xml: <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/NCT06020066</url>
    </required_header>
    <id_info>
      <org_study_id>2306276-14</org_study_id>
      <nct_id>NCT06020066</nct_id>
    </id_info>
    <brief_title>SRS for NSCLC With Oligo-residual Intracranial Disease After First-line 3rd Generation EGFR-TKI</brief_title>
    <official_title>Stereotactic Radiotherapy for Non-small Cell Lung Cancer With Oligo-residual Intracranial Disease After First-line Third-generation EGFR Inhibitors: a Multicenter, Randomized Clinical Trial.</official_title>
    <sponsors>
      <lead_sponsor>
        <agency>Fudan University</agency>
        <agency_class>Other</agency_class>
      </lead_sponsor>
    </sponsors>
    <source>Fudan University</source>
    <oversight_info>
      <is_fda_regulated_drug>No</is_fda_regulated_drug>
      <is_fda_regulated_device>No</is_fda_regulated_device>
    </oversight_info>
    <brief_summary>
      <textblock>
        Despite the impressive response rate to third-generation EGFR-TKIs, resistance inevitably&#xD;
        develops in most patients. Stereotactic radiotherapy plays a growing role in the management&#xD;
        of patients with brain metastasis. This study aims to evaluate the efficacy and safety of&#xD;
        stereotactic radiotherapy for oligo-residual intracranial disease after first-line&#xD;
        third-generation EGFR Inhibitors.&#xD;
      </textblock>
    </brief_summary>
    <overall_status>Recruiting</overall_status>
    <start_date type="Actual">August 10, 2023</start_date>
    <completion_date type="Anticipated">August 10, 2029</completion_date>
    <primary_completion_date type="Anticipated">August 10, 2028</primary_completion_date>
    <phase>Phase 2</phase>
    <study_type>Interventional</study_type>
    <has_expanded_access>No</has_expanded_access>
    <study_design_info>
      <allocation>Randomized</allocation>
      <intervention_model>Parallel Assignment</intervention_model>
      <primary_purpose>Treatment</primary_purpose>
      <masking>None (Open Label)</masking>
    </study_design_info>
    <primary_outcome>
      <measure>Progression-free survival</measure>
      <time_frame>Two years</time_frame>
      <description>PFS was measured from the date of the initiation of EGFR-TKI to the date of disease progression as defined by Response Evaluation Criteria in Solid Tumor (RECIST) Version 1.1 or death</description>
    </primary_outcome>
    <secondary_outcome>
      <measure>Overall Survival</measure>
      <time_frame>Three years</time_frame>
      <description>OS was defined as the time from the date of the initiation of EGFR-TKI until death by any cause. Participants still alive at the time of data analysis were censored at the date of last follow-up.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Intracranial progression-free survival</measure>
      <time_frame>Two years</time_frame>
      <description>iPFS was defined as the time from the start of third-generation EGFR-TKI treatment to the occurrence of intracranial disease progression or death. If the subject first experiences extracranial disease progression (without concurrent intracranial disease progression), the date of first extracranial disease progression will be used as the cut-off date. For patients who have not progressed at the time of analysis, the date of their last contact will be used as the cut-off date.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Health-related quality of life per QLQ-C30</measure>
      <time_frame>Two years</time_frame>
      <description>Health-related quality of life was evaluated using the QLQ-C30 questionnaires to assess health-related quality of life.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Health-related quality of life per QLQ-LC13</measure>
      <time_frame>Two years</time_frame>
      <description>Health-related quality of life was evaluated using the QLQ-LC13 questionnaires to assess health-related quality of life.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Percentage of Participants With Adverse Events</measure>
      <time_frame>Two years</time_frame>
      <description>Treatment-related adverse events were assessed and graded according to CTCAE v. 5.0.</description>
    </secondary_outcome>
    <number_of_arms>2</number_of_arms>
    <enrollment type="Anticipated">202</enrollment>
    <condition>Brain Metastases</condition>
    <condition>Non-small Cell Lung Cancer</condition>
    <arm_group>
      <arm_group_label>3rd generation EGFR-TKI+SRS</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>The experimental arm will undergo stereotactic radiotherapy targeting all residual lesions in the brain (completed in a single or multiple treatment courses within one month), while continuing EGFR-TKI therapy until disease progression or intolerable toxicity occurs.</description>
    </arm_group>
    <arm_group>
      <arm_group_label>3rd generation EGFR-TKI</arm_group_label>
      <arm_group_type>Active Comparator</arm_group_type>
      <description>The control group will receive 3rd generation EGFR-TKI until disease progression or intolerable toxicity occurs.</description>
    </arm_group>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>EGFR-TK Inhibitor</intervention_name>
      <description>Patients will receive EGFR-TKI until confirmed progression or unacceptable toxicity.</description>
      <arm_group_label>3rd generation EGFR-TKI</arm_group_label>
      <arm_group_label>3rd generation EGFR-TKI+SRS</arm_group_label>
    </intervention>
    <intervention>
      <intervention_type>Radiation</intervention_type>
      <intervention_name>Stereotactic radiotherapy</intervention_name>
      <description>Patients with oligo-residual intracranial disease after treatment with EGFR-TKI will be treated with SRS of all intracranial lesions. The choice of dose-fractionation regimen is at the discretion of the treating radiation oncologist.</description>
      <arm_group_label>3rd generation EGFR-TKI+SRS</arm_group_label>
    </intervention>
    <eligibility>
      <criteria>
        <textblock>
          Inclusion Criteria:&#xD;
  &#xD;
            -  Pathologically confirmed non-small cell lung cancer;&#xD;
  &#xD;
            -  Clinical stage IV (AJCC, 8th edition, 2017);&#xD;
  &#xD;
            -  EGFR mutations: EGFR L858R, EGFR exon 19 deletion;&#xD;
  &#xD;
            -  Age ≥18 years;&#xD;
  &#xD;
            -  KPS score ≥70;&#xD;
  &#xD;
            -  Brain metastasis at the time of diagnosis;&#xD;
  &#xD;
            -  Complete baseline imaging assessment of metastatic lesions, including enhanced MRI for&#xD;
               brain;&#xD;
  &#xD;
            -  Receiving first-line treatment with third-generation EGFR inhibitors;&#xD;
  &#xD;
            -  After 3-6 months of third-generation EGFR inhibitor treatment, imaging review&#xD;
               indicates no progression of extracranial lesions, and brain lesions are evaluated by&#xD;
               thin-layer (1mm layer) enhanced MRI, meeting the following criteria:&#xD;
  &#xD;
                 -  No more than 10 remaining brain lesions;&#xD;
  &#xD;
                      -  The maximum diameter of the remaining brain lesions does not exceed 3cm;&#xD;
  &#xD;
                           -  At least one remaining brain lesion has a diameter greater than 5mm;&#xD;
  &#xD;
                                -  After evaluation by the researcher, all remaining brain lesions&#xD;
                                   are suitable for stereotactic radiotherapy.&#xD;
  &#xD;
            -  Patient informed consent.&#xD;
  &#xD;
          Exclusion Criteria:&#xD;
  &#xD;
            -  Poor compliance with the study protocol in the investigator's opinion;&#xD;
  &#xD;
            -  Patients withdrew their informed consent and requested to withdraw from the study;&#xD;
  &#xD;
            -  Patients were unable to receive regular doses of third-generation EGFR inhibitors due&#xD;
               to other underlying conditions, viral side effects, economic factors, etc. (e.g.,&#xD;
               continuous discontinuation for more than 1 week, cumulative discontinuation for more&#xD;
               than 2 weeks).&#xD;
  &#xD;
            -  Patients did not follow the protocol for follow-up visits as required by this study.&#xD;
        </textblock>
      </criteria>
      <gender>All</gender>
      <minimum_age>18 Years</minimum_age>
      <maximum_age>75 Years</maximum_age>
      <healthy_volunteers>No</healthy_volunteers>
    </eligibility>
    <overall_official>
      <last_name>Zhengfei Zhu, MD</last_name>
      <role>Principal Investigator</role>
      <affiliation>Fudan University</affiliation>
    </overall_official>
    <overall_official>
      <last_name>Xuwei Cai</last_name>
      <role>Principal Investigator</role>
      <affiliation>Shanghai Chest Hospital</affiliation>
    </overall_official>
    <overall_official>
      <last_name>Qian Chu</last_name>
      <role>Principal Investigator</role>
      <affiliation>Tongji Hospital</affiliation>
    </overall_official>
    <overall_official>
      <last_name>Xiaorong Dong</last_name>
      <role>Principal Investigator</role>
      <affiliation>Wuhan Union Hospital, China</affiliation>
    </overall_official>
    <overall_official>
      <last_name>Lin Wu</last_name>
      <role>Principal Investigator</role>
      <affiliation>Hunan Cancer Hospital</affiliation>
    </overall_official>
    <overall_official>
      <last_name>Rongrong Zhou</last_name>
      <role>Principal Investigator</role>
      <affiliation>Xiangya Hospital of Central South University</affiliation>
    </overall_official>
    <overall_official>
      <last_name>Guang Han</last_name>
      <role>Principal Investigator</role>
      <affiliation>Hubei Cancer Hospital</affiliation>
    </overall_official>
    <overall_official>
      <last_name>Hui Zhu</last_name>
      <role>Principal Investigator</role>
      <affiliation>Shandong Cancer Hospital and Institute</affiliation>
    </overall_official>
    <overall_official>
      <last_name>Jinjun Ye</last_name>
      <role>Principal Investigator</role>
      <affiliation>Jiangsu Cancer Institute &amp; Hospital</affiliation>
    </overall_official>
    <overall_official>
      <last_name>Xiaojia Cui</last_name>
      <role>Principal Investigator</role>
      <affiliation>The Affiliated Tumor Hospital of Nantong University, Nantong, Jiangsu Province, China</affiliation>
    </overall_official>
    <overall_official>
      <last_name>Guomei Tai</last_name>
      <role>Principal Investigator</role>
      <affiliation>The Affiliated Tumor Hospital of Nantong University, Nantong, Jiangsu Province, China</affiliation>
    </overall_official>
    <overall_official>
      <last_name>Zhiyong Yuan</last_name>
      <role>Principal Investigator</role>
      <affiliation>Tianjin Medical University Cancer Institute and Hospital</affiliation>
    </overall_official>
    <overall_official>
      <last_name>Dejun XIng</last_name>
      <role>Principal Investigator</role>
      <affiliation>Jilin Provincial Tumor Hospital</affiliation>
    </overall_official>
    <overall_official>
      <last_name>Jichen Ren</last_name>
      <role>Principal Investigator</role>
      <affiliation>Jilin Provincial Tumor Hospital</affiliation>
    </overall_official>
    <overall_official>
      <last_name>Jiancheng Li</last_name>
      <role>Principal Investigator</role>
      <affiliation>Fujian Medical University Cancer Hospital</affiliation>
    </overall_official>
    <overall_official>
      <last_name>Yanyang Wang</last_name>
      <role>Principal Investigator</role>
      <affiliation>General Hospital of Ningxia Medical University</affiliation>
    </overall_official>
    <overall_official>
      <last_name>Chuangzhou Rao</last_name>
      <role>Principal Investigator</role>
      <affiliation>Ningbo No.2 Hospital</affiliation>
    </overall_official>
    <overall_official>
      <last_name>Bing Lu</last_name>
      <role>Principal Investigator</role>
      <affiliation>The Affiliated Hospital Of Guizhou Medical University</affiliation>
    </overall_official>
    <overall_official>
      <last_name>Zhongyi Dong</last_name>
      <role>Principal Investigator</role>
      <affiliation>Nanfang Hospital, Southern Medical University</affiliation>
    </overall_official>
    <overall_official>
      <last_name>Jiwei Liu</last_name>
      <role>Principal Investigator</role>
      <affiliation>The First Affiliated Hospital of Dalian Medical University</affiliation>
    </overall_official>
    <overall_official>
      <last_name>Zhenzhou Yang</last_name>
      <role>Principal Investigator</role>
      <affiliation>The Second Affiliated Hospital of Chongqing Medical University</affiliation>
    </overall_official>
    <overall_official>
      <last_name>Hongqing Zhuang</last_name>
      <role>Principal Investigator</role>
      <affiliation>Peking University Third Hospital</affiliation>
    </overall_official>
    <overall_official>
      <last_name>Anwen Liu</last_name>
      <role>Principal Investigator</role>
      <affiliation>Nanchang University Second Affiliated Hospital</affiliation>
    </overall_official>
    <overall_official>
      <last_name>Haihua Yang</last_name>
      <role>Principal Investigator</role>
      <affiliation>Taizhou Hospital Affiliated to Wenzhou Medical University</affiliation>
    </overall_official>
    <overall_official>
      <last_name>Fang Liu</last_name>
      <role>Principal Investigator</role>
      <affiliation>Chinese PLA General Hospital</affiliation>
    </overall_official>
    <overall_official>
      <last_name>Yong Mao</last_name>
      <role>Principal Investigator</role>
      <affiliation>Affiliated Hospital of Jiangnan University</affiliation>
    </overall_official>
    <overall_contact>
      <last_name>Zhengfei Zhu</last_name>
      <phone>+8618017312901</phone>
      <email>fuscczzf@163.com</email>
    </overall_contact>
    <location>
      <facility>
        <name>Fudan University Shanghai Cancer Center</name>
        <address>
          <city>Shanghai</city>
          <state>Shanghai</state>
          <zip>200030</zip>
          <country>China</country>
        </address>
      </facility>
      <status>Recruiting</status>
      <contact>
        <last_name>Zhengfei Zhu, MD</last_name>
        <phone>+8618017312901</phone>
        <email>fuscczzf@163.com</email>
      </contact>
      <contact_backup>
        <last_name>Jianjiao Ni, MD</last_name>
        <email>nijianjiao8@sina.com</email>
      </contact_backup>
    </location>
    <location_countries>
      <country>China</country>
    </location_countries>
    <verification_date>August 2023</verification_date>
    <study_first_submitted>August 18, 2023</study_first_submitted>
    <study_first_submitted_qc>August 27, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">August 31, 2023</study_first_posted>
    <last_update_submitted>August 27, 2023</last_update_submitted>
    <last_update_submitted_qc>August 27, 2023</last_update_submitted_qc>
    <last_update_posted type="Actual">August 31, 2023</last_update_posted>
    <responsible_party>
      <responsible_party_type>Principal Investigator</responsible_party_type>
      <investigator_affiliation>Fudan University</investigator_affiliation>
      <investigator_full_name>Zhengfei Zhu</investigator_full_name>
      <investigator_title>Professor</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>
      <mesh_term>Brain Neoplasms</mesh_term>
    </condition_browse>
    <!-- Results have not yet been posted for this study                                          -->
  </clinical_study>
  
  
text: 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/NCT06020066
  org study id: 2306276-14
  nct id: NCT06020066
  lead sponsor: 
  is fda regulated drug: No
  is fda regulated device: No
  Despite the impressive response rate to third-generation EGFR-TKIs, resistance inevitably
        develops in most patients. Stereotactic radiotherapy plays a growing role in the management
        of patients with brain metastasis. This study aims to evaluate the efficacy and safety of
        stereotactic radiotherapy for oligo-residual intracranial disease after first-line
        third-generation EGFR Inhibitors.
  allocation: Randomized
  intervention model: Parallel Assignment
  primary purpose: Treatment
  masking: None (Open Label)
  measure: Progression-free survival
  time frame: Two years
  description: PFS was measured from the date of the initiation of EGFR-TKI to the date of disease progression as defined by Response Evaluation Criteria in Solid Tumor (RECIST) Version 1.1 or death
  measure: Overall Survival
  time frame: Three years
  description: OS was defined as the time from the date of the initiation of EGFR-TKI until death by any cause. Participants still alive at the time of data analysis were censored at the date of last follow-up.
  measure: Intracranial progression-free survival
  time frame: Two years
  description: iPFS was defined as the time from the start of third-generation EGFR-TKI treatment to the occurrence of intracranial disease progression or death. If the subject first experiences extracranial disease progression (without concurrent intracranial disease progression), the date of first extracranial disease progression will be used as the cut-off date. For patients who have not progressed at the time of analysis, the date of their last contact will be used as the cut-off date.
  measure: Health-related quality of life per QLQ-C30
  time frame: Two years
  description: Health-related quality of life was evaluated using the QLQ-C30 questionnaires to assess health-related quality of life.
  measure: Health-related quality of life per QLQ-LC13
  time frame: Two years
  description: Health-related quality of life was evaluated using the QLQ-LC13 questionnaires to assess health-related quality of life.
  measure: Percentage of Participants With Adverse Events
  time frame: Two years
  description: Treatment-related adverse events were assessed and graded according to CTCAE v. 5.0.
  arm group label: 3rd generation EGFR-TKI+SRS
  arm group type: Experimental
  description: The experimental arm will undergo stereotactic radiotherapy targeting all residual lesions in the brain (completed in a single or multiple treatment courses within one month), while continuing EGFR-TKI therapy until disease progression or intolerable toxicity occurs.
  arm group label: 3rd generation EGFR-TKI
  arm group type: Active Comparator
  description: The control group will receive 3rd generation EGFR-TKI until disease progression or intolerable toxicity occurs.
  intervention type: Drug
  intervention name: EGFR-TK Inhibitor
  description: Patients will receive EGFR-TKI until confirmed progression or unacceptable toxicity.
  arm group label: 3rd generation EGFR-TKI
  arm group label: 3rd generation EGFR-TKI+SRS
  intervention type: Radiation
  intervention name: Stereotactic radiotherapy
  description: Patients with oligo-residual intracranial disease after treatment with EGFR-TKI will be treated with SRS of all intracranial lesions. The choice of dose-fractionation regimen is at the discretion of the treating radiation oncologist.
  arm group label: 3rd generation EGFR-TKI+SRS
  criteria: 
  gender: All
  minimum age: 18 Years
  maximum age: 75 Years
  healthy volunteers: No
  last name: Zhengfei Zhu, MD
  role: Principal Investigator
  affiliation: Fudan University
  last name: Xuwei Cai
  role: Principal Investigator
  affiliation: Shanghai Chest Hospital
  last name: Qian Chu
  role: Principal Investigator
  affiliation: Tongji Hospital
  last name: Xiaorong Dong
  role: Principal Investigator
  affiliation: Wuhan Union Hospital, China
  last name: Lin Wu
  role: Principal Investigator
  affiliation: Hunan Cancer Hospital
  last name: Rongrong Zhou
  role: Principal Investigator
  affiliation: Xiangya Hospital of Central South University
  last name: Guang Han
  role: Principal Investigator
  affiliation: Hubei Cancer Hospital
  last name: Hui Zhu
  role: Principal Investigator
  affiliation: Shandong Cancer Hospital and Institute
  last name: Jinjun Ye
  role: Principal Investigator
  affiliation: Jiangsu Cancer Institute & Hospital
  last name: Xiaojia Cui
  role: Principal Investigator
  affiliation: The Affiliated Tumor Hospital of Nantong University, Nantong, Jiangsu Province, China
  last name: Guomei Tai
  role: Principal Investigator
  affiliation: The Affiliated Tumor Hospital of Nantong University, Nantong, Jiangsu Province, China
  last name: Zhiyong Yuan
  role: Principal Investigator
  affiliation: Tianjin Medical University Cancer Institute and Hospital
  last name: Dejun XIng
  role: Principal Investigator
  affiliation: Jilin Provincial Tumor Hospital
  last name: Jichen Ren
  role: Principal Investigator
  affiliation: Jilin Provincial Tumor Hospital
  last name: Jiancheng Li
  role: Principal Investigator
  affiliation: Fujian Medical University Cancer Hospital
  last name: Yanyang Wang
  role: Principal Investigator
  affiliation: General Hospital of Ningxia Medical University
  last name: Chuangzhou Rao
  role: Principal Investigator
  affiliation: Ningbo No.2 Hospital
  last name: Bing Lu
  role: Principal Investigator
  affiliation: The Affiliated Hospital Of Guizhou Medical University
  last name: Zhongyi Dong
  role: Principal Investigator
  affiliation: Nanfang Hospital, Southern Medical University
  last name: Jiwei Liu
  role: Principal Investigator
  affiliation: The First Affiliated Hospital of Dalian Medical University
  last name: Zhenzhou Yang
  role: Principal Investigator
  affiliation: The Second Affiliated Hospital of Chongqing Medical University
  last name: Hongqing Zhuang
  role: Principal Investigator
  affiliation: Peking University Third Hospital
  last name: Anwen Liu
  role: Principal Investigator
  affiliation: Nanchang University Second Affiliated Hospital
  last name: Haihua Yang
  role: Principal Investigator
  affiliation: Taizhou Hospital Affiliated to Wenzhou Medical University
  last name: Fang Liu
  role: Principal Investigator
  affiliation: Chinese PLA General Hospital
  last name: Yong Mao
  role: Principal Investigator
  affiliation: Affiliated Hospital of Jiangnan University
  last name: Zhengfei Zhu
  phone: +8618017312901
  email: fuscczzf@163.com
  facility: 
  status: Recruiting
  contact: 
  contact backup: 
  country: China
  responsible party type: Principal Investigator
  investigator affiliation: Fudan University
  investigator full name: Zhengfei Zhu
  investigator title: Professor
  mesh term: Lung Neoplasms
  mesh term: Carcinoma, Non-Small-Cell Lung
  mesh term: Brain Neoplasms