<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/NCT02222194</url>
  </required_header>
  <id_info>
    <org_study_id>ASTER 3</org_study_id>
    <nct_id>NCT02222194</nct_id>
  </id_info>
  <brief_title>The Value of Surgical Mediastinal Staging in Clinical N1 Lung Cancer</brief_title>
  <acronym>ASTER3</acronym>
  <official_title>Assessment of Surgical Mediastinal sTaging in cN1 Lung canceR</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Johnny Moons</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>University Hospital, Gasthuisberg</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      In case of PET or CT based cN1 (suspected) NSCLC, ESTS guidelines propose mediastinal staging&#xD;
      by echo-endoscopy OR mediastinoscopy. Recent data show a sensitivity of less than 50% for&#xD;
      echo-endoscopy to detect N2 disease in cN1 NSCLC patients, while prevalence of mediastinal&#xD;
      nodal disease was 24% (unpublished data Aster II).2 The investigators plan to perform a&#xD;
      prospective multicentric observational study to measure the sensitivity of mediastinal&#xD;
      staging by video-assisted mediastinoscopy (VAM) in cN1 operable and resectable (suspected)&#xD;
      NSCLC patients.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Few reports in the literature evaluated the final pathological stage distribution of patients&#xD;
      with resectable and operable non-small cell lung cancer (NSCLC) with clinical stage cN1.&#xD;
      These retrospective series demonstrated that patients with computed tomography (CT) based cN1&#xD;
      often had clinically occult mediastinal lymph node metastases (N2/3 disease). Hishida et al.&#xD;
      reported that 30% of 143 patients with cN1 were diagnosed N2/3 by mediastinoscopy3. Watanabe&#xD;
      et al. reported that 37% of 168 patients with cN1 were diagnosed N2/3 by mediastinoscopy 4.&#xD;
      Adding FDG-positron emission tomography (PET) to CT might enable the detection of N2/3&#xD;
      disease among these cN1 patients, but negative PET findings do not necessarily exclude N2/3&#xD;
      disease. Kim et al reported that 19,2 % of 99 patients with cN1, in whom cN2 was ruled out by&#xD;
      PET-CT scan, were found to have pathologic N2 disease at pulmonary resection with mediastinal&#xD;
      lymph node dissection.5 In conclusion, 20-30% of patients with cN1 nodes on imaging, and&#xD;
      normal sized FDG-negative mediastinal lymph nodes on CT and PET have malignant involvement in&#xD;
      their mediastinal nodes.&#xD;
&#xD;
      The ACCP guidelines state that invasive preoperative mediastinal staging should be performed&#xD;
      in these cN1 patients 6. The updated ESTS guidelines recommend mediastinal staging by&#xD;
      echo-endoscopic or mediastinoscopy.1 Non-randomized trials suggested the potential of linear&#xD;
      endosonography for mediastinal staging 7-9. However, the patients with cN1 disease form only&#xD;
      a minority in these studies. A recently performed prospective ASTER 2 trial (N=100) showed a&#xD;
      sensitivity of echo-endoscopic for mediastinal staging of 38% (ITT analysis), while the&#xD;
      prevalence of mediastinal nodal disease was 24% (unpublished data Aster 2) 2. The conclusion&#xD;
      made by ASTER 2 is that a negative endosonography must be followed by a VAM. However, the&#xD;
      investigators consider such double approach not cost-effective in a setting with N2&#xD;
      prevalence &lt;30%. Therefore, it seems reasonable to perform a VAM instead of an endosonography&#xD;
      in cN1 patients, which is one of the proposed strategies in the recent ESTS guidelines.1&#xD;
      However, there is no prospective study to date that assessed the sensitivity, NPV and&#xD;
      accuracy of VAM in a well-defined group of cN1 patients.&#xD;
&#xD;
      Several publications have demonstrated a lobe-specific mediastinal nodal drainage for upper&#xD;
      versus lower lobe NSCLC. Shapiro et al conclude that in early lung cancer, including cN1&#xD;
      disease, lobe-specific mediastinal dissection is warranted 10. However, in this study the&#xD;
      only patient with a positive subcarinal node, upper lobe tumour, and negative superior&#xD;
      mediastinal nodes had positive N1 nodes. To the investigators knowledge there is no study&#xD;
      focussing on mediastinal nodal dissemination patterns in cN1 patients.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>August 2014</start_date>
  <completion_date type="Actual">May 30, 2017</completion_date>
  <primary_completion_date type="Actual">March 2017</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>Sensitivity of VAM</measure>
    <time_frame>at surgery (VAM)</time_frame>
    <description>Sensitivity (%) of surgical mediastinal staging by video-assisted mediastinoscopy in clinical N1; true positives (TP) = cN1 and pN1 - false negatives (FP) = cN1 and pN2/3; sensitivity is calculated as TP / (TP+FN)</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Prevalence of N2/3 disease after VAM</measure>
    <time_frame>at surgery (VAM)</time_frame>
    <description>% of patients with cN1 disease who show pN2/3 disease after VAM</description>
  </secondary_outcome>
  <number_of_groups>1</number_of_groups>
  <enrollment type="Actual">105</enrollment>
  <condition>Non Small Cell Lung Cancer</condition>
  <arm_group>
    <arm_group_label>VAM</arm_group_label>
    <description>Patients with operable and resectable cT1-2-selected T3 cN1cM0 NSCLC undergo VAM for mediastinal lymph node staging. After VAM, patients without tissue proof of N2/3 disease at surgical staging undergo a VATS or thoracotomy with systematic lymph node dissection during the same anaesthesia or at a later stage.&#xD;
Sensitivity, NPV and accuracy of staging with VAM will be calculated. Provided N2 lymph node metastases are proven by VAM the patient goes off study protocol and can further be assessed/treated according to local clinical practice.</description>
  </arm_group>
  <eligibility>
    <study_pop>
      <textblock>
        Patients with operable and resectable cT1-2- selectedT3 cN1 (suspected) NSCLC. (selected T3&#xD;
        = intraparenchymal tumour &gt;7cm or T3 chest wall or T3 additional nodule, excluding&#xD;
        mediastinal invasion or invasion of the main bronchus &lt; 2cm from the carina)&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
        (Suspected) NSCLC Medical operable and surgical resectable cT1, cT2 selected cT3 (i.e.&#xD;
        intraparenchymal tumour &gt;7cm, T3 chest wall, or T3 based on additional nodule in the lobe&#xD;
        of the primary tumour) cN1 based on CT or PET 18 years or older Informed Consent&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
        History of mediastinoscopy No integrated FDG PET/CT available No videomediastinoscopy&#xD;
        available EBUS/EUS for mediastinal staging of present N1 disease cN2: mediastinal nodes&#xD;
        enlarged on CT or Pet positive invasion of mediastinal pleura invasion of phrenic nerve&#xD;
        invasion of parietal pericardium tumour in main bronchus less than 2cm form the main carina&#xD;
        cT4 cM1 former therapy for lung cancer (chemotherapy, radiotherapy, surgery) technical&#xD;
        contraindication for videomediastinoscopy ( eg extreme kyphosis, cutaneous tracheostomy,&#xD;
        extreme goiter) pregnancy inability to consent&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>90 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Herbert Decaluwé, MD</last_name>
    <role>Study Director</role>
    <affiliation>Universitaire Ziekenhuizen KU Leuven</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>University Hospital Leuven</name>
      <address>
        <city>Leuven</city>
        <zip>3000</zip>
        <country>Belgium</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Aix-Marseille University &amp; Hospitals System of Marseille (AP-HM)</name>
      <address>
        <city>Marseille</city>
        <zip>13915</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>ELK Berlin Chest Hospital</name>
      <address>
        <city>Berlin</city>
        <zip>13125</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Albert-Ludwigs-University Freiburg</name>
      <address>
        <city>Freiburg</city>
        <zip>79106</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Katholisches Klinikum Koblenz</name>
      <address>
        <city>Koblenz</city>
        <zip>56073</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Katholisches Klinikum, Thoraxchirurgie</name>
      <address>
        <city>Koblenz</city>
        <zip>56073</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Universitari Mutua Terrassa</name>
      <address>
        <city>Barcelona</city>
        <zip>08017</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Clinic; Barcelona University</name>
      <address>
        <city>Barcelona</city>
        <zip>08036</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University Hospital, Division of Thoracic Surgery</name>
      <address>
        <city>Zurich</city>
        <zip>8091</zip>
        <country>Switzerland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Istanbul University, Cerrahpasa Medical Faculty</name>
      <address>
        <city>Istanbul</city>
        <zip>81080</zip>
        <country>Turkey</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Belgium</country>
    <country>France</country>
    <country>Germany</country>
    <country>Spain</country>
    <country>Switzerland</country>
    <country>Turkey</country>
  </location_countries>
  <verification_date>July 2017</verification_date>
  <study_first_submitted>August 18, 2014</study_first_submitted>
  <study_first_submitted_qc>August 19, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">August 21, 2014</study_first_posted>
  <last_update_submitted>July 22, 2017</last_update_submitted>
  <last_update_submitted_qc>July 22, 2017</last_update_submitted_qc>
  <last_update_posted type="Actual">July 25, 2017</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor-Investigator</responsible_party_type>
    <investigator_affiliation>University Hospital, Gasthuisberg</investigator_affiliation>
    <investigator_full_name>Johnny Moons</investigator_full_name>
    <investigator_title>Data Manager / Clinical Trial Coordinator</investigator_title>
  </responsible_party>
  <keyword>Lung cancer</keyword>
  <keyword>Surgery</keyword>
  <keyword>Videomediastinoscopy</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Lung 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/NCT02222194
org study id: ASTER 3
nct id: NCT02222194
lead sponsor: 
has dmc: No
In case of PET or CT based cN1 (suspected) NSCLC, ESTS guidelines propose mediastinal staging
      by echo-endoscopy OR mediastinoscopy. Recent data show a sensitivity of less than 50% for
      echo-endoscopy to detect N2 disease in cN1 NSCLC patients, while prevalence of mediastinal
      nodal disease was 24% (unpublished data Aster II).2 The investigators plan to perform a
      prospective multicentric observational study to measure the sensitivity of mediastinal
      staging by video-assisted mediastinoscopy (VAM) in cN1 operable and resectable (suspected)
      NSCLC patients.
Few reports in the literature evaluated the final pathological stage distribution of patients
      with resectable and operable non-small cell lung cancer (NSCLC) with clinical stage cN1.
      These retrospective series demonstrated that patients with computed tomography (CT) based cN1
      often had clinically occult mediastinal lymph node metastases (N2/3 disease). Hishida et al.
      reported that 30% of 143 patients with cN1 were diagnosed N2/3 by mediastinoscopy3. Watanabe
      et al. reported that 37% of 168 patients with cN1 were diagnosed N2/3 by mediastinoscopy 4.
      Adding FDG-positron emission tomography (PET) to CT might enable the detection of N2/3
      disease among these cN1 patients, but negative PET findings do not necessarily exclude N2/3
      disease. Kim et al reported that 19,2 % of 99 patients with cN1, in whom cN2 was ruled out by
      PET-CT scan, were found to have pathologic N2 disease at pulmonary resection with mediastinal
      lymph node dissection.5 In conclusion, 20-30% of patients with cN1 nodes on imaging, and
      normal sized FDG-negative mediastinal lymph nodes on CT and PET have malignant involvement in
      their mediastinal nodes.

      The ACCP guidelines state that invasive preoperative mediastinal staging should be performed
      in these cN1 patients 6. The updated ESTS guidelines recommend mediastinal staging by
      echo-endoscopic or mediastinoscopy.1 Non-randomized trials suggested the potential of linear
      endosonography for mediastinal staging 7-9. However, the patients with cN1 disease form only
      a minority in these studies. A recently performed prospective ASTER 2 trial (N=100) showed a
      sensitivity of echo-endoscopic for mediastinal staging of 38% (ITT analysis), while the
      prevalence of mediastinal nodal disease was 24% (unpublished data Aster 2) 2. The conclusion
      made by ASTER 2 is that a negative endosonography must be followed by a VAM. However, the
      investigators consider such double approach not cost-effective in a setting with N2
      prevalence <30%. Therefore, it seems reasonable to perform a VAM instead of an endosonography
      in cN1 patients, which is one of the proposed strategies in the recent ESTS guidelines.1
      However, there is no prospective study to date that assessed the sensitivity, NPV and
      accuracy of VAM in a well-defined group of cN1 patients.

      Several publications have demonstrated a lobe-specific mediastinal nodal drainage for upper
      versus lower lobe NSCLC. Shapiro et al conclude that in early lung cancer, including cN1
      disease, lobe-specific mediastinal dissection is warranted 10. However, in this study the
      only patient with a positive subcarinal node, upper lobe tumour, and negative superior
      mediastinal nodes had positive N1 nodes. To the investigators knowledge there is no study
      focussing on mediastinal nodal dissemination patterns in cN1 patients.
observational model: Cohort
time perspective: Prospective
measure: Sensitivity of VAM
time frame: at surgery (VAM)
description: Sensitivity (%) of surgical mediastinal staging by video-assisted mediastinoscopy in clinical N1; true positives (TP) = cN1 and pN1 - false negatives (FP) = cN1 and pN2/3; sensitivity is calculated as TP / (TP+FN)
measure: Prevalence of N2/3 disease after VAM
time frame: at surgery (VAM)
description: % of patients with cN1 disease who show pN2/3 disease after VAM
arm group label: VAM
description: Patients with operable and resectable cT1-2-selected T3 cN1cM0 NSCLC undergo VAM for mediastinal lymph node staging. After VAM, patients without tissue proof of N2/3 disease at surgical staging undergo a VATS or thoracotomy with systematic lymph node dissection during the same anaesthesia or at a later stage.
Sensitivity, NPV and accuracy of staging with VAM will be calculated. Provided N2 lymph node metastases are proven by VAM the patient goes off study protocol and can further be assessed/treated according to local clinical practice.
study pop: 
sampling method: Probability Sample
criteria: 
gender: All
minimum age: 18 Years
maximum age: 90 Years
healthy volunteers: No
last name: Herbert Decaluwé, MD
role: Study Director
affiliation: Universitaire Ziekenhuizen KU Leuven
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
country: Belgium
country: France
country: Germany
country: Spain
country: Switzerland
country: Turkey
responsible party type: Sponsor-Investigator
investigator affiliation: University Hospital, Gasthuisberg
investigator full name: Johnny Moons
investigator title: Data Manager / Clinical Trial Coordinator
mesh term: Lung Neoplasms