<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/NCT01726309</url>
  </required_header>
  <id_info>
    <org_study_id>ICORG 08-40</org_study_id>
    <nct_id>NCT01726309</nct_id>
  </id_info>
  <brief_title>Single Nucleotide Polymorphism(SNP)Study. ICORG 08-40, V4</brief_title>
  <official_title>Correlation of Single Nucleotide Polymorphism (SNP) Profile of Domain III of EGFR to Skin Toxicity and Disease Response to Treatment With Erbitux Requirements</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Cancer Trials Ireland</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Cancer Trials Ireland</source>
  <brief_summary>
    <textblock>
      Primary Objective:&#xD;
&#xD;
      Correlation of the skin and/or eye toxicity grade secondary to Cetuximab or Panitumumab and&#xD;
      the SNP profile of the Epidermal Growth Factor Receptor (EGFR) domain III region.&#xD;
&#xD;
      Secondary Objectives:&#xD;
&#xD;
      Correlation of SNP profile with indicators of tumour response parameters, such as&#xD;
      radiological response, duration of response, time to progression (TTP), overall survival (OS)&#xD;
      time, incidence of non-dermatological adverse events.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Baseline assessment:&#xD;
&#xD;
        -  Contact Lenses&#xD;
&#xD;
        -  Medical History&#xD;
&#xD;
        -  Previous chemotherapy&#xD;
&#xD;
        -  Vital Signs (weight, height, Karnofsky Performance status, heart rate, blood pressure)&#xD;
&#xD;
        -  Symptom Assessment (Pre-existing skin and/or eye conditions, CEA measurement (CRC only),&#xD;
           Disease status (TNM Staging))&#xD;
&#xD;
        -  Planned chemotherapy regimen&#xD;
&#xD;
        -  Radiotherapy&#xD;
&#xD;
      Blood Sample: A 2ml blood sample should be collected in ethylenediamine-tetraacetic acid&#xD;
      (EDTA) containing Vacutainer at any time before or after starting treatment. DNA will be&#xD;
      extracted from the samples and the 11 SNPs in the region of the EGFR gene encoding domain III&#xD;
      will be characterized.&#xD;
&#xD;
      Follow-up Assessment: with every second cycle of Cetuximab- or Panitumumab-containing regimen&#xD;
      (CRC: every 2. Week; NSCLC: every 3-4 weeks):&#xD;
&#xD;
        -  Visit Number and Date&#xD;
&#xD;
        -  Vital Signs (weight, height, Karnofsky Performance status, heart rate, blood pressure)&#xD;
&#xD;
        -  Symptom Assessment (CEA measurement (CRC only), Disease status (TMN Staging), Skin&#xD;
           Toxicity (CTCAE) grading)&#xD;
&#xD;
        -  Current chemotherapy regimen&#xD;
&#xD;
        -  Radiotherapy&#xD;
&#xD;
        -  CEA measurement only for CRC (every second cycle/every 4 weeks)&#xD;
&#xD;
      Long-term follow-up (up to 5 years):&#xD;
&#xD;
        -  CT restaging (TNM Staging) should be done 3 monthly for as long as the subject is&#xD;
           receiving Cetuximab- or Panitumumab- containing regimen or if there is suspicion of&#xD;
           disease progression.&#xD;
&#xD;
        -  OS&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Terminated</overall_status>
  <why_stopped>
    As per the HRBs new funding model, HRBs investment will not support costs associated with&#xD;
    routine patient care or translational studies, biobanks, patient registries and questionnaires.&#xD;
    Therefore, a decision was made to cease further study follow up.&#xD;
  </why_stopped>
  <start_date type="Actual">May 2011</start_date>
  <completion_date type="Actual">May 11, 2021</completion_date>
  <primary_completion_date type="Actual">May 11, 2021</primary_completion_date>
  <study_type>Observational</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <observational_model>Cohort</observational_model>
    <time_perspective>Prospective</time_perspective>
  </study_design_info>
  <primary_outcome>
    <measure>Correlation between the type and degree of reported skin and/or eye reaction and the SNP profile of the EGFR domain III region.</measure>
    <time_frame>Throughout treatment with up to 5 years in follow up</time_frame>
    <description>Using Common Terminology Criteria for Adverse Events (CTCAE) version 4</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Correlation between the SNP profile(s) and disease response</measure>
    <time_frame>Throughout treatment with up to 5 years in follow up</time_frame>
    <description>Time to progression TTP and OS over 5 years</description>
  </secondary_outcome>
  <number_of_groups>2</number_of_groups>
  <enrollment type="Actual">161</enrollment>
  <condition>Colorectal Cancer</condition>
  <condition>Non-Small Cell Lung Cancer</condition>
  <arm_group>
    <arm_group_label>Stage IV CRC</arm_group_label>
  </arm_group>
  <arm_group>
    <arm_group_label>Stage IV NSCLC</arm_group_label>
  </arm_group>
  <eligibility>
    <study_pop>
      <textblock>
        Patient Population:&#xD;
&#xD;
        150 Patients with histologically proven stage IV (AJCC 7th Edition) colorectal cancer (CRC)&#xD;
        expressing wild-type KRAS or stage IV non-small cell lung cancer (NSCLC) expressing EGFR&#xD;
        (tested by immunohistochemistry (IHC)), with no previous exposure to Cetuximab or&#xD;
        Panitumumab, who will receive treatment with an EGFR-antibody (Cetuximab or Panitumumab).&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Non-Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Stage IV (AJCC 7th Edition TMN Staging, Appendix C), histologically confirmed CRC with&#xD;
             wild-type KRAS and not a candidate for metastasectomy.&#xD;
&#xD;
          2. Stage IV (AJCC 7th Edition, TMN Staging, Appendix C) NSCLC expressing EGFR (IHC&#xD;
             tested)&#xD;
&#xD;
          3. Patients, who will receive treatment with an EGFR-antibody (Cetuximab or Panitumumab).&#xD;
&#xD;
          4. Karnofsky performance status (Appendix B) score ≥60.&#xD;
&#xD;
          5. Acceptable laboratory values:&#xD;
&#xD;
               -  Haemoglobin ≥ 9 g/dL.&#xD;
&#xD;
               -  Neutrophil count ≥ 1.0 x 10^9/L.&#xD;
&#xD;
               -  Platelet count ≥100 x 10^9/L.&#xD;
&#xD;
               -  Serum creatinine ≤1.5 times the upper limit of normal.&#xD;
&#xD;
               -  Bilirubin ≤1.5 times the upper limit of normal.&#xD;
&#xD;
               -  Aspartate aminotransferase and alanine aminotransferase ≤5 times the upper limit&#xD;
                  of normal.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Aged &lt; 18 years&#xD;
&#xD;
          2. Prior exposure to Cetuximab or Panitumumab&#xD;
&#xD;
          3. The CRC does not carry wild-type KRAS.&#xD;
&#xD;
          4. The NSCLC stains negative for EGFR protein expression&#xD;
&#xD;
          5. Second cancer diagnosis (apart from non-melanoma skin cancer)&#xD;
&#xD;
          6. Known hypersensitivity to Cetuximab or Panitumumab, or murine protein.&#xD;
&#xD;
          7. Known history of coronary artery disease, arrhythmias, or congestive heart failure (If&#xD;
             the treating physician feels that a patient's coronary artery disease / arrhythmia /&#xD;
             congestive heart failure does not place him/her at risk from treatment with an&#xD;
             anti-EGFR antibody, the person can be included. This is a clinical decision, which has&#xD;
             to be made by the treating physician).&#xD;
&#xD;
          8. Known to be pregnant (pregnancy test is not mandatory) or breast-feeding.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <location>
    <facility>
      <name>Letterkenny General Hospital</name>
      <address>
        <city>Letterkenny</city>
        <state>Donegal</state>
        <country>Ireland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Bon Secours Hospital</name>
      <address>
        <city>Cork</city>
        <country>Ireland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Cork University Hospital</name>
      <address>
        <city>Cork</city>
        <country>Ireland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>St Vincent's University Hospital</name>
      <address>
        <city>Dublin</city>
        <zip>4</zip>
        <country>Ireland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Mater Misericordiae University Hospital</name>
      <address>
        <city>Dublin</city>
        <zip>7</zip>
        <country>Ireland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Beaumont Hospital</name>
      <address>
        <city>Dublin</city>
        <country>Ireland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>The Adelaide &amp; Meath Hosptal, Dublin Incorporating The National Children's Hospital</name>
      <address>
        <city>Dublin</city>
        <country>Ireland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Galway University Hospital</name>
      <address>
        <city>Galway</city>
        <country>Ireland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Our Lady of Lourdes Hospital, Drogheda</name>
      <address>
        <city>Louth</city>
        <country>Ireland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Waterford Regional Hospital</name>
      <address>
        <city>Waterford</city>
        <country>Ireland</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Ireland</country>
  </location_countries>
  <verification_date>April 2023</verification_date>
  <study_first_submitted>November 9, 2012</study_first_submitted>
  <study_first_submitted_qc>November 9, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">November 14, 2012</study_first_posted>
  <last_update_submitted>April 4, 2023</last_update_submitted>
  <last_update_submitted_qc>April 4, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">April 6, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Carcinoma, Non-Small-Cell Lung</mesh_term>
    <mesh_term>Colorectal Neoplasms</mesh_term>
  </condition_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/NCT01726309
org study id: ICORG 08-40
nct id: NCT01726309
lead sponsor: 
Primary Objective:

      Correlation of the skin and/or eye toxicity grade secondary to Cetuximab or Panitumumab and
      the SNP profile of the Epidermal Growth Factor Receptor (EGFR) domain III region.

      Secondary Objectives:

      Correlation of SNP profile with indicators of tumour response parameters, such as
      radiological response, duration of response, time to progression (TTP), overall survival (OS)
      time, incidence of non-dermatological adverse events.
Baseline assessment:

        -  Contact Lenses

        -  Medical History

        -  Previous chemotherapy

        -  Vital Signs (weight, height, Karnofsky Performance status, heart rate, blood pressure)

        -  Symptom Assessment (Pre-existing skin and/or eye conditions, CEA measurement (CRC only),
           Disease status (TNM Staging))

        -  Planned chemotherapy regimen

        -  Radiotherapy

      Blood Sample: A 2ml blood sample should be collected in ethylenediamine-tetraacetic acid
      (EDTA) containing Vacutainer at any time before or after starting treatment. DNA will be
      extracted from the samples and the 11 SNPs in the region of the EGFR gene encoding domain III
      will be characterized.

      Follow-up Assessment: with every second cycle of Cetuximab- or Panitumumab-containing regimen
      (CRC: every 2. Week; NSCLC: every 3-4 weeks):

        -  Visit Number and Date

        -  Vital Signs (weight, height, Karnofsky Performance status, heart rate, blood pressure)

        -  Symptom Assessment (CEA measurement (CRC only), Disease status (TMN Staging), Skin
           Toxicity (CTCAE) grading)

        -  Current chemotherapy regimen

        -  Radiotherapy

        -  CEA measurement only for CRC (every second cycle/every 4 weeks)

      Long-term follow-up (up to 5 years):

        -  CT restaging (TNM Staging) should be done 3 monthly for as long as the subject is
           receiving Cetuximab- or Panitumumab- containing regimen or if there is suspicion of
           disease progression.

        -  OS
observational model: Cohort
time perspective: Prospective
measure: Correlation between the type and degree of reported skin and/or eye reaction and the SNP profile of the EGFR domain III region.
time frame: Throughout treatment with up to 5 years in follow up
description: Using Common Terminology Criteria for Adverse Events (CTCAE) version 4
measure: Correlation between the SNP profile(s) and disease response
time frame: Throughout treatment with up to 5 years in follow up
description: Time to progression TTP and OS over 5 years
arm group label: Stage IV CRC
arm group label: Stage IV NSCLC
study pop: 
sampling method: Non-Probability Sample
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
country: Ireland
responsible party type: Sponsor
mesh term: Carcinoma, Non-Small-Cell Lung
mesh term: Colorectal Neoplasms