<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/NCT02239432</url>
  </required_header>
  <id_info>
    <org_study_id>0067-14-MMC</org_study_id>
    <nct_id>NCT02239432</nct_id>
  </id_info>
  <brief_title>Telomere Biology in Early Adenocarcinoma of the Lung</brief_title>
  <official_title>Prospective Cohort Study of Telomere Biology Among Patients With Early Adenocarcinoma of the Lung</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Meir Medical Center</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Meir Medical Center</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      Early adenocarcinoma of the lung has an excellent five-year survival after resection.&#xD;
      However, its clinical and radiologic presentation is highly variable. Traditional means for&#xD;
      preoperative diagnosis such as Positron Emission Tomography (PET-CT) and trans-thoracic&#xD;
      needle biopsy demonstrate unacceptable false positive and negative rates.&#xD;
&#xD;
      Telomere biology is activated aberrantly is most lung cancers but has not been studied in&#xD;
      early stages to the best of our knowledge.&#xD;
&#xD;
      The objective of this study is to evaluate telomere length and activity with suspected early&#xD;
      stage adenocarcinoma of the lung.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Bronchoalveolar carcinoma has been traditionally used to refer to a subset of adenocarcinoma&#xD;
      distinguished by its peripheral location, typical &quot;lepidic&quot; growth pattern and tendency for&#xD;
      both bronchogenic and lymphatic spread. For the purpose of this discussion and consistency&#xD;
      with the revised 2011 criteria, BAC subtypes will be collectively referred to as early&#xD;
      adenocarcinoma.&#xD;
&#xD;
      The clinical presentation of early adenocarcinoma subtypes is highly variable ranging from a&#xD;
      small solitary nodule to extensive lobar consolidation. Many peripheral lesions have a&#xD;
      characteristic ground glass opacity appearance on Chest CT, which may correlate with an&#xD;
      improved prognosis. The reported five-year disease-free survival after resection for isolated&#xD;
      lesions may approaches 100%.&#xD;
&#xD;
      Preoperative diagnosis of such lesions is complicated by several limitations. First, the&#xD;
      differential diagnosis is broad including an extensive number of inflammatory and infectious&#xD;
      processes. Second, positron emission tomography (PET), which identifies regions of increased&#xD;
      metabolic activity, may be falsely negative due to the slow growth of early adenocarcinoma&#xD;
      lesions. Transbronchial needle biopsy is also unreliable to confirm or exclude disease in&#xD;
      non-solid type lesions.&#xD;
&#xD;
      The proportion of lung cancers classified as adenocarcinoma has steadily increased and now&#xD;
      comprises nearly ½ of cases. However, the proportion of adenocarcinoma in situ is uncertain.&#xD;
      Previous reports range from 5-10% in a large series to as high as 24% in the large&#xD;
      Surveillance, Epidemiology and End Results database. Thus, these early adenocarcinoma lesions&#xD;
      may represent a disproportionately large number of lung cancers which are PET negative yet&#xD;
      carry an excellent prognosis after early resection. The early adenocarcinoma subtypes&#xD;
      represent a clinical entity requiring further characterization to distinguish lesions more&#xD;
      likely to be malignant from benign.&#xD;
&#xD;
      Telomerase is activated aberrantly in most lung cancers and mutations in telomerase&#xD;
      components predispose to solid malignancies. For patients with non-small cell lung cancer,&#xD;
      numerous studies correlate increased tumor telomerase activity with increased likelihood of&#xD;
      Stage IIIB and Stage IV disease and/or reduced survival. Furthermore, telomerase inhibition&#xD;
      is currently being studied in clinical trials of patients with advanced non-small lung&#xD;
      cancer.&#xD;
&#xD;
      Problem:&#xD;
&#xD;
      The semi-solid lung lesion may represent early stage adenocarcinoma which has an excellent&#xD;
      prognosis upon early diagnosis and prompt surgical resection. However, the semi-solid lesion&#xD;
      has a broad differential diagnosis and preoperative features characteristic of adenocarcinoma&#xD;
      are needed to distinguish malignant from benign lesions.&#xD;
&#xD;
      Objective:&#xD;
&#xD;
      To study telomere length and telomerase activity in patients with suspected early&#xD;
      adenocarcinoma of the lung whom are referred for surgical biopsy of lung lesions.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Recruiting</last_known_status>
  <start_date>September 2014</start_date>
  <completion_date type="Anticipated">September 2017</completion_date>
  <primary_completion_date type="Anticipated">September 2016</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>Telomere Capture Percentage</measure>
    <time_frame>one-time peripheral blood sample</time_frame>
    <description>According to our previous experience with telomore biology in different disease states, we estimate a standard deviation (SD) of 1.3 of telomere capture (%) for the controls (healthy patients without known lung disease) and a SD of 2.4 (TC%) for biopsy-proven adenocarcinoma of the lung. For a clinically significance of at least 2%, we estimate a sample size of at least 16 patients with biopsy-proven disease to detect a statistically significant of 5% with a power of 80% (calculated by the independent t-test).</description>
  </primary_outcome>
  <number_of_groups>3</number_of_groups>
  <enrollment type="Anticipated">100</enrollment>
  <condition>Adenocarcinoma of the Lung</condition>
  <condition>Adenocarcinoma, Bronchiolo-Alveolar</condition>
  <arm_group>
    <arm_group_label>Suspected Adenocarcinoma of the Lung</arm_group_label>
    <description>Patients with suspected adenocarcinoma of the lung referred for surgical lung biopsy after multi-disciplinary team recommendation.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Healthy Control</arm_group_label>
    <description>Age and sex-matched patients with no known lung disease or other chronic inflammatory disease or malignancy</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Age-matched controls with proven solid lung malignancy</arm_group_label>
    <description>Patients with biopsy-proven advanced solid malignancy of the lung</description>
  </arm_group>
  <biospec_retention>Samples Without DNA</biospec_retention>
  <biospec_descr>
    <textblock>
      One peripheral blood sample is taken for lymphocyte culture and subsequently telomere length&#xD;
      and activity analysis (previously described, Laish I, Gene 2013;529:245-9)&#xD;
    </textblock>
  </biospec_descr>
  <eligibility>
    <study_pop>
      <textblock>
        Patients referred by a multi-disciplinary team meeting recommendation for surgical lung&#xD;
        biopsy due to suspected adenocarcinoma of the lung.&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Non-Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
        Patients referred by a multi-disciplinary team meeting recommendation for surgical lung&#xD;
        biopsy due to suspected adenocarcinoma of the lung and agree to a one-time peripheral blood&#xD;
        sample for telomere analysis as described.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
        Patients whom were not evaluated by the multi-disciplinary team discussion prior to&#xD;
        referral for surgical lung biopsy.&#xD;
&#xD;
        Patients with other chronic inflammatory disease requiring immunosuppressive therapy or&#xD;
        known extra-pulmonary malignancy.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>90 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_contact>
    <last_name>Matthew Koslow, M.D.</last_name>
    <phone>+972-3-52-603-5410</phone>
    <email>mkoslow73@gmail.com</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>David Shitrit, M.D.</last_name>
    <phone>+972-9-747-1556</phone>
    <email>Davids3@clalit.org.il</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>Soroka University Medical Center</name>
      <address>
        <city>Beer Sheva</city>
        <zip>84101</zip>
        <country>Israel</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Yael Rafaely, M.D.</last_name>
      <email>YaelRefaely@clalit.org.il</email>
    </contact>
    <contact_backup>
      <last_name>Alina Zilberman, Msc</last_name>
      <email>ElinuRu@clalit.org.il</email>
    </contact_backup>
    <investigator>
      <last_name>Yael Rafaely, M.D.</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Meir Medical Center</name>
      <address>
        <city>Kfar Saba</city>
        <zip>4428164</zip>
        <country>Israel</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Matthew Koslow, M.D.</last_name>
      <phone>+972-52-603-5410</phone>
      <email>mkoslow73@gmail.com</email>
    </contact>
    <investigator>
      <last_name>Matthew Koslow, M.D.</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location_countries>
    <country>Israel</country>
  </location_countries>
  <verification_date>September 2014</verification_date>
  <study_first_submitted>September 10, 2014</study_first_submitted>
  <study_first_submitted_qc>September 10, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">September 12, 2014</study_first_posted>
  <last_update_submitted>September 10, 2014</last_update_submitted>
  <last_update_submitted_qc>September 10, 2014</last_update_submitted_qc>
  <last_update_posted type="Estimate">September 12, 2014</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Adenocarcinoma of the Lung</keyword>
  <keyword>Adenocarcinoma, Bronchiolo-Alveolar</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Adenocarcinoma</mesh_term>
    <mesh_term>Adenocarcinoma of Lung</mesh_term>
    <mesh_term>Adenocarcinoma, Bronchiolo-Alveolar</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/NCT02239432
org study id: 0067-14-MMC
nct id: NCT02239432
lead sponsor: 
has dmc: No
Early adenocarcinoma of the lung has an excellent five-year survival after resection.
      However, its clinical and radiologic presentation is highly variable. Traditional means for
      preoperative diagnosis such as Positron Emission Tomography (PET-CT) and trans-thoracic
      needle biopsy demonstrate unacceptable false positive and negative rates.

      Telomere biology is activated aberrantly is most lung cancers but has not been studied in
      early stages to the best of our knowledge.

      The objective of this study is to evaluate telomere length and activity with suspected early
      stage adenocarcinoma of the lung.
Bronchoalveolar carcinoma has been traditionally used to refer to a subset of adenocarcinoma
      distinguished by its peripheral location, typical "lepidic" growth pattern and tendency for
      both bronchogenic and lymphatic spread. For the purpose of this discussion and consistency
      with the revised 2011 criteria, BAC subtypes will be collectively referred to as early
      adenocarcinoma.

      The clinical presentation of early adenocarcinoma subtypes is highly variable ranging from a
      small solitary nodule to extensive lobar consolidation. Many peripheral lesions have a
      characteristic ground glass opacity appearance on Chest CT, which may correlate with an
      improved prognosis. The reported five-year disease-free survival after resection for isolated
      lesions may approaches 100%.

      Preoperative diagnosis of such lesions is complicated by several limitations. First, the
      differential diagnosis is broad including an extensive number of inflammatory and infectious
      processes. Second, positron emission tomography (PET), which identifies regions of increased
      metabolic activity, may be falsely negative due to the slow growth of early adenocarcinoma
      lesions. Transbronchial needle biopsy is also unreliable to confirm or exclude disease in
      non-solid type lesions.

      The proportion of lung cancers classified as adenocarcinoma has steadily increased and now
      comprises nearly ½ of cases. However, the proportion of adenocarcinoma in situ is uncertain.
      Previous reports range from 5-10% in a large series to as high as 24% in the large
      Surveillance, Epidemiology and End Results database. Thus, these early adenocarcinoma lesions
      may represent a disproportionately large number of lung cancers which are PET negative yet
      carry an excellent prognosis after early resection. The early adenocarcinoma subtypes
      represent a clinical entity requiring further characterization to distinguish lesions more
      likely to be malignant from benign.

      Telomerase is activated aberrantly in most lung cancers and mutations in telomerase
      components predispose to solid malignancies. For patients with non-small cell lung cancer,
      numerous studies correlate increased tumor telomerase activity with increased likelihood of
      Stage IIIB and Stage IV disease and/or reduced survival. Furthermore, telomerase inhibition
      is currently being studied in clinical trials of patients with advanced non-small lung
      cancer.

      Problem:

      The semi-solid lung lesion may represent early stage adenocarcinoma which has an excellent
      prognosis upon early diagnosis and prompt surgical resection. However, the semi-solid lesion
      has a broad differential diagnosis and preoperative features characteristic of adenocarcinoma
      are needed to distinguish malignant from benign lesions.

      Objective:

      To study telomere length and telomerase activity in patients with suspected early
      adenocarcinoma of the lung whom are referred for surgical biopsy of lung lesions.
observational model: Cohort
time perspective: Prospective
measure: Telomere Capture Percentage
time frame: one-time peripheral blood sample
description: According to our previous experience with telomore biology in different disease states, we estimate a standard deviation (SD) of 1.3 of telomere capture (%) for the controls (healthy patients without known lung disease) and a SD of 2.4 (TC%) for biopsy-proven adenocarcinoma of the lung. For a clinically significance of at least 2%, we estimate a sample size of at least 16 patients with biopsy-proven disease to detect a statistically significant of 5% with a power of 80% (calculated by the independent t-test).
arm group label: Suspected Adenocarcinoma of the Lung
description: Patients with suspected adenocarcinoma of the lung referred for surgical lung biopsy after multi-disciplinary team recommendation.
arm group label: Healthy Control
description: Age and sex-matched patients with no known lung disease or other chronic inflammatory disease or malignancy
arm group label: Age-matched controls with proven solid lung malignancy
description: Patients with biopsy-proven advanced solid malignancy of the lung
One peripheral blood sample is taken for lymphocyte culture and subsequently telomere length
      and activity analysis (previously described, Laish I, Gene 2013;529:245-9)
study pop: 
sampling method: Non-Probability Sample
criteria: 
gender: All
minimum age: 18 Years
maximum age: 90 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Matthew Koslow, M.D.
phone: +972-3-52-603-5410
email: mkoslow73@gmail.com
last name: David Shitrit, M.D.
phone: +972-9-747-1556
email: Davids3@clalit.org.il
facility: 
status: Recruiting
contact: 
contact backup: 
investigator: 
facility: 
status: Recruiting
contact: 
investigator: 
country: Israel
responsible party type: Sponsor
mesh term: Adenocarcinoma
mesh term: Adenocarcinoma of Lung
mesh term: Adenocarcinoma, Bronchiolo-Alveolar