<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/NCT02250378</url>
  </required_header>
  <id_info>
    <org_study_id>2N-14-3</org_study_id>
    <secondary_id>NCI-2014-01916</secondary_id>
    <secondary_id>2N-14-3</secondary_id>
    <secondary_id>P30CA014089</secondary_id>
    <nct_id>NCT02250378</nct_id>
  </id_info>
  <brief_title>Stereotactic Radiosurgery Followed by Wedge Resection in Treating Patients With Early Stage Peripheral Non-small Cell Lung Cancer</brief_title>
  <official_title>Feasibility Study of Stereotactic Body Radiation Therapy Followed by Wedge Resection for Peripherally Located Early Stage Non-small Cell Lung Cancer</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of Southern California</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>National Cancer Institute (NCI)</agency>
      <agency_class>NIH</agency_class>
    </collaborator>
  </sponsors>
  <source>University of Southern California</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      This pilot clinical trial studies the side effects and how well stereotactic radiosurgery&#xD;
      followed by wedge resection works in treating patients with early stage non-small cell lung&#xD;
      cancer that is located in the outer, or peripheral, areas of the lung. Stereotactic&#xD;
      radiosurgery, also known as stereotactic body radiation therapy, is a specialized radiation&#xD;
      therapy that delivers a single, high dose of radiation directly to the tumor and may kill&#xD;
      more tumor cells and cause less damage to normal tissue. Wedge resection is a less invasive&#xD;
      type of surgery for removal of the tumor and a small amount of normal tissue around it.&#xD;
      Giving stereotactic radiosurgery followed by wedge resection may be a safe treatment option&#xD;
      for patients who cannot receive standard treatment with lobectomy.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      PRIMARY OBJECTIVES:&#xD;
&#xD;
      I. To assess the safety and feasibility of a wedge resection following stereotactic body&#xD;
      radiation therapy (SBRT) for early stage peripheral non-small cell lung cancer (NSCLC).&#xD;
&#xD;
      SECONDARY OBJECTIVES:&#xD;
&#xD;
      I. To assess pathologic response rates to SBRT as determined by pathologic examination of&#xD;
      resected tumors.&#xD;
&#xD;
      II. To prospectively assess patient quality of life when treated with SBRT and wedge&#xD;
      resection.&#xD;
&#xD;
      TERTIARY OBJECTIVES:&#xD;
&#xD;
      I. To describe the location of viable tumor and to correlate pathologic response rates with&#xD;
      radiation dose, size of tumor, and tumor histology.&#xD;
&#xD;
      II. To correlate pathologic response rates and functional imaging with pre- and&#xD;
      post-treatment dual-input perfusion (DP)-computed tomography (CT) and positron emission&#xD;
      tomography (PET)-CT.&#xD;
&#xD;
      III. To correlate changes in serum levels of deoxyribonucleic acid (DNA) methylation and&#xD;
      circulating tumor cells (CTC) with pathologic response rates.&#xD;
&#xD;
      OUTLINE:&#xD;
&#xD;
      Patients undergo stereotactic radiosurgery every other day for 3 or 5 fractions (depending on&#xD;
      the size tumor and proximity to the chest wall). Within 4-6 weeks after completion of&#xD;
      stereotactic radiosurgery, patients undergo wedge resection.&#xD;
&#xD;
      After completion of study treatment, patients are followed up at 1, 3, 6, and 12 months.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Withdrawn</overall_status>
  <why_stopped>
    No accrual&#xD;
  </why_stopped>
  <start_date>October 2014</start_date>
  <completion_date type="Actual">September 2015</completion_date>
  <primary_completion_date type="Actual">August 2015</primary_completion_date>
  <phase>N/A</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>N/A</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Rate of grade 3-5 adverse events, graded according to National Cancer Institute Common Terminology Criteria for Adverse Events version 4.03</measure>
    <time_frame>Up to 12 months after surgery</time_frame>
    <description>Treatment related toxicities will be assessed and recorded for each patient receiving treatment.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Rates of perioperative complications including blood loss, days in the intensive care unit, and operative time</measure>
    <time_frame>Up to 12 months after surgery</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Feasibility, determined by the number of patients who are able to complete wedge resection as well as receive the full dose of stereotactic radiosurgery</measure>
    <time_frame>Up to 12 months after surgery</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>Pathologic response rates</measure>
    <time_frame>Up to 12 months after surgery</time_frame>
    <description>The pathologic response rates will be determined by measuring the percent of viable cells in the resected specimen. Associations (e.g. between pathologic response rates and DP-CT, fludeoxyglucose [FDG] uptake, DNA methylation, and CTC levels) will be displayed visually with scatterplots or contingency tables and appropriate measure of association (Wilcoxon test, Fisher's exact test, Spearman correlation coefficient, and McNemar's test).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Quality of life assessment</measure>
    <time_frame>Up to 12 months after surgery</time_frame>
    <description>Quality of life assessments will be summarized over time with descriptive statistics.</description>
  </secondary_outcome>
  <other_outcome>
    <measure>Imaging characteristics that may predict response based on DP-CT and PET-CT scans</measure>
    <time_frame>Up to 30 days after stereotactic radiosurgery</time_frame>
    <description>Associations (e.g. between pathologic response rates and DP-CT, FDG uptake, DNA methylation, and CTC levels) will be displayed visually with scatterplots or contingency tables and appropriate measure of association (Wilcoxon test, Fisher's exact test, Spearman correlation coefficient, and McNemar's test).</description>
  </other_outcome>
  <other_outcome>
    <measure>Changes in perfusion using DP-CT scans</measure>
    <time_frame>Baseline to up to 30 days after stereotactic radiosurgery</time_frame>
    <description>Changes in DP-CT will be compared between pre- and post-stereotactic radiosurgery scans to determine if changes in perfusion correlates with pathologic response. Associations (e.g. between pathologic response rates and DP-CT, FDG uptake, DNA methylation, and CTC levels) will be displayed visually with scatterplots or contingency tables and appropriate measure of association (Wilcoxon test, Fisher's exact test, Spearman correlation coefficient, and McNemar's test).</description>
  </other_outcome>
  <other_outcome>
    <measure>Changes in FDG uptake</measure>
    <time_frame>Baseline to up to 12 months after surgery</time_frame>
    <description>Changes in FDG uptake will be compared between pre- and post-SBRT scans to determine if changes in FDG uptake correlates with pathologic response. Associations (e.g. between pathologic response rates and DP-CT, FDG uptake, DNA methylation, and CTC levels) will be displayed visually with scatterplots or contingency tables and appropriate measure of association (Wilcoxon test, Fisher's exact test, Spearman correlation coefficient, and McNemar's test).</description>
  </other_outcome>
  <other_outcome>
    <measure>Changes in DNA methylation analysis</measure>
    <time_frame>Baseline to up to 12 months after surgery</time_frame>
    <description>The amount of DNA methylation in the blood as well as relative changes in counts will be correlated with pathologic outcomes. DNA methylation will be summarized over time with descriptive statistics. Associations (e.g. between pathologic response rates and DP-CT, FDG uptake, DNA methylation, and CTC levels) will be displayed visually with scatterplots or contingency tables and appropriate measure of association (Wilcoxon test, Fisher's exact test, Spearman correlation coefficient, and McNemar's test).</description>
  </other_outcome>
  <other_outcome>
    <measure>Changes in CTC levels</measure>
    <time_frame>Baseline to up to 12 months after surgery</time_frame>
    <description>The amount of CTC in the blood as well as relative changes in counts will be correlated with pathologic outcomes. CTC levels will be summarized over time with descriptive statistics. Associations (e.g. between pathologic response rates and DP-CT, FDG uptake, DNA methylation, and CTC levels) will be displayed visually with scatterplots or contingency tables and appropriate measure of association (Wilcoxon test, Fisher's exact test, Spearman correlation coefficient, and McNemar's test).</description>
  </other_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">0</enrollment>
  <condition>Recurrent Non-small Cell Lung Cancer</condition>
  <condition>Stage IA Non-small Cell Lung Cancer</condition>
  <condition>Stage IB Non-small Cell Lung Cancer</condition>
  <arm_group>
    <arm_group_label>Treatment (stereotactic radiosurgery, wedge resection)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Patients undergo stereotactic radiosurgery every other day for 3 or 5 fractions (depending on the size tumor and proximity to the chest wall). Within 4-6 weeks after completion of stereotactic radiosurgery, patients undergo wedge resection.</description>
  </arm_group>
  <intervention>
    <intervention_type>Radiation</intervention_type>
    <intervention_name>stereotactic radiosurgery</intervention_name>
    <description>Undergo stereotactic radiosurgery</description>
    <arm_group_label>Treatment (stereotactic radiosurgery, wedge resection)</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Procedure</intervention_type>
    <intervention_name>therapeutic conventional surgery</intervention_name>
    <description>Undergo wedge resection</description>
    <arm_group_label>Treatment (stereotactic radiosurgery, wedge resection)</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>laboratory biomarker analysis</intervention_name>
    <description>Correlative studies</description>
    <arm_group_label>Treatment (stereotactic radiosurgery, wedge resection)</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>quality-of-life assessment</intervention_name>
    <description>Ancillary studies</description>
    <arm_group_label>Treatment (stereotactic radiosurgery, wedge resection)</arm_group_label>
    <other_name>quality of life assessment</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Eastern Cooperative Oncology Group (ECOG) performance status 0, 1, or 2&#xD;
&#xD;
          -  Biopsy proven non-small cell lung cancer&#xD;
&#xD;
          -  Maximum tumor dimension =&lt; 5 cm&#xD;
&#xD;
          -  No clinical evidence of N1, N2 or N3 lymph nodes as assessed by CT and/or PET-CT&#xD;
&#xD;
          -  No evidence of distant metastatic disease&#xD;
&#xD;
          -  Tumor verified by a thoracic surgeon to be in a location that will permit a sublobar&#xD;
             resection&#xD;
&#xD;
          -  Tumor located peripherally within the lung (peripheral defined as not touching any&#xD;
             surface within 2 cm of the proximal bronchial tree in all directions) and not touching&#xD;
             the mediastinal pleura&#xD;
&#xD;
          -  Pulmonary function tests (PFTs) with diffusing capacity of the lung for carbon&#xD;
             monoxide (DLCO) within 90 days prior to registration&#xD;
&#xD;
          -  Patient at high-risk of complications from lobectomy meeting a minimum of one major&#xD;
             criteria or two minor criteria as described below:&#xD;
&#xD;
               -  Major criteria&#xD;
&#xD;
                    -  Predicted postoperative forced expiratory volume in one second (FEV1) =&lt; 40%&#xD;
&#xD;
                    -  Predicted postoperative DLCO =&lt; 40%&#xD;
&#xD;
                    -  Age &gt;= 72&#xD;
&#xD;
               -  Minor criteria&#xD;
&#xD;
                    -  Predicted postoperative FEV1 41-60%&#xD;
&#xD;
                    -  Predicted postoperative DLCO 41-60%&#xD;
&#xD;
                    -  Pulmonary hypertension (defined by a pulmonary artery systolic pressure&#xD;
                       greater than 40 mm Hg) as estimated by echocardiography or right heart&#xD;
                       catheterization&#xD;
&#xD;
                    -  Poor left ventricular function (defined as an ejection fraction 40% or less)&#xD;
&#xD;
                    -  Resting or exercising arterial partial pressure of oxygen (pO2) =&lt; 55 mmHg&#xD;
                       or oxygen saturation (SpO2) =&lt; 88%&#xD;
&#xD;
                    -  Partial pressure of carbon monoxide (pCO2) &gt; 45 mm Hg&#xD;
&#xD;
                    -  Modified Medical Research Council Dyspnea Scale &gt;= 3&#xD;
&#xD;
          -  Women of child-bearing potential and men must agree to use adequate contraception&#xD;
             (hormonal or barrier method of birth control; abstinence) prior to study entry, for&#xD;
             the duration of study participation, and for 90 days following completion of therapy;&#xD;
             should a woman become pregnant or suspect she is pregnant while participating in this&#xD;
             study, she should inform her treating physician immediately&#xD;
&#xD;
               -  A female of child-bearing potential is any woman (regardless of sexual&#xD;
                  orientation, having undergone a tubal ligation, or remaining celibate by choice)&#xD;
                  who meets the following criteria:&#xD;
&#xD;
                    -  Has not undergone a hysterectomy or bilateral oophorectomy; or&#xD;
&#xD;
                    -  Has not been naturally postmenopausal for at least 12 consecutive months&#xD;
                       (i.e., has had menses at any time in the preceding 12 consecutive months)&#xD;
&#xD;
          -  Ability to understand and the willingness to sign a written informed consent&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Pregnant women&#xD;
&#xD;
          -  Patients with central tumors within the proximal tree or touching the mediastinal&#xD;
             pleura&#xD;
&#xD;
          -  Patients with evidence of distant metastatic disease&#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>Eugene Chung</last_name>
    <role>Principal Investigator</role>
    <affiliation>University of Southern California</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>USC Norris Comprehensive Cancer Center</name>
      <address>
        <city>Los Angeles</city>
        <state>California</state>
        <zip>90033</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>September 2015</verification_date>
  <study_first_submitted>September 23, 2014</study_first_submitted>
  <study_first_submitted_qc>September 23, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">September 26, 2014</study_first_posted>
  <last_update_submitted>September 14, 2015</last_update_submitted>
  <last_update_submitted_qc>September 14, 2015</last_update_submitted_qc>
  <last_update_posted type="Estimate">September 16, 2015</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>Lung Neoplasms</mesh_term>
    <mesh_term>Carcinoma, Non-Small-Cell Lung</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/NCT02250378
org study id: 2N-14-3
secondary id: NCI-2014-01916
secondary id: 2N-14-3
secondary id: P30CA014089
nct id: NCT02250378
lead sponsor: 
collaborator: 
has dmc: Yes
This pilot clinical trial studies the side effects and how well stereotactic radiosurgery
      followed by wedge resection works in treating patients with early stage non-small cell lung
      cancer that is located in the outer, or peripheral, areas of the lung. Stereotactic
      radiosurgery, also known as stereotactic body radiation therapy, is a specialized radiation
      therapy that delivers a single, high dose of radiation directly to the tumor and may kill
      more tumor cells and cause less damage to normal tissue. Wedge resection is a less invasive
      type of surgery for removal of the tumor and a small amount of normal tissue around it.
      Giving stereotactic radiosurgery followed by wedge resection may be a safe treatment option
      for patients who cannot receive standard treatment with lobectomy.
PRIMARY OBJECTIVES:

      I. To assess the safety and feasibility of a wedge resection following stereotactic body
      radiation therapy (SBRT) for early stage peripheral non-small cell lung cancer (NSCLC).

      SECONDARY OBJECTIVES:

      I. To assess pathologic response rates to SBRT as determined by pathologic examination of
      resected tumors.

      II. To prospectively assess patient quality of life when treated with SBRT and wedge
      resection.

      TERTIARY OBJECTIVES:

      I. To describe the location of viable tumor and to correlate pathologic response rates with
      radiation dose, size of tumor, and tumor histology.

      II. To correlate pathologic response rates and functional imaging with pre- and
      post-treatment dual-input perfusion (DP)-computed tomography (CT) and positron emission
      tomography (PET)-CT.

      III. To correlate changes in serum levels of deoxyribonucleic acid (DNA) methylation and
      circulating tumor cells (CTC) with pathologic response rates.

      OUTLINE:

      Patients undergo stereotactic radiosurgery every other day for 3 or 5 fractions (depending on
      the size tumor and proximity to the chest wall). Within 4-6 weeks after completion of
      stereotactic radiosurgery, patients undergo wedge resection.

      After completion of study treatment, patients are followed up at 1, 3, 6, and 12 months.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Rate of grade 3-5 adverse events, graded according to National Cancer Institute Common Terminology Criteria for Adverse Events version 4.03
time frame: Up to 12 months after surgery
description: Treatment related toxicities will be assessed and recorded for each patient receiving treatment.
measure: Rates of perioperative complications including blood loss, days in the intensive care unit, and operative time
time frame: Up to 12 months after surgery
measure: Feasibility, determined by the number of patients who are able to complete wedge resection as well as receive the full dose of stereotactic radiosurgery
time frame: Up to 12 months after surgery
measure: Pathologic response rates
time frame: Up to 12 months after surgery
description: The pathologic response rates will be determined by measuring the percent of viable cells in the resected specimen. Associations (e.g. between pathologic response rates and DP-CT, fludeoxyglucose [FDG] uptake, DNA methylation, and CTC levels) will be displayed visually with scatterplots or contingency tables and appropriate measure of association (Wilcoxon test, Fisher's exact test, Spearman correlation coefficient, and McNemar's test).
measure: Quality of life assessment
time frame: Up to 12 months after surgery
description: Quality of life assessments will be summarized over time with descriptive statistics.
measure: Imaging characteristics that may predict response based on DP-CT and PET-CT scans
time frame: Up to 30 days after stereotactic radiosurgery
description: Associations (e.g. between pathologic response rates and DP-CT, FDG uptake, DNA methylation, and CTC levels) will be displayed visually with scatterplots or contingency tables and appropriate measure of association (Wilcoxon test, Fisher's exact test, Spearman correlation coefficient, and McNemar's test).
measure: Changes in perfusion using DP-CT scans
time frame: Baseline to up to 30 days after stereotactic radiosurgery
description: Changes in DP-CT will be compared between pre- and post-stereotactic radiosurgery scans to determine if changes in perfusion correlates with pathologic response. Associations (e.g. between pathologic response rates and DP-CT, FDG uptake, DNA methylation, and CTC levels) will be displayed visually with scatterplots or contingency tables and appropriate measure of association (Wilcoxon test, Fisher's exact test, Spearman correlation coefficient, and McNemar's test).
measure: Changes in FDG uptake
time frame: Baseline to up to 12 months after surgery
description: Changes in FDG uptake will be compared between pre- and post-SBRT scans to determine if changes in FDG uptake correlates with pathologic response. Associations (e.g. between pathologic response rates and DP-CT, FDG uptake, DNA methylation, and CTC levels) will be displayed visually with scatterplots or contingency tables and appropriate measure of association (Wilcoxon test, Fisher's exact test, Spearman correlation coefficient, and McNemar's test).
measure: Changes in DNA methylation analysis
time frame: Baseline to up to 12 months after surgery
description: The amount of DNA methylation in the blood as well as relative changes in counts will be correlated with pathologic outcomes. DNA methylation will be summarized over time with descriptive statistics. Associations (e.g. between pathologic response rates and DP-CT, FDG uptake, DNA methylation, and CTC levels) will be displayed visually with scatterplots or contingency tables and appropriate measure of association (Wilcoxon test, Fisher's exact test, Spearman correlation coefficient, and McNemar's test).
measure: Changes in CTC levels
time frame: Baseline to up to 12 months after surgery
description: The amount of CTC in the blood as well as relative changes in counts will be correlated with pathologic outcomes. CTC levels will be summarized over time with descriptive statistics. Associations (e.g. between pathologic response rates and DP-CT, FDG uptake, DNA methylation, and CTC levels) will be displayed visually with scatterplots or contingency tables and appropriate measure of association (Wilcoxon test, Fisher's exact test, Spearman correlation coefficient, and McNemar's test).
arm group label: Treatment (stereotactic radiosurgery, wedge resection)
arm group type: Experimental
description: Patients undergo stereotactic radiosurgery every other day for 3 or 5 fractions (depending on the size tumor and proximity to the chest wall). Within 4-6 weeks after completion of stereotactic radiosurgery, patients undergo wedge resection.
intervention type: Radiation
intervention name: stereotactic radiosurgery
description: Undergo stereotactic radiosurgery
arm group label: Treatment (stereotactic radiosurgery, wedge resection)
intervention type: Procedure
intervention name: therapeutic conventional surgery
description: Undergo wedge resection
arm group label: Treatment (stereotactic radiosurgery, wedge resection)
intervention type: Other
intervention name: laboratory biomarker analysis
description: Correlative studies
arm group label: Treatment (stereotactic radiosurgery, wedge resection)
intervention type: Other
intervention name: quality-of-life assessment
description: Ancillary studies
arm group label: Treatment (stereotactic radiosurgery, wedge resection)
other name: quality of life assessment
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Eugene Chung
role: Principal Investigator
affiliation: University of Southern California
facility: 
country: United States
responsible party type: Sponsor
mesh term: Lung Neoplasms
mesh term: Carcinoma, Non-Small-Cell Lung