<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/NCT01675999</url>
  </required_header>
  <id_info>
    <org_study_id>P100131</org_study_id>
    <nct_id>NCT01675999</nct_id>
  </id_info>
  <brief_title>Trial of Neoadjuvant Chemotherapy in Locally Advanced Colon Cancer</brief_title>
  <acronym>ECKINOXE</acronym>
  <official_title>PRODIGE 22-ECKINOXE : Randomized Phase II Trial of Neoadjuvant FOLFOX 4 Versus FOLFOX 4 With Cetuximab Versus Immediate Surgery in Locally Advanced Colon Cancer</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Assistance Publique - Hôpitaux de Paris</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Federation Francophone de Cancerologie Digestive</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>UNICANCER</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Association de Recherche Experimentale et Clinique en Chirurgie Digestive</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Association Européenne de Recherche en Oncologie</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Merck Serono S.A., Geneva</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>Assistance Publique - Hôpitaux de Paris</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      In patients with locally advanced colon cancer (high risk stage II and stage III), curative&#xD;
      surgery followed by adjuvant FOLFOX-4 chemotherapy has become the standard of care. However,&#xD;
      for 30-40% of these patients, the current curative treatment strategy of surgical excision&#xD;
      followed by adjuvant chemotherapy fails either to clear locoregional spread or to eradicate&#xD;
      distant micrometastases, leading to disease recurrence. Preoperative chemotherapy is an&#xD;
      attractive concept for locally advanced colon cancer and has the potential to impact upon&#xD;
      both of these causes of failure. Optimum systemic therapy at the earliest possible&#xD;
      opportunity may be more effective at eradicating distant metastases than the same treatment&#xD;
      given after the delay and immunological stress of surgery. Added to this, shrinking the&#xD;
      primary tumor before surgery may reduce the risk of incomplete surgical excision, and the&#xD;
      risk of tumor cell shedding during surgery.&#xD;
&#xD;
      ECKINOXE is a multicenter randomized phase II trial designed to evaluate efficacy (response&#xD;
      rate) and feasibility (safety, tolerance) of these two chemotherapy regimens (FOLFOX-4 alone&#xD;
      and FOLFOX-4+Cetuximab) in a neoadjuvant strategy in patients with locally advanced colon&#xD;
      cancer. Control arm includes patients for whom standard treatment comprises surgery followed&#xD;
      by adjuvant FOLFOX-4 chemotherapy. This phase II study will assess the feasibility of a&#xD;
      neoadjuvant strategy in these patients and determine which neoadjuvant regimen is the most&#xD;
      effective in terms of response rate.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      See Synopsis below&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Recruiting</last_known_status>
  <start_date>May 2012</start_date>
  <completion_date type="Anticipated">February 2021</completion_date>
  <primary_completion_date type="Actual">May 2012</primary_completion_date>
  <phase>Phase 2</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Histological tumor response in the primary tumor according to the simplified Tumor Regression Grade (TRG) of Ryan</measure>
    <time_frame>2 years</time_frame>
    <description>This primary outcome will be evaluated on the surgical specimens: Immediately after surgery (arm C) or after neoadjuvant chemotherapy (4 cycles) and surgery (arms A and B)</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Safety and tolerability and efficacy of the neoadjuvant chemotherapy</measure>
    <time_frame>9 years</time_frame>
    <description>Tolerability of the neoadjuvant therapies. SAFETY ISSUE&#xD;
Postoperative morbidity at 60 days. SAFETY ISSUE</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>•Disease free survival and regression free survival at 3 years</measure>
    <time_frame>3 years</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>•Overall survival at 6 and 7 years</measure>
    <time_frame>6 and 7 years</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>•Quality of life (EORTC QLQ-C30, QLQ-CR29)</measure>
    <time_frame>5 years</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>•Quality and radicality of the surgical excision</measure>
    <time_frame>2 years</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>•Accuracy of pre-treatment CT scan staging and evaluation of radiological response to chemotherapy</measure>
    <time_frame>2 years</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>•Correlation between radiological and histological response</measure>
    <time_frame>2 years</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>•Evaluation of another histopathological grade</measure>
    <time_frame>2 years</time_frame>
  </secondary_outcome>
  <number_of_arms>3</number_of_arms>
  <enrollment type="Anticipated">186</enrollment>
  <condition>Colon Cancer</condition>
  <condition>Locally Advanced Malignant Neoplasm</condition>
  <arm_group>
    <arm_group_label>1</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Perioperative simplified FOLFOX-4 chemotherapy&#xD;
- Simplified FOLFOX-4 (IV oxaliplatin given over 120 min at a dose of 85 mg/m2 on day 1 followed by IV leucovorin 400 mg/m2 over 2h, IV bolus 5-FU 400 mg/m2 and IV infusional 5-FU 2400 mg/m2 over 46h) for 4 cycles followed by colectomy (3 to 5 weeks after) followed by simplified FOLFOX-4 (8 cycles).</description>
  </arm_group>
  <arm_group>
    <arm_group_label>2</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Perioperative FOLFOX4+Cetuximab chemotherapy Simplified FOLFOX-4 (IV oxaliplatin given over 120 min at a dose of 85 mg/m2 on day 1 followed by IV leucovorin 400 mg/m2 over 2h, IV bolus 5-FU 400 mg/m2 and IV infusional 5-FU 2400 mg/m2 over 46h)+ Cetuximab (IV 500 mg/m2 every 2 weeks) for 4 cycles followed by colectomy (3 to 5 weeks after), followed by simplified FOLFOX-4 + Cetuximab (8 cycles).</description>
  </arm_group>
  <arm_group>
    <arm_group_label>3</arm_group_label>
    <arm_group_type>Other</arm_group_type>
    <description>Surgery followed by FOLFOX4 chemotherapy No preoperative chemotherapy Colectomy (maximum 4 weeks after randomization) followed by simplified FOLFOX-4 (IV oxaliplatin given over 120 min at a dose of 85 mg/m2 on day 1 followed by IV leucovorin 400 mg/m2 over 2h, IV bolus 5-FU 400 mg/m2 and IV infusional 5-FU 2400 mg/m2 over 46h) for 12 cycles.</description>
  </arm_group>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Perioperative simplified FOLFOX-4 chemotherapy</intervention_name>
    <description>Preoperative chemotherapy</description>
    <arm_group_label>1</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Perioperative FOLFOX4+Cetuximab chemotherapy</intervention_name>
    <description>Preoperative chemotherapy</description>
    <arm_group_label>2</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Surgery followed by FOLFOX4 chemotherapy</intervention_name>
    <description>Preoperative chemotherapy</description>
    <arm_group_label>3</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Pathologically confirmed colon adenocarcinoma (≥ 15 cm from the anal verge)&#xD;
&#xD;
          -  Assessment of RAS status of the primary colon cancer on biopsies (WT or mutated)&#xD;
&#xD;
          -  Colon cancer classified: poor prognosis T3 (T3 bad) - T4 and/ or N2 by abdominal CT&#xD;
             scan.&#xD;
&#xD;
          -  Non metastatic colon cancer (lung, liver, peritoneal)&#xD;
&#xD;
          -  Non complicated primary tumor (obstruction, perforation, bleeding), patients with&#xD;
             cancer treated by stomie de derivation may be included in the study.&#xD;
&#xD;
        DPD deficency&#xD;
&#xD;
          -  Absence of synchronous colorectal cancer&#xD;
&#xD;
          -  Age ≥ 18 years and &lt; 76 years&#xD;
&#xD;
          -  ECOG performance status 0-1&#xD;
&#xD;
          -  No prior chemotherapy within the last 5 years&#xD;
&#xD;
          -  No prior abdominal or pelvic irradiation within the last 5 years&#xD;
&#xD;
          -  Life expectancy of 5 years or more&#xD;
&#xD;
          -  No history of colorectal cancer within the last 5 years&#xD;
&#xD;
          -  Patients with childbearing potential should use effective contraception during the&#xD;
             study and the following 6 months&#xD;
&#xD;
          -  White blood cell count of 3 x 109/L or more with neutrophils of1.5 x 109/L or more,&#xD;
             platelet count of 100 x 109/L or more, hemoglobin of 9 g/dL (5,6 mmol/l) or more&#xD;
&#xD;
          -  Total bilirubin of 1.5 x ULN (upper limit of normal) or less&#xD;
&#xD;
          -  ASAT and ALAT of 2.5 x ULN or less&#xD;
&#xD;
          -  Alkaline phosphatase of 1.5 x ULN or less&#xD;
&#xD;
          -  Serum creatinine of 1.5 x ULN or less&#xD;
&#xD;
          -  Signed written informed consent obtained prior to any study specific screening&#xD;
             procedures&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  contra-indication to iodinated contrast medium injection including allergy to&#xD;
             iodinated contrast medium and renal insufficiency proscribing iodinated injection&#xD;
&#xD;
          -  Age &gt; 70 years&#xD;
&#xD;
          -  Rectal cancer located within 15 cm from the anal verge by endoscopy or under the&#xD;
             peritoneal reflection at surgery or having received radiation therapy prior to surgery&#xD;
&#xD;
          -  Complicated primary colon cancer (obstruction, bleeding, perforation)&#xD;
&#xD;
          -  Synchronous colorectal cancer&#xD;
&#xD;
          -  Metastatic spread at baseline assessment (lung, liver, peritoneal)&#xD;
&#xD;
          -  History or current evidence on physical examination of central nervous system disease&#xD;
             or peripheral neuropathy ≥ grade 1 Common Toxicity Criteria for Adverse Events (CTCAE)&#xD;
             v.3.0&#xD;
&#xD;
          -  Known hypersensitivity reaction to any of the components of study treatments&#xD;
&#xD;
          -  Presence of inflammatory bowel disease&#xD;
&#xD;
          -  HNPCC syndrome or polyposis&#xD;
&#xD;
          -  Major surgical procedure, open biopsy or significant traumatic injury within 28 days&#xD;
             prior to study treatment start. Incompletely healed wounds or anticipation of the need&#xD;
             for major surgical procedure during the course of the study&#xD;
&#xD;
          -  Clinically relevant coronary artery disease or history of myocardial infarction in the&#xD;
             last 12 months, or high risk of uncontrolled arrhythmia&#xD;
&#xD;
          -  Pregnancy (absence to be confirmed by ß-hCG test) or breast-feeding period&#xD;
&#xD;
          -  Previous malignancy in the last 5 years&#xD;
&#xD;
          -  Medical, geographical, sociological, psychological or legal conditions that would not&#xD;
             permit the patient to complete the study or sign informed consent&#xD;
&#xD;
          -  Any significant disease which, in the investigator's opinion, would exclude the&#xD;
             patient from the study.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>76 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>mehdi karoui, PH</last_name>
    <role>Principal Investigator</role>
    <affiliation>Assistance Publique - Hôpitaux de Paris</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Mehdi karoui, PH</last_name>
    <phone>+33 (0) 1 42 17 56 11</phone>
    <email>mehdi.karoui@gmail.com</email>
  </overall_contact>
  <location>
    <facility>
      <name>Hopital Henri Mondor</name>
      <address>
        <city>Paris</city>
        <zip>94010</zip>
        <country>France</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Mehdi KAROUI, PH</last_name>
      <phone>+33 (0) 1 42 17 56 11</phone>
      <email>mehdi.karoui@gmail.com</email>
    </contact>
  </location>
  <location_countries>
    <country>France</country>
  </location_countries>
  <verification_date>January 2012</verification_date>
  <study_first_submitted>February 2, 2012</study_first_submitted>
  <study_first_submitted_qc>August 29, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">August 30, 2012</study_first_posted>
  <last_update_submitted>January 14, 2016</last_update_submitted>
  <last_update_submitted_qc>January 14, 2016</last_update_submitted_qc>
  <last_update_posted type="Estimate">January 15, 2016</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Neoadjuvant chemotherapy</keyword>
  <keyword>Locally advanced malignant neoplasm</keyword>
  <keyword>colon cancer</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Neoplasms</mesh_term>
    <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>Cetuximab</mesh_term>
    <mesh_term>Fluorouracil</mesh_term>
    <mesh_term>Oxaliplatin</mesh_term>
  </intervention_browse>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT01675999
org study id: P100131
nct id: NCT01675999
lead sponsor: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
has dmc: Yes
In patients with locally advanced colon cancer (high risk stage II and stage III), curative
      surgery followed by adjuvant FOLFOX-4 chemotherapy has become the standard of care. However,
      for 30-40% of these patients, the current curative treatment strategy of surgical excision
      followed by adjuvant chemotherapy fails either to clear locoregional spread or to eradicate
      distant micrometastases, leading to disease recurrence. Preoperative chemotherapy is an
      attractive concept for locally advanced colon cancer and has the potential to impact upon
      both of these causes of failure. Optimum systemic therapy at the earliest possible
      opportunity may be more effective at eradicating distant metastases than the same treatment
      given after the delay and immunological stress of surgery. Added to this, shrinking the
      primary tumor before surgery may reduce the risk of incomplete surgical excision, and the
      risk of tumor cell shedding during surgery.

      ECKINOXE is a multicenter randomized phase II trial designed to evaluate efficacy (response
      rate) and feasibility (safety, tolerance) of these two chemotherapy regimens (FOLFOX-4 alone
      and FOLFOX-4+Cetuximab) in a neoadjuvant strategy in patients with locally advanced colon
      cancer. Control arm includes patients for whom standard treatment comprises surgery followed
      by adjuvant FOLFOX-4 chemotherapy. This phase II study will assess the feasibility of a
      neoadjuvant strategy in these patients and determine which neoadjuvant regimen is the most
      effective in terms of response rate.
See Synopsis below
allocation: Randomized
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Histological tumor response in the primary tumor according to the simplified Tumor Regression Grade (TRG) of Ryan
time frame: 2 years
description: This primary outcome will be evaluated on the surgical specimens: Immediately after surgery (arm C) or after neoadjuvant chemotherapy (4 cycles) and surgery (arms A and B)
measure: Safety and tolerability and efficacy of the neoadjuvant chemotherapy
time frame: 9 years
description: Tolerability of the neoadjuvant therapies. SAFETY ISSUE
Postoperative morbidity at 60 days. SAFETY ISSUE
measure: •Disease free survival and regression free survival at 3 years
time frame: 3 years
measure: •Overall survival at 6 and 7 years
time frame: 6 and 7 years
measure: •Quality of life (EORTC QLQ-C30, QLQ-CR29)
time frame: 5 years
measure: •Quality and radicality of the surgical excision
time frame: 2 years
measure: •Accuracy of pre-treatment CT scan staging and evaluation of radiological response to chemotherapy
time frame: 2 years
measure: •Correlation between radiological and histological response
time frame: 2 years
measure: •Evaluation of another histopathological grade
time frame: 2 years
arm group label: 1
arm group type: Experimental
description: Perioperative simplified FOLFOX-4 chemotherapy
- Simplified FOLFOX-4 (IV oxaliplatin given over 120 min at a dose of 85 mg/m2 on day 1 followed by IV leucovorin 400 mg/m2 over 2h, IV bolus 5-FU 400 mg/m2 and IV infusional 5-FU 2400 mg/m2 over 46h) for 4 cycles followed by colectomy (3 to 5 weeks after) followed by simplified FOLFOX-4 (8 cycles).
arm group label: 2
arm group type: Experimental
description: Perioperative FOLFOX4+Cetuximab chemotherapy Simplified FOLFOX-4 (IV oxaliplatin given over 120 min at a dose of 85 mg/m2 on day 1 followed by IV leucovorin 400 mg/m2 over 2h, IV bolus 5-FU 400 mg/m2 and IV infusional 5-FU 2400 mg/m2 over 46h)+ Cetuximab (IV 500 mg/m2 every 2 weeks) for 4 cycles followed by colectomy (3 to 5 weeks after), followed by simplified FOLFOX-4 + Cetuximab (8 cycles).
arm group label: 3
arm group type: Other
description: Surgery followed by FOLFOX4 chemotherapy No preoperative chemotherapy Colectomy (maximum 4 weeks after randomization) followed by simplified FOLFOX-4 (IV oxaliplatin given over 120 min at a dose of 85 mg/m2 on day 1 followed by IV leucovorin 400 mg/m2 over 2h, IV bolus 5-FU 400 mg/m2 and IV infusional 5-FU 2400 mg/m2 over 46h) for 12 cycles.
intervention type: Other
intervention name: Perioperative simplified FOLFOX-4 chemotherapy
description: Preoperative chemotherapy
arm group label: 1
intervention type: Other
intervention name: Perioperative FOLFOX4+Cetuximab chemotherapy
description: Preoperative chemotherapy
arm group label: 2
intervention type: Other
intervention name: Surgery followed by FOLFOX4 chemotherapy
description: Preoperative chemotherapy
arm group label: 3
criteria: 
gender: All
minimum age: 18 Years
maximum age: 76 Years
healthy volunteers: No
last name: mehdi karoui, PH
role: Principal Investigator
affiliation: Assistance Publique - Hôpitaux de Paris
last name: Mehdi karoui, PH
phone: +33 (0) 1 42 17 56 11
email: mehdi.karoui@gmail.com
facility: 
status: Recruiting
contact: 
country: France
responsible party type: Sponsor
mesh term: Neoplasms
mesh term: Colonic Neoplasms
mesh term: Leucovorin
mesh term: Cetuximab
mesh term: Fluorouracil
mesh term: Oxaliplatin