<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/NCT02261805</url>
  </required_header>
  <id_info>
    <org_study_id>2013-1195</org_study_id>
    <nct_id>NCT02261805</nct_id>
  </id_info>
  <brief_title>A Phase I/II Study of Ganetespib in Combination With Doxorubicin</brief_title>
  <official_title>A Phase I/II Study of Ganetespib in Combination With Doxorubicin in Solid Tumors (Phase I) and Refractory Small Cell Lung Cancer (Safety Dose Expansion, Phase II)</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Georgetown University</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Synta Pharmaceuticals Corp.</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>Georgetown University</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      This is a Phase I/safety dose expansion study of the combination of the drug ganetespib and&#xD;
      doxorubicin in patients with advanced solid tumors. The purpose of the Phase I part of the&#xD;
      study is to determine the recommended phase II dose of ganetespib when given in combination&#xD;
      with doxorubicin. The recommended Phase II dose determined at the end of the dose escalation&#xD;
      phase will be used to conduct a safety dose expansion phase in relapsed/refractory small cell&#xD;
      lung cancer to determine if there is a signal of efficacy in this population.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The dose escalation phase of the study will follow a standard 3+ 3 dose escalation scheme&#xD;
      with two dose levels of ganetespib (1-- mg/m2 and 150 mg/m2) administered weekly on Days 1&#xD;
      and 8 of a 21-day cycle, in combination with a fixed dose of doxorubicin at 50 mg/m2&#xD;
      administered on Day 1 alone. After 4-6 cycles of combination therapy, continuation of single&#xD;
      agent ganetespib will be permitted for subjects who are deriving clinical benefit.&#xD;
&#xD;
      Pharmacokinetic samples for plasma drug levels of ganetespib will be collected pre-dose and 4&#xD;
      hours after completion of treatment on Day 1 and Day 8 of cycle 1 only in subjects in the&#xD;
      dose escalation phase.&#xD;
&#xD;
      The recommended Phase II dose determined at the end of the dose escalation phase will be used&#xD;
      to conduct a safety dose expansion phase in relapsed/ refractory small cell lung cancer to&#xD;
      determine if there is a signal of efficacy in this population.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Terminated</overall_status>
  <why_stopped>
    Company terminated drug support&#xD;
  </why_stopped>
  <start_date type="Actual">October 2014</start_date>
  <completion_date type="Actual">October 2016</completion_date>
  <primary_completion_date type="Actual">October 2016</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>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>Maximum Tolerated Dose</measure>
    <time_frame>1 year</time_frame>
    <description>The dose of ganetespib at which 1 or more out of 3-6 patients experiences a dose-limiting toxicity</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Objective Response Rate</measure>
    <time_frame>2 years</time_frame>
    <description>Objective response rate included the count of confirmed complete responses (CR) and partial responses (PR) and was based on Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1.</description>
  </secondary_outcome>
  <number_of_arms>3</number_of_arms>
  <enrollment type="Actual">11</enrollment>
  <condition>Cancer</condition>
  <condition>Small Cell Lung Cancer</condition>
  <arm_group>
    <arm_group_label>Ganetespib and doxorubicin - Phase Ib Dose Level 1</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Ganetespib 100 mg/m2 IV on days 1 and 8 of a 21-day cycle Doxorubicin 50 mg/m2 IV on day 1 of a 21-day cycle</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Ganetespib and doxorubicin - Phase Ib Dose Level 2</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Ganetespib 150 mg/m2 IV on days 1 and 8 of a 21-day cycle Doxorubicin 50 mg/m2 IV on day 1 of a 21-day cycle</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Ganetespib and doxorubicin - Phase II Expansion</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Ganetespib 150 mg/m2 IV on days 1 and 8 of a 21-day cycle Doxorubicin 50 mg/m2 IV on day 1 of a 21-day cycle</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Ganetespib</intervention_name>
    <arm_group_label>Ganetespib and doxorubicin - Phase II Expansion</arm_group_label>
    <arm_group_label>Ganetespib and doxorubicin - Phase Ib Dose Level 1</arm_group_label>
    <arm_group_label>Ganetespib and doxorubicin - Phase Ib Dose Level 2</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Doxorubicin</intervention_name>
    <arm_group_label>Ganetespib and doxorubicin - Phase II Expansion</arm_group_label>
    <arm_group_label>Ganetespib and doxorubicin - Phase Ib Dose Level 1</arm_group_label>
    <arm_group_label>Ganetespib and doxorubicin - Phase Ib Dose Level 2</arm_group_label>
    <other_name>Adriamycin</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Dose escalation phase: histologically confirmed malignancy that is metastatic or&#xD;
             unresectable and for which standard curative or palliative measures do not exist or&#xD;
             are no longer effective. OR safety dose expansion phase: histologically or&#xD;
             cytologically confirmed relapsed or refractory small cell lung cancer&#xD;
&#xD;
          -  No more than 3 prior lines of chemotherapy; prior therapy with doxorubicin is&#xD;
             permitted but no more than lifetime cumulative dose of 150 mg/m2; at least 3 weeks&#xD;
             since prior chemotherapy or radiotherapy; at least 6 weeks if the last regimen&#xD;
             included BCNU (1,3-bis(2-chloroethyl)-1-nitrosourea bis-chloronitrosourea) or&#xD;
             mitomycin C&#xD;
&#xD;
          -  Age &gt;/= 18 years&#xD;
&#xD;
          -  ECOG (Eastern Cooperative Oncology Group) performance status 0-1&#xD;
&#xD;
          -  Life expectancy of greater than 3 months&#xD;
&#xD;
          -  Adequate organ and marrow function&#xD;
&#xD;
          -  Women of child-bearing potential must agree to avoid becoming pregnant and men must&#xD;
             agree not to father a child for the duration of study participation.&#xD;
&#xD;
          -  Ability to understand and willingness to sign a written informed consent document&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Chemotherapy or radiotherapy within 3 weeks (6 weeks for nitrosureas or mitomycin C)&#xD;
             prior to entering the study or those who have not recovered from adverse events due to&#xD;
             agents administered more than 3 weeks earlier.&#xD;
&#xD;
          -  Receiving any other investigational agents&#xD;
&#xD;
          -  Untreated symptomatic brain metastases&#xD;
&#xD;
          -  History of allergic reactions attributed to compounds of similar chemical or biologic&#xD;
             composition to ganetespib or other agents used in the study&#xD;
&#xD;
          -  Receiving any medications or substances that are strong inhibitors or inducers of&#xD;
             CYP3A4 or CYP2C18&#xD;
&#xD;
          -  Left ventricular ejection fraction &lt; 50%&#xD;
&#xD;
          -  Known serious cardiac illness or medical conditions&#xD;
&#xD;
          -  uncontrolled inter-current illness including, but not limited to, ongoing or active&#xD;
             infection, unstable angina pectoris, or psychiatric illness/social situations that&#xD;
             would limit compliance with study requirements.&#xD;
&#xD;
          -  Pregnant women&#xD;
&#xD;
          -  HIV-positive on combination antiretroviral therapy&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Giuseppe Giaccone, MD PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Georgetown University</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Georgetown Lombardi Comprehensive Cancer Center</name>
      <address>
        <city>Washington</city>
        <state>District of Columbia</state>
        <zip>20007</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>March 2018</verification_date>
  <study_first_submitted>October 7, 2014</study_first_submitted>
  <study_first_submitted_qc>October 7, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">October 10, 2014</study_first_posted>
  <results_first_submitted>January 12, 2018</results_first_submitted>
  <results_first_submitted_qc>January 12, 2018</results_first_submitted_qc>
  <results_first_posted type="Actual">February 7, 2018</results_first_posted>
  <last_update_submitted>March 22, 2018</last_update_submitted>
  <last_update_submitted_qc>March 22, 2018</last_update_submitted_qc>
  <last_update_posted type="Actual">April 23, 2018</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Lung Neoplasms</mesh_term>
    <mesh_term>Small Cell Lung Carcinoma</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Doxorubicin</mesh_term>
  </intervention_browse>

  <clinical_results>

    <participant_flow>
      <group_list>
        <group group_id="P1">
          <title>Ganetespib and Doxorubicin - Phase Ib Dose Level 1</title>
          <description>Ganetespib 100 mg/m2 IV on days 1 and 8 of a 21-day cycle Doxorubicin 50 mg/m2 IV on day 1 of a 21-day cycle</description>
        </group>
        <group group_id="P2">
          <title>Ganetespib and Doxorubicin - Phase Ib Dose Level 2</title>
          <description>Ganetespib 150 mg/m2 IV on days 1 and 8 of a 21-day cycle Doxorubicin 50 mg/m2 IV on day 1 of a 21-day cycle</description>
        </group>
        <group group_id="P3">
          <title>Ganetespib and Doxorubicin - Phase II Expansion</title>
          <description>Ganetespib 150 mg/m2 IV on days 1 and 8 of a 21-day cycle Doxorubicin 50 mg/m2 IV on day 1 of a 21-day cycle</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="3"/>
                <participants group_id="P2" count="6"/>
                <participants group_id="P3" count="2"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="3"/>
                <participants group_id="P2" count="6"/>
                <participants group_id="P3" count="2"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="0"/>
              </participants_list>
            </milestone>
          </milestone_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>Ganetespib and Doxorubicin</title>
          <description>Ganetespib 100 or 150 mg/m2 IV on days 1 and 8 of a 21-day cycle Doxorubicin 50 mg/m2 IV on day 1 of a 21-day cycle Ganetespib and doxorubicin&#xD;
Ganetespib and doxorubicin: IV ganetespib and doxorubicin</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="11"/>
          </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_list>
                </category>
                <category>
                  <title>Between 18 and 65 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="9"/>
                  </measurement_list>
                </category>
                <category>
                  <title>&gt;=65 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="2"/>
                  </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="4"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="7"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Maximum Tolerated Dose</title>
        <description>The dose of ganetespib at which 1 or more out of 3-6 patients experiences a dose-limiting toxicity</description>
        <time_frame>1 year</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Ganetespib and Doxorubicin - Phase Ib Dose Level 1</title>
            <description>Ganetespib 100 mg/m2 IV on days 1 and 8 of a 21-day cycle Doxorubicin 50 mg/m2 IV on day 1 of a 21-day cycle</description>
          </group>
          <group group_id="O2">
            <title>Ganetespib and Doxorubicin - Phase Ib Dose Level 2</title>
            <description>Ganetespib 150 mg/m2 IV on days 1 and 8 of a 21-day cycle Doxorubicin 50 mg/m2 IV on day 1 of a 21-day cycle</description>
          </group>
        </group_list>
        <measure>
          <title>Maximum Tolerated Dose</title>
          <description>The dose of ganetespib at which 1 or more out of 3-6 patients experiences a dose-limiting toxicity</description>
          <units>mg/m^2</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="3"/>
                <count group_id="O2" value="6"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="100"/>
                    <measurement group_id="O2" value="150"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Objective Response Rate</title>
        <description>Objective response rate included the count of confirmed complete responses (CR) and partial responses (PR) and was based on Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1.</description>
        <time_frame>2 years</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Ganetespib and Doxorubicin - Phase Ib Dose Level 1</title>
            <description>Ganetespib 100 mg/m2 IV on days 1 and 8 of a 21-day cycle Doxorubicin 50 mg/m2 IV on day 1 of a 21-day cycle</description>
          </group>
          <group group_id="O2">
            <title>Ganetespib and Doxorubicin - Phase Ib Dose Level 2</title>
            <description>Ganetespib 150 mg/m2 IV on days 1 and 8 of a 21-day cycle Doxorubicin 50 mg/m2 IV on day 1 of a 21-day cycle</description>
          </group>
          <group group_id="O3">
            <title>Ganetespib and Doxorubicin - Phase II Expansion</title>
            <description>Ganetespib 150 mg/m2 IV on days 1 and 8 of a 21-day cycle Doxorubicin 50 mg/m2 IV on day 1 of a 21-day cycle</description>
          </group>
        </group_list>
        <measure>
          <title>Objective Response Rate</title>
          <description>Objective response rate included the count of confirmed complete responses (CR) and partial responses (PR) and was based on Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1.</description>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="3"/>
                <count group_id="O2" value="6"/>
                <count group_id="O3" value="2"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                    <measurement group_id="O2" value="1"/>
                    <measurement group_id="O3" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <desc>Adverse events were reported as pooling all subjects together and were not broken out by group.</desc>
      <group_list>
        <group group_id="E1">
          <title>Ganetespib and Doxorubicin</title>
          <description>Ganetespib 100 or 150 mg/m2 IV on days 1 and 8 of a 21-day cycle Doxorubicin 50 mg/m2 IV on day 1 of a 21-day cycle</description>
        </group>
      </group_list>
      <serious_events>
        <default_assessment>Systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, all-cause mortality</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="11"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="11"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Immune system disorders</title>
            <event_list>
              <event>
                <sub_title>Neutrophil count decreased</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="11"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>0</frequency_threshold>
        <default_assessment>Systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, other adverse events</sub_title>
                <counts group_id="E1" subjects_affected="11" subjects_at_risk="11"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Blood and lymphatic system disorders</title>
            <event_list>
              <event>
                <sub_title>Alkaline phosphatase increased</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="11"/>
              </event>
              <event>
                <sub_title>Anemia</sub_title>
                <counts group_id="E1" events="4" subjects_affected="3" subjects_at_risk="11"/>
              </event>
              <event>
                <sub_title>Hyponatremia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="11"/>
              </event>
              <event>
                <sub_title>Hypokalemia</sub_title>
                <counts group_id="E1" events="3" subjects_affected="3" subjects_at_risk="11"/>
              </event>
              <event>
                <sub_title>Hypophosphatemia</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="11"/>
              </event>
              <event>
                <sub_title>Platelet count decreased</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="11"/>
              </event>
              <event>
                <sub_title>Thrombocytopenia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="11"/>
              </event>
              <event>
                <sub_title>Elavated LDH</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="11"/>
              </event>
              <event>
                <sub_title>Hypermagnesemia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="11"/>
              </event>
              <event>
                <sub_title>Hypomagnesemia</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="11"/>
              </event>
              <event>
                <sub_title>Leukopenia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="11"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Eye disorders</title>
            <event_list>
              <event>
                <sub_title>Blurred vision</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="11"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Constipation</sub_title>
                <counts group_id="E1" events="3" subjects_affected="3" subjects_at_risk="11"/>
              </event>
              <event>
                <sub_title>Diarrhea</sub_title>
                <counts group_id="E1" events="10" subjects_affected="5" subjects_at_risk="11"/>
              </event>
              <event>
                <sub_title>Dyspepsia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="11"/>
              </event>
              <event>
                <sub_title>Gastrointestinal anastomotic leak</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="11"/>
              </event>
              <event>
                <sub_title>Weight loss</sub_title>
                <counts group_id="E1" events="3" subjects_affected="3" subjects_at_risk="11"/>
              </event>
              <event>
                <sub_title>Epigastric pain</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="11"/>
              </event>
              <event>
                <sub_title>Vomiting</sub_title>
                <counts group_id="E1" events="2" subjects_affected="1" subjects_at_risk="11"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Fatigue</sub_title>
                <counts group_id="E1" events="7" subjects_affected="6" subjects_at_risk="11"/>
              </event>
              <event>
                <sub_title>Nausea</sub_title>
                <counts group_id="E1" events="8" subjects_affected="8" subjects_at_risk="11"/>
              </event>
              <event>
                <sub_title>Anorexia</sub_title>
                <counts group_id="E1" events="4" subjects_affected="3" subjects_at_risk="11"/>
              </event>
              <event>
                <sub_title>Insomnia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="11"/>
              </event>
              <event>
                <sub_title>Infusion related reaction</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="11"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Hepatobiliary disorders</title>
            <event_list>
              <event>
                <sub_title>Aspartate aminotransferase increased</sub_title>
                <counts group_id="E1" events="3" subjects_affected="2" subjects_at_risk="11"/>
              </event>
              <event>
                <sub_title>Hypoalbuminemia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="11"/>
              </event>
              <event>
                <sub_title>AST elevation</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="11"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Immune system disorders</title>
            <event_list>
              <event>
                <sub_title>Neutrophil count decreased</sub_title>
                <counts group_id="E1" events="4" subjects_affected="4" subjects_at_risk="11"/>
              </event>
              <event>
                <sub_title>Lymphocyte count decreased</sub_title>
                <counts group_id="E1" events="2" subjects_affected="1" subjects_at_risk="11"/>
              </event>
              <event>
                <sub_title>White blood cell decreased</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="11"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Musculoskeletal and connective tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Joint effusion</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="11"/>
              </event>
              <event>
                <sub_title>Back stiffness</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="11"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Dysgeusia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="11"/>
              </event>
              <event>
                <sub_title>Headache</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="11"/>
              </event>
              <event>
                <sub_title>Pain</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="11"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Psychiatric disorders</title>
            <event_list>
              <event>
                <sub_title>Depression</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="11"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Dyspnea</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="11"/>
              </event>
              <event>
                <sub_title>Cough</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="11"/>
              </event>
              <event>
                <sub_title>Hoarseness</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="11"/>
              </event>
              <event>
                <sub_title>Shortness of Breath</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="11"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Skin and subcutaneous tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Rash maculo-papular</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="11"/>
              </event>
              <event>
                <sub_title>Alopecia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="11"/>
              </event>
              <event>
                <sub_title>Mucositis oral</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="11"/>
              </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>Giuseppe Giaccone</name_or_title>
      <organization>Lombardi Comprehensive Cancer Center</organization>
      <phone>202-687-7072</phone>
      <email>gg496@georgetown.edu</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/NCT02261805
org study id: 2013-1195
nct id: NCT02261805
lead sponsor: 
collaborator: 
has dmc: Yes
This is a Phase I/safety dose expansion study of the combination of the drug ganetespib and
      doxorubicin in patients with advanced solid tumors. The purpose of the Phase I part of the
      study is to determine the recommended phase II dose of ganetespib when given in combination
      with doxorubicin. The recommended Phase II dose determined at the end of the dose escalation
      phase will be used to conduct a safety dose expansion phase in relapsed/refractory small cell
      lung cancer to determine if there is a signal of efficacy in this population.
The dose escalation phase of the study will follow a standard 3+ 3 dose escalation scheme
      with two dose levels of ganetespib (1-- mg/m2 and 150 mg/m2) administered weekly on Days 1
      and 8 of a 21-day cycle, in combination with a fixed dose of doxorubicin at 50 mg/m2
      administered on Day 1 alone. After 4-6 cycles of combination therapy, continuation of single
      agent ganetespib will be permitted for subjects who are deriving clinical benefit.

      Pharmacokinetic samples for plasma drug levels of ganetespib will be collected pre-dose and 4
      hours after completion of treatment on Day 1 and Day 8 of cycle 1 only in subjects in the
      dose escalation phase.

      The recommended Phase II dose determined at the end of the dose escalation phase will be used
      to conduct a safety dose expansion phase in relapsed/ refractory small cell lung cancer to
      determine if there is a signal of efficacy in this population.
allocation: Non-Randomized
intervention model: Sequential Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Maximum Tolerated Dose
time frame: 1 year
description: The dose of ganetespib at which 1 or more out of 3-6 patients experiences a dose-limiting toxicity
measure: Objective Response Rate
time frame: 2 years
description: Objective response rate included the count of confirmed complete responses (CR) and partial responses (PR) and was based on Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1.
arm group label: Ganetespib and doxorubicin - Phase Ib Dose Level 1
arm group type: Experimental
description: Ganetespib 100 mg/m2 IV on days 1 and 8 of a 21-day cycle Doxorubicin 50 mg/m2 IV on day 1 of a 21-day cycle
arm group label: Ganetespib and doxorubicin - Phase Ib Dose Level 2
arm group type: Experimental
description: Ganetespib 150 mg/m2 IV on days 1 and 8 of a 21-day cycle Doxorubicin 50 mg/m2 IV on day 1 of a 21-day cycle
arm group label: Ganetespib and doxorubicin - Phase II Expansion
arm group type: Experimental
description: Ganetespib 150 mg/m2 IV on days 1 and 8 of a 21-day cycle Doxorubicin 50 mg/m2 IV on day 1 of a 21-day cycle
intervention type: Drug
intervention name: Ganetespib
arm group label: Ganetespib and doxorubicin - Phase II Expansion
arm group label: Ganetespib and doxorubicin - Phase Ib Dose Level 1
arm group label: Ganetespib and doxorubicin - Phase Ib Dose Level 2
intervention type: Drug
intervention name: Doxorubicin
arm group label: Ganetespib and doxorubicin - Phase II Expansion
arm group label: Ganetespib and doxorubicin - Phase Ib Dose Level 1
arm group label: Ganetespib and doxorubicin - Phase Ib Dose Level 2
other name: Adriamycin
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Giuseppe Giaccone, MD PhD
role: Principal Investigator
affiliation: Georgetown University
facility: 
country: United States
responsible party type: Sponsor
mesh term: Lung Neoplasms
mesh term: Small Cell Lung Carcinoma
mesh term: Doxorubicin
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 