<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/NCT03776591</url>
  </required_header>
  <id_info>
    <org_study_id>REK 2015/2396</org_study_id>
    <nct_id>NCT03776591</nct_id>
  </id_info>
  <brief_title>Open D3 Right Hemicolectomy Compared to Laparoscopic CME for Right Sided Colon Cancer</brief_title>
  <acronym>D3/CME</acronym>
  <official_title>Open D3 Right Colectomy Compared to Laparoscopic CME Right Colectomy for Right Sided Colon Cancer; an Open Randomized Controlled Study</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Haraldsplass Deaconess Hospital</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Helse-Bergen HF</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>University of Bergen</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Haraldsplass Deaconess Hospital</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>
      The primary focus in this study is to investigate and improve the surgical technique. In&#xD;
      addition the collection of clinical data during diagnostic and follow up and the collection&#xD;
      of tumor and blood gives us the opportunity to investigate tumor biology and its relevance in&#xD;
      terms of determine appropriate treatment strategy both surgically and oncological and to&#xD;
      assess and predict treatment outcome.&#xD;
&#xD;
      The aim of this study is to compare short and long-term outcomes between open D3 and&#xD;
      laparoscopic CME (complete mesocolic excision) with CVL (central vascular ligation) right&#xD;
      colectomy for right-sided colon cancer. Our primary hypothesis is that laparoscopic surgery&#xD;
      improves quality of life by reducing pain, postoperative complications and thereby reduces&#xD;
      hospital stay and convalescence. On the other hand it is to prove non-inferiority of the&#xD;
      laparoscopic group compared to the open group by means of oncological outcome (survival,&#xD;
      recurrence). Secondary aim is to evaluate surgical quality by comparing actual vascular stump&#xD;
      length between the two groups by postoperative CT and compare number of lymph nodes removed&#xD;
      with the specimen. With the use of liquid biopsy we want to detect circulating tumor DNA&#xD;
      (ctDNA) and circulating tumor cells (CTCs) and evaluate their value as tumor markers by&#xD;
      comparing the prognostic and predictive value. The hypothesis is that ctDNA and CTCs are more&#xD;
      sensitive than standard parameters and imaging (CT CEA).&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This is a prospective, randomized, multi-center clinical study. The short term outcome, 2 and&#xD;
      5 year survival and mortality rates will be compared between the groups operated with open D3&#xD;
      resection at Haukeland University hospital and laparoscopic CME with CVL right hemicolectomy&#xD;
      at Haraldsplass Deaconess hospital. Computer generated block randomization will be used.&#xD;
&#xD;
      All patients ≤ 85 years with tumor localized in the right colon will be considered to&#xD;
      participate in the study. The patients will be summoned to the first consultation to the&#xD;
      hospital they are referred to. They will be informed of the study. A patient who meets the&#xD;
      inclusion criteria will be asked to participate in the study and sign the informed consent. A&#xD;
      patient who accepts will be assigned a sequential participant number and then referred to&#xD;
      open D3 or laparoscopic CME (right hemicolectomy) according to a pre-specified randomized&#xD;
      list of treatments.&#xD;
&#xD;
      All patients referred with right sided colon cancer in the inclusion period will be&#xD;
      registered, and the reason why some do not participate in the study will be documented.&#xD;
      Patients who decline to participate in the study will be assigned standard treatment in the&#xD;
      institution they are referred to.&#xD;
&#xD;
      Blood samples for analysis of ctDNA/CTCs will be collected preoperatively, 3-10th&#xD;
      postoperative day, at 3 months and at each check the next five years at six months intervals.&#xD;
      All sample times except the first postoperative control, correspond to the time of CEA and CT&#xD;
      in ordinary follow-up. Proteomic technology based analysis of tumor tissue&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">September 1, 2016</start_date>
  <completion_date type="Anticipated">September 1, 2026</completion_date>
  <primary_completion_date type="Anticipated">September 1, 2026</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>Complications</measure>
    <time_frame>30 days</time_frame>
    <description>Surgical and general complications by Clavien-Dindo Classification og surgical complications</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Surgical quality vascular resection</measure>
    <time_frame>6 months</time_frame>
    <description>Vascular stump length in mm</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Surgical quality lymph nodes</measure>
    <time_frame>6 months</time_frame>
    <description>Number of lymph nodes</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Patient outcome general</measure>
    <time_frame>6 months</time_frame>
    <description>15D Health-related quality of life (HRQoL) preoperative and at 6 months. Scale 0-1. a higher score reflects a better HRQoL</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Patient outcome bowel function</measure>
    <time_frame>6 months</time_frame>
    <description>Quality of life (LARS (low anterior resection syndrome) score preoperative and at 6 months. Scale 0-42, where 0 reflects no LARS and 30-42 major LARS.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Oncological outcome survival</measure>
    <time_frame>60 months</time_frame>
    <description>Survival in months</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Oncological outcome recurrence</measure>
    <time_frame>60 months</time_frame>
    <description>Time to recurrence in months</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Prognostic significance of ctDNA</measure>
    <time_frame>60 months</time_frame>
    <description>copies/mL plasma or % fractional abundance (mutant/total ctDNA)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Prognostic significance of CTCs</measure>
    <time_frame>60 months</time_frame>
    <description>CTC/ml blood</description>
  </secondary_outcome>
  <other_outcome>
    <measure>Compare the D3 specimen with the CME specimen morphologically</measure>
    <time_frame>4 weeks</time_frame>
    <description>West classification</description>
  </other_outcome>
  <other_outcome>
    <measure>Operative parameters time</measure>
    <time_frame>1 day</time_frame>
    <description>Operating time in minutes</description>
  </other_outcome>
  <other_outcome>
    <measure>Operative parameters blood loss</measure>
    <time_frame>1 day</time_frame>
    <description>Intraoperative blood loss in ml</description>
  </other_outcome>
  <other_outcome>
    <measure>Operative parameters bleeding</measure>
    <time_frame>1 day</time_frame>
    <description>Incidents of bleeding from central vascular structures; yes/no</description>
  </other_outcome>
  <other_outcome>
    <measure>Postoperative parameters</measure>
    <time_frame>6 months</time_frame>
    <description>Incisional hernias; yes/no</description>
  </other_outcome>
  <other_outcome>
    <measure>Hospitalization</measure>
    <time_frame>30 days</time_frame>
    <description>Total length of stay, including readmissions within 30 days</description>
  </other_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">126</enrollment>
  <condition>Complication</condition>
  <condition>Quality of Life</condition>
  <condition>Surgical Procedure, Unspecified</condition>
  <condition>Lymph Node Metastases</condition>
  <condition>Circulating Tumor Cell</condition>
  <arm_group>
    <arm_group_label>Open D3</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Right colectomy Open surgery Central lymphadenectomy and vascular ligation</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Laparoscopic CME with CVL</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Right colectomy Laparoscopic surgery Central lymphadenectomy and vascular ligation</description>
  </arm_group>
  <intervention>
    <intervention_type>Procedure</intervention_type>
    <intervention_name>Open surgery</intervention_name>
    <arm_group_label>Open D3</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Procedure</intervention_type>
    <intervention_name>Right colectomy</intervention_name>
    <arm_group_label>Laparoscopic CME with CVL</arm_group_label>
    <arm_group_label>Open D3</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Procedure</intervention_type>
    <intervention_name>Laparoscopic surgery</intervention_name>
    <arm_group_label>Laparoscopic CME with CVL</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Procedure</intervention_type>
    <intervention_name>Central lymphadenectomy and vascular ligation</intervention_name>
    <arm_group_label>Laparoscopic CME with CVL</arm_group_label>
    <arm_group_label>Open D3</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  • Patients with malignant tumor of the right colon (cecum, ascending colon, right&#xD;
             flexure and right transverse) at CT, colonoscopy.&#xD;
&#xD;
               -  Patients medically cleared by anesthesiologist for general anesthesia and&#xD;
                  oncological radical resection&#xD;
&#xD;
               -  Patients ≤ 85 years&#xD;
&#xD;
               -  Signed informed consent form&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  • Patients with recurrent cancer after previous surgery&#xD;
&#xD;
               -  Patients with synchronous distant metastasis&#xD;
&#xD;
               -  Patients with ongoing oncological treatment due to other cancer&#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>Kristin B. Lygre, M.D</last_name>
    <role>Study Director</role>
    <affiliation>Haraldsplass Deaconess Hospital</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Kristin B Lygre, M.D</last_name>
    <phone>004755978500</phone>
    <email>kristin.bentung.lygre@haraldsplass.no</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Frank Pfeffer, Ph.D</last_name>
    <phone>004755975000</phone>
    <email>frank.pfeffer@helse-bergen.no</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>Haraldsplass</name>
      <address>
        <city>Bergen</city>
        <zip>5021</zip>
        <country>Norway</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Kristin B Lygre, M.D</last_name>
    </contact>
  </location>
  <location_countries>
    <country>Norway</country>
  </location_countries>
  <verification_date>August 2021</verification_date>
  <study_first_submitted>December 6, 2018</study_first_submitted>
  <study_first_submitted_qc>December 13, 2018</study_first_submitted_qc>
  <study_first_posted type="Actual">December 14, 2018</study_first_posted>
  <last_update_submitted>August 24, 2021</last_update_submitted>
  <last_update_submitted_qc>August 24, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">August 25, 2021</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Haraldsplass Deaconess Hospital</investigator_affiliation>
    <investigator_full_name>Kristin Bentung Lygre</investigator_full_name>
    <investigator_title>Consultant Doctor</investigator_title>
  </responsible_party>
  <keyword>D3 lymphadenectomy</keyword>
  <keyword>Right-sided</keyword>
  <keyword>Colon cancer</keyword>
  <keyword>Complications</keyword>
  <keyword>Circulating tumor cells</keyword>
  <keyword>Circulating DNA (cDNA)</keyword>
  <keyword>Laparoscopy</keyword>
  <keyword>Complete mesocolic excision</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Colonic Neoplasms</mesh_term>
    <mesh_term>Neoplastic Cells, Circulating</mesh_term>
    <mesh_term>Lymphatic Metastasis</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT03776591
org study id: REK 2015/2396
nct id: NCT03776591
lead sponsor: 
collaborator: 
collaborator: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
The primary focus in this study is to investigate and improve the surgical technique. In
      addition the collection of clinical data during diagnostic and follow up and the collection
      of tumor and blood gives us the opportunity to investigate tumor biology and its relevance in
      terms of determine appropriate treatment strategy both surgically and oncological and to
      assess and predict treatment outcome.

      The aim of this study is to compare short and long-term outcomes between open D3 and
      laparoscopic CME (complete mesocolic excision) with CVL (central vascular ligation) right
      colectomy for right-sided colon cancer. Our primary hypothesis is that laparoscopic surgery
      improves quality of life by reducing pain, postoperative complications and thereby reduces
      hospital stay and convalescence. On the other hand it is to prove non-inferiority of the
      laparoscopic group compared to the open group by means of oncological outcome (survival,
      recurrence). Secondary aim is to evaluate surgical quality by comparing actual vascular stump
      length between the two groups by postoperative CT and compare number of lymph nodes removed
      with the specimen. With the use of liquid biopsy we want to detect circulating tumor DNA
      (ctDNA) and circulating tumor cells (CTCs) and evaluate their value as tumor markers by
      comparing the prognostic and predictive value. The hypothesis is that ctDNA and CTCs are more
      sensitive than standard parameters and imaging (CT CEA).
This is a prospective, randomized, multi-center clinical study. The short term outcome, 2 and
      5 year survival and mortality rates will be compared between the groups operated with open D3
      resection at Haukeland University hospital and laparoscopic CME with CVL right hemicolectomy
      at Haraldsplass Deaconess hospital. Computer generated block randomization will be used.

      All patients ≤ 85 years with tumor localized in the right colon will be considered to
      participate in the study. The patients will be summoned to the first consultation to the
      hospital they are referred to. They will be informed of the study. A patient who meets the
      inclusion criteria will be asked to participate in the study and sign the informed consent. A
      patient who accepts will be assigned a sequential participant number and then referred to
      open D3 or laparoscopic CME (right hemicolectomy) according to a pre-specified randomized
      list of treatments.

      All patients referred with right sided colon cancer in the inclusion period will be
      registered, and the reason why some do not participate in the study will be documented.
      Patients who decline to participate in the study will be assigned standard treatment in the
      institution they are referred to.

      Blood samples for analysis of ctDNA/CTCs will be collected preoperatively, 3-10th
      postoperative day, at 3 months and at each check the next five years at six months intervals.
      All sample times except the first postoperative control, correspond to the time of CEA and CT
      in ordinary follow-up. Proteomic technology based analysis of tumor tissue
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Complications
time frame: 30 days
description: Surgical and general complications by Clavien-Dindo Classification og surgical complications
measure: Surgical quality vascular resection
time frame: 6 months
description: Vascular stump length in mm
measure: Surgical quality lymph nodes
time frame: 6 months
description: Number of lymph nodes
measure: Patient outcome general
time frame: 6 months
description: 15D Health-related quality of life (HRQoL) preoperative and at 6 months. Scale 0-1. a higher score reflects a better HRQoL
measure: Patient outcome bowel function
time frame: 6 months
description: Quality of life (LARS (low anterior resection syndrome) score preoperative and at 6 months. Scale 0-42, where 0 reflects no LARS and 30-42 major LARS.
measure: Oncological outcome survival
time frame: 60 months
description: Survival in months
measure: Oncological outcome recurrence
time frame: 60 months
description: Time to recurrence in months
measure: Prognostic significance of ctDNA
time frame: 60 months
description: copies/mL plasma or % fractional abundance (mutant/total ctDNA)
measure: Prognostic significance of CTCs
time frame: 60 months
description: CTC/ml blood
measure: Compare the D3 specimen with the CME specimen morphologically
time frame: 4 weeks
description: West classification
measure: Operative parameters time
time frame: 1 day
description: Operating time in minutes
measure: Operative parameters blood loss
time frame: 1 day
description: Intraoperative blood loss in ml
measure: Operative parameters bleeding
time frame: 1 day
description: Incidents of bleeding from central vascular structures; yes/no
measure: Postoperative parameters
time frame: 6 months
description: Incisional hernias; yes/no
measure: Hospitalization
time frame: 30 days
description: Total length of stay, including readmissions within 30 days
arm group label: Open D3
arm group type: Experimental
description: Right colectomy Open surgery Central lymphadenectomy and vascular ligation
arm group label: Laparoscopic CME with CVL
arm group type: Active Comparator
description: Right colectomy Laparoscopic surgery Central lymphadenectomy and vascular ligation
intervention type: Procedure
intervention name: Open surgery
arm group label: Open D3
intervention type: Procedure
intervention name: Right colectomy
arm group label: Laparoscopic CME with CVL
arm group label: Open D3
intervention type: Procedure
intervention name: Laparoscopic surgery
arm group label: Laparoscopic CME with CVL
intervention type: Procedure
intervention name: Central lymphadenectomy and vascular ligation
arm group label: Laparoscopic CME with CVL
arm group label: Open D3
criteria: 
gender: All
minimum age: 18 Years
maximum age: 85 Years
healthy volunteers: No
last name: Kristin B. Lygre, M.D
role: Study Director
affiliation: Haraldsplass Deaconess Hospital
last name: Kristin B Lygre, M.D
phone: 004755978500
email: kristin.bentung.lygre@haraldsplass.no
last name: Frank Pfeffer, Ph.D
phone: 004755975000
email: frank.pfeffer@helse-bergen.no
facility: 
status: Recruiting
contact: 
country: Norway
responsible party type: Principal Investigator
investigator affiliation: Haraldsplass Deaconess Hospital
investigator full name: Kristin Bentung Lygre
investigator title: Consultant Doctor
mesh term: Colonic Neoplasms
mesh term: Neoplastic Cells, Circulating
mesh term: Lymphatic Metastasis
sharing ipd: No