<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/NCT01733589</url>
  </required_header>
  <id_info>
    <org_study_id>[2012]-10-24</org_study_id>
    <nct_id>NCT01733589</nct_id>
  </id_info>
  <brief_title>Recombinant Human Endostatin Continued Pumping Into Vein Combining With CCRT in Unresectable Stage III NSCLC</brief_title>
  <official_title>Multicenter Phase I/II Clinical Trial of Recombinant Human Endostatin Continued Pumping Into Vein Combining With Concurrent Chemo-Radiotherapy in the Patients With Unresectable Stage III Non-small-Cell Lung Cancer</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Zhejiang Cancer Hospital</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Cancer Institute and Hospital, Chinese Academy of Medical Sciences</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Fudan University</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Peking University Cancer Hospital &amp; Institute</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Tianjin Medical University Cancer Institute and Hospital</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Shandong Cancer Hospital and Institute</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Jiangsu Cancer Institute &amp; Hospital</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Fujian Cancer Hospital</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>The First People's Hospital of Lianyungang</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Zhejiang Cancer Hospital</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      Resistance of hypoxic tumor cells to radiation is a significant reason of failure in the&#xD;
      local control of tumors, especially the squamous cell carcinomas. Preclinical models have&#xD;
      shown that Endostar may transiently &quot;normalize&quot; the tumor vasculature to make it more&#xD;
      efficient for oxygen delivery, thereby providing a window of opportunity for enhanced&#xD;
      sensitivity to radiation treatment. This study is to evaluate the safety, toxicity, and&#xD;
      efficacy of the addition of Endostar Continued Pumping into Vein to the standard CCRT regimen&#xD;
      in patients with unresectable stage III NSCLC.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Primary&#xD;
&#xD;
      Evaluate the efficacy and safety of Endostar combined with concurrent chemo-radiotherapy&#xD;
      (CCRT) in patients with unresectable stage III non-small-cell lung cancer (NSCLC).&#xD;
&#xD;
      Secondary&#xD;
&#xD;
      Measure changes in VEGF and other angiogenic cytokines and antiangiogenic factors in plasma&#xD;
      samples from these patients.&#xD;
&#xD;
      Evaluate the application of CT perfusion imaging to determine changes in tumor vascular&#xD;
      mophology and function during treatment.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">November 2012</start_date>
  <completion_date type="Actual">June 2015</completion_date>
  <primary_completion_date type="Actual">June 2015</primary_completion_date>
  <phase>Phase 1/Phase 2</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>N/A</allocation>
    <intervention_model>Single Group 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>2-year</time_frame>
    <description>from beginning treatment to progressive disease or the last follow-up</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Response rate</measure>
    <time_frame>1 month</time_frame>
    <description>complete response(CR); partial response(PR); stable disease(SD); progressive disease(PD)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>overall survival</measure>
    <time_frame>5 years</time_frame>
    <description>from date of beginning treatment until date of death</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>treatment related toxicities</measure>
    <time_frame>3 months</time_frame>
    <description>radiation-induced esophagitis; radiation-induced pneumonia</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">73</enrollment>
  <condition>Stage III Non-small-Cell Lung Cancer</condition>
  <arm_group>
    <arm_group_label>Recombinant Human Endostatin</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>All patients received recombinant human endostatin(7.5mg/m2/24h) Continued Pumping Into Vein through 5 days at week 1, 3, 5, and 7. During week 2 through 8, patients received etoposide 50mg/m2 days 1-5 and cisplatin 50mg/m2 on day 1,8, every 4 weeks for two cycles with concurrent thoracic radiation at 60~66Gy in 30~33 fractions for 6~7 weeks.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Recombinant human endostatin</intervention_name>
    <description>Recombinant human endostatin(7.5mg/m2/24h) Continued Pumping Into Vein through 5 days at week 1, 3, 5, and 7,combined with concurrent chemo-radiotherapy.</description>
    <arm_group_label>Recombinant Human Endostatin</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Etoposide (50mg/m2) IV (in the vein) on day 1 to day 5 of a 28-day cycle for 2 cycles</intervention_name>
    <arm_group_label>Recombinant Human Endostatin</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>cisplatinum (50mg/m2) IV (in the vein) on day 1 and day 8 of a 28-day cycle for 2 cycles</intervention_name>
    <arm_group_label>Recombinant Human Endostatin</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>laboratory biomarker analysis</intervention_name>
    <arm_group_label>Recombinant Human Endostatin</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>CT perfusion imaging</intervention_name>
    <arm_group_label>Recombinant Human Endostatin</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  untreated histologic or cytologic of NSCLC verified&#xD;
&#xD;
          -  inoperable stage IIIA or IIIB NSCLC&#xD;
&#xD;
          -  measurable disease by RECIST&#xD;
&#xD;
          -  18~70 years of age&#xD;
&#xD;
          -  an ECOG PS of 0 to 1&#xD;
&#xD;
          -  absolute neutrophil count (ANC) of ≥1500/μL, hemoglobin ≥10gm/dL, platelet ≥100,000/μL&#xD;
&#xD;
          -  serum creatinine ≤1.25 times of upper limit of normal (ULN), calculated creatinine&#xD;
             clearance (CrCl) of ≥60ml/min&#xD;
&#xD;
          -  bilirubin 1.5×ULN, AST and ALT less than 2.5×ULN, alkaline phosphatase less than 5×ULN&#xD;
&#xD;
          -  forced vital capacity in 1 second (FEV1) higher than 0.8 L&#xD;
&#xD;
          -  CB6 is normal&#xD;
&#xD;
          -  Written informed consent&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  a history of other malignant diseases&#xD;
&#xD;
          -  any contraindications for chemoradiotherapy&#xD;
&#xD;
          -  distant metastasis&#xD;
&#xD;
          -  malignant pleural and/or pericardial effusion&#xD;
&#xD;
          -  pregnant or nursing&#xD;
&#xD;
          -  preexisting bleeding diatheses or coagulopathy&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>70 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Ming Chen, M.D.</last_name>
    <role>Principal Investigator</role>
    <affiliation>Zhejiang Cancer Hospital</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Zhejiang Cancer Hospital</name>
      <address>
        <city>Hangzhou</city>
        <state>Zhejiang</state>
        <zip>310022</zip>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>China</country>
  </location_countries>
  <verification_date>July 2017</verification_date>
  <study_first_submitted>November 2, 2012</study_first_submitted>
  <study_first_submitted_qc>November 20, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">November 27, 2012</study_first_posted>
  <last_update_submitted>July 11, 2017</last_update_submitted>
  <last_update_submitted_qc>July 11, 2017</last_update_submitted_qc>
  <last_update_posted type="Actual">July 14, 2017</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Recombinant human endostatin</keyword>
  <keyword>Non-small-Cell Lung Cancer</keyword>
  <keyword>chemoradiotherapy</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>Etoposide</mesh_term>
    <mesh_term>Cisplatin</mesh_term>
    <mesh_term>Endostatins</mesh_term>
  </intervention_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/NCT01733589
org study id: [2012]-10-24
nct id: NCT01733589
lead sponsor: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
has dmc: Yes
Resistance of hypoxic tumor cells to radiation is a significant reason of failure in the
      local control of tumors, especially the squamous cell carcinomas. Preclinical models have
      shown that Endostar may transiently "normalize" the tumor vasculature to make it more
      efficient for oxygen delivery, thereby providing a window of opportunity for enhanced
      sensitivity to radiation treatment. This study is to evaluate the safety, toxicity, and
      efficacy of the addition of Endostar Continued Pumping into Vein to the standard CCRT regimen
      in patients with unresectable stage III NSCLC.
Primary

      Evaluate the efficacy and safety of Endostar combined with concurrent chemo-radiotherapy
      (CCRT) in patients with unresectable stage III non-small-cell lung cancer (NSCLC).

      Secondary

      Measure changes in VEGF and other angiogenic cytokines and antiangiogenic factors in plasma
      samples from these patients.

      Evaluate the application of CT perfusion imaging to determine changes in tumor vascular
      mophology and function during treatment.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: progression-free survival
time frame: 2-year
description: from beginning treatment to progressive disease or the last follow-up
measure: Response rate
time frame: 1 month
description: complete response(CR); partial response(PR); stable disease(SD); progressive disease(PD)
measure: overall survival
time frame: 5 years
description: from date of beginning treatment until date of death
measure: treatment related toxicities
time frame: 3 months
description: radiation-induced esophagitis; radiation-induced pneumonia
arm group label: Recombinant Human Endostatin
arm group type: Experimental
description: All patients received recombinant human endostatin(7.5mg/m2/24h) Continued Pumping Into Vein through 5 days at week 1, 3, 5, and 7. During week 2 through 8, patients received etoposide 50mg/m2 days 1-5 and cisplatin 50mg/m2 on day 1,8, every 4 weeks for two cycles with concurrent thoracic radiation at 60~66Gy in 30~33 fractions for 6~7 weeks.
intervention type: Drug
intervention name: Recombinant human endostatin
description: Recombinant human endostatin(7.5mg/m2/24h) Continued Pumping Into Vein through 5 days at week 1, 3, 5, and 7,combined with concurrent chemo-radiotherapy.
arm group label: Recombinant Human Endostatin
intervention type: Drug
intervention name: Etoposide (50mg/m2) IV (in the vein) on day 1 to day 5 of a 28-day cycle for 2 cycles
arm group label: Recombinant Human Endostatin
intervention type: Drug
intervention name: cisplatinum (50mg/m2) IV (in the vein) on day 1 and day 8 of a 28-day cycle for 2 cycles
arm group label: Recombinant Human Endostatin
intervention type: Other
intervention name: laboratory biomarker analysis
arm group label: Recombinant Human Endostatin
intervention type: Other
intervention name: CT perfusion imaging
arm group label: Recombinant Human Endostatin
criteria: 
gender: All
minimum age: 18 Years
maximum age: 70 Years
healthy volunteers: No
last name: Ming Chen, M.D.
role: Principal Investigator
affiliation: Zhejiang Cancer Hospital
facility: 
country: China
responsible party type: Sponsor
mesh term: Lung Neoplasms
mesh term: Carcinoma, Non-Small-Cell Lung
mesh term: Etoposide
mesh term: Cisplatin
mesh term: Endostatins