<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/NCT01711697</url>
  </required_header>
  <id_info>
    <org_study_id>IRB00056552</org_study_id>
    <secondary_id>NCI-2012-01934</secondary_id>
    <secondary_id>RAD2179-12</secondary_id>
    <nct_id>NCT01711697</nct_id>
  </id_info>
  <brief_title>An Alternative Radiation Fractionation Strategy for Locally Advanced Non-Small Cell Lung Cancer (NSCLC)</brief_title>
  <official_title>An Alternative Radiation Fractionation Strategy for Locally Advanced Non-Small Cell Lung Cancer (NSCLC)</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Emory University</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Washington University Siteman Cancer Center</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Emory University</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      This phase I trial studies the best dose of radiation therapy in treating patients with&#xD;
      locally advanced non-small cell lung cancer that cannot be removed by surgery. Radiation&#xD;
      therapy uses high energy x rays to kill tumor cells. Specialized radiation therapy, such as&#xD;
      stereotactic body radiation therapy (SBRT), that delivers a high dose of radiation directly&#xD;
      to the tumor may kill more tumor cells and cause less damage to normal tissue. SBRT has been&#xD;
      shown to provide excellent results when used in early stage lung cancer, but has not yet been&#xD;
      applied to patients with more advanced disease.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      PRIMARY OBJECTIVE:&#xD;
&#xD;
      To test the safety and tolerability of an alternative fractionation regimen in locally&#xD;
      advanced non-small cell lung cancer (NSCLC), consisting of 44 Gy with concurrent chemotherapy&#xD;
      followed by a stereotactic body radiation therapy (SBRT) boost to remaining parenchymal and&#xD;
      nodal disease. The maximum tolerated dose of the SBRT boost will be determined.&#xD;
&#xD;
      SECONDARY OBJECTIVES:&#xD;
&#xD;
        1. To assess local control.&#xD;
&#xD;
        2. To assess distant metastasis and patterns of failure.&#xD;
&#xD;
        3. To assess overall survival at 1 and 2 years.&#xD;
&#xD;
      OUTLINE: This is a dose-escalation study of radiation therapy and SBRT.&#xD;
&#xD;
      Patients undergo radiation therapy daily and receive carboplatin and paclitaxel weekly for&#xD;
      4.5 weeks. Patients then undergo 2 boost SBRT treatments 2-3 days apart.&#xD;
&#xD;
      After completion of study treatment, patients are followed up for 5 years.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Active, not recruiting</last_known_status>
  <start_date type="Actual">September 4, 2012</start_date>
  <completion_date type="Anticipated">May 31, 2022</completion_date>
  <primary_completion_date type="Anticipated">May 31, 2022</primary_completion_date>
  <phase>Phase 1</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>Maximum tolerated dose (MTD) defined to be the dose level that results in a probability equal to 0.33 that a dose limiting toxicity (DLT) will be manifest using Common Terminology Criteria for Adverse Events (CTCAE) version 4 (v.4)</measure>
    <time_frame>Up to 1 year</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Acute toxicities associated with this regimen using CTCAE v.4</measure>
    <time_frame>Up to 90 days</time_frame>
    <description>Crude rates of grade 3 and greater acute toxicities will be reported.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Late toxicities associated with this regimen using CTCAE v.4</measure>
    <time_frame>After 90 days</time_frame>
    <description>Crude rates of grade 3 and greater late toxicities will be reported.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Local control</measure>
    <time_frame>Up to 5 years</time_frame>
    <description>Will be calculated for the entire cohort using Kaplan-Meier methodology.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Distant metastasis</measure>
    <time_frame>Up to 5 years</time_frame>
    <description>Will be calculated for the entire cohort using Kaplan-Meier methodology.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Patterns of failure</measure>
    <time_frame>Up to 5 years</time_frame>
    <description>Will be assessed with standard follow-up imaging, and the percentages of in-field failures versus regional nodal failures calculated.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Overall survival</measure>
    <time_frame>At 1 year</time_frame>
    <description>Will be calculated for the entire cohort using Kaplan-Meier methodology.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Overall survival</measure>
    <time_frame>At 2 years</time_frame>
    <description>Will be calculated for the entire cohort using Kaplan-Meier methodology.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Overall survival</measure>
    <time_frame>At 5 years</time_frame>
    <description>Will be calculated for the entire cohort using Kaplan-Meier methodology.</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">16</enrollment>
  <condition>Stage IIA Non-small Cell Lung Cancer</condition>
  <condition>Stage IIB Non-small Cell Lung Cancer</condition>
  <condition>Stage IIIA Non-small Cell Lung Cancer</condition>
  <condition>Stage IIIB Non-small Cell Lung Cancer</condition>
  <arm_group>
    <arm_group_label>Treatment (radiation therapy, carboplatin, paclitaxel, SBRT)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Patients undergo radiation therapy daily and receive carboplatin and paclitaxel weekly for 4.5 weeks. Patients then undergo 2 boost SBRT treatments 2-3 days apart.</description>
  </arm_group>
  <intervention>
    <intervention_type>Radiation</intervention_type>
    <intervention_name>stereotactic body radiation therapy</intervention_name>
    <description>Undergo SBRT</description>
    <arm_group_label>Treatment (radiation therapy, carboplatin, paclitaxel, SBRT)</arm_group_label>
    <other_name>SBRT</other_name>
    <other_name>stereotactic radiation therapy</other_name>
    <other_name>stereotactic radiotherapy</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>carboplatin</intervention_name>
    <arm_group_label>Treatment (radiation therapy, carboplatin, paclitaxel, SBRT)</arm_group_label>
    <other_name>Carboplat</other_name>
    <other_name>CBDCA</other_name>
    <other_name>JM-8</other_name>
    <other_name>Paraplat</other_name>
    <other_name>Paraplatin</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>paclitaxel</intervention_name>
    <arm_group_label>Treatment (radiation therapy, carboplatin, paclitaxel, SBRT)</arm_group_label>
    <other_name>Anzatax</other_name>
    <other_name>Asotax</other_name>
    <other_name>TAX</other_name>
    <other_name>Taxol</other_name>
  </intervention>
  <intervention>
    <intervention_type>Radiation</intervention_type>
    <intervention_name>radiation therapy</intervention_name>
    <description>Undergo radiation therapy</description>
    <arm_group_label>Treatment (radiation therapy, carboplatin, paclitaxel, SBRT)</arm_group_label>
    <other_name>irradiation</other_name>
    <other_name>radiotherapy</other_name>
    <other_name>therapy, radiation</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Biopsy proven NSCLC, within 8 weeks prior to patient registration&#xD;
&#xD;
          -  Unresectable disease&#xD;
&#xD;
          -  Clinical stage Tx, T1-T4, N1-3, M0&#xD;
&#xD;
          -  Karnofsky performance status (KPS) ≥ 70&#xD;
&#xD;
          -  Pretreatment positron emission tomography (PET) CT scan to rule out metastatic disease&#xD;
&#xD;
               -  The primary tumor may not be larger than 8 cm in maximum dimension&#xD;
&#xD;
               -  If the primary tumor is central in location, defined as within 2 cm from the&#xD;
                  tracheobronchial tree, it must be no larger than 5 cm&#xD;
&#xD;
               -  Mediastinal and hilar lymphadenopathy can be no larger than 5 cm at any nodal&#xD;
                  station&#xD;
&#xD;
          -  Pretreatment brain CT with contrast or brain MRI to rule out metastases&#xD;
&#xD;
          -  Pathologic assessment of the mediastinum to document involved nodal stations&#xD;
&#xD;
          -  All of the above inclusion criteria must occur within 8 weeks prior to patient&#xD;
             registration, with the exception of pathologic assessment of the mediastinum and&#xD;
             biopsy to confirm NSCLC, which can be done within 12 weeks of patient registration&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Prior history of lung cancer&#xD;
&#xD;
          -  Pregnancy&#xD;
&#xD;
          -  Prior history of radiation to the chest&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>80 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Kristin Higgins, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Emory University</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Grady Health System</name>
      <address>
        <city>Atlanta</city>
        <state>Georgia</state>
        <zip>30303</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Emory University Hospital Midtown</name>
      <address>
        <city>Atlanta</city>
        <state>Georgia</state>
        <zip>30308</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Emory University Winship Cancer Institute</name>
      <address>
        <city>Atlanta</city>
        <state>Georgia</state>
        <zip>30322</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Siteman Cancer Center - Washington University</name>
      <address>
        <city>Saint Louis</city>
        <state>Missouri</state>
        <zip>63110</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>June 2021</verification_date>
  <study_first_submitted>October 18, 2012</study_first_submitted>
  <study_first_submitted_qc>October 18, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">October 22, 2012</study_first_posted>
  <last_update_submitted>June 22, 2021</last_update_submitted>
  <last_update_submitted_qc>June 22, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">June 23, 2021</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Emory University</investigator_affiliation>
    <investigator_full_name>Kristin Higgins, MD</investigator_full_name>
    <investigator_title>Principal Investigator</investigator_title>
  </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>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Paclitaxel</mesh_term>
    <mesh_term>Carboplatin</mesh_term>
  </intervention_browse>
  <pending_results>
    <submitted>July 19, 2022</submitted>
    <returned>May 31, 2023</returned>
    <submitted>August 4, 2023</submitted>
  </pending_results>
  <!-- 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/NCT01711697
org study id: IRB00056552
secondary id: NCI-2012-01934
secondary id: RAD2179-12
nct id: NCT01711697
lead sponsor: 
collaborator: 
has dmc: Yes
This phase I trial studies the best dose of radiation therapy in treating patients with
      locally advanced non-small cell lung cancer that cannot be removed by surgery. Radiation
      therapy uses high energy x rays to kill tumor cells. Specialized radiation therapy, such as
      stereotactic body radiation therapy (SBRT), that delivers a high dose of radiation directly
      to the tumor may kill more tumor cells and cause less damage to normal tissue. SBRT has been
      shown to provide excellent results when used in early stage lung cancer, but has not yet been
      applied to patients with more advanced disease.
PRIMARY OBJECTIVE:

      To test the safety and tolerability of an alternative fractionation regimen in locally
      advanced non-small cell lung cancer (NSCLC), consisting of 44 Gy with concurrent chemotherapy
      followed by a stereotactic body radiation therapy (SBRT) boost to remaining parenchymal and
      nodal disease. The maximum tolerated dose of the SBRT boost will be determined.

      SECONDARY OBJECTIVES:

        1. To assess local control.

        2. To assess distant metastasis and patterns of failure.

        3. To assess overall survival at 1 and 2 years.

      OUTLINE: This is a dose-escalation study of radiation therapy and SBRT.

      Patients undergo radiation therapy daily and receive carboplatin and paclitaxel weekly for
      4.5 weeks. Patients then undergo 2 boost SBRT treatments 2-3 days apart.

      After completion of study treatment, patients are followed up for 5 years.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Maximum tolerated dose (MTD) defined to be the dose level that results in a probability equal to 0.33 that a dose limiting toxicity (DLT) will be manifest using Common Terminology Criteria for Adverse Events (CTCAE) version 4 (v.4)
time frame: Up to 1 year
measure: Acute toxicities associated with this regimen using CTCAE v.4
time frame: Up to 90 days
description: Crude rates of grade 3 and greater acute toxicities will be reported.
measure: Late toxicities associated with this regimen using CTCAE v.4
time frame: After 90 days
description: Crude rates of grade 3 and greater late toxicities will be reported.
measure: Local control
time frame: Up to 5 years
description: Will be calculated for the entire cohort using Kaplan-Meier methodology.
measure: Distant metastasis
time frame: Up to 5 years
description: Will be calculated for the entire cohort using Kaplan-Meier methodology.
measure: Patterns of failure
time frame: Up to 5 years
description: Will be assessed with standard follow-up imaging, and the percentages of in-field failures versus regional nodal failures calculated.
measure: Overall survival
time frame: At 1 year
description: Will be calculated for the entire cohort using Kaplan-Meier methodology.
measure: Overall survival
time frame: At 2 years
description: Will be calculated for the entire cohort using Kaplan-Meier methodology.
measure: Overall survival
time frame: At 5 years
description: Will be calculated for the entire cohort using Kaplan-Meier methodology.
arm group label: Treatment (radiation therapy, carboplatin, paclitaxel, SBRT)
arm group type: Experimental
description: Patients undergo radiation therapy daily and receive carboplatin and paclitaxel weekly for 4.5 weeks. Patients then undergo 2 boost SBRT treatments 2-3 days apart.
intervention type: Radiation
intervention name: stereotactic body radiation therapy
description: Undergo SBRT
arm group label: Treatment (radiation therapy, carboplatin, paclitaxel, SBRT)
other name: SBRT
other name: stereotactic radiation therapy
other name: stereotactic radiotherapy
intervention type: Drug
intervention name: carboplatin
arm group label: Treatment (radiation therapy, carboplatin, paclitaxel, SBRT)
other name: Carboplat
other name: CBDCA
other name: JM-8
other name: Paraplat
other name: Paraplatin
intervention type: Drug
intervention name: paclitaxel
arm group label: Treatment (radiation therapy, carboplatin, paclitaxel, SBRT)
other name: Anzatax
other name: Asotax
other name: TAX
other name: Taxol
intervention type: Radiation
intervention name: radiation therapy
description: Undergo radiation therapy
arm group label: Treatment (radiation therapy, carboplatin, paclitaxel, SBRT)
other name: irradiation
other name: radiotherapy
other name: therapy, radiation
criteria: 
gender: All
minimum age: 18 Years
maximum age: 80 Years
healthy volunteers: No
last name: Kristin Higgins, MD
role: Principal Investigator
affiliation: Emory University
facility: 
facility: 
facility: 
facility: 
country: United States
responsible party type: Principal Investigator
investigator affiliation: Emory University
investigator full name: Kristin Higgins, MD
investigator title: Principal Investigator
mesh term: Lung Neoplasms
mesh term: Carcinoma, Non-Small-Cell Lung
mesh term: Paclitaxel
mesh term: Carboplatin
submitted: July 19, 2022
returned: May 31, 2023
submitted: August 4, 2023