<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/NCT01661790</url>
  </required_header>
  <id_info>
    <org_study_id>PLA304DN-001</org_study_id>
    <nct_id>NCT01661790</nct_id>
  </id_info>
  <brief_title>Intrapleural Bevacizumab and Cisplatin Therapy for Malignant Pleural Effusion Caused by Non-small Cell Lung Cancer</brief_title>
  <official_title>Open-labeled, Randomized, Multicenter Phase III Study of Adjuvant Chemotherapy Comparing Bevacizumab Plus Cisplatin With Cisplatin Regimen in Malignant Pleural Effusion of Advanced Stage Non-Small-Cell Lung Cancer Patients</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Chinese PLA General Hospital</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Roche Pharma AG</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>Chinese PLA General Hospital</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      To determine the efficacy and Safety of intrapleural Bevacizumab and cisplatin as a treatment&#xD;
      for malignant pleural effusions (MPE) in patients with non-small cell lung cancer (NSCLC).&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date>August 2009</start_date>
  <completion_date type="Actual">October 2012</completion_date>
  <primary_completion_date type="Actual">June 2012</primary_completion_date>
  <phase>Phase 3</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>Number of Participants With &quot;Complete Response&quot; and &quot;Partial Response&quot;</measure>
    <time_frame>from randomization, This treatment was given every two weeks,responses were made by biweekly</time_frame>
    <description>Response assessed by type-B ultrasonic tests; Complete remission (CR) was considered when the accumulated fluid had disappeared and was stable for at least four weeks; partial remission (PR) was considered when &gt;50% of the accumulated fluid had disappeared, symptoms had improved, and the remaining fluid had failed to increase for at least four weeks; The total efficiency ORR was calculated by taking the sum of CR+PR</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Median Progression Free Survival (PFS)</measure>
    <time_frame>baseline to biweekly,until disease progression</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Overall Survival (OS)</measure>
    <time_frame>randomization to four weeks,until death</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Adverse Reactions</measure>
    <time_frame>Up to 1 month after the last treatment</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Qualify of Life (QoL)</measure>
    <time_frame>baseline to biweekly,until death</time_frame>
  </secondary_outcome>
  <other_outcome>
    <measure>Quantitative RT-PCR(Reverse Transcription-Polymerase Chain Reaction) for VEGF-A(Vascular Endothelial Growth Factor A)</measure>
    <time_frame>before intrapleural administration</time_frame>
  </other_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">72</enrollment>
  <condition>Malignant Pleural Effusion</condition>
  <arm_group>
    <arm_group_label>Bevacizumab &amp; Cisplatin</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Bevacizumab 300mg plus Cisplatin 30mg by intrapleural given every two weeks</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Cisplatin</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Cisplatin 30mg by intrapleural given every two weeks</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Bevacizumab</intervention_name>
    <description>Bevacizumab300mg&amp;Cispltin30mg by intrapleural administration of each 2 week</description>
    <arm_group_label>Bevacizumab &amp; Cisplatin</arm_group_label>
    <other_name>Avastin</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Cisplatin</intervention_name>
    <description>Cisplatin 30mg,intrapleural administration,each 2 week</description>
    <arm_group_label>Bevacizumab &amp; Cisplatin</arm_group_label>
    <arm_group_label>Cisplatin</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Patients with advanced recurrent or progressive NSCLC proven cytohistologically&#xD;
&#xD;
          -  Karnofsky performance status (KPS) ≥60&#xD;
&#xD;
          -  Life expectancy ≥ 2 months&#xD;
&#xD;
          -  No history of severe diseases of major organs including liver, heart, and kidney&#xD;
&#xD;
          -  No previous intrapleural therapy&#xD;
&#xD;
          -  Written informed consent&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Active thoracic cavity or systemic bleeding&#xD;
&#xD;
          -  Active pleural or systemic infection.&#xD;
&#xD;
          -  Known sensitivity to Bevacizumab or Cisplatin&#xD;
&#xD;
          -  Refusal to participate in the study.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>85 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Nan Du</last_name>
    <role>Principal Investigator</role>
    <affiliation>PLA 304 hospital</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>PLA 304 hospital</name>
      <address>
        <city>Beijing</city>
        <state>Beijing</state>
        <zip>100048</zip>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>China</country>
  </location_countries>
  <verification_date>March 2015</verification_date>
  <study_first_submitted>July 25, 2012</study_first_submitted>
  <study_first_submitted_qc>August 6, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">August 10, 2012</study_first_posted>
  <results_first_submitted>February 16, 2015</results_first_submitted>
  <results_first_submitted_qc>March 13, 2015</results_first_submitted_qc>
  <results_first_posted type="Estimate">March 25, 2015</results_first_posted>
  <last_update_submitted>March 13, 2015</last_update_submitted>
  <last_update_submitted_qc>March 13, 2015</last_update_submitted_qc>
  <last_update_posted type="Estimate">March 25, 2015</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Chinese PLA General Hospital</investigator_affiliation>
    <investigator_full_name>DuNan</investigator_full_name>
    <investigator_title>director of oncology department in PLA 304 hospital</investigator_title>
  </responsible_party>
  <keyword>Bevacizumab;</keyword>
  <keyword>non-small cell lung cancer;</keyword>
  <keyword>malignant pleural effusion;</keyword>
  <keyword>intrapleural administration</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>
    <mesh_term>Pleural Effusion, Malignant</mesh_term>
    <mesh_term>Pleural Effusion</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Bevacizumab</mesh_term>
  </intervention_browse>

  <clinical_results>

    <participant_flow>
      <group_list>
        <group group_id="P1">
          <title>Bevacizumab &amp; Cisplatin</title>
          <description>Bevacizumab 300mg plus Cisplatin 30mg by intrapleural given every two weeks&#xD;
Bevacizumab: Bevacizumab300mg&amp;Cisplatin 30mg by intrapleural administration of each 2 week&#xD;
Cisplatin: Cisplatin 30mg,intrapleural administration,each 2 week</description>
        </group>
        <group group_id="P2">
          <title>Cisplatin</title>
          <description>Cisplatin 30mg by intrapleural given every two weeks&#xD;
Cisplatin: Cisplatin 30mg,intrapleural administration,Q2W</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="36"/>
                <participants group_id="P2" count="36"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="36"/>
                <participants group_id="P2" count="34"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="2"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Lost to Follow-up</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="2"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>Bevacizumab &amp; Cisplatin</title>
          <description>Bevacizumab 300mg plus Cisplatin 30mg by intrapleural given every two weeks&#xD;
Bevacizumab: Bevacizumab300mg&amp;Cisplatin 30mg by intrapleural administration of each 2 week&#xD;
Cisplatin: Cisplatin 30mg,intrapleural administration,Q2W</description>
        </group>
        <group group_id="B2">
          <title>Cisplatin</title>
          <description>Cisplatin 30mg by intrapleural given every two weeks&#xD;
Cisplatin: Cisplatin 30mg,intrapleural administration,Q2W</description>
        </group>
        <group group_id="B3">
          <title>Total</title>
          <description>Total of all reporting groups</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="36"/>
            <count group_id="B2" value="34"/>
            <count group_id="B3" value="70"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>&lt;=18 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Between 18 and 65 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="16"/>
                    <measurement group_id="B2" value="16"/>
                    <measurement group_id="B3" value="32"/>
                  </measurement_list>
                </category>
                <category>
                  <title>&gt;=65 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="20"/>
                    <measurement group_id="B2" value="18"/>
                    <measurement group_id="B3" value="38"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Sex: Female, Male</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Female</title>
                  <measurement_list>
                    <measurement group_id="B1" value="17"/>
                    <measurement group_id="B2" value="15"/>
                    <measurement group_id="B3" value="32"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="19"/>
                    <measurement group_id="B2" value="19"/>
                    <measurement group_id="B3" value="38"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Number of Participants With &quot;Complete Response&quot; and &quot;Partial Response&quot;</title>
        <description>Response assessed by type-B ultrasonic tests; Complete remission (CR) was considered when the accumulated fluid had disappeared and was stable for at least four weeks; partial remission (PR) was considered when &gt;50% of the accumulated fluid had disappeared, symptoms had improved, and the remaining fluid had failed to increase for at least four weeks; The total efficiency ORR was calculated by taking the sum of CR+PR</description>
        <time_frame>from randomization, This treatment was given every two weeks,responses were made by biweekly</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Bevacizumab &amp; Cisplatin</title>
            <description>Bevacizumab 300mg plus Cisplatin 30mg by intrapleural given every two weeks&#xD;
Bevacizumab: Bevacizumab300mg&amp;Cisplatin 30mg by intrapleural administration of each 2 week&#xD;
Cisplatin: Cisplatin 30mg,intrapleural administration,Q2W</description>
          </group>
          <group group_id="O2">
            <title>Cisplatin</title>
            <description>Cisplatin 30mg by intrapleural given every two weeks&#xD;
Cisplatin: Cisplatin 30mg,intrapleural administration,Q2W</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Participants With &quot;Complete Response&quot; and &quot;Partial Response&quot;</title>
          <description>Response assessed by type-B ultrasonic tests; Complete remission (CR) was considered when the accumulated fluid had disappeared and was stable for at least four weeks; partial remission (PR) was considered when &gt;50% of the accumulated fluid had disappeared, symptoms had improved, and the remaining fluid had failed to increase for at least four weeks; The total efficiency ORR was calculated by taking the sum of CR+PR</description>
          <units>participants</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="36"/>
                <count group_id="O2" value="34"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>CR</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="17"/>
                    <measurement group_id="O2" value="2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>PR</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="13"/>
                    <measurement group_id="O2" value="15"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Median Progression Free Survival (PFS)</title>
        <time_frame>baseline to biweekly,until disease progression</time_frame>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Overall Survival (OS)</title>
        <time_frame>randomization to four weeks,until death</time_frame>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Adverse Reactions</title>
        <time_frame>Up to 1 month after the last treatment</time_frame>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Qualify of Life (QoL)</title>
        <time_frame>baseline to biweekly,until death</time_frame>
      </outcome>
      <outcome>
        <type>Other Pre-specified</type>
        <title>Quantitative RT-PCR(Reverse Transcription-Polymerase Chain Reaction) for VEGF-A(Vascular Endothelial Growth Factor A)</title>
        <time_frame>before intrapleural administration</time_frame>
      </outcome>
    </outcome_list>

    <reported_events>
      <group_list>
        <group group_id="E1">
          <title>Bevacizumab &amp; Cisplatin</title>
          <description>Bevacizumab 300mg plus Cisplatin 30mg by intrapleural given every two weeks&#xD;
Bevacizumab: Bevacizumab300mg&amp;Cisplatin 30mg by intrapleural administration of each 2 week&#xD;
Cisplatin: Cisplatin 30mg,intrapleural administration,Q2W</description>
        </group>
        <group group_id="E2">
          <title>Cisplatin</title>
          <description>Cisplatin 30mg by intrapleural given every two weeks&#xD;
Cisplatin: Cisplatin 30mg,intrapleural administration,Q2W</description>
        </group>
      </group_list>
      <serious_events>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="36"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="36"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>1</frequency_threshold>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, other adverse events</sub_title>
                <counts group_id="E1" subjects_affected="24" subjects_at_risk="36"/>
                <counts group_id="E2" subjects_affected="22" subjects_at_risk="36"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Blood and lymphatic system disorders</title>
            <event_list>
              <event>
                <sub_title>Leucocytopenia</sub_title>
                <counts group_id="E1" events="24" subjects_affected="24" subjects_at_risk="36"/>
                <counts group_id="E2" events="22" subjects_affected="22" subjects_at_risk="36"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </other_events>
    </reported_events>

    <certain_agreements>
      <pi_employee>All Principal Investigators ARE employed by the organization sponsoring the study.</pi_employee>
      <restrictive_agreement>There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed. </restrictive_agreement>
    </certain_agreements>
    <point_of_contact>
      <name_or_title>Dr. Nan Du</name_or_title>
      <organization>China PLA General Hospital</organization>
      <phone>86-13911599657</phone>
      <email>dunan05@aliyun.com</email>
    </point_of_contact>
  </clinical_results>
</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/NCT01661790
org study id: PLA304DN-001
nct id: NCT01661790
lead sponsor: 
collaborator: 
has dmc: Yes
To determine the efficacy and Safety of intrapleural Bevacizumab and cisplatin as a treatment
      for malignant pleural effusions (MPE) in patients with non-small cell lung cancer (NSCLC).
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Number of Participants With "Complete Response" and "Partial Response"
time frame: from randomization, This treatment was given every two weeks,responses were made by biweekly
description: Response assessed by type-B ultrasonic tests; Complete remission (CR) was considered when the accumulated fluid had disappeared and was stable for at least four weeks; partial remission (PR) was considered when >50% of the accumulated fluid had disappeared, symptoms had improved, and the remaining fluid had failed to increase for at least four weeks; The total efficiency ORR was calculated by taking the sum of CR+PR
measure: Median Progression Free Survival (PFS)
time frame: baseline to biweekly,until disease progression
measure: Overall Survival (OS)
time frame: randomization to four weeks,until death
measure: Adverse Reactions
time frame: Up to 1 month after the last treatment
measure: Qualify of Life (QoL)
time frame: baseline to biweekly,until death
measure: Quantitative RT-PCR(Reverse Transcription-Polymerase Chain Reaction) for VEGF-A(Vascular Endothelial Growth Factor A)
time frame: before intrapleural administration
arm group label: Bevacizumab & Cisplatin
arm group type: Experimental
description: Bevacizumab 300mg plus Cisplatin 30mg by intrapleural given every two weeks
arm group label: Cisplatin
arm group type: Active Comparator
description: Cisplatin 30mg by intrapleural given every two weeks
intervention type: Drug
intervention name: Bevacizumab
description: Bevacizumab300mg&Cispltin30mg by intrapleural administration of each 2 week
arm group label: Bevacizumab & Cisplatin
other name: Avastin
intervention type: Drug
intervention name: Cisplatin
description: Cisplatin 30mg,intrapleural administration,each 2 week
arm group label: Bevacizumab & Cisplatin
arm group label: Cisplatin
criteria: 
gender: All
minimum age: 18 Years
maximum age: 85 Years
healthy volunteers: No
last name: Nan Du
role: Principal Investigator
affiliation: PLA 304 hospital
facility: 
country: China
responsible party type: Principal Investigator
investigator affiliation: Chinese PLA General Hospital
investigator full name: DuNan
investigator title: director of oncology department in PLA 304 hospital
mesh term: Lung Neoplasms
mesh term: Carcinoma, Non-Small-Cell Lung
mesh term: Pleural Effusion, Malignant
mesh term: Pleural Effusion
mesh term: Bevacizumab
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 