<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/NCT03029611</url>
  </required_header>
  <id_info>
    <org_study_id>9760</org_study_id>
    <secondary_id>NCI-2017-00034</secondary_id>
    <secondary_id>RG1717017</secondary_id>
    <secondary_id>P30CA015704</secondary_id>
    <nct_id>NCT03029611</nct_id>
  </id_info>
  <brief_title>IGFBP-2 Vaccine and Combination Chemotherapy in Treating Patients With Stage III-IV Ovarian, Fallopian Tube, or Primary Peritoneal Cancer Undergoing Surgery</brief_title>
  <official_title>A Phase II Study of Concurrent IGFBP-2 Vaccination and Neoadjuvant Chemotherapy to Increase the Rate of Pathologic Complete Response at the Time of Cytoreductive Surgery</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of Washington</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>National Cancer Institute (NCI)</agency>
      <agency_class>NIH</agency_class>
    </collaborator>
  </sponsors>
  <source>University of Washington</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      This phase II trial studies how well pUMVC3-IGFBP2 plasmid deoxyribonucleic acid (DNA)&#xD;
      vaccine (IGFBP-2 vaccine) and combination chemotherapy work in treating patients with stage&#xD;
      III-IV ovarian, fallopian tube, or primary peritoneal cancer undergoing surgery. IGFBP-2 is a&#xD;
      protein found in the blood and tumor cells of most who have been diagnosed with ovarian&#xD;
      cancer. Too much IGFBP-2 has been associated with more invasive disease. Vaccines made from&#xD;
      DNA may help the body build an effective immune response to kill tumor cells that express&#xD;
      IGFBP-2. Drugs used in chemotherapy, such as paclitaxel and carboplatin, work in different&#xD;
      ways to stop the growth of tumor cells, either by killing the cells, by stopping them from&#xD;
      dividing, or by stopping them from spreading. Giving IGFBP-2 vaccine and combination&#xD;
      chemotherapy may work better in treating patients with stage III-IV ovarian, fallopian tube,&#xD;
      or primary peritoneal cancer undergoing surgery.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      PRIMARY OBJECTIVES:&#xD;
&#xD;
      I. Determine whether the addition of an IGFBP-2 vaccine to neoadjuvant chemotherapy increases&#xD;
      the rate of complete pathologic response (CR).&#xD;
&#xD;
      SECONDARY OBJECTIVES:&#xD;
&#xD;
      I. Determine whether the addition of an IGFBP-2 vaccine to neoadjuvant chemotherapy increases&#xD;
      progression free survival at 12 months.&#xD;
&#xD;
      II. Determine whether the addition of an IGFBP-2 vaccine to neoadjuvant chemotherapy improves&#xD;
      overall survival.&#xD;
&#xD;
      III. To determine whether IGFBP-2 vaccination in combination with chemotherapy increases the&#xD;
      level of tumor infiltrating lymphocytes (TIL) in the tumor.&#xD;
&#xD;
      IV. To assess the level of IGFBP-2 type 1 helper cells (Th1) elicited with vaccination&#xD;
      concurrent with chemotherapy.&#xD;
&#xD;
      EXPLORATORY OBJECTIVES:&#xD;
&#xD;
      I. To explore whether there is a predictive genomic signature for CR induction when IGFBP-2&#xD;
      vaccination is used in combination with chemotherapy.&#xD;
&#xD;
      OUTLINE:&#xD;
&#xD;
      Patients receive paclitaxel intravenously (IV) over 3 hours and carboplatin IV over 1 hour&#xD;
      followed by IGFBP-2 vaccine intradermally (ID) 2 weeks later. Treatment repeats every 3 weeks&#xD;
      for up to 3 cycles in the absence of disease progression or unacceptable toxicity. After&#xD;
      completion of 3 cycles, patients then undergo cytoreductive surgery.&#xD;
&#xD;
      After completion of study treatment, patients are followed up at 6 months and then once a&#xD;
      year for 5 years.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Terminated</overall_status>
  <why_stopped>
    Terminated due to lack of funding&#xD;
  </why_stopped>
  <start_date type="Actual">April 3, 2017</start_date>
  <completion_date type="Actual">December 10, 2019</completion_date>
  <primary_completion_date type="Actual">October 17, 2018</primary_completion_date>
  <phase>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>Rate of Pathologic Complete Response (CR)</measure>
    <time_frame>At the time of cytoreductive surgery after receiving study treatment (vaccinations given intradermally approximately two weeks after each combination chemotherapy for 3 doses.)</time_frame>
    <description>The tissue collected at time of cytoreductive surgery, post study treatment, was evaluated by the attending pathologist assigned to look at the tissue for viable tumor cells. The corresponding surgical pathology report was reviewed to evaluate individual pCR (absence of viable tumor cells).</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Immunohistochemistry (IHC) Staining for CD3, CD4, CD8, and CD27</measure>
    <time_frame>At the time of cytoreductive surgery</time_frame>
    <description>Will be performed and quantitated using published methods and will be correlated with surgical CR by the Man-Whitney U or one-way analysis of variance test depending on the distribution of TIL outcomes.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Level of IGFBP-2 Th1 Cells Elicited With Vaccine Assessed by Enzyme-linked Immunosorbent Spot Assay</measure>
    <time_frame>Up to 6 months after last vaccine</time_frame>
    <description>Will be correlated to tumor burden at definitive surgery.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Level of Tumor Infiltrating Lymphocytes (TIL) in Tumor</measure>
    <time_frame>At the time of cytoreductive surgery after receiving study treatment (vaccinations given intradermally approximately two weeks after each combination chemotherapy for 3 doses.)</time_frame>
    <description>Will be assessed by immunohistochemistry (IHC) to determine whether IGFBP-2 vaccination in combination with chemotherapy increases the level of TIL in the tumor. This was done by assessing the level of IGFBP-2 Th1 elicited by study treatment (vaccination concurrent with chemotherapy). we are looking for an increase in TIL.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Overall Survival (OS)</measure>
    <time_frame>Up to 5 years</time_frame>
    <description>Will be compared between the treatment arms. Large differences in PFS if observed between the treatment groups will be noted and described. Will be plotted by Kaplan-Meier curve, and compared to the survival data reported by Vergote et al which reported median PFS of 12 months and median OS of 30 months for patients treated with neoadjuvant chemotherapy by a log-rank test.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Progression Free Survival (PFS)</measure>
    <time_frame>Up to 12 months</time_frame>
    <description>Large differences in PFS if observed between the treatment groups will be noted and described. Will be plotted by Kaplan-Meier curve, and compared to the survival data reported by Vergote et al which reported median PFS of 12 months and median overall survival (OS) of 30 months for patients treated with neoadjuvant chemotherapy by a log-rank test.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Tumor Burden</measure>
    <time_frame>At the time of cytoreductive surgery</time_frame>
    <description>Will be correlated to level of IGFBP-2 Th1 cells.</description>
  </secondary_outcome>
  <other_outcome>
    <measure>Predictive Signature of CR Induction When Vaccinated With an IGFBP-2 Vaccine in Combination With Neoadjuvant Chemotherapy Assessed by Whole Exome Sequencing on Vaccinated Patients' Tumors</measure>
    <time_frame>At the time of cytoreductive surgery</time_frame>
    <description>Will use the LASSO regularized regression method to generate preliminary data for a predictive signature. Will correlate mutational profiles with primary platinum sensitive, resistance and refractory outcomes, leveraging the Cancer Genome Atlas data publicly available, to determine differences induced by vaccination.</description>
  </other_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">11</enrollment>
  <condition>Stage III Fallopian Tube Cancer</condition>
  <condition>Stage III Ovarian Cancer</condition>
  <condition>Stage III Primary Peritoneal Cancer</condition>
  <condition>Stage IIIA Fallopian Tube Cancer</condition>
  <condition>Stage IIIA Ovarian Cancer</condition>
  <condition>Stage IIIA Primary Peritoneal Cancer</condition>
  <condition>Stage IIIB Fallopian Tube Cancer</condition>
  <condition>Stage IIIB Ovarian Cancer</condition>
  <condition>Stage IIIB Primary Peritoneal Cancer</condition>
  <condition>Stage IIIC Fallopian Tube Cancer</condition>
  <condition>Stage IIIC Ovarian Cancer</condition>
  <condition>Stage IIIC Primary Peritoneal Cancer</condition>
  <condition>Stage IV Fallopian Tube Cancer</condition>
  <condition>Stage IV Ovarian Cancer</condition>
  <condition>Stage IV Primary Peritoneal Cancer</condition>
  <arm_group>
    <arm_group_label>Treatment (chemotherapy, IGFBP-2 vaccine)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Patients receive paclitaxel IV over 3 hours and carboplatin IV over 1 hour followed by IGFBP-2 vaccine ID 2 weeks later. Treatment repeats every 3 weeks for up to 3 cycles in the absence of disease progression or unacceptable toxicity. After completion of 3 cycles, patients then undergo cytoreductive surgery.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Carboplatin</intervention_name>
    <description>Given IV</description>
    <arm_group_label>Treatment (chemotherapy, IGFBP-2 vaccine)</arm_group_label>
    <other_name>Blastocarb</other_name>
    <other_name>Carboplat</other_name>
    <other_name>Carboplatin Hexal</other_name>
    <other_name>Carboplatino</other_name>
    <other_name>Carbosin</other_name>
    <other_name>Carbosol</other_name>
    <other_name>Carbotec</other_name>
    <other_name>CBDCA</other_name>
    <other_name>Displata</other_name>
    <other_name>Ercar</other_name>
    <other_name>JM-8</other_name>
    <other_name>Nealorin</other_name>
    <other_name>Novoplatinum</other_name>
    <other_name>Paraplatin</other_name>
    <other_name>Paraplatin AQ</other_name>
    <other_name>Paraplatine</other_name>
    <other_name>Platinwas</other_name>
    <other_name>Ribocarbo</other_name>
  </intervention>
  <intervention>
    <intervention_type>Procedure</intervention_type>
    <intervention_name>Gynecological Surgical Procedure</intervention_name>
    <description>Undergo cytoreductive surgery</description>
    <arm_group_label>Treatment (chemotherapy, IGFBP-2 vaccine)</arm_group_label>
    <other_name>gynecologic surgery</other_name>
    <other_name>Gynecologic Surgical Procedure</other_name>
    <other_name>gynecologic surgical procedures</other_name>
    <other_name>gynecological surgery</other_name>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Laboratory Biomarker Analysis</intervention_name>
    <description>Correlative studies</description>
    <arm_group_label>Treatment (chemotherapy, IGFBP-2 vaccine)</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Paclitaxel</intervention_name>
    <description>Given IV</description>
    <arm_group_label>Treatment (chemotherapy, IGFBP-2 vaccine)</arm_group_label>
    <other_name>Anzatax</other_name>
    <other_name>Asotax</other_name>
    <other_name>Bristaxol</other_name>
    <other_name>Praxel</other_name>
    <other_name>Taxol</other_name>
    <other_name>Taxol Konzentrat</other_name>
  </intervention>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>pUMVC3-hIGFBP-2 Multi-Epitope Plasmid DNA Vaccine</intervention_name>
    <description>Given ID</description>
    <arm_group_label>Treatment (chemotherapy, IGFBP-2 vaccine)</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Patients with newly diagnosed advanced stage (III/IV) ovarian cancer&#xD;
             (ovarian/fallopian tube/peritoneal cancer) who have been recommended to receive&#xD;
             neoadjuvant carboplatin/paclitaxel chemotherapy with subsequent cytoreductive surgery&#xD;
&#xD;
          -  Patients must have Eastern Cooperative Oncology Group (ECOG) performance status score&#xD;
             of =&lt; 2&#xD;
&#xD;
          -  Patients must have recovered from major infections and/or surgical procedures, and in&#xD;
             the opinion of the investigator, not have any significant active concurrent medical&#xD;
             illnesses precluding protocol treatment&#xD;
&#xD;
          -  Estimated life expectancy of more than 6 months&#xD;
&#xD;
          -  White blood cells (WBC) &gt;= 3000/mm^3 within 30 days of enrollment to study&#xD;
&#xD;
          -  Hemoglobin (Hgb) &gt;= 10 g/dl within 30 days of enrollment to study&#xD;
&#xD;
          -  Hematocrit (Hct) &gt;= 28% within 30 days of enrollment to study&#xD;
&#xD;
          -  Serum creatinine =&lt; 2.0 mg/dl or creatinine clearance &gt; 60 ml/min within 30 days of&#xD;
             enrollment to study&#xD;
&#xD;
          -  Total bilirubin =&lt; 2.5 mg/dl within 30 days of enrollment to study&#xD;
&#xD;
          -  Aspartate aminotransferase (AST)/serum glutamic oxaloacetic transaminase (SGOT) =&lt; 3&#xD;
             times upper limit of normal (ULN) within 30 days of enrollment to study&#xD;
&#xD;
          -  Blood glucose &lt;1.5 ULN within 30 days of enrollment to study&#xD;
&#xD;
          -  All patients who are having sex that can lead to pregnancy must agree to contraception&#xD;
             for the duration of the study&#xD;
&#xD;
          -  Patients must be at least 18 years of age&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Patients with any of the following cardiac conditions:&#xD;
&#xD;
               -  Symptomatic restrictive cardiomyopathy&#xD;
&#xD;
               -  Unstable angina within 4 months prior to enrollment&#xD;
&#xD;
               -  New York Heart Association functional class III-IV heart failure on active&#xD;
                  treatment&#xD;
&#xD;
               -  Symptomatic pericardial effusion&#xD;
&#xD;
          -  Uncontrolled diabetes&#xD;
&#xD;
          -  History of (non-infectious) pneumonitis that required steroids or current pneumonitis&#xD;
&#xD;
          -  Patients with any contraindication to receiving rhuGM-CSF based products&#xD;
&#xD;
          -  Patients with any clinically significant autoimmune disease uncontrolled with&#xD;
             treatment&#xD;
&#xD;
          -  Patients who are currently receiving an anti-IGF-IR monoclonal antibody as part of&#xD;
             their treatment regimen&#xD;
&#xD;
          -  Patients who are simultaneously enrolled in any other treatment study&#xD;
&#xD;
          -  Patients who are pregnant or breastfeeding&#xD;
      </textblock>
    </criteria>
    <gender>Female</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>John Liao</last_name>
    <role>Principal Investigator</role>
    <affiliation>Fred Hutch/University of Washington Cancer Consortium</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Fred Hutch/University of Washington Cancer Consortium</name>
      <address>
        <city>Seattle</city>
        <state>Washington</state>
        <zip>98109</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>December 2021</verification_date>
  <study_first_submitted>January 10, 2017</study_first_submitted>
  <study_first_submitted_qc>January 20, 2017</study_first_submitted_qc>
  <study_first_posted type="Estimate">January 24, 2017</study_first_posted>
  <results_first_submitted>July 30, 2021</results_first_submitted>
  <results_first_submitted_qc>December 17, 2021</results_first_submitted_qc>
  <results_first_posted type="Actual">January 14, 2022</results_first_posted>
  <disposition_first_submitted>June 14, 2021</disposition_first_submitted>
  <disposition_first_submitted_qc>December 17, 2021</disposition_first_submitted_qc>
  <disposition_first_posted type="Actual">January 14, 2022</disposition_first_posted>
  <last_update_submitted>December 17, 2021</last_update_submitted>
  <last_update_submitted_qc>December 17, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">January 14, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>University of Washington</investigator_affiliation>
    <investigator_full_name>Mary (Nora) Disis</investigator_full_name>
    <investigator_title>Professor, Department of Medicine, Division of Oncology</investigator_title>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Ovarian Neoplasms</mesh_term>
    <mesh_term>Carcinoma, Ovarian Epithelial</mesh_term>
    <mesh_term>Fallopian Tube Neoplasms</mesh_term>
    <mesh_term>Peritoneal Neoplasms</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Paclitaxel</mesh_term>
    <mesh_term>Carboplatin</mesh_term>
    <mesh_term>Albumin-Bound Paclitaxel</mesh_term>
  </intervention_browse>
  <provided_document_section>
    <provided_document>
      <document_type>Study Protocol and Statistical Analysis Plan</document_type>
      <document_has_protocol>Yes</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>Yes</document_has_sap>
      <document_date>December 22, 2020</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/11/NCT03029611/Prot_SAP_001.pdf</document_url>
    </provided_document>
    <provided_document>
      <document_type>Informed Consent Form</document_type>
      <document_has_protocol>No</document_has_protocol>
      <document_has_icf>Yes</document_has_icf>
      <document_has_sap>No</document_has_sap>
      <document_date>December 22, 2020</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/11/NCT03029611/ICF_002.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <group_list>
        <group group_id="P1">
          <title>Treatment (Chemotherapy, IGFBP-2 Vaccine)</title>
          <description>Patients receive paclitaxel IV over 3 hours and carboplatin IV over 1 hour followed by IGFBP-2 vaccine ID 2 weeks later. Treatment repeats every 3 weeks for up to 3 cycles in the absence of disease progression or unacceptable toxicity. After completion of 3 cycles, patients then undergo cytoreductive surgery.&#xD;
Carboplatin: Given IV&#xD;
Gynecological Surgical Procedure: Undergo cytoreductive surgery&#xD;
Laboratory Biomarker Analysis: Correlative studies&#xD;
Paclitaxel: Given IV&#xD;
pUMVC3-hIGFBP-2 Multi-Epitope Plasmid DNA Vaccine: Given ID</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="9">We had 11 patients sign consent with 2 patients deciding not to continue to receive treatment.</participants>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="9">Please note that we did not fully enroll this study due to lack of funding. The complete date here relates to the last treatment administration.</participants>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
              </participants_list>
            </milestone>
          </milestone_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <population>11 participants signed consent 9 participants received treatment 9 participants completed all 3 vaccines and 1 month follow-up</population>
      <group_list>
        <group group_id="B1">
          <title>Treatment (Chemotherapy, IGFBP-2 Vaccine)</title>
          <description>Patients receive paclitaxel IV over 3 hours and carboplatin IV over 1 hour followed by IGFBP-2 vaccine ID 2 weeks later. Treatment repeats every 3 weeks for up to 3 cycles in the absence of disease progression or unacceptable toxicity. After completion of 3 cycles, patients then undergo cytoreductive surgery.&#xD;
Carboplatin: Given IV&#xD;
Gynecological Surgical Procedure: Undergo cytoreductive surgery&#xD;
Laboratory Biomarker Analysis: Correlative studies&#xD;
Paclitaxel: Given IV&#xD;
pUMVC3-hIGFBP-2 Multi-Epitope Plasmid DNA Vaccine: Given ID</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="9"/>
          </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="5"/>
                  </measurement_list>
                </category>
                <category>
                  <title>&gt;=65 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Age</title>
          <units>years</units>
          <param>Mean</param>
          <dispersion>Full Range</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="64" lower_limit="54" upper_limit="77"/>
                  </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="9"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Ethnicity (NIH/OMB)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Not Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="9"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Race (NIH/OMB)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>American Indian or Alaska Native</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Asian</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Native Hawaiian or Other Pacific Islander</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Black or African American</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                  </measurement_list>
                </category>
                <category>
                  <title>White</title>
                  <measurement_list>
                    <measurement group_id="B1" value="7"/>
                  </measurement_list>
                </category>
                <category>
                  <title>More than one race</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Region of Enrollment</title>
          <units>participants</units>
          <param>Number</param>
          <class_list>
            <class>
              <title>United States</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="9"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Rate of Pathologic Complete Response (CR)</title>
        <description>The tissue collected at time of cytoreductive surgery, post study treatment, was evaluated by the attending pathologist assigned to look at the tissue for viable tumor cells. The corresponding surgical pathology report was reviewed to evaluate individual pCR (absence of viable tumor cells).</description>
        <time_frame>At the time of cytoreductive surgery after receiving study treatment (vaccinations given intradermally approximately two weeks after each combination chemotherapy for 3 doses.)</time_frame>
        <population>Review of the pathology report from cytoreductive surgery.</population>
        <group_list>
          <group group_id="O1">
            <title>Treatment (Chemotherapy, IGFBP-2 Vaccine)</title>
            <description>Patients receive paclitaxel IV over 3 hours and carboplatin IV over 1 hour followed by IGFBP-2 vaccine ID 2 weeks later. Treatment repeats every 3 weeks for up to 3 cycles in the absence of disease progression or unacceptable toxicity. After completion of 3 cycles, patients then undergo cytoreductive surgery.&#xD;
Carboplatin: Given IV&#xD;
Gynecological Surgical Procedure: Undergo cytoreductive surgery&#xD;
Laboratory Biomarker Analysis: Correlative studies&#xD;
Paclitaxel: Given IV&#xD;
pUMVC3-hIGFBP-2 Multi-Epitope Plasmid DNA Vaccine: Given ID</description>
          </group>
        </group_list>
        <measure>
          <title>Rate of Pathologic Complete Response (CR)</title>
          <description>The tissue collected at time of cytoreductive surgery, post study treatment, was evaluated by the attending pathologist assigned to look at the tissue for viable tumor cells. The corresponding surgical pathology report was reviewed to evaluate individual pCR (absence of viable tumor cells).</description>
          <population>Review of the pathology report from cytoreductive surgery.</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="9"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Immunohistochemistry (IHC) Staining for CD3, CD4, CD8, and CD27</title>
        <description>Will be performed and quantitated using published methods and will be correlated with surgical CR by the Man-Whitney U or one-way analysis of variance test depending on the distribution of TIL outcomes.</description>
        <time_frame>At the time of cytoreductive surgery</time_frame>
        <population>Target enrollment was not met. Samples were collected but planned laboratory/statistical analyses were not performed due to termination of study, lack of funding, and insufficient enrollment.</population>
        <group_list>
          <group group_id="O1">
            <title>Treatment (Chemotherapy, IGFBP-2 Vaccine)</title>
            <description>Patients receive paclitaxel IV over 3 hours and carboplatin IV over 1 hour followed by IGFBP-2 vaccine ID 2 weeks later. Treatment repeats every 3 weeks for up to 3 cycles in the absence of disease progression or unacceptable toxicity. After completion of 3 cycles, patients then undergo cytoreductive surgery.&#xD;
Carboplatin: Given IV&#xD;
Gynecological Surgical Procedure: Undergo cytoreductive surgery&#xD;
Laboratory Biomarker Analysis: Correlative studies&#xD;
Paclitaxel: Given IV&#xD;
pUMVC3-hIGFBP-2 Multi-Epitope Plasmid DNA Vaccine: Given ID</description>
          </group>
        </group_list>
        <measure>
          <title>Immunohistochemistry (IHC) Staining for CD3, CD4, CD8, and CD27</title>
          <description>Will be performed and quantitated using published methods and will be correlated with surgical CR by the Man-Whitney U or one-way analysis of variance test depending on the distribution of TIL outcomes.</description>
          <population>Target enrollment was not met. Samples were collected but planned laboratory/statistical analyses were not performed due to termination of study, lack of funding, and insufficient enrollment.</population>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="0"/>
              </count_list>
            </analyzed>
          </analyzed_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Level of IGFBP-2 Th1 Cells Elicited With Vaccine Assessed by Enzyme-linked Immunosorbent Spot Assay</title>
        <description>Will be correlated to tumor burden at definitive surgery.</description>
        <time_frame>Up to 6 months after last vaccine</time_frame>
        <population>Target enrollment was not met. Samples were collected but planned laboratory/statistical analyses were not performed due to termination of study, lack of funding, and insufficient enrollment.</population>
        <group_list>
          <group group_id="O1">
            <title>Treatment (Chemotherapy, IGFBP-2 Vaccine)</title>
            <description>Patients receive paclitaxel IV over 3 hours and carboplatin IV over 1 hour followed by IGFBP-2 vaccine ID 2 weeks later. Treatment repeats every 3 weeks for up to 3 cycles in the absence of disease progression or unacceptable toxicity. After completion of 3 cycles, patients then undergo cytoreductive surgery.&#xD;
Carboplatin: Given IV&#xD;
Gynecological Surgical Procedure: Undergo cytoreductive surgery&#xD;
Laboratory Biomarker Analysis: Correlative studies&#xD;
Paclitaxel: Given IV&#xD;
pUMVC3-hIGFBP-2 Multi-Epitope Plasmid DNA Vaccine: Given ID</description>
          </group>
        </group_list>
        <measure>
          <title>Level of IGFBP-2 Th1 Cells Elicited With Vaccine Assessed by Enzyme-linked Immunosorbent Spot Assay</title>
          <description>Will be correlated to tumor burden at definitive surgery.</description>
          <population>Target enrollment was not met. Samples were collected but planned laboratory/statistical analyses were not performed due to termination of study, lack of funding, and insufficient enrollment.</population>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="0"/>
              </count_list>
            </analyzed>
          </analyzed_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Level of Tumor Infiltrating Lymphocytes (TIL) in Tumor</title>
        <description>Will be assessed by immunohistochemistry (IHC) to determine whether IGFBP-2 vaccination in combination with chemotherapy increases the level of TIL in the tumor. This was done by assessing the level of IGFBP-2 Th1 elicited by study treatment (vaccination concurrent with chemotherapy). we are looking for an increase in TIL.</description>
        <time_frame>At the time of cytoreductive surgery after receiving study treatment (vaccinations given intradermally approximately two weeks after each combination chemotherapy for 3 doses.)</time_frame>
        <population>Target enrollment was not met. Samples were collected but planned laboratory/statistical analyses were not performed due to termination of study, lack of funding, and insufficient enrollment.</population>
        <group_list>
          <group group_id="O1">
            <title>Treatment (Chemotherapy, IGFBP-2 Vaccine)</title>
            <description>Patients receive paclitaxel IV over 3 hours and carboplatin IV over 1 hour followed by IGFBP-2 vaccine ID 2 weeks later. Treatment repeats every 3 weeks for up to 3 cycles in the absence of disease progression or unacceptable toxicity. After completion of 3 cycles, patients then undergo cytoreductive surgery.&#xD;
Carboplatin: Given IV&#xD;
Gynecological Surgical Procedure: Undergo cytoreductive surgery&#xD;
Laboratory Biomarker Analysis: Correlative studies&#xD;
Paclitaxel: Given IV&#xD;
pUMVC3-hIGFBP-2 Multi-Epitope Plasmid DNA Vaccine: Given ID</description>
          </group>
        </group_list>
        <measure>
          <title>Level of Tumor Infiltrating Lymphocytes (TIL) in Tumor</title>
          <description>Will be assessed by immunohistochemistry (IHC) to determine whether IGFBP-2 vaccination in combination with chemotherapy increases the level of TIL in the tumor. This was done by assessing the level of IGFBP-2 Th1 elicited by study treatment (vaccination concurrent with chemotherapy). we are looking for an increase in TIL.</description>
          <population>Target enrollment was not met. Samples were collected but planned laboratory/statistical analyses were not performed due to termination of study, lack of funding, and insufficient enrollment.</population>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="0"/>
              </count_list>
            </analyzed>
          </analyzed_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Overall Survival (OS)</title>
        <description>Will be compared between the treatment arms. Large differences in PFS if observed between the treatment groups will be noted and described. Will be plotted by Kaplan-Meier curve, and compared to the survival data reported by Vergote et al which reported median PFS of 12 months and median OS of 30 months for patients treated with neoadjuvant chemotherapy by a log-rank test.</description>
        <time_frame>Up to 5 years</time_frame>
        <population>Target enrollment was not met. The study was terminated. Planned statistical analysis was not performed due to termination of study, lack of funding, and insufficient enrollment.</population>
        <group_list>
          <group group_id="O1">
            <title>Treatment (Chemotherapy, IGFBP-2 Vaccine)</title>
            <description>Patients receive paclitaxel IV over 3 hours and carboplatin IV over 1 hour followed by IGFBP-2 vaccine ID 2 weeks later. Treatment repeats every 3 weeks for up to 3 cycles in the absence of disease progression or unacceptable toxicity. After completion of 3 cycles, patients then undergo cytoreductive surgery.&#xD;
Carboplatin: Given IV&#xD;
Gynecological Surgical Procedure: Undergo cytoreductive surgery&#xD;
Laboratory Biomarker Analysis: Correlative studies&#xD;
Paclitaxel: Given IV&#xD;
pUMVC3-hIGFBP-2 Multi-Epitope Plasmid DNA Vaccine: Given ID</description>
          </group>
        </group_list>
        <measure>
          <title>Overall Survival (OS)</title>
          <description>Will be compared between the treatment arms. Large differences in PFS if observed between the treatment groups will be noted and described. Will be plotted by Kaplan-Meier curve, and compared to the survival data reported by Vergote et al which reported median PFS of 12 months and median OS of 30 months for patients treated with neoadjuvant chemotherapy by a log-rank test.</description>
          <population>Target enrollment was not met. The study was terminated. Planned statistical analysis was not performed due to termination of study, lack of funding, and insufficient enrollment.</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="9"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Alive</title>
                  <measurement_list>
                    <measurement group_id="O1" value="6"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Deceased - passed away after they left the study</title>
                  <measurement_list>
                    <measurement group_id="O1" value="3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Progression Free Survival (PFS)</title>
        <description>Large differences in PFS if observed between the treatment groups will be noted and described. Will be plotted by Kaplan-Meier curve, and compared to the survival data reported by Vergote et al which reported median PFS of 12 months and median overall survival (OS) of 30 months for patients treated with neoadjuvant chemotherapy by a log-rank test.</description>
        <time_frame>Up to 12 months</time_frame>
        <population>Target enrollment was not met. The study was terminated. Planned statistical analysis was not performed due to termination of study, lack of funding, and insufficient enrollment.</population>
        <group_list>
          <group group_id="O1">
            <title>Treatment (Chemotherapy, IGFBP-2 Vaccine)</title>
            <description>Patients receive paclitaxel IV over 3 hours and carboplatin IV over 1 hour followed by IGFBP-2 vaccine ID 2 weeks later. Treatment repeats every 3 weeks for up to 3 cycles in the absence of disease progression or unacceptable toxicity. After completion of 3 cycles, patients then undergo cytoreductive surgery.&#xD;
Carboplatin: Given IV&#xD;
Gynecological Surgical Procedure: Undergo cytoreductive surgery&#xD;
Laboratory Biomarker Analysis: Correlative studies&#xD;
Paclitaxel: Given IV&#xD;
pUMVC3-hIGFBP-2 Multi-Epitope Plasmid DNA Vaccine: Given ID</description>
          </group>
        </group_list>
        <measure>
          <title>Progression Free Survival (PFS)</title>
          <description>Large differences in PFS if observed between the treatment groups will be noted and described. Will be plotted by Kaplan-Meier curve, and compared to the survival data reported by Vergote et al which reported median PFS of 12 months and median overall survival (OS) of 30 months for patients treated with neoadjuvant chemotherapy by a log-rank test.</description>
          <population>Target enrollment was not met. The study was terminated. Planned statistical analysis was not performed due to termination of study, lack of funding, and insufficient enrollment.</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="9"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>PFS</title>
                  <measurement_list>
                    <measurement group_id="O1" value="2"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Recurrence</title>
                  <measurement_list>
                    <measurement group_id="O1" value="2"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Deceased - passed away after they left the study</title>
                  <measurement_list>
                    <measurement group_id="O1" value="3"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Status unchanged</title>
                  <measurement_list>
                    <measurement group_id="O1" value="2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Tumor Burden</title>
        <description>Will be correlated to level of IGFBP-2 Th1 cells.</description>
        <time_frame>At the time of cytoreductive surgery</time_frame>
        <population>Target enrollment was not met. The study was terminated. Planned statistical analysis was not performed due to termination of study, lack of funding, and insufficient enrollment.</population>
        <group_list>
          <group group_id="O1">
            <title>Treatment (Chemotherapy, IGFBP-2 Vaccine)</title>
            <description>Patients receive paclitaxel IV over 3 hours and carboplatin IV over 1 hour followed by IGFBP-2 vaccine ID 2 weeks later. Treatment repeats every 3 weeks for up to 3 cycles in the absence of disease progression or unacceptable toxicity. After completion of 3 cycles, patients then undergo cytoreductive surgery.&#xD;
Carboplatin: Given IV&#xD;
Gynecological Surgical Procedure: Undergo cytoreductive surgery&#xD;
Laboratory Biomarker Analysis: Correlative studies&#xD;
Paclitaxel: Given IV&#xD;
pUMVC3-hIGFBP-2 Multi-Epitope Plasmid DNA Vaccine: Given ID</description>
          </group>
        </group_list>
        <measure>
          <title>Tumor Burden</title>
          <description>Will be correlated to level of IGFBP-2 Th1 cells.</description>
          <population>Target enrollment was not met. The study was terminated. Planned statistical analysis was not performed due to termination of study, lack of funding, and insufficient enrollment.</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="9"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Debulking surgery</title>
                  <measurement_list>
                    <measurement group_id="O1" value="7"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Not evaluable</title>
                  <measurement_list>
                    <measurement group_id="O1" value="2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Other Pre-specified</type>
        <title>Predictive Signature of CR Induction When Vaccinated With an IGFBP-2 Vaccine in Combination With Neoadjuvant Chemotherapy Assessed by Whole Exome Sequencing on Vaccinated Patients' Tumors</title>
        <description>Will use the LASSO regularized regression method to generate preliminary data for a predictive signature. Will correlate mutational profiles with primary platinum sensitive, resistance and refractory outcomes, leveraging the Cancer Genome Atlas data publicly available, to determine differences induced by vaccination.</description>
        <time_frame>At the time of cytoreductive surgery</time_frame>
        <population>Target enrollment was not met. Samples were collected but planned laboratory/statistical analyses were not performed due to termination of study, lack of funding, and insufficient enrollment.</population>
        <group_list>
          <group group_id="O1">
            <title>Treatment (Chemotherapy, IGFBP-2 Vaccine)</title>
            <description>Patients receive paclitaxel IV over 3 hours and carboplatin IV over 1 hour followed by IGFBP-2 vaccine ID 2 weeks later. Treatment repeats every 3 weeks for up to 3 cycles in the absence of disease progression or unacceptable toxicity. After completion of 3 cycles, patients then undergo cytoreductive surgery.&#xD;
Carboplatin: Given IV&#xD;
Gynecological Surgical Procedure: Undergo cytoreductive surgery&#xD;
Laboratory Biomarker Analysis: Correlative studies&#xD;
Paclitaxel: Given IV&#xD;
pUMVC3-hIGFBP-2 Multi-Epitope Plasmid DNA Vaccine: Given ID</description>
          </group>
        </group_list>
        <measure>
          <title>Predictive Signature of CR Induction When Vaccinated With an IGFBP-2 Vaccine in Combination With Neoadjuvant Chemotherapy Assessed by Whole Exome Sequencing on Vaccinated Patients' Tumors</title>
          <description>Will use the LASSO regularized regression method to generate preliminary data for a predictive signature. Will correlate mutational profiles with primary platinum sensitive, resistance and refractory outcomes, leveraging the Cancer Genome Atlas data publicly available, to determine differences induced by vaccination.</description>
          <population>Target enrollment was not met. Samples were collected but planned laboratory/statistical analyses were not performed due to termination of study, lack of funding, and insufficient enrollment.</population>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="0"/>
              </count_list>
            </analyzed>
          </analyzed_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>The Adverse Events were collected after first vaccination and through to 6 months post vaccination.</time_frame>
      <desc>We used CTCAE v4.0 for this study. The adverse events reported here include all events regardless of whether they were unrelated and related to study treatment). Please note that these tables record every adverse event for every subject regardless of severity. For example, a subject may have an injection site reaction at each of the three vaccines where another may not. Each one of these injection site reactions is recorded for that one subject.</desc>
      <group_list>
        <group group_id="E1">
          <title>Treatment (Chemotherapy, IGFBP-2 Vaccine)</title>
          <description>Patients receive paclitaxel IV over 3 hours and carboplatin IV over 1 hour followed by IGFBP-2 vaccine ID 2 weeks later. Treatment repeats every 3 weeks for up to 3 cycles in the absence of disease progression or unacceptable toxicity. After completion of 3 cycles, patients then undergo cytoreductive surgery.&#xD;
Carboplatin: Given IV&#xD;
Gynecological Surgical Procedure: Undergo cytoreductive surgery&#xD;
Laboratory Biomarker Analysis: Correlative studies&#xD;
Paclitaxel: Given IV&#xD;
pUMVC3-hIGFBP-2 Multi-Epitope Plasmid DNA Vaccine: Given ID</description>
        </group>
      </group_list>
      <serious_events>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, all-cause mortality</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="9"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="9"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>0</frequency_threshold>
        <default_assessment>Non-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="9" subjects_at_risk="9"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Blood and lymphatic system disorders</title>
            <event_list>
              <event>
                <sub_title>Anemia</sub_title>
                <description>4 of 6 events are unrelated to study treatment</description>
                <counts group_id="E1" events="6" subjects_affected="5" subjects_at_risk="9"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Cardiac disorders</title>
            <event_list>
              <event>
                <sub_title>Palpitations</sub_title>
                <description>1 of 2 events is unrelated to study treatment</description>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="9"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Diarrhea</sub_title>
                <description>Unrelated to study treatment</description>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="9"/>
              </event>
              <event>
                <sub_title>Nausea</sub_title>
                <description>1 of 3 events is unrelated to the study treatment</description>
                <counts group_id="E1" events="3" subjects_affected="2" subjects_at_risk="9"/>
              </event>
              <event>
                <sub_title>Vomiting</sub_title>
                <description>1 of 3 events is unrelated to the study treatment</description>
                <counts group_id="E1" events="3" subjects_affected="2" subjects_at_risk="9"/>
              </event>
              <event>
                <sub_title>Constipation</sub_title>
                <description>2 of 5 events are unrelated to the study treatment</description>
                <counts group_id="E1" events="5" subjects_affected="4" subjects_at_risk="9"/>
              </event>
              <event>
                <sub_title>Abdominal distension</sub_title>
                <description>Unrelated to study treatment</description>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="9"/>
              </event>
              <event>
                <sub_title>Abdominal pain</sub_title>
                <description>Unrelated to study treatment</description>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="9"/>
              </event>
              <event>
                <sub_title>Ascites</sub_title>
                <description>Unrelated to study treatment</description>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="9"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Fatigue</sub_title>
                <counts group_id="E1" events="3" subjects_affected="2" subjects_at_risk="9"/>
              </event>
              <event>
                <sub_title>Edema limbs</sub_title>
                <description>Unrelated to study treatment</description>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="9"/>
              </event>
              <event>
                <sub_title>Non-cardiac chest pain</sub_title>
                <description>Unrelated to study treatment</description>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="9"/>
              </event>
              <event>
                <sub_title>Pain</sub_title>
                <description>5 of 6 events are unrelated to the study drug</description>
                <counts group_id="E1" events="6" subjects_affected="5" subjects_at_risk="9"/>
              </event>
              <event>
                <sub_title>Injection site reaction</sub_title>
                <counts group_id="E1" events="4" subjects_affected="4" subjects_at_risk="9"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Urinary tract infection</sub_title>
                <description>1 of 2 events is unrelated to study treatment</description>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="9"/>
              </event>
              <event>
                <sub_title>Other Infection</sub_title>
                <description>Unrelated to study treatment</description>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="9"/>
              </event>
              <event>
                <sub_title>Wound infection</sub_title>
                <description>Unrelated to study treatment</description>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="9"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Investigations</title>
            <event_list>
              <event>
                <sub_title>White blood cell decreased</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="9"/>
              </event>
              <event>
                <sub_title>Platelet count decreased</sub_title>
                <description>Unrelated to study treatment</description>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="9"/>
              </event>
              <event>
                <sub_title>Weight loss</sub_title>
                <description>Unrelated to study treatment</description>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="9"/>
              </event>
              <event>
                <sub_title>Creatinine increased</sub_title>
                <description>Unrelated to study treatment</description>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="9"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Metabolism and nutrition disorders</title>
            <event_list>
              <event>
                <sub_title>Hypocalcemia</sub_title>
                <description>Unrelated to study treatment</description>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="9"/>
              </event>
              <event>
                <sub_title>Hypoalbuminemia</sub_title>
                <description>Unrelated to study treatment</description>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="9"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Musculoskeletal and connective tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Arthralgia</sub_title>
                <counts group_id="E1" events="4" subjects_affected="3" subjects_at_risk="9"/>
              </event>
              <event>
                <sub_title>Myalgia</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="9"/>
              </event>
              <event>
                <sub_title>Bone pain</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="9"/>
              </event>
              <event>
                <sub_title>Other - leg weakness</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="9"/>
              </event>
              <event>
                <sub_title>Other - &quot;pulled muscle&quot; in left upper quadrant</sub_title>
                <description>Unrelated to study treatment</description>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="9"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Cognitive disturbance</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="9"/>
              </event>
              <event>
                <sub_title>Dizziness</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="9"/>
              </event>
              <event>
                <sub_title>Headache</sub_title>
                <description>1 of 3 events is unrelated to the study treatment</description>
                <counts group_id="E1" events="3" subjects_affected="3" subjects_at_risk="9"/>
              </event>
              <event>
                <sub_title>Peripheral sensory neuropathy</sub_title>
                <counts group_id="E1" events="5" subjects_affected="5" subjects_at_risk="9"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Renal and urinary disorders</title>
            <event_list>
              <event>
                <sub_title>Cystitis noninfective</sub_title>
                <description>Unrelated to study treatment</description>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="9"/>
              </event>
              <event>
                <sub_title>Hematuria</sub_title>
                <description>Unrelated to study treatment</description>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="9"/>
              </event>
              <event>
                <sub_title>Acute kidney injury</sub_title>
                <description>Unrelated to study treatment</description>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="9"/>
              </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="1" subjects_affected="1" subjects_at_risk="9"/>
              </event>
              <event>
                <sub_title>Pleural effusion</sub_title>
                <description>Unrelated to study treatment</description>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="9"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Skin and subcutaneous tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Rash acneiform</sub_title>
                <description>Unrelated to study treatment</description>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="9"/>
              </event>
              <event>
                <sub_title>Rash maculo-papular</sub_title>
                <description>Unrelated to study treatment</description>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="9"/>
              </event>
              <event>
                <sub_title>Alopecia</sub_title>
                <description>1 of 12 events are unrelated to the study treatment</description>
                <counts group_id="E1" events="12" subjects_affected="9" subjects_at_risk="9"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Surgical and medical procedures</title>
            <event_list>
              <event>
                <sub_title>Other - paracentisis</sub_title>
                <description>Unrelated to study treatment</description>
                <counts group_id="E1" events="4" subjects_affected="4" subjects_at_risk="9"/>
              </event>
              <event>
                <sub_title>Other - IVC filter placed due to clots</sub_title>
                <description>Unrelated to study treatment</description>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="9"/>
              </event>
              <event>
                <sub_title>Other - thoracentesis x 2 due to pleural effusion. Hospitalized</sub_title>
                <description>Unrelated to study treatment</description>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="9"/>
              </event>
              <event>
                <sub_title>Other - ex-lap, RSO, omentectomy, appendectomy, tumor debulking</sub_title>
                <description>Unrelated to study treatment</description>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="9"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Vascular disorders</title>
            <event_list>
              <event>
                <sub_title>Flushing</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="9"/>
              </event>
              <event>
                <sub_title>Hypotension</sub_title>
                <description>Unrelated to study treatment</description>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="9"/>
              </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>Director of Clinical Operations</name_or_title>
      <organization>UWashington (University of Washington)</organization>
      <phone>206-616-2305</phone>
      <email>childj@u.washington.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/NCT03029611
org study id: 9760
secondary id: NCI-2017-00034
secondary id: RG1717017
secondary id: P30CA015704
nct id: NCT03029611
lead sponsor: 
collaborator: 
has dmc: No
is fda regulated drug: Yes
is fda regulated device: No
This phase II trial studies how well pUMVC3-IGFBP2 plasmid deoxyribonucleic acid (DNA)
      vaccine (IGFBP-2 vaccine) and combination chemotherapy work in treating patients with stage
      III-IV ovarian, fallopian tube, or primary peritoneal cancer undergoing surgery. IGFBP-2 is a
      protein found in the blood and tumor cells of most who have been diagnosed with ovarian
      cancer. Too much IGFBP-2 has been associated with more invasive disease. Vaccines made from
      DNA may help the body build an effective immune response to kill tumor cells that express
      IGFBP-2. Drugs used in chemotherapy, such as paclitaxel and carboplatin, work in different
      ways to stop the growth of tumor cells, either by killing the cells, by stopping them from
      dividing, or by stopping them from spreading. Giving IGFBP-2 vaccine and combination
      chemotherapy may work better in treating patients with stage III-IV ovarian, fallopian tube,
      or primary peritoneal cancer undergoing surgery.
PRIMARY OBJECTIVES:

      I. Determine whether the addition of an IGFBP-2 vaccine to neoadjuvant chemotherapy increases
      the rate of complete pathologic response (CR).

      SECONDARY OBJECTIVES:

      I. Determine whether the addition of an IGFBP-2 vaccine to neoadjuvant chemotherapy increases
      progression free survival at 12 months.

      II. Determine whether the addition of an IGFBP-2 vaccine to neoadjuvant chemotherapy improves
      overall survival.

      III. To determine whether IGFBP-2 vaccination in combination with chemotherapy increases the
      level of tumor infiltrating lymphocytes (TIL) in the tumor.

      IV. To assess the level of IGFBP-2 type 1 helper cells (Th1) elicited with vaccination
      concurrent with chemotherapy.

      EXPLORATORY OBJECTIVES:

      I. To explore whether there is a predictive genomic signature for CR induction when IGFBP-2
      vaccination is used in combination with chemotherapy.

      OUTLINE:

      Patients receive paclitaxel intravenously (IV) over 3 hours and carboplatin IV over 1 hour
      followed by IGFBP-2 vaccine intradermally (ID) 2 weeks later. Treatment repeats every 3 weeks
      for up to 3 cycles in the absence of disease progression or unacceptable toxicity. After
      completion of 3 cycles, patients then undergo cytoreductive surgery.

      After completion of study treatment, patients are followed up at 6 months and then once a
      year for 5 years.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Rate of Pathologic Complete Response (CR)
time frame: At the time of cytoreductive surgery after receiving study treatment (vaccinations given intradermally approximately two weeks after each combination chemotherapy for 3 doses.)
description: The tissue collected at time of cytoreductive surgery, post study treatment, was evaluated by the attending pathologist assigned to look at the tissue for viable tumor cells. The corresponding surgical pathology report was reviewed to evaluate individual pCR (absence of viable tumor cells).
measure: Immunohistochemistry (IHC) Staining for CD3, CD4, CD8, and CD27
time frame: At the time of cytoreductive surgery
description: Will be performed and quantitated using published methods and will be correlated with surgical CR by the Man-Whitney U or one-way analysis of variance test depending on the distribution of TIL outcomes.
measure: Level of IGFBP-2 Th1 Cells Elicited With Vaccine Assessed by Enzyme-linked Immunosorbent Spot Assay
time frame: Up to 6 months after last vaccine
description: Will be correlated to tumor burden at definitive surgery.
measure: Level of Tumor Infiltrating Lymphocytes (TIL) in Tumor
time frame: At the time of cytoreductive surgery after receiving study treatment (vaccinations given intradermally approximately two weeks after each combination chemotherapy for 3 doses.)
description: Will be assessed by immunohistochemistry (IHC) to determine whether IGFBP-2 vaccination in combination with chemotherapy increases the level of TIL in the tumor. This was done by assessing the level of IGFBP-2 Th1 elicited by study treatment (vaccination concurrent with chemotherapy). we are looking for an increase in TIL.
measure: Overall Survival (OS)
time frame: Up to 5 years
description: Will be compared between the treatment arms. Large differences in PFS if observed between the treatment groups will be noted and described. Will be plotted by Kaplan-Meier curve, and compared to the survival data reported by Vergote et al which reported median PFS of 12 months and median OS of 30 months for patients treated with neoadjuvant chemotherapy by a log-rank test.
measure: Progression Free Survival (PFS)
time frame: Up to 12 months
description: Large differences in PFS if observed between the treatment groups will be noted and described. Will be plotted by Kaplan-Meier curve, and compared to the survival data reported by Vergote et al which reported median PFS of 12 months and median overall survival (OS) of 30 months for patients treated with neoadjuvant chemotherapy by a log-rank test.
measure: Tumor Burden
time frame: At the time of cytoreductive surgery
description: Will be correlated to level of IGFBP-2 Th1 cells.
measure: Predictive Signature of CR Induction When Vaccinated With an IGFBP-2 Vaccine in Combination With Neoadjuvant Chemotherapy Assessed by Whole Exome Sequencing on Vaccinated Patients' Tumors
time frame: At the time of cytoreductive surgery
description: Will use the LASSO regularized regression method to generate preliminary data for a predictive signature. Will correlate mutational profiles with primary platinum sensitive, resistance and refractory outcomes, leveraging the Cancer Genome Atlas data publicly available, to determine differences induced by vaccination.
arm group label: Treatment (chemotherapy, IGFBP-2 vaccine)
arm group type: Experimental
description: Patients receive paclitaxel IV over 3 hours and carboplatin IV over 1 hour followed by IGFBP-2 vaccine ID 2 weeks later. Treatment repeats every 3 weeks for up to 3 cycles in the absence of disease progression or unacceptable toxicity. After completion of 3 cycles, patients then undergo cytoreductive surgery.
intervention type: Drug
intervention name: Carboplatin
description: Given IV
arm group label: Treatment (chemotherapy, IGFBP-2 vaccine)
other name: Blastocarb
other name: Carboplat
other name: Carboplatin Hexal
other name: Carboplatino
other name: Carbosin
other name: Carbosol
other name: Carbotec
other name: CBDCA
other name: Displata
other name: Ercar
other name: JM-8
other name: Nealorin
other name: Novoplatinum
other name: Paraplatin
other name: Paraplatin AQ
other name: Paraplatine
other name: Platinwas
other name: Ribocarbo
intervention type: Procedure
intervention name: Gynecological Surgical Procedure
description: Undergo cytoreductive surgery
arm group label: Treatment (chemotherapy, IGFBP-2 vaccine)
other name: gynecologic surgery
other name: Gynecologic Surgical Procedure
other name: gynecologic surgical procedures
other name: gynecological surgery
intervention type: Other
intervention name: Laboratory Biomarker Analysis
description: Correlative studies
arm group label: Treatment (chemotherapy, IGFBP-2 vaccine)
intervention type: Drug
intervention name: Paclitaxel
description: Given IV
arm group label: Treatment (chemotherapy, IGFBP-2 vaccine)
other name: Anzatax
other name: Asotax
other name: Bristaxol
other name: Praxel
other name: Taxol
other name: Taxol Konzentrat
intervention type: Biological
intervention name: pUMVC3-hIGFBP-2 Multi-Epitope Plasmid DNA Vaccine
description: Given ID
arm group label: Treatment (chemotherapy, IGFBP-2 vaccine)
criteria: 
gender: Female
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: John Liao
role: Principal Investigator
affiliation: Fred Hutch/University of Washington Cancer Consortium
facility: 
country: United States
responsible party type: Principal Investigator
investigator affiliation: University of Washington
investigator full name: Mary (Nora) Disis
investigator title: Professor, Department of Medicine, Division of Oncology
mesh term: Ovarian Neoplasms
mesh term: Carcinoma, Ovarian Epithelial
mesh term: Fallopian Tube Neoplasms
mesh term: Peritoneal Neoplasms
mesh term: Paclitaxel
mesh term: Carboplatin
mesh term: Albumin-Bound Paclitaxel
provided document: 
provided document: 
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 