<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/NCT01703390</url>
  </required_header>
  <id_info>
    <org_study_id>AGMT_ERCC1</org_study_id>
    <secondary_id>2011-003217-41</secondary_id>
    <nct_id>NCT01703390</nct_id>
  </id_info>
  <brief_title>Biomarker Directed Treatment in Metastatic Colorectal Cancer</brief_title>
  <official_title>Pilot Study: Biomarker Directed Treatment in Metastatic Colorectal Cancer</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Arbeitsgemeinschaft medikamentoese Tumortherapie</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Merck Sharp &amp; Dohme LLC</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>Arbeitsgemeinschaft medikamentoese Tumortherapie</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      This pilot study is being mounted to assess whether treatment assignment by ERCC-1 gene&#xD;
      expression status suggests better clinical results from historical experience in metastatic&#xD;
      colorectal cancer (mCRC). In wild type KRAS mCRC patients treated with either FOLFOX or&#xD;
      FOLFIRI in combination with cetuximab the median response rate is approximately 60-65%.&#xD;
      Biomarker directed treatment in this study may demonstrate that patients with low ERCC-1&#xD;
      treated with FOLFOX and cetuximab, and those with high ERCC-1 treated with FOLFIRI and&#xD;
      cetuximab, will improve response rate to 70-75%. KRAS wild type patients will be treated with&#xD;
      6 cycles of one of the following regimens chosen for optimization based on patient&#xD;
      characteristics (primary treatment phase). Patients with ERCC-1 &lt; 1.7 relative gene&#xD;
      expression of ERCC-1 over ß-actin (ERCC-1 low) will be assigned to treatment with mFOLFOX6 in&#xD;
      combination with Cetuximab. Patients with ERCC-1 gene expression &gt; 1.7 relative gene&#xD;
      expression of ERCC-1 over over ß-actin (ERCC-1 high) will be assigned to treatment with&#xD;
      FOLFIRI in combination with Cetuximab.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">December 4, 2012</start_date>
  <completion_date type="Actual">July 3, 2020</completion_date>
  <primary_completion_date type="Actual">February 23, 2018</primary_completion_date>
  <phase>Phase 2</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Non-Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Response</measure>
    <time_frame>5 years</time_frame>
    <description>Treatment response according to Response Evaluation Criteria In Solid Tumors [RECIST]</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Progression free survival (PFS)</measure>
    <time_frame>5 years</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Response rate</measure>
    <time_frame>5 years</time_frame>
    <description>Description of group differences between ERCC-1 low and ERCC-1 high patients with respect to response rate, PFS and OS</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Patient characteristics</measure>
    <time_frame>5 years</time_frame>
    <description>Description of group differences between ERCC-1 low and ERCC-1 high patients with respect to KRAS status</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Secondary resection rate</measure>
    <time_frame>5 years</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Molecular markers for toxicity</measure>
    <time_frame>5 years</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of adverse events during study treatment</measure>
    <time_frame>5 years</time_frame>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">47</enrollment>
  <condition>Metastatic Colorectal Cancer</condition>
  <arm_group>
    <arm_group_label>ERCC-1 low</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>modifiedFOLFOX6 + Cetuximab oxaliplatin 85 mg/m2 on day 1, 15 q d29 for 6 cycles folinic acid (FA) 400 mg/m2 on days 1 and 15 and q d29 for 6 cycles fluorouracil (5-FU) 400 mg/m2 bolus day 1 + 2400 mg/m2 46-hour infusion on days 1, 2 and 15, 16 and q d29 for 6 cycles or until unacceptable toxicity Cetuximab will be administered as a 120- minute intravenous infusion at 500 mg/m2 on day 1 then 500 mg/m2 bi-weekly</description>
  </arm_group>
  <arm_group>
    <arm_group_label>ERCC-1 high</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>FOLFIRI + Cetuximab irinotecan 180 mg/m² on day 1, 15 q d29 for 6 cycles folinic acid (FA)400 mg/m2 on days 1 and 15 and q d29 for 6 cycles fluorouracil (5-FU) 400 mg/m2 bolus + 2400 mg/m2 46-hour infusion on days 1, 2 and 15, 16 and q d29 for 6 cycles or until unacceptable toxicity Cetuximab will be administered as a 120- minute intravenous infusion at 500 mg/m2 on day 1 then 500 mg/m2 bi-weekly</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>FOLFIRI + Cetuximab</intervention_name>
    <arm_group_label>ERCC-1 high</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>modifiedFOLFOX6 + Cetuximab</intervention_name>
    <arm_group_label>ERCC-1 low</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
        1.1 Inclusion criteria for pre-screening phase:&#xD;
&#xD;
          -  Untreated advanced metastatic colorectal cancer patients&#xD;
&#xD;
          -  Adequate tissue to evaluate for genotyping (10 x 10µm thick formalin fixed paraffin&#xD;
             embedded tissue sections and one corresponding HE stained slide or a FFPE tumor block)&#xD;
&#xD;
        1.2 Inclusion criteria for treatment phase:&#xD;
&#xD;
        Patients must fulfill all criteria listed below prior to enrolment in the study:&#xD;
&#xD;
          -  Untreated wild-type KRAS metastatic colorectal cancer&#xD;
&#xD;
          -  Previous adjuvant therapy must have been completed &gt; 6 months before therapy&#xD;
             initiation on this study&#xD;
&#xD;
          -  Age &gt;18 years&#xD;
&#xD;
          -  Measureable disease with CT or MRI&#xD;
&#xD;
          -  ECOG performance status of 0-2&#xD;
&#xD;
          -  Adequate organ function&#xD;
&#xD;
               -  Hematologic:&#xD;
&#xD;
                    -  Absolute neutrophil count &gt; 1,500/µL&#xD;
&#xD;
                    -  Hemoglobin &gt;9 mg/dl&#xD;
&#xD;
                    -  Platelet count &gt;100,000 /µl&#xD;
&#xD;
               -  Renal:&#xD;
&#xD;
                    -  Serum creatinine &lt;1.5 x Upper limit of normal (UPN) or estimated clearance &gt;&#xD;
                       30 ml/min&#xD;
&#xD;
               -  Hepatic:&#xD;
&#xD;
                    -  Serum bilirubin &lt; 1.5 mg/dl&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Creatinine clearance below 30 ml/min&#xD;
&#xD;
          -  Patients with a history of other malignancies within 2 years prior to study entry,&#xD;
             except for adequately treated carcinoma in situ of the cervix; basal or squamous cell&#xD;
             skin cancer; low grade, early stage localized prostate cancer treated surgically with&#xD;
             curative intent; good prognosis DCIS of the breast treated with lumpectomy alone with&#xD;
             curative intent.&#xD;
&#xD;
          -  Patients with a history of severe cardiac disease; e.g. NYHA Functional Class III or&#xD;
             IV heart failure, myocardial infarction within 6 months, ventricular tachyarrhythmias&#xD;
             requiring ongoing treatment, or unstable angina.&#xD;
&#xD;
          -  Other known co-morbidity with the potential to dominate survival&#xD;
&#xD;
          -  Hypersensitivity with anaphylactic reaction to humanized monoclonal antibodies or any&#xD;
             of the applied drugs&#xD;
&#xD;
          -  Pregnant or breast feeding women&#xD;
&#xD;
          -  Any co-existing medical or psychological condition that would preclude participation&#xD;
             in the study or compromise ability to give informed consent.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Thomas Winder, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>LKH Feldkirch, Interne E</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>KUK Linz - Med Campus III.: Univ.-Klinik für Hämatologie und Internistische Onkologie</name>
      <address>
        <city>Linz</city>
        <state>Oberösterreich</state>
        <zip>4021</zip>
        <country>Austria</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>A.ö. Bezirkskrankenhaus Kufstein, Innere Medizin / Hämatologie / Onkologie</name>
      <address>
        <city>Kufstein</city>
        <state>Tirol</state>
        <zip>6330</zip>
        <country>Austria</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>LKH Feldkirch, Interne E</name>
      <address>
        <city>Feldkirch</city>
        <state>Vorarlberg</state>
        <zip>6807</zip>
        <country>Austria</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>LKH Bludenz Innere Medizin</name>
      <address>
        <city>Bludenz</city>
        <zip>6700</zip>
        <country>Austria</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>LKH Bregenz</name>
      <address>
        <city>Bregenz</city>
        <zip>6900</zip>
        <country>Austria</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>KH Dornbirn, Innere Medizin</name>
      <address>
        <city>Dornbirn</city>
        <zip>6850</zip>
        <country>Austria</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Universitätsklinikum Graz</name>
      <address>
        <city>Graz</city>
        <zip>8036</zip>
        <country>Austria</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>LKH Hohenems, Interne Intensivmedizin</name>
      <address>
        <city>Hohenems</city>
        <zip>6845</zip>
        <country>Austria</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Krankenhaus d. Barmherzigen Schwestern Linz</name>
      <address>
        <city>Linz</city>
        <zip>A-4010</zip>
        <country>Austria</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Universitätsklinik für Innere Medizin III mit Hämatologie, internistischer Onkologie, Infektologie, Rheumatologie und Onkologisches Zentrum</name>
      <address>
        <city>Salzburg</city>
        <zip>5020</zip>
        <country>Austria</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Medizinische Universität Wien, Univ.Klinik für Innere Medizin I, Abteilung für Onkologie</name>
      <address>
        <city>Vienna</city>
        <zip>1090</zip>
        <country>Austria</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Austria</country>
  </location_countries>
  <verification_date>December 2020</verification_date>
  <study_first_submitted>October 4, 2012</study_first_submitted>
  <study_first_submitted_qc>October 8, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">October 10, 2012</study_first_posted>
  <last_update_submitted>December 18, 2020</last_update_submitted>
  <last_update_submitted_qc>December 18, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">December 21, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>metastatic colorectal cancer</keyword>
  <keyword>mCRC</keyword>
  <keyword>ERCC-1</keyword>
  <keyword>ERCC1</keyword>
  <keyword>AGMT</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Colorectal Neoplasms</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Cetuximab</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/NCT01703390
org study id: AGMT_ERCC1
secondary id: 2011-003217-41
nct id: NCT01703390
lead sponsor: 
collaborator: 
has dmc: No
This pilot study is being mounted to assess whether treatment assignment by ERCC-1 gene
      expression status suggests better clinical results from historical experience in metastatic
      colorectal cancer (mCRC). In wild type KRAS mCRC patients treated with either FOLFOX or
      FOLFIRI in combination with cetuximab the median response rate is approximately 60-65%.
      Biomarker directed treatment in this study may demonstrate that patients with low ERCC-1
      treated with FOLFOX and cetuximab, and those with high ERCC-1 treated with FOLFIRI and
      cetuximab, will improve response rate to 70-75%. KRAS wild type patients will be treated with
      6 cycles of one of the following regimens chosen for optimization based on patient
      characteristics (primary treatment phase). Patients with ERCC-1 < 1.7 relative gene
      expression of ERCC-1 over ß-actin (ERCC-1 low) will be assigned to treatment with mFOLFOX6 in
      combination with Cetuximab. Patients with ERCC-1 gene expression > 1.7 relative gene
      expression of ERCC-1 over over ß-actin (ERCC-1 high) will be assigned to treatment with
      FOLFIRI in combination with Cetuximab.
allocation: Non-Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Response
time frame: 5 years
description: Treatment response according to Response Evaluation Criteria In Solid Tumors [RECIST]
measure: Progression free survival (PFS)
time frame: 5 years
measure: Response rate
time frame: 5 years
description: Description of group differences between ERCC-1 low and ERCC-1 high patients with respect to response rate, PFS and OS
measure: Patient characteristics
time frame: 5 years
description: Description of group differences between ERCC-1 low and ERCC-1 high patients with respect to KRAS status
measure: Secondary resection rate
time frame: 5 years
measure: Molecular markers for toxicity
time frame: 5 years
measure: Number of adverse events during study treatment
time frame: 5 years
arm group label: ERCC-1 low
arm group type: Experimental
description: modifiedFOLFOX6 + Cetuximab oxaliplatin 85 mg/m2 on day 1, 15 q d29 for 6 cycles folinic acid (FA) 400 mg/m2 on days 1 and 15 and q d29 for 6 cycles fluorouracil (5-FU) 400 mg/m2 bolus day 1 + 2400 mg/m2 46-hour infusion on days 1, 2 and 15, 16 and q d29 for 6 cycles or until unacceptable toxicity Cetuximab will be administered as a 120- minute intravenous infusion at 500 mg/m2 on day 1 then 500 mg/m2 bi-weekly
arm group label: ERCC-1 high
arm group type: Experimental
description: FOLFIRI + Cetuximab irinotecan 180 mg/m² on day 1, 15 q d29 for 6 cycles folinic acid (FA)400 mg/m2 on days 1 and 15 and q d29 for 6 cycles fluorouracil (5-FU) 400 mg/m2 bolus + 2400 mg/m2 46-hour infusion on days 1, 2 and 15, 16 and q d29 for 6 cycles or until unacceptable toxicity Cetuximab will be administered as a 120- minute intravenous infusion at 500 mg/m2 on day 1 then 500 mg/m2 bi-weekly
intervention type: Drug
intervention name: FOLFIRI + Cetuximab
arm group label: ERCC-1 high
intervention type: Drug
intervention name: modifiedFOLFOX6 + Cetuximab
arm group label: ERCC-1 low
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Thomas Winder, MD
role: Principal Investigator
affiliation: LKH Feldkirch, Interne E
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
country: Austria
responsible party type: Sponsor
mesh term: Colorectal Neoplasms
mesh term: Cetuximab