<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/NCT04492969</url>
  </required_header>
  <id_info>
    <org_study_id>2019-CSCOBMS</org_study_id>
    <nct_id>NCT04492969</nct_id>
  </id_info>
  <brief_title>Prospective Observation of Failure Patterns in NSCLC Treated With ICIs</brief_title>
  <official_title>Prospective Observational Study of Failure Patterns in Non-small Cell Lung Cancer Patients Treated With Immune Checkpoint Inhibitors</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>
    <is_us_export>No</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      By prospectively observing the time to the best therapeutic effect of non-small cell lung&#xD;
      cancer after ICI treatment, the characteristics of lesion distribution when the best&#xD;
      therapeutic effect is reached, and the phenotype of disease progression after ICI treatment&#xD;
      response, the investigators intended to explore the failure pattern of NSCLC after the once&#xD;
      effective ICI treatment. The investigators also aim to evaluate the feasibility and clinical&#xD;
      value of radiotherapy for the treatment of oligo-progressive lesions after ICI.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Not yet recruiting</overall_status>
  <start_date type="Anticipated">September 1, 2020</start_date>
  <completion_date type="Anticipated">August 31, 2025</completion_date>
  <primary_completion_date type="Anticipated">August 31, 2023</primary_completion_date>
  <study_type>Observational [Patient Registry]</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <observational_model>Cohort</observational_model>
    <time_perspective>Prospective</time_perspective>
  </study_design_info>
  <target_duration>3 Years</target_duration>
  <primary_outcome>
    <measure>Oligo-progression disease rate in NSCLC patients developing acquired resistance to ICI treatment.</measure>
    <time_frame>at least 2 months after ICI treatment.</time_frame>
    <description>Acquired resistance (AR) was defined as disease progression after partial or complete response (PR or CR) to ICI treatment. (by RECIST standard v1.1)&#xD;
When observing disease progression in ICI treatment, the number and distribution of progression lesions were recorded.&#xD;
Oligo-progression disease (OPD) was defined as 1-3 progression lesions in 1-2 organs. The OPD rate in all AR cases will be calculated.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Overall objective response rate to radiotherapy.</measure>
    <time_frame>at least 4 weeks after radiotherapy.</time_frame>
    <description>When radiotherapy to at least one of the OPD lesions is indicated in the opinion of the investigator. Overall objective response rate (ORR) to radiotherapy will be recorded. ORR was defined as the proportion of participants with partial response (PR) or complete response (CR) to treatment as defined by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Objective response rate in non-irradiated lesion</measure>
    <time_frame>at least 4 weeks after radiotherapy.</time_frame>
    <description>Objective response rate (ORR) in Non-irradiated Lesion was defined as the proportion of patients with at least 30% reduction from baseline in the longest diameter of any of non-irradiated target lesions defined by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 at any time-point from the date of treatment initiation to the date of last follow-up.</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>
  <secondary_outcome>
    <measure>Overall Survival since AR development.</measure>
    <time_frame>Two years</time_frame>
    <description>OS was defined as the time from the date of enrollment 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>
  <enrollment type="Anticipated">320</enrollment>
  <condition>NSCLC Stage IV</condition>
  <condition>NSCLC, Recurrent</condition>
  <eligibility>
    <study_pop>
      <textblock>
        stage IV NSCLC developing acquired resistance under ICI treatment.&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Non-Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria (Part I):&#xD;
&#xD;
          -  Age between 18 and 75 years.&#xD;
&#xD;
          -  ECOG PS 0-1.&#xD;
&#xD;
          -  Pathologically confirmed stage IV NSCLC.&#xD;
&#xD;
          -  Negative for driver genes including EGFR, ALK, and ROS-1.&#xD;
&#xD;
          -  Patients achieved PR or CR after ICI treatment, as defined by RECIST 1.1.&#xD;
&#xD;
          -  Patients with complete radiological information of baseline lesions.&#xD;
&#xD;
          -  Life expectancy of more than 3 months.&#xD;
&#xD;
          -  Ability to understand and willingness to provide the informed consent.&#xD;
&#xD;
        Exclusion Criteria (Part I):&#xD;
&#xD;
          -  Severe autoimmune disease or other contradictions to ICI treatment.&#xD;
&#xD;
          -  Mixed small cell with non-small cell lung cancer histology.&#xD;
&#xD;
          -  Driver gene positive, including EGFR, ALK, and ROS-1.&#xD;
&#xD;
          -  Pregnant or lactating women.&#xD;
&#xD;
          -  History of any other malignancy.&#xD;
&#xD;
          -  Active infection, congestive heart failure, myocardial infarction within the 6 months&#xD;
             prior to enrollment, unstable angina pectoris or cardiac arrhythmia.&#xD;
&#xD;
          -  Patients receiving immunosuppressive agents,or other investigational treatment.&#xD;
             Long-term corticosteroid users are also excluded.&#xD;
&#xD;
          -  Mental disorders, drug abuse, and social condition that may negatively impact&#xD;
             compliance in the opinion of the investigator.&#xD;
&#xD;
        Inclusion Criteria (Part II, patients with OPD):&#xD;
&#xD;
          -  Patients with oligo-progression disease (1-3 progression lesions in 1-2 organs) when&#xD;
             developing acquired resistance to ICI.&#xD;
&#xD;
          -  Radiotherapy to at least one of the OPD lesions is indicated in the opinion of the&#xD;
             investigator. At least one of the irradiated lesion(s) should be evaluable according&#xD;
             to RECIST 1.1.&#xD;
&#xD;
          -  ECOG PS 0-2.&#xD;
&#xD;
          -  Life expectancy of more than 3 months.&#xD;
&#xD;
          -  Complete radiological information of all lesions during the follow-up.&#xD;
&#xD;
          -  Patients with a prior history of surgery are eligible if they have recovered&#xD;
             adequately from the toxicity and/or complications of surgery.&#xD;
&#xD;
          -  Adequate bone marrow function within 1 week prior to the enrollment: hemoglobin&#xD;
             ≥80g/L, white blood cell (WBC) count ≥ 4.0 * 10 ^ 9/L or neutrophil count ≥ 1.5 * 10 ^&#xD;
             9/L, and platelet count ≥ 100 * 10 ^ 9/L;&#xD;
&#xD;
          -  Ability to understand and willingness to provide the informed consent.&#xD;
&#xD;
        Exclusion Criteria (Part II):&#xD;
&#xD;
          -  Secondary malignancy.&#xD;
&#xD;
          -  Histology transformation to non-NSCLC.&#xD;
&#xD;
          -  Ineligible for radiotherapy in the opinion of the investigator. Or none of the OPD are&#xD;
             evaluable by RECIST 1.1.&#xD;
&#xD;
          -  ECOG PS 3 or worse.&#xD;
&#xD;
          -  Short life expectancy (less than 3 months).&#xD;
&#xD;
          -  Unable to provide complete radiological information of lesions.&#xD;
&#xD;
          -  Inadequate bone marrow function.&#xD;
&#xD;
          -  Cannot understand or unwilling to provide the informed consent.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>75 Years</maximum_age>
  </eligibility>
  <overall_official>
    <last_name>Zhengfei Zhu, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Fudan University</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Zhengfei Zhu, MD</last_name>
    <phone>+86-18017312901</phone>
    <email>fuscczzf@163.com</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Xiao Chu, PhD</last_name>
    <phone>+86-15821383376</phone>
    <email>crazychu0044@163.com</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>Fudan University Shanghai Cancer Center</name>
      <address>
        <city>Shanghai</city>
        <state>Shanghai</state>
        <zip>200031</zip>
        <country>China</country>
      </address>
    </facility>
    <contact>
      <last_name>Zhengfei Zhu, MD</last_name>
      <phone>+86-18017312901</phone>
      <email>fuscczzf@163.com</email>
    </contact>
    <contact_backup>
      <last_name>Xiao Chu</last_name>
      <phone>15821383376</phone>
      <email>crazychu0044@163.com</email>
    </contact_backup>
  </location>
  <location_countries>
    <country>China</country>
  </location_countries>
  <verification_date>July 2020</verification_date>
  <study_first_submitted>July 27, 2020</study_first_submitted>
  <study_first_submitted_qc>July 27, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">July 30, 2020</study_first_posted>
  <last_update_submitted>July 29, 2020</last_update_submitted>
  <last_update_submitted_qc>July 29, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">July 31, 2020</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>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/NCT04492969
org study id: 2019-CSCOBMS
nct id: NCT04492969
lead sponsor: 
is fda regulated drug: No
is fda regulated device: No
is us export: No
By prospectively observing the time to the best therapeutic effect of non-small cell lung
      cancer after ICI treatment, the characteristics of lesion distribution when the best
      therapeutic effect is reached, and the phenotype of disease progression after ICI treatment
      response, the investigators intended to explore the failure pattern of NSCLC after the once
      effective ICI treatment. The investigators also aim to evaluate the feasibility and clinical
      value of radiotherapy for the treatment of oligo-progressive lesions after ICI.
observational model: Cohort
time perspective: Prospective
measure: Oligo-progression disease rate in NSCLC patients developing acquired resistance to ICI treatment.
time frame: at least 2 months after ICI treatment.
description: Acquired resistance (AR) was defined as disease progression after partial or complete response (PR or CR) to ICI treatment. (by RECIST standard v1.1)
When observing disease progression in ICI treatment, the number and distribution of progression lesions were recorded.
Oligo-progression disease (OPD) was defined as 1-3 progression lesions in 1-2 organs. The OPD rate in all AR cases will be calculated.
measure: Overall objective response rate to radiotherapy.
time frame: at least 4 weeks after radiotherapy.
description: When radiotherapy to at least one of the OPD lesions is indicated in the opinion of the investigator. Overall objective response rate (ORR) to radiotherapy will be recorded. ORR was defined as the proportion of participants with partial response (PR) or complete response (CR) to treatment as defined by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1.
measure: Objective response rate in non-irradiated lesion
time frame: at least 4 weeks after radiotherapy.
description: Objective response rate (ORR) in Non-irradiated Lesion was defined as the proportion of patients with at least 30% reduction from baseline in the longest diameter of any of non-irradiated target lesions defined by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 at any time-point from the date of treatment initiation to the date of last follow-up.
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.
measure: Overall Survival since AR development.
time frame: Two years
description: OS was defined as the time from the date of enrollment until death by any cause. Participants still alive at the time of data analysis were censored at the date of last follow-up.
study pop: 
sampling method: Non-Probability Sample
criteria: 
gender: All
minimum age: 18 Years
maximum age: 75 Years
last name: Zhengfei Zhu, MD
role: Principal Investigator
affiliation: Fudan University
last name: Zhengfei Zhu, MD
phone: +86-18017312901
email: fuscczzf@163.com
last name: Xiao Chu, PhD
phone: +86-15821383376
email: crazychu0044@163.com
facility: 
contact: 
contact backup: 
country: China
responsible party type: Principal Investigator
investigator affiliation: Fudan University
investigator full name: Zhengfei Zhu
investigator title: Professor
mesh term: Carcinoma, Non-Small-Cell Lung