<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/NCT04488159</url>
  </required_header>
  <id_info>
    <org_study_id>iMAGINE</org_study_id>
    <secondary_id>2020-000401-91</secondary_id>
    <nct_id>NCT04488159</nct_id>
  </id_info>
  <brief_title>Immunoscore as Decision Guidance for Adjuvant Chemotherapy in Colon Cancer</brief_title>
  <acronym>iMAGINE</acronym>
  <official_title>iMmunoscore Associated Decision GuIdance for adjuvaNt Chemotherapy and Physical Exercise in Stage III Colon Cancer (iMAGINE): a Prospective, Randomized, Open-label, Multicenter, Phase III Clinical Trial</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Johannes Laengle, MD, PhD</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Medical University of Vienna</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>
    <is_us_export>No</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      The overall aim of this study is to prospectively validate the superiority of the Immunoscore&#xD;
      as a decision guidance for adjuvant chemotherapy in stage III colon cancer patients, in&#xD;
      comparison to the conventional TNM-based high- or low-risk classification.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Not yet recruiting</overall_status>
  <start_date type="Anticipated">December 1, 2023</start_date>
  <completion_date type="Anticipated">June 1, 2026</completion_date>
  <primary_completion_date type="Anticipated">December 1, 2025</primary_completion_date>
  <phase>Phase 3</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>Disease-free survival (DFS)</measure>
    <time_frame>3 years</time_frame>
    <description>Impact of Immunoscore stratification on DFS at 3 years (time from surgery to first observation of disease recurrence or death due to any cause)</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Overall survival (OS)</measure>
    <time_frame>3 years</time_frame>
    <description>Impact of Immunoscore stratification on OS at 3 years (time from surgery to death due to any cause)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time to recurrence (TTR)</measure>
    <time_frame>3 years</time_frame>
    <description>Impact of Immunoscore stratification on TTR at 3 years (time from surgery to disease recurrence)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Treatment-related adverse events (AE)</measure>
    <time_frame>3 years</time_frame>
    <description>Impact of Immunoscore stratification on treatment-related AEs assessed according to the latest Common Terminology Criteria of Adverse Events (CTCAE).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Quality of life</measure>
    <time_frame>3 years</time_frame>
    <description>Impact of Immunoscore stratification on quality of life assessed by the latest version of the European Organization for Research and Treatment of Cancer (EORCT) Quality of Life Group (QLG) questionnaires C30 and CR29.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Cost analysis</measure>
    <time_frame>3 years</time_frame>
    <description>Impact of Immunoscore stratification on treatment-related costs, assessed by cost-effectiveness analysis (CEA) according to the latest Good Research Practices for Cost-Effectiveness Analysis Alongside Clinical Trials of the International Society for Pharmacoeconomics and Outcomes Research (ISPOR).</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">1638</enrollment>
  <condition>Colon Cancer Stage III</condition>
  <arm_group>
    <arm_group_label>Immunoscore stratification</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Immunoscore low (I-Low; I0-1): 3 months CAPOX (oxaliplatin 130 mg/m2 IV over 2 h and capecitabine 1000 mg/m2 PO twice daily (days 1-14). 21-day treatment cycle.). Concomitantly, standardised physical excise (stair walking excise twice a week for 12 weeks), which will be monitored by an electronic sports device.&#xD;
Immunoscore intermediate-high (I-IntHi; I2-3): 6 months FOLFOX (oxaliplatin 85 mg/m2 IV (on day 1) and folinic acid 200 mg/m2 IV over 2 h, followed by a bolus of fluorouracil 400 mg/m2 IV over 2-4 min, followed by fluorouracil 600 mg/m2 IV over 22 h (for 2 consecutive days). 14-day treatment cycle.)&#xD;
Immunoscore high (I high; I4): no adjuvant treatment.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>TNM stratification</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>TNM-based low-risk (pT1, pT2 or pT3 and pN1): 3 months CAPOX (oxaliplatin 130 mg/m2 IV over 2 h and capecitabine 1000 mg/m2 PO twice daily (days 1-14). 21-day treatment cycle.)&#xD;
TNM-based high-risk (pT4 and/or pN2): 6 months FOLFOX (oxaliplatin 85 mg/m2 IV (on day 1) and folinic acid 200 mg/m2 IV over 2 h, followed by a bolus of fluorouracil 400 mg/m2 IV over 2-4 min, followed by fluorouracil 600 mg/m2 IV over 22 h (for 2 consecutive days). 14-day treatment cycle.)</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Capecitabine</intervention_name>
    <description>Tablet</description>
    <arm_group_label>Immunoscore stratification</arm_group_label>
    <arm_group_label>TNM stratification</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Oxaliplatin</intervention_name>
    <description>Infusion</description>
    <arm_group_label>Immunoscore stratification</arm_group_label>
    <arm_group_label>TNM stratification</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Fluorouracil</intervention_name>
    <description>Infusion</description>
    <arm_group_label>Immunoscore stratification</arm_group_label>
    <arm_group_label>TNM stratification</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Leucovorin</intervention_name>
    <description>Infusion</description>
    <arm_group_label>Immunoscore stratification</arm_group_label>
    <arm_group_label>TNM stratification</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Device</intervention_type>
    <intervention_name>Immunoscore® assay</intervention_name>
    <description>Whole-slide tissue analysis of CD3+ and cytotoxic CD8+ T cells in the tumor and in the invasive margin</description>
    <arm_group_label>Immunoscore stratification</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Physical exercise</intervention_name>
    <description>Increasing stair walking exercise twice a week over 12 weeks total.</description>
    <arm_group_label>Immunoscore stratification</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  18-75 years of age&#xD;
&#xD;
          -  All sexes&#xD;
&#xD;
          -  Histologically confirmed stage III carcinoma of the colon&#xD;
&#xD;
          -  Medical need for an adjuvant chemotherapy&#xD;
&#xD;
          -  Suitable to withstand the course of an adjuvant chemotherapy&#xD;
&#xD;
          -  Written informed consent form (ICF) for participation in the study&#xD;
&#xD;
          -  Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Neoadjuvant treatment&#xD;
&#xD;
          -  Metastatic disease&#xD;
&#xD;
          -  Pregnancy, breastfeeding or expectancy to conceive&#xD;
&#xD;
          -  Disagreement of participants with reproductive potential to use contraception&#xD;
             throughout the study period and for up to 180 days after the last dose of study&#xD;
             therapy&#xD;
&#xD;
          -  Uncontrolled or significant cardiovascular disease (myocardial infarction,&#xD;
             uncontrolled angina, any history of clinically significant arrhythmias, QTc&#xD;
             prolongation in males &gt; 450 ms and &gt; 470 ms in females, participants with history of&#xD;
             myocarditis)&#xD;
&#xD;
          -  Hepatitis B or C&#xD;
&#xD;
          -  Human immunodeficiency virus (HIV)&#xD;
&#xD;
          -  Immunodeficiency&#xD;
&#xD;
          -  Allogeneic tissue or solid organ transplantation&#xD;
&#xD;
          -  Systemic steroids or any other form of immunosuppressive therapy within 7 days prior&#xD;
             to the first dose of study treatment&#xD;
&#xD;
          -  Diagnosed and/or treated additional malignancy within 5 years of randomization, with&#xD;
             the exception of curatively-treated basal cell or squamous cell carcinoma of the skin&#xD;
             and/or curatively-resected in situ cervical and/or breast cancers&#xD;
&#xD;
          -  Participants with serious or uncontrolled medical disorders&#xD;
&#xD;
          -  Allergies and adverse drug reaction (history of allergy or hypersensitivity to study&#xD;
             drug components, contraindications to any of the study drugs of the chemotherapy&#xD;
             regimen)&#xD;
&#xD;
          -  Other exclusion criteria: Prisoners or participants who are involuntarily&#xD;
             incarcerated, participants who are compulsorily detained for treatment of either a&#xD;
             psychiatric or physical (i.e. infectious disease) illness&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>100 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Jérôme Galon, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Laboratory of Integrative Cancer Immunology, INSERM, Cordeliers Research Center</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Johannes Laengle, MD, PhD</last_name>
    <phone>+43 1 40400 69260</phone>
    <email>johannes.laengle@meduniwien.ac.at</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Michael Bergmann, MD</last_name>
    <phone>+43 1 40400 69260</phone>
    <email>michael.bergmann@meduniwien.ac.at</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>Medical University of Vienna</name>
      <address>
        <city>Vienna</city>
        <zip>1090</zip>
        <country>Austria</country>
      </address>
    </facility>
    <contact>
      <last_name>Johannes Laengle, MD, PhD</last_name>
      <phone>+43 1 40400 69260</phone>
      <email>johannes.laengle@meduniwien.ac.at</email>
    </contact>
    <contact_backup>
      <last_name>Michale Bergmann, MD</last_name>
      <phone>+43 1 40400 69260</phone>
      <email>michael.bergmann@meduniwien.ac.at</email>
    </contact_backup>
    <investigator>
      <last_name>Johannes Laengle, MD, PhD</last_name>
      <role>Sub-Investigator</role>
    </investigator>
    <investigator>
      <last_name>Michael Bergmann, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location_countries>
    <country>Austria</country>
  </location_countries>
  <verification_date>March 2023</verification_date>
  <study_first_submitted>July 21, 2020</study_first_submitted>
  <study_first_submitted_qc>July 23, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">July 27, 2020</study_first_posted>
  <last_update_submitted>March 14, 2023</last_update_submitted>
  <last_update_submitted_qc>March 14, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">March 15, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor-Investigator</responsible_party_type>
    <investigator_affiliation>Medical University of Vienna</investigator_affiliation>
    <investigator_full_name>Johannes Laengle, MD, PhD</investigator_full_name>
    <investigator_title>Sponsor-Investigator</investigator_title>
  </responsible_party>
  <keyword>Colon cancer</keyword>
  <keyword>Immunoscore</keyword>
  <keyword>CAPOX</keyword>
  <keyword>FOLFOX</keyword>
  <keyword>Physical exercise</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Colonic Neoplasms</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Leucovorin</mesh_term>
    <mesh_term>Fluorouracil</mesh_term>
    <mesh_term>Capecitabine</mesh_term>
    <mesh_term>Oxaliplatin</mesh_term>
  </intervention_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/NCT04488159
org study id: iMAGINE
secondary id: 2020-000401-91
nct id: NCT04488159
lead sponsor: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
is us export: No
The overall aim of this study is to prospectively validate the superiority of the Immunoscore
      as a decision guidance for adjuvant chemotherapy in stage III colon cancer patients, in
      comparison to the conventional TNM-based high- or low-risk classification.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Disease-free survival (DFS)
time frame: 3 years
description: Impact of Immunoscore stratification on DFS at 3 years (time from surgery to first observation of disease recurrence or death due to any cause)
measure: Overall survival (OS)
time frame: 3 years
description: Impact of Immunoscore stratification on OS at 3 years (time from surgery to death due to any cause)
measure: Time to recurrence (TTR)
time frame: 3 years
description: Impact of Immunoscore stratification on TTR at 3 years (time from surgery to disease recurrence)
measure: Treatment-related adverse events (AE)
time frame: 3 years
description: Impact of Immunoscore stratification on treatment-related AEs assessed according to the latest Common Terminology Criteria of Adverse Events (CTCAE).
measure: Quality of life
time frame: 3 years
description: Impact of Immunoscore stratification on quality of life assessed by the latest version of the European Organization for Research and Treatment of Cancer (EORCT) Quality of Life Group (QLG) questionnaires C30 and CR29.
measure: Cost analysis
time frame: 3 years
description: Impact of Immunoscore stratification on treatment-related costs, assessed by cost-effectiveness analysis (CEA) according to the latest Good Research Practices for Cost-Effectiveness Analysis Alongside Clinical Trials of the International Society for Pharmacoeconomics and Outcomes Research (ISPOR).
arm group label: Immunoscore stratification
arm group type: Experimental
description: Immunoscore low (I-Low; I0-1): 3 months CAPOX (oxaliplatin 130 mg/m2 IV over 2 h and capecitabine 1000 mg/m2 PO twice daily (days 1-14). 21-day treatment cycle.). Concomitantly, standardised physical excise (stair walking excise twice a week for 12 weeks), which will be monitored by an electronic sports device.
Immunoscore intermediate-high (I-IntHi; I2-3): 6 months FOLFOX (oxaliplatin 85 mg/m2 IV (on day 1) and folinic acid 200 mg/m2 IV over 2 h, followed by a bolus of fluorouracil 400 mg/m2 IV over 2-4 min, followed by fluorouracil 600 mg/m2 IV over 22 h (for 2 consecutive days). 14-day treatment cycle.)
Immunoscore high (I high; I4): no adjuvant treatment.
arm group label: TNM stratification
arm group type: Active Comparator
description: TNM-based low-risk (pT1, pT2 or pT3 and pN1): 3 months CAPOX (oxaliplatin 130 mg/m2 IV over 2 h and capecitabine 1000 mg/m2 PO twice daily (days 1-14). 21-day treatment cycle.)
TNM-based high-risk (pT4 and/or pN2): 6 months FOLFOX (oxaliplatin 85 mg/m2 IV (on day 1) and folinic acid 200 mg/m2 IV over 2 h, followed by a bolus of fluorouracil 400 mg/m2 IV over 2-4 min, followed by fluorouracil 600 mg/m2 IV over 22 h (for 2 consecutive days). 14-day treatment cycle.)
intervention type: Drug
intervention name: Capecitabine
description: Tablet
arm group label: Immunoscore stratification
arm group label: TNM stratification
intervention type: Drug
intervention name: Oxaliplatin
description: Infusion
arm group label: Immunoscore stratification
arm group label: TNM stratification
intervention type: Drug
intervention name: Fluorouracil
description: Infusion
arm group label: Immunoscore stratification
arm group label: TNM stratification
intervention type: Drug
intervention name: Leucovorin
description: Infusion
arm group label: Immunoscore stratification
arm group label: TNM stratification
intervention type: Device
intervention name: Immunoscore® assay
description: Whole-slide tissue analysis of CD3+ and cytotoxic CD8+ T cells in the tumor and in the invasive margin
arm group label: Immunoscore stratification
intervention type: Other
intervention name: Physical exercise
description: Increasing stair walking exercise twice a week over 12 weeks total.
arm group label: Immunoscore stratification
criteria: 
gender: All
minimum age: 18 Years
maximum age: 100 Years
healthy volunteers: No
last name: Jérôme Galon, PhD
role: Principal Investigator
affiliation: Laboratory of Integrative Cancer Immunology, INSERM, Cordeliers Research Center
last name: Johannes Laengle, MD, PhD
phone: +43 1 40400 69260
email: johannes.laengle@meduniwien.ac.at
last name: Michael Bergmann, MD
phone: +43 1 40400 69260
email: michael.bergmann@meduniwien.ac.at
facility: 
contact: 
contact backup: 
investigator: 
investigator: 
country: Austria
responsible party type: Sponsor-Investigator
investigator affiliation: Medical University of Vienna
investigator full name: Johannes Laengle, MD, PhD
investigator title: Sponsor-Investigator
mesh term: Colonic Neoplasms
mesh term: Leucovorin
mesh term: Fluorouracil
mesh term: Capecitabine
mesh term: Oxaliplatin
sharing ipd: No