submitted>February 8, 2019</results_first_submitted>
  <results_first_submitted_qc>July 21, 2019</results_first_submitted_qc>
  <results_first_posted type="Actual">August 29, 2019</results_first_posted>
  <last_update_submitted>March 22, 2022</last_update_submitted>
  <last_update_submitted_qc>March 22, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">March 31, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Ege University</investigator_affiliation>
    <investigator_full_name>Zekeriya Erhan Akgün</investigator_full_name>
    <investigator_title>Professor of surgery</investigator_title>
  </responsible_party>
  <keyword>Locally advanced rectal cancer</keyword>
  <keyword>Neoadjuvant chemoradiation</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Rectal Neoplasms</mesh_term>
  </condition_browse>

  <clinical_results>

    <participant_flow>
      <group_list>
        <group group_id="P1">
          <title>Classic Interval Group</title>
          <description>İn this arm patients will go under surgery before eight weeks, after neoadjuvant chemoradiation therapy.&#xD;
Total mesorectal excision before 56 days (4-8 weeks): Low anterior resection or abdominoperineal resection</description>
        </group>
        <group group_id="P2">
          <title>Long Interval Group</title>
          <description>İn this arm patients will go under surgery after eight weeks, after neoadjuvant chemoradiation therapy.&#xD;
Total mesorectal excision after 56 days (8-12 weeks): Low anterior resection or abdominoperineal resection</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="175"/>
                <participants group_id="P2" count="175"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>Excluded</title>
              <participants_list>
                <participants group_id="P1" count="12">No surgery n=5 R2 resection n=5 Stage IV n=2</participants>
                <participants group_id="P2" count="8">No surgery n=4 R2 resection n=2 Stage IV n=2</participants>
              </participants_list>
            </milestone>
            <milestone>
              <title>Lost to Follow up</title>
              <participants_list>
                <participants group_id="P1" count="3"/>
                <participants group_id="P2" count="0"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="160"/>
                <participants group_id="P2" count="167"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="15"/>
                <participants group_id="P2" count="8"/>
              </participants_list>
            </milestone>
          </milestone_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <population>350 patients were randomly assigned. After perioperative evaluation of 350 patients who underwent CRT , 15 patients in the CI group (no surgery, 5; R2 resection, 5; stage IV disease, 2; lost to follow-up, 3) and eight in the LI group (no surgery, 4; R2 resection, 2; stage IV disease, 2) were excluded from the study. 327 included in the analysis.</population>
      <group_list>
        <group group_id="B1">
          <title>Classic Interval Group</title>
          <description>İn this arm patients will go under surgery before eight weeks, after neoadjuvant chemoradiation therapy.&#xD;
Total mesorectal excision before 56 days (4-8 weeks): Low anterior resection or abdominoperineal resection</description>
        </group>
        <group group_id="B2">
          <title>Long Interval Group</title>
          <description>İn this arm patients will go under surgery after eight weeks, after neoadjuvant chemoradiation therapy.&#xD;
Total mesorectal excision after 56 days (8-12 weeks): Low anterior resection or abdominoperineal resection</description>
        </group>
        <group group_id="B3">
          <title>Total</title>
          <description>Total of all reporting groups</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="160"/>
            <count group_id="B2" value="167"/>
            <count group_id="B3" value="327"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>years</units>
          <param>Mean</param>
          <dispersion>Inter-Quartile Range</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="60.4" lower_limit="22" upper_limit="85"/>
                    <measurement group_id="B2" value="61.7" lower_limit="32" upper_limit="85"/>
                    <measurement group_id="B3" value="61.0" lower_limit="22" upper_limit="85"/>
                  </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>
              <category_list>
                <category>
                  <title>Female</title>
                  <measurement_list>
                    <measurement group_id="B1" value="65"/>
                    <measurement group_id="B2" value="71"/>
                    <measurement group_id="B3" value="136"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="95"/>
                    <measurement group_id="B2" value="96"/>
                    <measurement group_id="B3" value="191"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Pathological Complete Response Rate</title>
        <description>Complete pathological response, defined as the absence of viable tumor cells, may develop after neoadjuvant treatment for rectal cancer. Prognostic factors affecting pathological complete response will be evaluated.</description>
        <time_frame>2 months</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Classic Interval Group</title>
            <description>İn this arm patients will go under surgery before eight weeks, after neoadjuvant chemoradiation therapy.&#xD;
Total mesorectal excision before 56 days (4-8 weeks): Low anterior resection or abdominoperineal resection</description>
          </group>
          <group group_id="O2">
            <title>Long Interval Group</title>
            <description>İn this arm patients will go under surgery after eight weeks, after neoadjuvant chemoradiation therapy.&#xD;
Total mesorectal excision after 56 days (8-12 weeks): Low anterior resection or abdominoperineal resection</description>
          </group>
        </group_list>
        <measure>
          <title>Pathological Complete Response Rate</title>
          <description>Complete pathological response, defined as the absence of viable tumor cells, may develop after neoadjuvant treatment for rectal cancer. Prognostic factors affecting pathological complete response will be evaluated.</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="160"/>
                <count group_id="O2" value="167"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="16"/>
                    <measurement group_id="O2" value="31"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Completeness of the Mesorectal Dissection</title>
        <description>Examination will be made in a fresh state for completeness of the mesorectal dissection and will be graded according to the criteria of Quirke as follows:&#xD;
Low: (Grade 1) Little bulk of the mesorectum with defects down into the muscularis propria and/or very irregular circumferential resection margin.&#xD;
Moderate: (Grade 2) Moderate bulk of the mesorectum but there is irregularity in the mesorectal surface. Moderate coning of the specimen toward the distal margin. At no site is the muscularis propria visible with exception of the insertion of the levator muscles. Moderate irregularity of the circumferential resection margin.&#xD;
High: (Grade 3) Intact mesorectum with smooth mesorectal surface. No defect deeper than 5 mm. No coning on the specimen. Smooth circumferential resection margins on slicing.</description>
        <time_frame>30 days after surgery</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Classic Interval Group</title>
            <description>İn this arm patients will go under surgery before eight weeks, after neoadjuvant chemoradiation therapy.&#xD;
Total mesorectal excision before 56 days (4-8 weeks): Low anterior resection or abdominoperineal resection</description>
          </group>
          <group group_id="O2">
            <title>Long Interval Group</title>
            <description>İn this arm patients will go under surgery after eight weeks, after neoadjuvant chemoradiation therapy.&#xD;
Total mesorectal excision after 56 days (8-12 weeks): Low anterior resection or abdominoperineal resection</description>
          </group>
        </group_list>
        <measure>
          <title>Completeness of the Mesorectal Dissection</title>
          <description>Examination will be made in a fresh state for completeness of the mesorectal dissection and will be graded according to the criteria of Quirke as follows:&#xD;
Low: (Grade 1) Little bulk of the mesorectum with defects down into the muscularis propria and/or very irregular circumferential resection margin.&#xD;
Moderate: (Grade 2) Moderate bulk of the mesorectum but there is irregularity in the mesorectal surface. Moderate coning of the specimen toward the distal margin. At no site is the muscularis propria visible with exception of the insertion of the levator muscles. Moderate irregularity of the circumferential resection margin.&#xD;
High: (Grade 3) Intact mesorectum with smooth mesorectal surface. No defect deeper than 5 mm. No coning on the specimen. Smooth circumferential resection margins on slicing.</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="160"/>
                <count group_id="O2" value="167"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Low</title>
                  <measurement_list>
                    <measurement group_id="O1" value="5"/>
                    <measurement group_id="O2" value="8"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Moderate</title>
                  <measurement_list>
                    <measurement group_id="O1" value="11"/>
                    <measurement group_id="O2" value="10"/>
                  </measurement_list>
                </category>
                <category>
                  <title>High</title>
                  <measurement_list>
                    <measurement group_id="O1" value="144"/>
                    <measurement group_id="O2" value="149"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Tumour Regression Grade</title>
        <description>All pathological examinations were undertaken by two experienced gastrointestinal pathologists. Pathological treatment response to neoadjuvant chemoradiotherapy was evaluated by a five-tiered system described by Mandard.&#xD;
Tumor regression grade groups were identified as:&#xD;
Grade 1: the absence of residual cancer Grade 2: the presence of residual cancer cells scattered throughout the fibrosis Grade 3: an increase in the number of residual cancer cells but fibrosis still predominant Grade 4: residual cancer outgrowing fibrosis Grade 5, the absence of regressive changes&#xD;
Grade 1 considered as complete response. Grade 2-4 considered as partial response and Grade 5 considered as no response.</description>
        <time_frame>30 days after surgery</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Classic Interval Group</title>
            <description>İn this arm patients will go under surgery before eight weeks, after neoadjuvant chemoradiation therapy.&#xD;
Total mesorectal excision before 56 days (4-8 weeks): Low anterior resection or abdominoperineal resection</description>
          </group>
          <group group_id="O2">
            <title>Long Interval Group</title>
            <description>İn this arm patients will go under surgery after eight weeks, after neoadjuvant chemoradiation therapy.&#xD;
Total mesorectal excision after 56 days (8-12 weeks): Low anterior resection or abdominoperineal resection</description>
          </group>
        </group_list>
        <measure>
          <title>Tumour Regression Grade</title>
          <description>All pathological examinations were undertaken by two experienced gastrointestinal pathologists. Pathological treatment response to neoadjuvant chemoradiotherapy was evaluated by a five-tiered system described by Mandard.&#xD;
Tumor regression grade groups were identified as:&#xD;
Grade 1: the absence of residual cancer Grade 2: the presence of residual cancer cells scattered throughout the fibrosis Grade 3: an increase in the number of residual cancer cells but fibrosis still predominant Grade 4: residual cancer outgrowing fibrosis Grade 5, the absence of regressive changes&#xD;
Grade 1 considered as complete response. Grade 2-4 considered as partial response and Grade 5 considered as no response.</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="160"/>
                <count group_id="O2" value="167"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Mandard Grade 1</title>
                  <measurement_list>
                    <measurement group_id="O1" value="16"/>
                    <measurement group_id="O2" value="31"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Mandard Grade 2</title>
                  <measurement_list>
                    <measurement group_id="O1" value="37"/>
                    <measurement group_id="O2" value="36"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Mandard Grade 3</title>
                  <measurement_list>
                    <measurement group_id="O1" value="73"/>
                    <measurement group_id="O2" value="67"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Mandard Grade 4</title>
                  <measurement_list>
                    <measurement group_id="O1" value="31"/>
                    <measurement group_id="O2" value="29"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Mandard Grade 5</title>
                  <measurement_list>
                    <measurement group_id="O1" value="3"/>
                    <measurement group_id="O2" value="4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Surgical Complications</title>
        <description>Morbidity will be assessed according to the classification of Clavien-Dindo as follows:&#xD;
Grade 1: Any deviation from the normal postoperative course without the need for pharmacological treatment or surgical, endoscopic, and radiological interventions. Allowed therapeutic regimens are: drugs as antiemetics, antipyretics, analgetics, diuretics, electrolytes, and physiotherapy. This grade also includes wound infections opened at the bedside Grade 2: Requiring pharmacological treatment with drugs other than such allowed for grade I complications. Blood transfusions and total parenteral nutrition are also included.&#xD;
Grade 3: Requiring surgical, endoscopic or radiological intervention (Grade 3a: Intervention not under general anesthesia, Grade 3b: Intervention under general anesthesia) Grade 4: Life-threatening complication requiring Intensive Care Unit management (Grade 4a: Single organ dysfunction (including dialysis), Grade 4b: Multiorgan dysfunction) Grade 5 Death</description>
        <time_frame>90 days after surgery</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Classic Interval Group</title>
            <description>İn this arm patients will go under surgery before eight weeks, after neoadjuvant chemoradiation therapy.&#xD;
Total mesorectal excision before 56 days (4-8 weeks): Low anterior resection or abdominoperineal resection</description>
          </group>
          <group group_id="O2">
            <title>Long Interval Group</title>
            <description>İn this arm patients will go under surgery after eight weeks, after neoadjuvant chemoradiation therapy.&#xD;
Total mesorectal excision after 56 days (8-12 weeks): Low anterior resection or abdominoperineal resection</description>
          </group>
        </group_list>
        <measure>
          <title>Surgical Complications</title>
          <description>Morbidity will be assessed according to the classification of Clavien-Dindo as follows:&#xD;
Grade 1: Any deviation from the normal postoperative course without the need for pharmacological treatment or surgical, endoscopic, and radiological interventions. Allowed therapeutic regimens are: drugs as antiemetics, antipyretics, analgetics, diuretics, electrolytes, and physiotherapy. This grade also includes wound infections opened at the bedside Grade 2: Requiring pharmacological treatment with drugs other than such allowed for grade I complications. Blood transfusions and total parenteral nutrition are also included.&#xD;
Grade 3: Requiring surgical, endoscopic or radiological intervention (Grade 3a: Intervention not under general anesthesia, Grade 3b: Intervention under general anesthesia) Grade 4: Life-threatening complication requiring Intensive Care Unit management (Grade 4a: Single organ dysfunction (including dialysis), Grade 4b: Multiorgan dysfunction) Grade 5 Death</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="160"/>
                <count group_id="O2" value="167"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Clavien Dindo 1</title>
                  <measurement_list>
                    <measurement group_id="O1" value="4"/>
                    <measurement group_id="O2" value="7"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Clavien Dindo 2</title>
                  <measurement_list>
                    <measurement group_id="O1" value="15"/>
                    <measurement group_id="O2" value="14"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Clavien Dindo 3a</title>
                  <measurement_list>
                    <measurement group_id="O1" value="4"/>
                    <measurement group_id="O2" value="3"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Clavien Dindo 3b</title>
                  <measurement_list>
                    <measurement group_id="O1" value="8"/>
                    <measurement group_id="O2" value="2"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Clavien Dindo 4a</title>
                  <measurement_list>
                    <measurement group_id="O1" value="4"/>
                    <measurement group_id="O2" value="2"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Clavien Dindo 4b</title>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="1"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Clavien Dindo 5</title>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                    <measurement group_id="O2" value="4"/>
                  </measurement_list>
                </category>
                <category>
                  <title>No complication</title>
                  <measurement_list>
                    <measurement group_id="O1" value="124"/>
                    <measurement group_id="O2" value="134"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Recurrence</title>
        <description>Both pelvic recurrence and distant metastasis will be assessed.</description>
        <time_frame>5 years after surgery</time_frame>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Disease-free Survival</title>
        <description>Recurrence free survival</description>
        <time_frame>5 years after surgery</time_frame>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Overall Survival</title>
        <description>Total survival with or without disease</description>
        <time_frame>5 years after surgery</time_frame>
      </outcome>
    </outcome_list>

    <reported_events>
      <group_list>
        <group group_id="E1">
          <title>Classic Interval Group</title>
          <description>İn this arm patients will go under surgery before eight weeks, after neoadjuvant chemoradiation therapy.&#xD;
Total mesorectal excision before 56 days (4-8 weeks): Low anterior resection or abdominoperineal resection</description>
        </group>
        <group group_id="E2">
          <title>Long Interval Group</title>
          <description>İn this arm patients will go under surgery after eight weeks, after neoadjuvant chemoradiation therapy.&#xD;
Total mesorectal excision after 56 days (8-12 weeks): Low anterior resection or abdominoperineal resection</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="1" subjects_at_risk="160"/>
                <counts group_id="E2" subjects_affected="4" subjects_at_risk="167"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="36" subjects_at_risk="160"/>
                <counts group_id="E2" subjects_affected="33" subjects_at_risk="167"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Anastomotic leakage</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="160"/>
                <counts group_id="E2" subjects_affected="4" subjects_at_risk="167"/>
              </event>
              <event>
                <sub_title>Mechanical bowel obstruction</sub_title>
                <counts group_id="E1" subjects_affected="5" subjects_at_risk="160"/>
                <counts group_id="E2" subjects_affected="4" subjects_at_risk="167"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Pelvic abscess</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="160"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="167"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Renal and urinary disorders</title>
            <event_list>
              <event>
                <sub_title>Urinary leakage</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="160"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="167"/>
              </event>
              <event>
                <sub_title>Urinary tract infectio</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="160"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="167"/>
              </event>
              <event>
                <sub_title>Prerenal insufficiency</sub_title>
                <counts group_id="E1" subjects_affected="5" subjects_at_risk="160"/>
                <counts group_id="E2" subjects_affected="4" subjects_at_risk="167"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Atelectasis</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="160"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="167"/>
              </event>
              <event>
                <sub_title>Pneumonia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="160"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="167"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Surgical and medical procedures</title>
            <event_list>
              <event>
                <sub_title>Wound infection</sub_title>
                <counts group_id="E1" subjects_affected="6" subjects_at_risk="160"/>
                <counts group_id="E2" subjects_affected="9" subjects_at_risk="167"/>
              </event>
              <event>
                <sub_title>Postoperative bleeding</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="160"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="167"/>
              </event>
              <event>
                <sub_title>Other</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="160"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="167"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Vascular disorders</title>
            <event_list>
              <event>
                <sub_title>Deep vein thrombosis, pulmonary embolism</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="160"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="167"/>
              </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="160"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="167"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </other_events>
    </reported_events>

    <certain_agreements>
      <pi_employee>Principal Investigators are NOT 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>Erhan Akgun,MD, Proffessor</name_or_title>
      <organization>Ege University Hospital</organization>
      <phone>+902323905050</phone>
      <email>z.erhan.akgun@ege.edu.tr</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/NCT03287843
org study id: 17-4.1/13
nct id: NCT03287843
lead sponsor: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
This study aimed to compare the outcomes of early versus late surgical resection in patients
      who underwent curative total mesorectal excision after neoadjuvant chemoradiation. Half of
      the participants will undergo surgery before 8 weeks, while the other half will undergo
      surgery after 8 weeks.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Pathological Complete Response Rate
time frame: 2 months
description: Complete pathological response, defined as the absence of viable tumor cells, may develop after neoadjuvant treatment for rectal cancer. Prognostic factors affecting pathological complete response will be evaluated.
measure: Completeness of the Mesorectal Dissection
time frame: 30 days after surgery
description: Examination will be made in a fresh state for completeness of the mesorectal dissection and will be graded according to the criteria of Quirke as follows:
Low: (Grade 1) Little bulk of the mesorectum with defects down into the muscularis propria and/or very irregular circumferential resection margin.
Moderate: (Grade 2) Moderate bulk of the mesorectum but there is irregularity in the mesorectal surface. Moderate coning of the specimen toward the distal margin. At no site is the muscularis propria visible with exception of the insertion of the levator muscles. Moderate irregularity of the circumferential resection margin.
High: (Grade 3) Intact mesorectum with smooth mesorectal surface. No defect deeper than 5 mm. No coning on the specimen. Smooth circumferential resection margins on slicing.
measure: Tumour Regression Grade
time frame: 30 days after surgery
description: All pathological examinations were undertaken by two experienced gastrointestinal pathologists. Pathological treatment response to neoadjuvant chemoradiotherapy was evaluated by a five-tiered system described by Mandard.
Tumor regression grade groups were identified as:
Grade 1: the absence of residual cancer Grade 2: the presence of residual cancer cells scattered throughout the fibrosis Grade 3: an increase in the number of residual cancer cells but fibrosis still predominant Grade 4: residual cancer outgrowing fibrosis Grade 5, the absence of regressive changes
Grade 1 considered as complete response. Grade 2-4 considered as partial response and Grade 5 considered as no response.
measure: Surgical Complications
time frame: 90 days after surgery
description: Morbidity will be assessed according to the classification of Clavien-Dindo as follows:
Grade 1: Any deviation from the normal postoperative course without the need for pharmacological treatment or surgical, endoscopic, and radiological interventions. Allowed therapeutic regimens are: drugs as antiemetics, antipyretics, analgetics, diuretics, electrolytes, and physiotherapy. This grade also includes wound infections opened at the bedside Grade 2: Requiring pharmacological treatment with drugs other than such allowed for grade I complications. Blood transfusions and total parenteral nutrition are also included.
Grade 3: Requiring surgical, endoscopic or radiological intervention (Grade 3a: Intervention not under general anesthesia, Grade 3b: Intervention under general anesthesia) Grade 4: Life-threatening complication requiring Intensive Care Unit management (Grade 4a: Single organ dysfunction (including dialysis), Grade 4b: Multiorgan dysfunction) Grade 5 Death
measure: Recurrence
time frame: 5 years after surgery
description: Both pelvic recurrence and distant metastasis will be assessed.
measure: Disease-free Survival
time frame: 5 years after surgery
description: Recurrence free survival
measure: Overall Survival
time frame: 5 years after surgery
description: Total survival with or without disease
arm group label: Early surgery group
arm group type: Experimental
description: İn this arm patients will go under surgery before eight weeks, after neoadjuvant chemoradiation therapy.
arm group label: Late surgery group
arm group type: Experimental
description: İn this arm patients will go under surgery after eight weeks, after neoadjuvant chemoradiation therapy.
intervention type: Procedure
intervention name: Total mesorectal excision before 56 days (4-8 weeks)
description: Low anterior resection or abdominoperineal resection
arm group label: Early surgery group
intervention type: Procedure
intervention name: Total mesorectal excision after 56 days (8-12 weeks)
description: Low anterior resection or abdominoperineal resection
arm group label: Late surgery group
criteria: 
gender: All
minimum age: 18 Years
maximum age: 85 Years
healthy volunteers: No
last name: Z.Erhan Akgun, Proffesor
role: Principal Investigator
affiliation: Ege University
responsible party type: Principal Investigator
investigator affiliation: Ege University
investigator full name: Zekeriya Erhan Akgün
investigator title: Professor of surgery
mesh term: Rectal Neoplasms
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 