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/NCT06014450</url>
    </required_header>
    <id_info>
      <org_study_id>PCI for stage IV NSCLC</org_study_id>
      <nct_id>NCT06014450</nct_id>
    </id_info>
    <brief_title>Prophylactic Cranial Irradiation Versus Observation in Stage IV NSCLC Randomized Controlled Clinical Study</brief_title>
    <official_title>Department of Oncology, Affiliated Hospital of Guizhou Medical University Affiliated Cancer Hospital of Guizhou Medical University</official_title>
    <sponsors>
      <lead_sponsor>
        <agency>Guizhou Medical University</agency>
        <agency_class>Other</agency_class>
      </lead_sponsor>
    </sponsors>
    <source>Guizhou Medical 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>
        Lung cancer has remained the leading cause of cancer-related deaths worldwide. An important&#xD;
        and frequent cause of morbidity in this patient group is the development of brain metastases&#xD;
        (BM). Lung cancer represents the leading cause of BM, and previous reports have shown that&#xD;
        approximately 40% of patients will develop BM throughout their disease. Additionally, due to&#xD;
        the improved use of advanced imaging techniques as part of routine initial staging. Another&#xD;
        factor to consider is the considerably prolonged survival in patients with lung cancer as a&#xD;
        direct result of the medical advances that have improved systemic disease control in the past&#xD;
        2 decades.&#xD;
  &#xD;
        The development of BM has recognized as one of the most detrimental factors for patient&#xD;
        prognosis, with a negative impact on quality of life (QoL), concomitant neurocognitive&#xD;
        disorders, and, importantly, a significant decrease in OS.&#xD;
  &#xD;
        RTOG 0214 shows that In patients with stage III disease without progression of disease after&#xD;
        therapy, PCI decreased the rate of BM. NVALT-11/DLCRG-02 Study shows that PCI significantly&#xD;
        decreased the proportion of patients who developed symptomatic brain metastases with an&#xD;
        increase in low-grade toxicity. In conclusion, PCI improved DFS and decreased the risk of BM&#xD;
        in patients with LA-NSCLC.Recent studies suggest NSCLC, including stage IV NSCLC, PCI&#xD;
        significantly decreased CBM in addition to increasing progression-free survival and OS.&#xD;
  &#xD;
        At present, few studies on whether prophylactic radiation therapy can reduce the rate of&#xD;
        brain metastasis and OS in stage IV NSCLC. In this randomized controlled study of stage IV&#xD;
        NSCLC, we investigated whether PCI reduces the chance of brain metastases and whether it has&#xD;
        a survival benefit.&#xD;
      </textblock>
    </brief_summary>
    <detailed_description>
      <textblock>
        Group sample sizes of 72 in Group 1 and 72 in Group 2 achieve 90.140% power to detect a&#xD;
        difference between the group proportions of 0.3100. The Group 2 proportion is 0.0700. The&#xD;
        Group 1 proportion is assumed to be 0.1700 under the null hypothesis and 0.3800 under the&#xD;
        alternative hypothesis. The test statistic used is the one-sided Z test (unpooled). The&#xD;
        significance level of the test is 0.0250.&#xD;
  &#xD;
        For all patients with positive TKI detection, TKI combined with concurrent radiotherapy&#xD;
        DT60-70Gy for the primary tumor. Imaging reexamination 2 months after TKI treatment confirmed&#xD;
        the efficacy of CR, PR, and SD; meanwhile, reexamination of head MR Examination confirmed no&#xD;
        intracranial metastasis.&#xD;
  &#xD;
        For all patients with negative TKI detection, the treatment mode was platinum-based regimen&#xD;
        chemotherapy combined with concurrent radiotherapy for DT60-70Gy for the primary tumor.&#xD;
        Imaging reexamination after 2 cycles of chemotherapy confirmed the efficacy of CR, PR, and&#xD;
        SD, and skull MR Examination confirmed that there was no intracranial metastasis.&#xD;
  &#xD;
        Then,for the experiment arm,patients will receive prophylactic cranial irradiation DT:&#xD;
        30Gy/10f. Followed systematic imaging examinations in the first month following systemic&#xD;
        treatment, every 3 months in 2 years, and every 6 months in 5 years.&#xD;
  &#xD;
        For the observation arm,without prophylactic cranial irradiation,Followed systematic imaging&#xD;
        examinations in the first month following systemic treatment, every 3 months in 2 years, and&#xD;
        every 6 months in 5 years.&#xD;
  &#xD;
        The primary end point was incidence of brain metastases（CBM）, PFS, and the secondary end&#xD;
        point was OS、quality of life (QoL), concomitant neurocognitive disorders。&#xD;
      </textblock>
    </detailed_description>
    <overall_status>Recruiting</overall_status>
    <start_date type="Anticipated">September 1, 2023</start_date>
    <completion_date type="Anticipated">August 1, 2025</completion_date>
    <primary_completion_date type="Anticipated">August 1, 2025</primary_completion_date>
    <phase>N/A</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>PFS is defined as the duration of time from start of treatment to time of progression or death,whichever occurs first.,CBM is defined as cumulative incidence of brain metastases.</measure>
      <time_frame>Systematic imaging examinations in the first month following systemic treatment, every 3 months in 2 years, and every 6 months in 5 years.</time_frame>
    </primary_outcome>
    <secondary_outcome>
      <measure>Overall survival is defined as the time interval from date of diagnosis to date of death from any cause. Quality of life and neurocognitive function.</measure>
      <time_frame>Systematic imaging examinations in the first month following systemic treatment, every 3 months in 2 years, and every 6 months in 5 years.</time_frame>
    </secondary_outcome>
    <number_of_arms>2</number_of_arms>
    <enrollment type="Anticipated">144</enrollment>
    <condition>Prophylactic Cranial Irradiation, Cumulative Incidence of Brain Metastases</condition>
    <arm_group>
      <arm_group_label>PCI arm</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>72 stage IV NSCLC patients were randomly enrolled in the group. And all required to have a baseline negative MRI scan for central nervous system (CNS) disease.&#xD;
  For patients with positive TKI detection, TKI combined with concurrent radiotherapy DT60-70Gy for the primary tumor. Imaging reexamination 2 months after TKI treatment confirmed the efficacy of CR, PR, and SD; meanwhile, reexamination of head MR Examination confirmed no intracranial metastasis, and PCI was performed DT 30Gy/10f.&#xD;
  For patients with negative TKI detection, the treatment mode was platinum-based regimen chemotherapy combined with concurrent radiotherapy for DT60-70Gy for the primary tumor. Imaging reexamination after 2 cycles of chemotherapy confirmed the efficacy of CR, PR, and SD, and skull MR Examination confirmed that there was no intracranial metastasis. PCI DT: 30Gy/10f.Systematic imaging examinations in the first month following systemic treatment, every 3 months in 2 years, and every 6 months in 5 years.</description>
    </arm_group>
    <arm_group>
      <arm_group_label>observation arm</arm_group_label>
      <arm_group_type>Placebo Comparator</arm_group_type>
      <description>72 stage IV NSCLC enrolled in the observation group. And all required to have a baseline negative magnetic resonance imaging (MRI) scan for central nervous system (CNS) disease. For patients with positive TKI detection, TKI combined with concurrent radiotherapy DT60-70Gy for the primary tumor.&#xD;
  For patients with negative TKI detection, the treatment mode was platinum-based regimen chemotherapy combined with concurrent radiotherapy for DT60-70Gy for the primary tumor. Imaging reexamination after 2 cycles of chemotherapy confirmed the efficacy of CR, PR, and SD, and skull MR Examination confirmed that there was no intracranial metastasis. then observation. Systematic imaging examinations in the first month following systemic treatment, every 3 months in 2 years, and every 6 months in 5 years.</description>
    </arm_group>
    <intervention>
      <intervention_type>Radiation</intervention_type>
      <intervention_name>Prophylactic Cranial Irradiation for experiment arm</intervention_name>
      <description>Prophylactic Cranial Irradiation DT30Gy/10f</description>
      <arm_group_label>PCI arm</arm_group_label>
      <arm_group_label>observation arm</arm_group_label>
    </intervention>
    <eligibility>
      <criteria>
        <textblock>
          Inclusion Criteria:&#xD;
  &#xD;
            -  Patients with pathologically or cytologically confirmed NSCLC; patients with clinical&#xD;
               stage IV and no brain metastases [AJCC 8th edition]; no previous treatment&#xD;
  &#xD;
            -  Age 18 ~ 80 years old, body condition score ECOG 0 ~ 2 or KPS≥70;&#xD;
  &#xD;
            -  No contraindications such as radiotherapy, EGFR-TKI, chemotherapy, or immunotherapy;&#xD;
  &#xD;
            -  IMRT is required for primary tumor radiotherapy. DT: 60-70Gy&#xD;
  &#xD;
            -  Metastases are treated with three-dimensional radiotherapy (IMRT/SRT/SBRT/VMAT, etc.)&#xD;
               and large segmentation radiotherapy.&#xD;
  &#xD;
            -  The subject must have no major organ dysfunction or laboratory tests that meet the&#xD;
               following requirements:&#xD;
  &#xD;
            -  Hematological tests such as liver and kidney function were in the normal range of&#xD;
               laboratory standards;&#xD;
  &#xD;
            -  Cardiac function: electrocardiogram excluded organic arrhythmia;&#xD;
  &#xD;
            -  Pulmonary function test: FEV1&gt;50%, mild-moderate lung function limited.&#xD;
  &#xD;
            -  Signed informed consent before treatment (radiotherapy, chemotherapy, immunization,&#xD;
               targeted drug therapy); The patient had good compliance with the treatment and&#xD;
               follow-up received.&#xD;
  &#xD;
          Exclusion Criteria:&#xD;
  &#xD;
            -  Patients with brain metastasis;&#xD;
  &#xD;
            -  Stage IV NSCLC patients with malignant pleural effusion, pericardial effusion and&#xD;
               other serous effusion;&#xD;
  &#xD;
            -  Patients with extensive liver metastasis and intrapulmonary metastasis that have&#xD;
               seriously affected liver and lung function;&#xD;
  &#xD;
            -  Patients with uncontrolled hypertension, diabetes, unstable angina, history of&#xD;
               myocardial infarction, or symptomatic congestive heart failure or uncontrolled&#xD;
               arrhythmia within the past 12 months; Have a clinically clear diagnosis of heart valve&#xD;
               disease; The disease active phase of bacterial, fungal, or viral infection; Mental&#xD;
               disorders; Severe impaired lung function;&#xD;
  &#xD;
            -  Pregnant or lactating patients;&#xD;
  &#xD;
            -  Patients with a history of active malignancy other than small cell lung cancer prior&#xD;
               to enrollment; Non-melanoma skin basal cell carcinoma, in situ cervical cancer, cured&#xD;
               early prostate cancer excepted;&#xD;
  &#xD;
            -  Patients with an allergy and known or suspected allergy to any investigational drug&#xD;
               for which no alternative medicine is available;&#xD;
  &#xD;
            -  Patients with poor compliance;&#xD;
  &#xD;
            -  Researchers consider it inappropriate to participate in this experiment.&#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_contact>
      <last_name>Bing Lu, Bachelor</last_name>
      <phone>13809432527</phone>
      <email>lbgymaaaa@163.com</email>
    </overall_contact>
    <location>
      <facility>
        <name>Guizhou Cancer Hospital</name>
        <address>
          <city>Guiyang</city>
          <state>Guizhou</state>
          <zip>550004</zip>
          <country>China</country>
        </address>
      </facility>
      <status>Recruiting</status>
      <contact>
        <last_name>Lu Bing, MD</last_name>
        <phone>86-13765066737</phone>
        <email>574679514@qq.com</email>
      </contact>
    </location>
    <location_countries>
      <country>China</country>
    </location_countries>
    <verification_date>August 2023</verification_date>
    <study_first_submitted>August 8, 2023</study_first_submitted>
    <study_first_submitted_qc>August 23, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">August 28, 2023</study_first_posted>
    <last_update_submitted>August 23, 2023</last_update_submitted>
    <last_update_submitted_qc>August 23, 2023</last_update_submitted_qc>
    <last_update_posted type="Actual">August 28, 2023</last_update_posted>
    <responsible_party>
      <responsible_party_type>Principal Investigator</responsible_party_type>
      <investigator_affiliation>Guizhou Medical University</investigator_affiliation>
      <investigator_full_name>Bing Lu</investigator_full_name>
      <investigator_title>Chief physician</investigator_title>
    </responsible_party>
    <keyword>stage IV non-small cell lung cancer</keyword>
    <keyword>PCI</keyword>
    <condition_browse>
      <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
      <mesh_term>Brain Neoplasms</mesh_term>
    </condition_browse>
    <patient_data>
      <sharing_ipd>No</sharing_ipd>
    </patient_data>
    <!-- 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/NCT06014450
  org study id: PCI for stage IV NSCLC
  nct id: NCT06014450
  lead sponsor: 
  is fda regulated drug: No
  is fda regulated device: No
  Lung cancer has remained the leading cause of cancer-related deaths worldwide. An important
        and frequent cause of morbidity in this patient group is the development of brain metastases
        (BM). Lung cancer represents the leading cause of BM, and previous reports have shown that
        approximately 40% of patients will develop BM throughout their disease. Additionally, due to
        the improved use of advanced imaging techniques as part of routine initial staging. Another
        factor to consider is the considerably prolonged survival in patients with lung cancer as a
        direct result of the medical advances that have improved systemic disease control in the past
        2 decades.
  
        The development of BM has recognized as one of the most detrimental factors for patient
        prognosis, with a negative impact on quality of life (QoL), concomitant neurocognitive
        disorders, and, importantly, a significant decrease in OS.
  
        RTOG 0214 shows that In patients with stage III disease without progression of disease after
        therapy, PCI decreased the rate of BM. NVALT-11/DLCRG-02 Study shows that PCI significantly
        decreased the proportion of patients who developed symptomatic brain metastases with an
        increase in low-grade toxicity. In conclusion, PCI improved DFS and decreased the risk of BM
        in patients with LA-NSCLC.Recent studies suggest NSCLC, including stage IV NSCLC, PCI
        significantly decreased CBM in addition to increasing progression-free survival and OS.
  
        At present, few studies on whether prophylactic radiation therapy can reduce the rate of
        brain metastasis and OS in stage IV NSCLC. In this randomized controlled study of stage IV
        NSCLC, we investigated whether PCI reduces the chance of brain metastases and whether it has
        a survival benefit.
  Group sample sizes of 72 in Group 1 and 72 in Group 2 achieve 90.140% power to detect a
        difference between the group proportions of 0.3100. The Group 2 proportion is 0.0700. The
        Group 1 proportion is assumed to be 0.1700 under the null hypothesis and 0.3800 under the
        alternative hypothesis. The test statistic used is the one-sided Z test (unpooled). The
        significance level of the test is 0.0250.
  
        For all patients with positive TKI detection, TKI combined with concurrent radiotherapy
        DT60-70Gy for the primary tumor. Imaging reexamination 2 months after TKI treatment confirmed
        the efficacy of CR, PR, and SD; meanwhile, reexamination of head MR Examination confirmed no
        intracranial metastasis.
  
        For all patients with negative TKI detection, the treatment mode was platinum-based regimen
        chemotherapy combined with concurrent radiotherapy for DT60-70Gy for the primary tumor.
        Imaging reexamination after 2 cycles of chemotherapy confirmed the efficacy of CR, PR, and
        SD, and skull MR Examination confirmed that there was no intracranial metastasis.
  
        Then,for the experiment arm,patients will receive prophylactic cranial irradiation DT:
        30Gy/10f. Followed systematic imaging examinations in the first month following systemic
        treatment, every 3 months in 2 years, and every 6 months in 5 years.
  
        For the observation arm,without prophylactic cranial irradiation,Followed systematic imaging
        examinations in the first month following systemic treatment, every 3 months in 2 years, and
        every 6 months in 5 years.
  
        The primary end point was incidence of brain metastases（CBM）, PFS, and the secondary end
        point was OS、quality of life (QoL), concomitant neurocognitive disorders。
  allocation: Randomized
  intervention model: Parallel Assignment
  primary purpose: Treatment
  masking: None (Open Label)
  measure: PFS is defined as the duration of time from start of treatment to time of progression or death,whichever occurs first.,CBM is defined as cumulative incidence of brain metastases.
  time frame: Systematic imaging examinations in the first month following systemic treatment, every 3 months in 2 years, and every 6 months in 5 years.
  measure: Overall survival is defined as the time interval from date of diagnosis to date of death from any cause. Quality of life and neurocognitive function.
  time frame: Systematic imaging examinations in the first month following systemic treatment, every 3 months in 2 years, and every 6 months in 5 years.
  arm group label: PCI arm
  arm group type: Experimental
  description: 72 stage IV NSCLC patients were randomly enrolled in the group. And all required to have a baseline negative MRI scan for central nervous system (CNS) disease.
  For patients with positive TKI detection, TKI combined with concurrent radiotherapy DT60-70Gy for the primary tumor. Imaging reexamination 2 months after TKI treatment confirmed the efficacy of CR, PR, and SD; meanwhile, reexamination of head MR Examination confirmed no intracranial metastasis, and PCI was performed DT 30Gy/10f.
  For patients with negative TKI detection, the treatment mode was platinum-based regimen chemotherapy combined with concurrent radiotherapy for DT60-70Gy for the primary tumor. Imaging reexamination after 2 cycles of chemotherapy confirmed the efficacy of CR, PR, and SD, and skull MR Examination confirmed that there was no intracranial metastasis. PCI DT: 30Gy/10f.Systematic imaging examinations in the first month following systemic treatment, every 3 months in 2 years, and every 6 months in 5 years.
  arm group label: observation arm
  arm group type: Placebo Comparator
  description: 72 stage IV NSCLC enrolled in the observation group. And all required to have a baseline negative magnetic resonance imaging (MRI) scan for central nervous system (CNS) disease. For patients with positive TKI detection, TKI combined with concurrent radiotherapy DT60-70Gy for the primary tumor.
  For patients with negative TKI detection, the treatment mode was platinum-based regimen chemotherapy combined with concurrent radiotherapy for DT60-70Gy for the primary tumor. Imaging reexamination after 2 cycles of chemotherapy confirmed the efficacy of CR, PR, and SD, and skull MR Examination confirmed that there was no intracranial metastasis. then observation. Systematic imaging examinations in the first month following systemic treatment, every 3 months in 2 years, and every 6 months in 5 years.
  intervention type: Radiation
  intervention name: Prophylactic Cranial Irradiation for experiment arm
  description: Prophylactic Cranial Irradiation DT30Gy/10f
  arm group label: PCI arm
  arm group label: observation arm
  criteria: 
  gender: All
  minimum age: 18 Years
  maximum age: 80 Years
  healthy volunteers: No
  last name: Bing Lu, Bachelor
  phone: 13809432527
  email: lbgymaaaa@163.com
  facility: 
  status: Recruiting
  contact: 
  country: China
  responsible party type: Principal Investigator
  investigator affiliation: Guizhou Medical University
  investigator full name: Bing Lu
  investigator title: Chief physician
  mesh term: Brain Neoplasms
  sharing ipd: No