<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/NCT01662635</url>
  </required_header>
  <id_info>
    <org_study_id>INCAN/CC/039/11</org_study_id>
    <nct_id>NCT01662635</nct_id>
  </id_info>
  <brief_title>Clinicopathological Features of NSCLC Patients Associated With the Chromosome 2p (EML4-ALK)</brief_title>
  <acronym>ALK</acronym>
  <official_title>CLINICOPATHOLOGICAL FEATURES OF NON-SMALL CELL LUNG CANCER PATIENTS ASSOCIATED WITH THE CHOROMOSOME 2p (EML4-ALK) INVERSION IN MEXICAN POPULATION.</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Instituto Nacional de Cancerologia de Mexico</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Instituto Nacional de Cancerologia de Mexico</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      Because ALK-positive lung cancer constitutes less than 5% of all lung cancers, it is&#xD;
      critically important to select those patients who are more likely to have the ALK mutation.&#xD;
      Clinical characteristics of patients with mutations in the target gene should also be known,&#xD;
      so that the incidence of a given target mutation is established in a specific population.&#xD;
      There is not incidence known in Mexican population, but it is believed it is greater.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Lung adenocarcinoma studies. The only inclusion criterion was the availability of tissue for&#xD;
      biomarker studies. To identify ALK rearrangements, fluorescence in situ hybridization (FISH)&#xD;
      studies were performed on 3 to 4 mm thick paraffin sections from NSCLCs. The commercially&#xD;
      labeled Vysis LSI ALK Dual Color (split-apart), break-apart rearrangement probe (Abbott&#xD;
      Molecular, Abbott Park, IL) was used to detect any rearrangement involving the ALK gene. The&#xD;
      probe hybridizes to band 2p23, on either side of the ALK gene breakpoint. Criteria for probe&#xD;
      signal interpretation in at least 200 interphase nuclei were as follow: 1) separated green&#xD;
      and orange signals or single red signals identified cells with rearranged ALK; 2) overlapping&#xD;
      of red and green signals (yellowish) indicated cells in which ALK was not rearranged.&#xD;
&#xD;
      FISH-positive samples for ALK rearrangement were defined as having cells with a clearly&#xD;
      separated pair of probe signals, or with &gt;15% of cells having loss of the 5´(centromeric)&#xD;
      probe. The higher threshold for loss is necessary because parts of probes can be lost during&#xD;
      sectioning.&#xD;
&#xD;
      The aim of our study is to evaluate the utility of IHC with 5A4 and RT-qPCR in the detection&#xD;
      of ALK rearrangements in NSCLC compared with the current method of choice, FISH. Further, we&#xD;
      report on the demographics, and clinicopathologic features of ALK-rearranged NSCLC in a&#xD;
      Latin-American population.&#xD;
&#xD;
      Clinical details of these patients were included in a database. Further results will be&#xD;
      analyzed with the program SPSS17&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>February 2011</start_date>
  <completion_date type="Actual">September 2014</completion_date>
  <primary_completion_date type="Actual">September 2014</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>Cross-Sectional</time_perspective>
  </study_design_info>
  <primary_outcome>
    <measure>FISH, IHC, RT-qPCR Comparison</measure>
    <time_frame>TWO YEARS</time_frame>
    <description>200 samples underwent FISH, from them 63 underwent IHC and 48 RT-qPCR.</description>
  </primary_outcome>
  <number_of_groups>1</number_of_groups>
  <enrollment type="Actual">230</enrollment>
  <condition>Non Small-cell Lung Cancer</condition>
  <arm_group>
    <arm_group_label>ALK-BREAK APART</arm_group_label>
    <description>We reviewed 230 consecutive cases of NSCLC that were retrieved from oncologic molecular laboratory and diagnostic pathology unit at the Instituto Nacional de Cancerologia, Mexico city, between 2011 and 2014. Samples were sent to the unit of pathological anatomy, a Pathologist confirmed the histologic diagnosis. The only inclusion criterion was the availability of tissue for biomarker studies. Clinical and pathologic details of these patients were included in a database, obtained from medical records.&#xD;
For ALK fusion testing, we applied dual-color, break-apart FISH, RT-qPCR, and immunohistochemistry. Interpretation of the results was done in double-blind manner without knowing the results by other methods.</description>
  </arm_group>
  <biospec_retention>Samples With DNA</biospec_retention>
  <biospec_descr>
    <textblock>
      FISH studies were performed in 3-mm to 4-mm thick paraffin sections from 230 NSCLCs and 1&#xD;
      ALCL specimen with t(2;5) that was used as a positive control for the break-apart detection.&#xD;
&#xD;
      48 patients were analyzed for the presence of EML4-ALK gene fusion variants using the RNA&#xD;
      from frozen tissue sections&#xD;
    </textblock>
  </biospec_descr>
  <eligibility>
    <study_pop>
      <textblock>
        Mexican pupulation, with Non small-cell lung cancer.&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Non-Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  The only inclusion criterion was the availability of tissue for biomarker studies.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Disease Progression&#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>Oscar Arrieta, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Instituto de Cancerología</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Instituto Nacional de Cancerologia</name>
      <address>
        <city>Mexico</city>
        <state>DF</state>
        <zip>14080</zip>
        <country>Mexico</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Mexico</country>
  </location_countries>
  <reference>
    <citation>Jemal A, Freddie Bray, Melissa M, et al. Cancer statistics, 2011. CA Cancer J Clin. 61: 69-90, 2011. Wong DW. The EML4-ALK Fusion Gene Is Involved in Various Histologic Types of Lung Cancers From Non smokers With Wild-type EGFR and KRAS. Cancer 15, 1723-1733, 2009. Shaw, A. T. et al. Clinical Features and outcome of patients with non-small-cell lung cancer who harbor EML4-ALK. J. Clin. Oncol. 27, 4247-4253 2009. Kwak, E. L. et al. Anaplatic lymphoma kinase Inhibition in non-small cell lung cancer. N. Engl. J. Med. 363, 1693- 1703 2010. Soda M., Takada, S., Takeuchi, K., Choi, Y.L., Enomoto, M., Ueno, T. et al. A mouse model for EML4-ALK- positive lung cáncer. Proc Natl Acad Sci U S A 105: 19893-19897, 2008.</citation>
  </reference>
  <verification_date>August 2016</verification_date>
  <study_first_submitted>August 8, 2012</study_first_submitted>
  <study_first_submitted_qc>August 9, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">August 10, 2012</study_first_posted>
  <results_first_submitted>September 23, 2014</results_first_submitted>
  <results_first_submitted_qc>November 14, 2014</results_first_submitted_qc>
  <results_first_posted type="Estimate">November 21, 2014</results_first_posted>
  <last_update_submitted>December 18, 2018</last_update_submitted>
  <last_update_submitted_qc>December 18, 2018</last_update_submitted_qc>
  <last_update_posted type="Actual">January 9, 2019</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Instituto Nacional de Cancerologia de Mexico</investigator_affiliation>
    <investigator_full_name>Oscar Gerardo Arrieta Rodríguez MD</investigator_full_name>
    <investigator_title>MD and medical oncologist</investigator_title>
  </responsible_party>
  <keyword>Non-small cell lung cancer.</keyword>
  <keyword>Diagnosis,</keyword>
  <keyword>Adenocarcinoma,</keyword>
  <keyword>ALK,</keyword>
  <keyword>FISH,</keyword>
  <keyword>IHC</keyword>
  <keyword>RT-qPCR</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Lung Neoplasms</mesh_term>
    <mesh_term>Carcinoma, Non-Small-Cell Lung</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>Undecided</sharing_ipd>
  </patient_data>

  <clinical_results>

    <participant_flow>
      <recruitment_details>The recruitment began on February 01, 2011 and finished on September 01, 2014. All samples were obtained at the Instituto Nacional de Cancerología, in Mexico.</recruitment_details>
      <pre_assignment_details>Samples were sent to the unit of Anatomic Pathology, where a pathologist confirmed the histologic diagnosis. The only inclusion criterion was the availability of tissue for biomarker studies.</pre_assignment_details>
      <group_list>
        <group group_id="P1">
          <title>Determination of ALK by FISH, IHC and RT-qPCR</title>
          <description>The only inclusion criterion was the availability of tissue for biomarker studies.&#xD;
We use a commercially available break-apart probe kit specific to the ALK locus (Vysis LSI ALK Dual Color (split-apart); using the commercially mouse monoclonal ALK antibody for IHC and . Variants 1, 2, 3a, 4 and 5. The qPCR reactions were performed using the TaqMan Universal PCR MasterMix (Applied Biosystems/TaqMan, Life Technologies)</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="230"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="200"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="30"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>scarce samples for evaluation</title>
              <participants_list>
                <participants group_id="P1" count="30"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <population>The population evaluated included mexican patients, females and males, with ages between 18 and 80 years old, who had advanced lung cancer, who were referred to the Instituto Nacional de Cancerología in Mexico, between February 01, 2011 and September 01, 2014</population>
      <group_list>
        <group group_id="B1">
          <title>Demographics and Clinical Features of Overall Population</title>
          <description>The baseline characteristics of our population were on basis of the presence or absence of ALK gene.</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="200"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age, Customized</title>
          <units>participants</units>
          <param>Number</param>
          <class_list>
            <class>
              <title>&lt; 55 years old</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="91"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>55 to 87 years old</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="109"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Sex: Female, Male</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Female</title>
                  <measurement_list>
                    <measurement group_id="B1" value="113"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="87"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Sex: Female, Male</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Female</title>
                  <measurement_list>
                    <measurement group_id="B1" value="113"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="87"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Smoking history</title>
          <units>participants</units>
          <param>Number</param>
          <class_list>
            <class>
              <title>Non smokers ALK +</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="12"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Smokers ALK+</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="7"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Non smokers ALK-</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="95"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>smokers ALK-</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="86"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>ECOG Performance status</title>
          <description>There were two groups:&#xD;
with an ECOG PS of 0-1( 0= Fully active, able to carry on all pre-disease performance without restriction, 1= Restricted in physically strenuous activity but ambulatory and able to carry out work of a light or sedentary nature, e.g., light house work, office work).&#xD;
ECOG PS of 2-3;( 2=Ambulatory and capable of all selfcare but unable to carry out any work activities. Up and about more than 50% of waking hours. 3=Capable of only limited selfcare, confined to bed or chair more than 50% of waking hours).</description>
          <units>participants</units>
          <param>Number</param>
          <class_list>
            <class>
              <title>ECOG 0-1; ALK +</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="15"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>ECOG 2-3; ALK +</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>ECOG 0-1; ALK -</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="148"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>ECOG 2-3; ALK -</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="33"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Histology</title>
          <units>participants</units>
          <param>Number</param>
          <class_list>
            <class>
              <title>Squamus; ALK+</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="17"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Non-squamus; ALK +</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Squamus; ALK -</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="176"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Non-squamus; ALK -</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Wood smoke expossure</title>
          <units>participants</units>
          <param>Number</param>
          <class_list>
            <class>
              <title>Absent; ALK +</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="9"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Present; ALK +</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="10"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Absent; ALK -</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="117"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Present; ALK -</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="64"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Histology Subtype</title>
          <units>participants</units>
          <param>Number</param>
          <class_list>
            <class>
              <title>Lepidic; ALK +</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Acinar; ALK +</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Papilar; ALK +</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Micropapilar; ALK +</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Solid; ALK +</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Adenousquamous; ALK +</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>No otherwise specified; ALK +</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Lepidic; ALK -</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="14"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Acinar; ALK -</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="39"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Papilar; ALK -</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="13"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Micropapilar; ALK -</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="10"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Solid; ALK -</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="47"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Adenousquamous; ALK -</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="16"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>No otherwise specified; ALK -</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="42"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>FISH, IHC, RT-qPCR Comparison</title>
        <description>200 samples underwent FISH, from them 63 underwent IHC and 48 RT-qPCR.</description>
        <time_frame>TWO YEARS</time_frame>
        <population>The only selection criteria of our subjets was the availability of tumor tissue to perform tests.</population>
        <group_list>
          <group group_id="O1">
            <title>FISH Test</title>
            <description>We use a commercially available break-apart probe kit specific to the ALK locus (Vysis LSI ALK Dual Color (split-apart); Abbott Molecular, Abbott Park, IL, USA). Slide washing, and counterstaining by DAPI were done following the manufacturer´s protocol (Abbott Molecular, Abbott Park, IL, USA).</description>
          </group>
          <group group_id="O2">
            <title>IHC Test</title>
            <description>using the commercially mouse monoclonal ALK antibody (dilution 1:25, clone 5A4; Abcam, Cambridge, UK), with OptiView DAB detection Kit (Ventana, Tucson, Arizona, USA). ALK IHC was performed according to the protocols provided by the antibody.</description>
          </group>
          <group group_id="O3">
            <title>RT-qPCR Test</title>
            <description>The qPCR reactions were performed using the TaqMan Universal PCR MasterMix (Applied Biosystems/TaqMan, Life Technologies) and the following Taqman assays: Hs03654556_ft (E13;A20), Hs03654557_ft (E20;A20), Hs03654558_ft (E6;A20), Hs03654560_ft (E17;A20), and Hs03654559_ft (E18;A20). Hs02758991_ft (GAPDH) assays, whose expression levels are known to be nearly stable among lung tumors</description>
          </group>
        </group_list>
        <measure>
          <title>FISH, IHC, RT-qPCR Comparison</title>
          <description>200 samples underwent FISH, from them 63 underwent IHC and 48 RT-qPCR.</description>
          <population>The only selection criteria of our subjets was the availability of tumor tissue to perform tests.</population>
          <units>participants</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="200"/>
                <count group_id="O2" value="63"/>
                <count group_id="O3" value="48"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>ALK+</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="18"/>
                    <measurement group_id="O2" value="15"/>
                    <measurement group_id="O3" value="5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>ALK-</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="182"/>
                    <measurement group_id="O2" value="48"/>
                    <measurement group_id="O3" value="43"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
              <group_id>O3</group_id>
            </group_id_list>
            <groups_desc>Continuous variables were summarized as arithmetic means, medians and standard deviations; and categorical variables were reported as proportions with 95% confidence intervals. Inferential comparisons were performed using Student's t test. The x2 or Fisher's exact tests were used to assess significance among categorical variables.</groups_desc>
            <non_inferiority_type>Superiority or Other</non_inferiority_type>
            <p_value>&lt; 0.05</p_value>
            <method>t-test, 2 sided</method>
          </analysis>
        </analysis_list>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>Adverse events not collected</time_frame>
      <desc>Adverse events not collected</desc>
      <group_list>
        <group group_id="E1">
          <title>Adverse Events Not Collected</title>
          <description>&quot;Serious and Other were not collected/assessed in this observational study.&quot;</description>
        </group>
      </group_list>
      <serious_events>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="0"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>0</frequency_threshold>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, other adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="0"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </other_events>
    </reported_events>

    <certain_agreements>
      <pi_employee>All Principal Investigators ARE employed by the organization sponsoring the study.</pi_employee>
      <restrictive_agreement>There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed. </restrictive_agreement>
    </certain_agreements>
    <limitations_and_caveats>There were no limitations in obtaining the planned number of samples. Two-hundred and thirty patients with advanced NSCLC were analyzed by FISH. Among the FISH tests performed, 30 were not evaluable due to scarce samples.</limitations_and_caveats>
    <point_of_contact>
      <name_or_title>Oscar Gerardo Arrieta-Rodríguez</name_or_title>
      <organization>Thoracic Oncology Unit. Instituto Nacional de Cancerología</organization>
      <phone>+52 55 56280400 ext 832</phone>
      <email>ogar@unam.mx</email>
    </point_of_contact>
  </clinical_results>
</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/NCT01662635
org study id: INCAN/CC/039/11
nct id: NCT01662635
lead sponsor: 
has dmc: No
Because ALK-positive lung cancer constitutes less than 5% of all lung cancers, it is
      critically important to select those patients who are more likely to have the ALK mutation.
      Clinical characteristics of patients with mutations in the target gene should also be known,
      so that the incidence of a given target mutation is established in a specific population.
      There is not incidence known in Mexican population, but it is believed it is greater.
Lung adenocarcinoma studies. The only inclusion criterion was the availability of tissue for
      biomarker studies. To identify ALK rearrangements, fluorescence in situ hybridization (FISH)
      studies were performed on 3 to 4 mm thick paraffin sections from NSCLCs. The commercially
      labeled Vysis LSI ALK Dual Color (split-apart), break-apart rearrangement probe (Abbott
      Molecular, Abbott Park, IL) was used to detect any rearrangement involving the ALK gene. The
      probe hybridizes to band 2p23, on either side of the ALK gene breakpoint. Criteria for probe
      signal interpretation in at least 200 interphase nuclei were as follow: 1) separated green
      and orange signals or single red signals identified cells with rearranged ALK; 2) overlapping
      of red and green signals (yellowish) indicated cells in which ALK was not rearranged.

      FISH-positive samples for ALK rearrangement were defined as having cells with a clearly
      separated pair of probe signals, or with >15% of cells having loss of the 5´(centromeric)
      probe. The higher threshold for loss is necessary because parts of probes can be lost during
      sectioning.

      The aim of our study is to evaluate the utility of IHC with 5A4 and RT-qPCR in the detection
      of ALK rearrangements in NSCLC compared with the current method of choice, FISH. Further, we
      report on the demographics, and clinicopathologic features of ALK-rearranged NSCLC in a
      Latin-American population.

      Clinical details of these patients were included in a database. Further results will be
      analyzed with the program SPSS17
observational model: Cohort
time perspective: Cross-Sectional
measure: FISH, IHC, RT-qPCR Comparison
time frame: TWO YEARS
description: 200 samples underwent FISH, from them 63 underwent IHC and 48 RT-qPCR.
arm group label: ALK-BREAK APART
description: We reviewed 230 consecutive cases of NSCLC that were retrieved from oncologic molecular laboratory and diagnostic pathology unit at the Instituto Nacional de Cancerologia, Mexico city, between 2011 and 2014. Samples were sent to the unit of pathological anatomy, a Pathologist confirmed the histologic diagnosis. The only inclusion criterion was the availability of tissue for biomarker studies. Clinical and pathologic details of these patients were included in a database, obtained from medical records.
For ALK fusion testing, we applied dual-color, break-apart FISH, RT-qPCR, and immunohistochemistry. Interpretation of the results was done in double-blind manner without knowing the results by other methods.
FISH studies were performed in 3-mm to 4-mm thick paraffin sections from 230 NSCLCs and 1
      ALCL specimen with t(2;5) that was used as a positive control for the break-apart detection.

      48 patients were analyzed for the presence of EML4-ALK gene fusion variants using the RNA
      from frozen tissue sections
study pop: 
sampling method: Non-Probability Sample
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Oscar Arrieta, MD
role: Principal Investigator
affiliation: Instituto de Cancerología
facility: 
country: Mexico
citation: Jemal A, Freddie Bray, Melissa M, et al. Cancer statistics, 2011. CA Cancer J Clin. 61: 69-90, 2011. Wong DW. The EML4-ALK Fusion Gene Is Involved in Various Histologic Types of Lung Cancers From Non smokers With Wild-type EGFR and KRAS. Cancer 15, 1723-1733, 2009. Shaw, A. T. et al. Clinical Features and outcome of patients with non-small-cell lung cancer who harbor EML4-ALK. J. Clin. Oncol. 27, 4247-4253 2009. Kwak, E. L. et al. Anaplatic lymphoma kinase Inhibition in non-small cell lung cancer. N. Engl. J. Med. 363, 1693- 1703 2010. Soda M., Takada, S., Takeuchi, K., Choi, Y.L., Enomoto, M., Ueno, T. et al. A mouse model for EML4-ALK- positive lung cáncer. Proc Natl Acad Sci U S A 105: 19893-19897, 2008.
responsible party type: Principal Investigator
investigator affiliation: Instituto Nacional de Cancerologia de Mexico
investigator full name: Oscar Gerardo Arrieta Rodríguez MD
investigator title: MD and medical oncologist
mesh term: Lung Neoplasms
mesh term: Carcinoma, Non-Small-Cell Lung
sharing ipd: Undecided
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
limitations and caveats: There were no limitations in obtaining the planned number of samples. Two-hundred and thirty patients with advanced NSCLC were analyzed by FISH. Among the FISH tests performed, 30 were not evaluable due to scarce samples.
point of contact: 