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/NCT06031597</url>
    </required_header>
    <id_info>
      <org_study_id>IRB-2023-700(IIT)</org_study_id>
      <nct_id>NCT06031597</nct_id>
    </id_info>
    <brief_title>Radiotherapy Combined With ICIs as Treatment for LA-NSCLC After Failing Induction Immunochemotherapy</brief_title>
    <official_title>Radiotherapy Combined With Immune Checkpoint Inhibitors (ICIs) as Treatment for Locally Advanced Non-small-cell Lung Cancer After Failing Induction Immuno-chemotherapy: a Prospective, Real-world Cohort Study.</official_title>
    <sponsors>
      <lead_sponsor>
        <agency>Zhejiang Cancer Hospital</agency>
        <agency_class>Other</agency_class>
      </lead_sponsor>
    </sponsors>
    <source>Zhejiang Cancer Hospital</source>
    <oversight_info>
      <has_dmc>No</has_dmc>
      <is_fda_regulated_drug>No</is_fda_regulated_drug>
      <is_fda_regulated_device>No</is_fda_regulated_device>
    </oversight_info>
    <brief_summary>
      <textblock>
        Patients with stage III non-small-cell lung cancer initially evaluated as unresectable are&#xD;
        selected for the program, who are remained unresectable after 2-4 cycles of conversion&#xD;
        chemotherapy combined with immune checkpoint inhibitors. Investigators will stratify the&#xD;
        treatment according to different performance status scores and radiotherapy plan bi-lung&#xD;
        receptor volume to evaluate the safety and efficacy of immunotherapy followed by combined&#xD;
        radiotherapy.&#xD;
      </textblock>
    </brief_summary>
    <detailed_description>
      <textblock>
        This is a prospective, real-world cohort study, which aimed to evaluate the safety and&#xD;
        efficacy of immunotherapy followed by combined radiotherapy. Participants will be selected&#xD;
        and entered into three different cohorts according to different performance status(PS) scores&#xD;
        and radiotherapy schedules based on the amount of bilateral lungs treated. Cohort A: PS=0-1&#xD;
        and bilateral lung V20≤20%, mean lung dose(MLD)≤11 gray(Gy), radiotherapy and immunotherapy,&#xD;
        followed by immunotherapy for up to 1 year; Cohort B: PS=0-1 and 20%&lt;bilateral lung V20≤25%&#xD;
        or 11 Gy&lt;MLD≤13 Gy, radiotherapy combined with immunotherapy, followed by immunotherapy for&#xD;
        up to 1 year; Cohort C: PS=2 or 25%&lt;bilateral V20≤30% and 3 Gy &lt;MLD≤ 17 Gy, radiotherapy&#xD;
        alone, followed by immunotherapy for up to 1 year.&#xD;
      </textblock>
    </detailed_description>
    <overall_status>Not yet recruiting</overall_status>
    <start_date type="Anticipated">September 15, 2023</start_date>
    <completion_date type="Anticipated">December 31, 2025</completion_date>
    <primary_completion_date type="Anticipated">December 31, 2025</primary_completion_date>
    <phase>Phase 3</phase>
    <study_type>Interventional</study_type>
    <has_expanded_access>No</has_expanded_access>
    <study_design_info>
      <allocation>Non-Randomized</allocation>
      <intervention_model>Sequential Assignment</intervention_model>
      <primary_purpose>Treatment</primary_purpose>
      <masking>None (Open Label)</masking>
    </study_design_info>
    <primary_outcome>
      <measure>radiation pneumonitis</measure>
      <time_frame>Within 6 months after radiation therapy</time_frame>
      <description>Incidence of grade 2 or higher radiation pneumonitis.</description>
    </primary_outcome>
    <secondary_outcome>
      <measure>progression-free survival</measure>
      <time_frame>2 years</time_frame>
      <description>Time from enrolment to disease progression or death from any cause or censored at the last follow-up.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>overall survival</measure>
      <time_frame>3 years</time_frame>
      <description>Time from enrolment to death or censored at the last follow-up.</description>
    </secondary_outcome>
    <number_of_arms>3</number_of_arms>
    <enrollment type="Anticipated">105</enrollment>
    <condition>Non-small Cell Lung Cancer Stage III</condition>
    <arm_group>
      <arm_group_label>Cohort A: concurrent chemoradiotherapy combined with ICIs</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>For performance status (PS)=0-1 and both lungs V20≤20%, mean lung dose (MLD)≤11 gray(Gy), then the patient should be treated with concurrent chemo-radiotherapy and immunotherapy, and immunotherapy should be given after chemo-radiotherapy to maintain up to 1 year. Participants eligible for enrollment will receive radiotherapy within 8 weeks of the end of chemotherapy combined with Immune checkpoint inhibitors (ICIs) at a radical prescribed dose of 60 Gy ± 10% at 2 Gy once daily for 5 days per week. The chemotherapy regimen will be cisplatin at a dose of 25 mg/m2 once a week for 5-6 cycles. Marketed programmed cell death 1 (PD-1) or programmed cell death L1 (PD-L1) inhibitors are chosen as immunotherapy agents. Immunotherapy will be given every 3 weeks, with no more than 3 cycles of immunotherapy during radiotherapy. The dosage is recommended according to the drug insert.</description>
    </arm_group>
    <arm_group>
      <arm_group_label>Cohort B: concurrent radiotherapy combined with ICIs</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>For PS=0-1 and 20%&lt;both lungs V20≤25% or 11Gy&lt;MLD≤13Gy, radiotherapy alone combined with concurrent immunotherapy, followed by immunotherapy up to 1 year. Participants eligible for enrollment will receive radiotherapy within 8 weeks of the end of chemotherapy combined with ICIs at a radical prescribed dose of 60 Gy ± 10% at 2 Gy once daily for 5 days per week. Marketed PD-1 or PD-L1 inhibitors are chosen as immunotherapy agents. Immunotherapy will be given every 3 weeks, with no more than 3 cycles of immunotherapy during radiotherapy. The dosage is recommended according to the drug insert.</description>
    </arm_group>
    <arm_group>
      <arm_group_label>Cohort C: radiotherapy</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>For PS=2 or 25%&lt;both lungs V20≤30% or 13Gy&lt;MLD≤17Gy, radiotherapy alone, followed by immunotherapy for up to 1 year. Participants eligible for enrollment will receive radiotherapy within 8 weeks of the end of chemotherapy combined with ICIs at a radical prescribed dose of 60 Gy ± 10% at 2 Gy once daily for 5 days per week. Marketed PD-1 or PD-L1 inhibitors are chosen as immunotherapy agents. The dosage is recommended according to the drug insert.</description>
    </arm_group>
    <intervention>
      <intervention_type>Radiation</intervention_type>
      <intervention_name>radiotherapy</intervention_name>
      <description>Radiotherapy techniques: Volumetric-modulated arc therapy (VMAT) and image guided radiotherapy (IGRT).&#xD;
  Radiotherapy dose: Radical prescription dose of 60 gray (Gy) ± 10%, 2 Gy per session, once a day, 5 days a week.</description>
      <arm_group_label>Cohort A: concurrent chemoradiotherapy combined with ICIs</arm_group_label>
      <arm_group_label>Cohort B: concurrent radiotherapy combined with ICIs</arm_group_label>
      <arm_group_label>Cohort C: radiotherapy</arm_group_label>
    </intervention>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>Platinum-Based Drug</intervention_name>
      <description>Cisplatin 25 mg/m2 once per week for a total of 5-6 cycles. For participants who have not completed 4 cycles of conversion chemotherapy in combination with immunotherapy, the original chemotherapy regimen may also be used, with the total number of chemotherapy cycles not exceeding 6 cycles.</description>
      <arm_group_label>Cohort A: concurrent chemoradiotherapy combined with ICIs</arm_group_label>
      <other_name>Cisplatin</other_name>
    </intervention>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>Immunotherapy</intervention_name>
      <description>Concurrent programmed cell death 1 (PD-1) or programmed cell death L1 (PD-L1) inhibitors every 3 weeks during radiotherapy and no more than 3 doses during the course of radiotherapy.</description>
      <arm_group_label>Cohort A: concurrent chemoradiotherapy combined with ICIs</arm_group_label>
      <arm_group_label>Cohort B: concurrent radiotherapy combined with ICIs</arm_group_label>
      <other_name>Nivolumab</other_name>
      <other_name>Atezolizumab</other_name>
      <other_name>Durvalumab</other_name>
      <other_name>Pembrolizumab</other_name>
      <other_name>Tislelizumab</other_name>
      <other_name>Sugemalimab</other_name>
      <other_name>Sintilimab</other_name>
      <other_name>Camrelizumab</other_name>
    </intervention>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>Immunotherapeutic Agent</intervention_name>
      <description>All participants will be evaluated within 1-42 days after receiving radiation (chemotherapy). If disease progression does not occur, adjuvant therapy with a PD-1 or PD-L1 inhibitor is continued until disease progression up to 1 year.</description>
      <arm_group_label>Cohort A: concurrent chemoradiotherapy combined with ICIs</arm_group_label>
      <arm_group_label>Cohort B: concurrent radiotherapy combined with ICIs</arm_group_label>
      <arm_group_label>Cohort C: radiotherapy</arm_group_label>
      <other_name>Nivolumab</other_name>
      <other_name>Atezolizumab</other_name>
      <other_name>Durvalumab</other_name>
      <other_name>Pembrolizumab</other_name>
      <other_name>Tislelizumab</other_name>
      <other_name>Sugemalimab</other_name>
      <other_name>Sintilimab</other_name>
      <other_name>Camrelizumab</other_name>
    </intervention>
    <eligibility>
      <criteria>
        <textblock>
          Inclusion Criteria:&#xD;
  &#xD;
            1. Histologically or cytologically confirmed non-small cell lung cancer&#xD;
  &#xD;
            2. Presence of at least one measurable lesion according to RECIST 1.1 criteria&#xD;
  &#xD;
            3. Classified as American Joint Committee on Cancer staging system, eighth edition&#xD;
               (AJCC-8) Stage III, initially evaluated as unresectable and reevaluated as&#xD;
               unresectable after 2-4 cycles of induction chemotherapy combined with immunotherapy&#xD;
  &#xD;
            4. Age 18-75&#xD;
  &#xD;
            5. Eastern Cooperative Oncology Group (ECOG) physical state score of 0-2&#xD;
  &#xD;
            6. Patients with the pathologic type of adenocarcinoma should be negative for driver&#xD;
               genes (EGFR, anaplastic lymphoma kinase, ROS1)&#xD;
  &#xD;
            7. Serum hemoglobin ≥ 90 g/L, platelets ≥ 90 × 109/L, absolute neutrophil count ≥ 1.2 ×&#xD;
               109/L&#xD;
  &#xD;
            8. Serum creatinine ≤ 1.25 times upper limit of normal(ULN) or creatinine clearance ≥ 60&#xD;
               mL/min&#xD;
  &#xD;
            9. Serum bilirubin ≤ 1.5 times ULN, (AST) and alanine aminotransferase aspartate&#xD;
               aminotransferase (ALT) ≤ 2.5 times ULN, alkaline phosphatase ≤ 5 times ULN&#xD;
  &#xD;
           10. Forced expiratory volume in one second (FEV1)&gt;0.8 liter&#xD;
  &#xD;
           11. Normal coagulation function (Prothrombin time prolonged by no more than 3s and&#xD;
               activated partial thromboplastin time prolonged by no more than 10s)&#xD;
  &#xD;
           12. Patients signed a formal informed consent form to indicate that they understood that&#xD;
               the study complied with the hospital's policies and ethical requirements&#xD;
  &#xD;
          Exclusion Criteria:&#xD;
  &#xD;
            1. The pathologic type is lung carcinoid or small cell lung cancer&#xD;
  &#xD;
            2. Patients with any distant metastases&#xD;
  &#xD;
            3. Grade 2 or higher unresolved toxic effects after conversion therapy (according to the&#xD;
               Common Terminology Criteria for Adverse Events CTCAE)&#xD;
  &#xD;
            4. A recent efficacy rating of PD after conversion therapy&#xD;
  &#xD;
            5. Radiotherapy plan for normal lung tissue V20 &gt; 30%, or average lung dose MLD &gt; 17 Gy&#xD;
  &#xD;
            6. Active or previous autoimmune disease (within the past 2 years) or history of primary&#xD;
               immunodeficiency&#xD;
  &#xD;
            7. Patients with any other previous or current malignancy, except non-melanoma skin or&#xD;
               cervical cancer in situ&#xD;
  &#xD;
            8. Any other disease or condition suggesting a contraindication to radiotherapy (e.g.,&#xD;
               active infection, within 6 months of myocardial infarction, symptomatic cardiac&#xD;
               disease including unstable angina pectoris, congestive heart failure, or uncontrolled&#xD;
               arrhythmias, immunosuppressive therapy)&#xD;
  &#xD;
            9. Pregnant or nursing women&#xD;
  &#xD;
           10. Women and men who are at risk of becoming pregnant but are unwilling to use adequate&#xD;
               contraception&#xD;
  &#xD;
           11. Evidence of hereditary bleeding disorders or coagulation disorders.&#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>Xu Yujin, PhD</last_name>
      <role>Study Director</role>
      <affiliation>Zhejiang Cancer Hospital</affiliation>
    </overall_official>
    <overall_contact>
      <last_name>Xu Yujin, PhD</last_name>
      <phone>86-13858037993</phone>
      <email>xuyj@zjcc.org.cn</email>
    </overall_contact>
    <verification_date>August 2023</verification_date>
    <study_first_submitted>August 28, 2023</study_first_submitted>
    <study_first_submitted_qc>September 4, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">September 11, 2023</study_first_posted>
    <last_update_submitted>September 10, 2023</last_update_submitted>
    <last_update_submitted_qc>September 10, 2023</last_update_submitted_qc>
    <last_update_posted type="Actual">September 13, 2023</last_update_posted>
    <responsible_party>
      <responsible_party_type>Principal Investigator</responsible_party_type>
      <investigator_affiliation>Zhejiang Cancer Hospital</investigator_affiliation>
      <investigator_full_name>Xu Yujin, MD</investigator_full_name>
      <investigator_title>Chief Physician, Department of Thoracic Radiotherapy</investigator_title>
    </responsible_party>
    <keyword>Non-small cell lung cancer</keyword>
    <keyword>Immune checkpoint inhibitors</keyword>
    <keyword>Radiotherapy</keyword>
    <keyword>Radiation pneumonitis</keyword>
    <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>Cisplatin</mesh_term>
      <mesh_term>Pembrolizumab</mesh_term>
      <mesh_term>Nivolumab</mesh_term>
      <mesh_term>Atezolizumab</mesh_term>
      <mesh_term>Durvalumab</mesh_term>
      <mesh_term>Tislelizumab</mesh_term>
      <mesh_term>Antibodies, Monoclonal</mesh_term>
      <mesh_term>Immunomodulating Agents</mesh_term>
    </intervention_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/NCT06031597
  org study id: IRB-2023-700(IIT)
  nct id: NCT06031597
  lead sponsor: 
  has dmc: No
  is fda regulated drug: No
  is fda regulated device: No
  Patients with stage III non-small-cell lung cancer initially evaluated as unresectable are
        selected for the program, who are remained unresectable after 2-4 cycles of conversion
        chemotherapy combined with immune checkpoint inhibitors. Investigators will stratify the
        treatment according to different performance status scores and radiotherapy plan bi-lung
        receptor volume to evaluate the safety and efficacy of immunotherapy followed by combined
        radiotherapy.
  This is a prospective, real-world cohort study, which aimed to evaluate the safety and
        efficacy of immunotherapy followed by combined radiotherapy. Participants will be selected
        and entered into three different cohorts according to different performance status(PS) scores
        and radiotherapy schedules based on the amount of bilateral lungs treated. Cohort A: PS=0-1
        and bilateral lung V20≤20%, mean lung dose(MLD)≤11 gray(Gy), radiotherapy and immunotherapy,
        followed by immunotherapy for up to 1 year; Cohort B: PS=0-1 and 20%<bilateral lung V20≤25%
        or 11 Gy<MLD≤13 Gy, radiotherapy combined with immunotherapy, followed by immunotherapy for
        up to 1 year; Cohort C: PS=2 or 25%<bilateral V20≤30% and 3 Gy <MLD≤ 17 Gy, radiotherapy
        alone, followed by immunotherapy for up to 1 year.
  allocation: Non-Randomized
  intervention model: Sequential Assignment
  primary purpose: Treatment
  masking: None (Open Label)
  measure: radiation pneumonitis
  time frame: Within 6 months after radiation therapy
  description: Incidence of grade 2 or higher radiation pneumonitis.
  measure: progression-free survival
  time frame: 2 years
  description: Time from enrolment to disease progression or death from any cause or censored at the last follow-up.
  measure: overall survival
  time frame: 3 years
  description: Time from enrolment to death or censored at the last follow-up.
  arm group label: Cohort A: concurrent chemoradiotherapy combined with ICIs
  arm group type: Experimental
  description: For performance status (PS)=0-1 and both lungs V20≤20%, mean lung dose (MLD)≤11 gray(Gy), then the patient should be treated with concurrent chemo-radiotherapy and immunotherapy, and immunotherapy should be given after chemo-radiotherapy to maintain up to 1 year. Participants eligible for enrollment will receive radiotherapy within 8 weeks of the end of chemotherapy combined with Immune checkpoint inhibitors (ICIs) at a radical prescribed dose of 60 Gy ± 10% at 2 Gy once daily for 5 days per week. The chemotherapy regimen will be cisplatin at a dose of 25 mg/m2 once a week for 5-6 cycles. Marketed programmed cell death 1 (PD-1) or programmed cell death L1 (PD-L1) inhibitors are chosen as immunotherapy agents. Immunotherapy will be given every 3 weeks, with no more than 3 cycles of immunotherapy during radiotherapy. The dosage is recommended according to the drug insert.
  arm group label: Cohort B: concurrent radiotherapy combined with ICIs
  arm group type: Experimental
  description: For PS=0-1 and 20%<both lungs V20≤25% or 11Gy<MLD≤13Gy, radiotherapy alone combined with concurrent immunotherapy, followed by immunotherapy up to 1 year. Participants eligible for enrollment will receive radiotherapy within 8 weeks of the end of chemotherapy combined with ICIs at a radical prescribed dose of 60 Gy ± 10% at 2 Gy once daily for 5 days per week. Marketed PD-1 or PD-L1 inhibitors are chosen as immunotherapy agents. Immunotherapy will be given every 3 weeks, with no more than 3 cycles of immunotherapy during radiotherapy. The dosage is recommended according to the drug insert.
  arm group label: Cohort C: radiotherapy
  arm group type: Experimental
  description: For PS=2 or 25%<both lungs V20≤30% or 13Gy<MLD≤17Gy, radiotherapy alone, followed by immunotherapy for up to 1 year. Participants eligible for enrollment will receive radiotherapy within 8 weeks of the end of chemotherapy combined with ICIs at a radical prescribed dose of 60 Gy ± 10% at 2 Gy once daily for 5 days per week. Marketed PD-1 or PD-L1 inhibitors are chosen as immunotherapy agents. The dosage is recommended according to the drug insert.
  intervention type: Radiation
  intervention name: radiotherapy
  description: Radiotherapy techniques: Volumetric-modulated arc therapy (VMAT) and image guided radiotherapy (IGRT).
  Radiotherapy dose: Radical prescription dose of 60 gray (Gy) ± 10%, 2 Gy per session, once a day, 5 days a week.
  arm group label: Cohort A: concurrent chemoradiotherapy combined with ICIs
  arm group label: Cohort B: concurrent radiotherapy combined with ICIs
  arm group label: Cohort C: radiotherapy
  intervention type: Drug
  intervention name: Platinum-Based Drug
  description: Cisplatin 25 mg/m2 once per week for a total of 5-6 cycles. For participants who have not completed 4 cycles of conversion chemotherapy in combination with immunotherapy, the original chemotherapy regimen may also be used, with the total number of chemotherapy cycles not exceeding 6 cycles.
  arm group label: Cohort A: concurrent chemoradiotherapy combined with ICIs
  other name: Cisplatin
  intervention type: Drug
  intervention name: Immunotherapy
  description: Concurrent programmed cell death 1 (PD-1) or programmed cell death L1 (PD-L1) inhibitors every 3 weeks during radiotherapy and no more than 3 doses during the course of radiotherapy.
  arm group label: Cohort A: concurrent chemoradiotherapy combined with ICIs
  arm group label: Cohort B: concurrent radiotherapy combined with ICIs
  other name: Nivolumab
  other name: Atezolizumab
  other name: Durvalumab
  other name: Pembrolizumab
  other name: Tislelizumab
  other name: Sugemalimab
  other name: Sintilimab
  other name: Camrelizumab
  intervention type: Drug
  intervention name: Immunotherapeutic Agent
  description: All participants will be evaluated within 1-42 days after receiving radiation (chemotherapy). If disease progression does not occur, adjuvant therapy with a PD-1 or PD-L1 inhibitor is continued until disease progression up to 1 year.
  arm group label: Cohort A: concurrent chemoradiotherapy combined with ICIs
  arm group label: Cohort B: concurrent radiotherapy combined with ICIs
  arm group label: Cohort C: radiotherapy
  other name: Nivolumab
  other name: Atezolizumab
  other name: Durvalumab
  other name: Pembrolizumab
  other name: Tislelizumab
  other name: Sugemalimab
  other name: Sintilimab
  other name: Camrelizumab
  criteria: 
  gender: All
  minimum age: 18 Years
  maximum age: 75 Years
  healthy volunteers: No
  last name: Xu Yujin, PhD
  role: Study Director
  affiliation: Zhejiang Cancer Hospital
  last name: Xu Yujin, PhD
  phone: 86-13858037993
  email: xuyj@zjcc.org.cn
  responsible party type: Principal Investigator
  investigator affiliation: Zhejiang Cancer Hospital
  investigator full name: Xu Yujin, MD
  investigator title: Chief Physician, Department of Thoracic Radiotherapy
  mesh term: Lung Neoplasms
  mesh term: Carcinoma, Non-Small-Cell Lung
  mesh term: Cisplatin
  mesh term: Pembrolizumab
  mesh term: Nivolumab
  mesh term: Atezolizumab
  mesh term: Durvalumab
  mesh term: Tislelizumab
  mesh term: Antibodies, Monoclonal
  mesh term: Immunomodulating Agents
  sharing ipd: No