<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/NCT03258671</url>
  </required_header>
  <id_info>
    <org_study_id>CSWOG</org_study_id>
    <nct_id>NCT03258671</nct_id>
  </id_info>
  <brief_title>IMRT and Timing in Combination With EGFRTKI for Stage IV Non-small-cell Lung Cancer</brief_title>
  <official_title>IMRT and Timing in Combination With EGFRTKI for Stage IV Non-small-cell Lung Cancer: Results of a Randomised,Openlabel,Multicentre Study</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>LuBing</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Guizhou Medical University</source>
  <oversight_info>
    <has_dmc>Yes</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>
      This study is for patients with EFGR gene sensitive mutations diagnosed by pathology or&#xD;
      cytology, having a course of chest radiotherapy treatment and molecular Target Therapy for&#xD;
      the treatment of stage IV non-small cell lung cancer. Patients with non-small cell lung&#xD;
      cancer have a risk of the tumour in the lung recurring or progressing after treatment.&#xD;
&#xD;
      In this study, the investigators aim to verify the following hypothesis:&#xD;
&#xD;
        -  whether in combination with concurrent or concomitant EGFR-TKI regimen chemotherapy,&#xD;
           Intensity Modulated Radiation Therapy can reduce the risk of the tumour in the lung&#xD;
           recurring or progressing similarily.&#xD;
&#xD;
        -  Intensity Modulated Radiation Therapy concomitant with EGFR-TKI has a better normal&#xD;
           tissue dose/volume tolerance than concurrent regimen.&#xD;
&#xD;
        -  the survival can be improved by using this new molecular Target-radiotherapy method.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Not yet recruiting</last_known_status>
  <start_date type="Anticipated">October 1, 2017</start_date>
  <completion_date type="Anticipated">December 30, 2020</completion_date>
  <primary_completion_date type="Anticipated">December 30, 2020</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>Therapeutic efficacy of EGFR-TKI and concurrent/concomitant local RT in NSCLC patients.</measure>
    <time_frame>&gt;4 weeks post treatment</time_frame>
    <description>Tumor Response will be evaluated using the RECIST system. Modified WHO criteria will be used for measurement of tumors. The irradiated lesion will be excluded from the assessment of response.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Overall survival (OS)</measure>
    <time_frame>Up to 5 years</time_frame>
    <description>Overall survival is defined as the time interval from date of diagnosis to date of death from any cause</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Progression-free survival (PFS)</measure>
    <time_frame>Up to 5 years</time_frame>
    <description>PFS is defined as the duration of time from start of treatment to time of progression or death, whichever occurs first.&#xD;
Progressive disease (PD) = at least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study, appearance of one or more non-target lesion(s) and/or unequivocal progression of existing non-target lesions</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Objective response rate(ORR)</measure>
    <time_frame>Up to 5 years</time_frame>
    <description>Partial response + complete response per RECIST 1.1 criteria Complete response (CR) = disappearance of all target lesions, non-target lesions, and normalization of tumor marker level&#xD;
Partial response (PR) = at least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline of sum diameters</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Disease control rate (DCR)</measure>
    <time_frame>Up to 5 years</time_frame>
    <description>Percentage of patients who achieve complete response, partial response, or stable disease per RECIST 1.1 criteria.&#xD;
Complete response (CR) = disappearance of all target lesions, non-target lesions, and normalization of tumor marker level&#xD;
Partial response (PR) = at least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline of sum diameters&#xD;
Stable Disease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters while on study.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Adverse events (toxicities)</measure>
    <time_frame>Up to 5 years</time_frame>
    <description>The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 will be utilized for all toxicity reporting.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Local regional progression-free survival（LRPFS）</measure>
    <time_frame>Time Frame: Up to 5 years</time_frame>
    <description>LRPFS is defined as the duration of time from start of treatment to time of progression or recurrence, whichever occurs first..The target lesions is only for primary tumor and regional positive lymph nodes.&#xD;
Progressive disease (PD) = at least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study, appearance of one or more target lesion(s) and/or unequivocal progression of existing target lesions.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">160</enrollment>
  <condition>Non-Small Cell Lung Cancer</condition>
  <condition>Nonsmall Cell Lung Cancer</condition>
  <condition>Carcinoma, Non-Small-Cell Lung</condition>
  <arm_group>
    <arm_group_label>Mutation+ concurrent</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>IMRT concurrent with EGFR-TKI on paticipants with known sensitive EGFR mutations.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Mutation+ concomitant</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>IMRT concomitant with EGFR-TKI on paticipants with known sensitive EGFR mutations.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>EGFR-TK Inhibitor</intervention_name>
    <description>·EGFR-TKI：gefitinib will be administered 250mg/d ivgtt qd; icotinib will be administered 150mg/d ivgtt tid;</description>
    <arm_group_label>Mutation+ concomitant</arm_group_label>
    <arm_group_label>Mutation+ concurrent</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Radiation</intervention_type>
    <intervention_name>Intensity Modulated Radiation Therapy</intervention_name>
    <description>High dose group：DTGTV=70Gy；&#xD;
first course radiotherapy：40Gy/20f/4w（DTPTV：36Gy/20f/4w）,2Gy/f/d；&#xD;
late course radiotherapy：1.5Gy/f、2f/d、interval≥6 hs、DTGTV=30Gy（DTPTV=27Gy）。&#xD;
Low dose group：DTGTV=50Gy;&#xD;
first course radiotherapy：32Gy/16f/3w（DTPTV为28.8Gy/16f/3w），2Gy/f/d；&#xD;
late course radiotherapy：1.5Gy/f、2f/d、interval≥6小时、DTGTV为18Gy（DTPTV为16.2Gy）。</description>
    <arm_group_label>Mutation+ concomitant</arm_group_label>
    <arm_group_label>Mutation+ concurrent</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Histologically or cytologically confirmed stage IV NSCLC[UICC 2017 8th edition] with&#xD;
             known sensitive EGFR mutations(confirmed by tissue or blood).&#xD;
&#xD;
          -  Have not received one or more prior treatments&#xD;
&#xD;
          -  18 to 80 years of age.ECOG performance status 0～2 or KPS≥60&#xD;
&#xD;
          -  Have distant metastatic lesions≤5；and have clear consciousness when the metastatic&#xD;
             sites were brain; and have no influence on pulmonary function when the metastatic&#xD;
             sites were lung.&#xD;
&#xD;
          -  Have no contraindications in radiotherapy, EGFR-TKI and chemotherapy&#xD;
&#xD;
          -  Normal bone marrow and organ function as defined below:&#xD;
&#xD;
        Absolute neutrophil count ≥ 1,500/mcl Platelets ≥ 100,000/mcl Hemoglobin ≥ 9.0 g/dL Total&#xD;
        bilirubin ≤ 2.0 x IULN AST (SGOT) / ALT (SGPT) ≤ 3.0 x IULN; if liver metastases, ≤ 5.0 x&#xD;
        IULN Serum creatinine ≤ 1.5 x ULN LVEF ≥ 50% performed no more than 4 weeks prior to&#xD;
        enrollment. FEV1&gt;50%，mild-moderate pulmonary function dysfunction.&#xD;
&#xD;
          -  Able to understand and willing to sign a Human Research Protection Office (HRPO)&#xD;
             approved written informed consent document (or that of legally authorized&#xD;
             representative, if applicable).&#xD;
&#xD;
          -  With good compliance to the treatment and Follow-up&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Evidence of small cell, large cell neuroendocrine or carcinoid histology.&#xD;
&#xD;
          -  Non-stage IV NSCLC and ECOG performance status 3～5 or KPS&lt;60&#xD;
&#xD;
          -  Have a serious or uncontrolled medical condition that could compromise the patients'&#xD;
             ability to adhere to the protocol.&#xD;
&#xD;
          -  Malignant pleural effusion and pericardial effusion&#xD;
&#xD;
          -  Uncontrolled intercurrent illness including, but not limited to, hypertension ,&#xD;
             diabetes mellitus ,ongoing or active infection, symptomatic congestive heart failure,&#xD;
             unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations&#xD;
             that would limit compliance with study requirements.&#xD;
&#xD;
          -  Pregnant and/or breastfeeding: Patient must have a negative pregnancy test within 14&#xD;
             days of study entry.&#xD;
&#xD;
          -  Have a secondary malignancy (except adequately treated non-melanomatous skin cancer,&#xD;
             or other cancer such as in situ of the cervix. considered cured by surgical resection&#xD;
             or radiation). Patients who have had another malignancy in the past but have been&#xD;
             disease free for more than 5 years are eligible.&#xD;
&#xD;
          -  A history of allergic reactions attributed to compounds of similar chemical or&#xD;
             biologic composition to EGFR-TKI or other agents used in the study.&#xD;
&#xD;
          -  With poor compliance&#xD;
&#xD;
          -  The researchers consider it inappropriate to participate in the study&#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>Lu Bing, Director</last_name>
    <role>Study Director</role>
    <affiliation>ouyangww103173@163.com</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Lu Bing, Director</last_name>
    <phone>86-18275356814</phone>
    <email>ouyangww103173@163.com</email>
  </overall_contact>
  <location>
    <facility>
      <name>The affiliated hospital of Guizhou medical university</name>
      <address>
        <city>Guiyang</city>
        <state>Guizhou</state>
        <zip>550004</zip>
        <country>China</country>
      </address>
    </facility>
    <contact>
      <last_name>Lu Bing, MD</last_name>
      <phone>86-18275356814</phone>
      <email>ouyangww103173@163.com</email>
    </contact>
  </location>
  <location_countries>
    <country>China</country>
  </location_countries>
  <verification_date>August 2017</verification_date>
  <study_first_submitted>August 21, 2017</study_first_submitted>
  <study_first_submitted_qc>August 21, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">August 23, 2017</study_first_posted>
  <last_update_submitted>August 23, 2017</last_update_submitted>
  <last_update_submitted_qc>August 23, 2017</last_update_submitted_qc>
  <last_update_posted type="Actual">August 25, 2017</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor-Investigator</responsible_party_type>
    <investigator_affiliation>Guizhou Medical University</investigator_affiliation>
    <investigator_full_name>LuBing</investigator_full_name>
    <investigator_title>Director</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>
  <!-- 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/NCT03258671
org study id: CSWOG
nct id: NCT03258671
lead sponsor: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
This study is for patients with EFGR gene sensitive mutations diagnosed by pathology or
      cytology, having a course of chest radiotherapy treatment and molecular Target Therapy for
      the treatment of stage IV non-small cell lung cancer. Patients with non-small cell lung
      cancer have a risk of the tumour in the lung recurring or progressing after treatment.

      In this study, the investigators aim to verify the following hypothesis:

        -  whether in combination with concurrent or concomitant EGFR-TKI regimen chemotherapy,
           Intensity Modulated Radiation Therapy can reduce the risk of the tumour in the lung
           recurring or progressing similarily.

        -  Intensity Modulated Radiation Therapy concomitant with EGFR-TKI has a better normal
           tissue dose/volume tolerance than concurrent regimen.

        -  the survival can be improved by using this new molecular Target-radiotherapy method.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Therapeutic efficacy of EGFR-TKI and concurrent/concomitant local RT in NSCLC patients.
time frame: >4 weeks post treatment
description: Tumor Response will be evaluated using the RECIST system. Modified WHO criteria will be used for measurement of tumors. The irradiated lesion will be excluded from the assessment of response.
measure: Overall survival (OS)
time frame: Up to 5 years
description: Overall survival is defined as the time interval from date of diagnosis to date of death from any cause
measure: Progression-free survival (PFS)
time frame: Up to 5 years
description: PFS is defined as the duration of time from start of treatment to time of progression or death, whichever occurs first.
Progressive disease (PD) = at least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study, appearance of one or more non-target lesion(s) and/or unequivocal progression of existing non-target lesions
measure: Objective response rate(ORR)
time frame: Up to 5 years
description: Partial response + complete response per RECIST 1.1 criteria Complete response (CR) = disappearance of all target lesions, non-target lesions, and normalization of tumor marker level
Partial response (PR) = at least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline of sum diameters
measure: Disease control rate (DCR)
time frame: Up to 5 years
description: Percentage of patients who achieve complete response, partial response, or stable disease per RECIST 1.1 criteria.
Complete response (CR) = disappearance of all target lesions, non-target lesions, and normalization of tumor marker level
Partial response (PR) = at least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline of sum diameters
Stable Disease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters while on study.
measure: Adverse events (toxicities)
time frame: Up to 5 years
description: The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 will be utilized for all toxicity reporting.
measure: Local regional progression-free survival（LRPFS）
time frame: Time Frame: Up to 5 years
description: LRPFS is defined as the duration of time from start of treatment to time of progression or recurrence, whichever occurs first..The target lesions is only for primary tumor and regional positive lymph nodes.
Progressive disease (PD) = at least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study, appearance of one or more target lesion(s) and/or unequivocal progression of existing target lesions.
arm group label: Mutation+ concurrent
arm group type: Experimental
description: IMRT concurrent with EGFR-TKI on paticipants with known sensitive EGFR mutations.
arm group label: Mutation+ concomitant
arm group type: Experimental
description: IMRT concomitant with EGFR-TKI on paticipants with known sensitive EGFR mutations.
intervention type: Drug
intervention name: EGFR-TK Inhibitor
description: ·EGFR-TKI：gefitinib will be administered 250mg/d ivgtt qd; icotinib will be administered 150mg/d ivgtt tid;
arm group label: Mutation+ concomitant
arm group label: Mutation+ concurrent
intervention type: Radiation
intervention name: Intensity Modulated Radiation Therapy
description: High dose group：DTGTV=70Gy；
first course radiotherapy：40Gy/20f/4w（DTPTV：36Gy/20f/4w）,2Gy/f/d；
late course radiotherapy：1.5Gy/f、2f/d、interval≥6 hs、DTGTV=30Gy（DTPTV=27Gy）。
Low dose group：DTGTV=50Gy;
first course radiotherapy：32Gy/16f/3w（DTPTV为28.8Gy/16f/3w），2Gy/f/d；
late course radiotherapy：1.5Gy/f、2f/d、interval≥6小时、DTGTV为18Gy（DTPTV为16.2Gy）。
arm group label: Mutation+ concomitant
arm group label: Mutation+ concurrent
criteria: 
gender: All
minimum age: 18 Years
maximum age: 80 Years
healthy volunteers: No
last name: Lu Bing, Director
role: Study Director
affiliation: ouyangww103173@163.com
last name: Lu Bing, Director
phone: 86-18275356814
email: ouyangww103173@163.com
facility: 
contact: 
country: China
responsible party type: Sponsor-Investigator
investigator affiliation: Guizhou Medical University
investigator full name: LuBing
investigator title: Director
mesh term: Lung Neoplasms
mesh term: Carcinoma, Non-Small-Cell Lung