<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/NCT03029585</url>
  </required_header>
  <id_info>
    <org_study_id>NANOPAC-2016-01</org_study_id>
    <nct_id>NCT03029585</nct_id>
  </id_info>
  <brief_title>Phase II Study of Intraperitoneal NanoPac® in Patients With Ovarian Cancer</brief_title>
  <official_title>Phase II Study of Four Dose Levels of Intraperitoneal NanoPac® Plus IV Carboplatin and Paclitaxel in Patients With Epithelial Ovarian Cancer Undergoing Cytoreductive Surgery</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>NanOlogy, LLC</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>US Biotest, Inc.</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>NanOlogy, LLC</source>
  <oversight_info>
    <has_dmc>Yes</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 study will evaluate NanoPac® administered intraperitoneally (IP) immediately&#xD;
      post-cytoreductive surgery, followed by standard of care (SOC) intravenous (IV) chemotherapy,&#xD;
      in women with ovarian cancer. The study will compare IP NanoPac® (plus IV chemotherapy) with&#xD;
      SOC IV chemotherapy alone.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Research has shown that the administration of chemotherapy directly into the peritoneal&#xD;
      cavity (intraperitoneal [IP] chemotherapy) may provide a significant survival benefit to&#xD;
      women with ovarian cancer when combined with cytoreductive surgery and IV chemotherapy.&#xD;
&#xD;
      This study will include a dose-finding phase and an efficacy phase to evaluate IP NanoPac®&#xD;
      administered immediately post-cytoreductive surgery in women with ovarian cancer. In the&#xD;
      dose-finding phase, subjects will be enrolled in dose-escalated cohorts of three subjects and&#xD;
      receive IP NanoPac® at 100, 200, 300, or 400 mg/m2 plus standard of care (SOC) IV&#xD;
      chemotherapy. Subjects will be followed for disease status for 12 months. The two best doses&#xD;
      from the dose-finding phase will be determined. In the efficacy phase, subjects will be&#xD;
      randomized 1:1:1 to one of the two best doses plus SOC IV chemotherapy or SOC alone.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Terminated</overall_status>
  <why_stopped>
    Business reasons&#xD;
  </why_stopped>
  <start_date type="Actual">April 19, 2017</start_date>
  <completion_date type="Actual">November 4, 2019</completion_date>
  <primary_completion_date type="Actual">November 4, 2019</primary_completion_date>
  <phase>Phase 2</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Treatment-emergent Adverse Events</measure>
    <time_frame>12 months</time_frame>
    <description>Adverse events will include any clinically relevant changes in laboratory values, vital signs, and physical examination. Treatment-emergent adverse events occur when the date and time of the adverse event onset is on or after the first application of the investigational agent and any time up to when the intravenous chemotherapy commences. Treatment-emergent adverse events will be summarized for each treatment group. The summaries will include an overall summary of the number of subjects reporting and the number of events reported, summaries of adverse events leading to termination or death, and summaries by severity and relatedness (separately and combined). Of greatest interest will be post-surgery signs of toxicity (e.g., severe abdominal pain after 5-7 days, neutropenia, thrombocytopenia, bowel dehiscence, prolonged ileus).</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Maximum Plasma Concentration of Paclitaxel (Cmax)</measure>
    <time_frame>12 months</time_frame>
    <description>Plasma samples will be taken on Day 1 at 1, 2, 4, 8, and 24 hours post-intraperitoneal administration of NanoPac® and weekly thereafter until IV chemotherapy begins. Additionally, a pharmacokinetics (PK) sample will be collected from every subject prior to each cycle of IV chemotherapy for determination of paclitaxel concentrations to assess potential NanoPac® persistence. PK levels of paclitaxel in the plasma will be summarized descriptively.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Progression Free Survival (PFS) at 12 Months</measure>
    <time_frame>12 months post-treatment</time_frame>
    <description>Progression free survival (PFS) was assessed every 3 months until the end of the 12-month follow-up period, and every 6 months thereafter until progression or the last subject in the trial has completed 12 months of follow-up. Factors taken into account to determine time-to-progression included CA-125 levels, tumor burden as assessed by imaging and utilizing RECIST version 1.1 for assessment of response, and cancer-related symptoms such as bowel obstruction and ascites.</description>
  </secondary_outcome>
  <number_of_arms>5</number_of_arms>
  <enrollment type="Actual">10</enrollment>
  <condition>Ovarian Carcinoma</condition>
  <arm_group>
    <arm_group_label>NanoPac® 100 mg/m2</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Intraperitoneal NanoPac® 100 mg/m2 applied immediately post-cytoreductive surgery, followed by standard of care intravenous chemotherapy.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>NanoPac® 200 mg/m2</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Intraperitoneal NanoPac® 200 mg/m2 applied immediately post-cytoreductive surgery, followed by standard of care intravenous chemotherapy.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>NanoPac® 300 mg/m2</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Intraperitoneal NanoPac® 300 mg/m2 applied immediately post-cytoreductive surgery, followed by standard of care intravenous chemotherapy.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>NanoPac® 400 mg/m2</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Intraperitoneal NanoPac® 400 mg/m2 applied immediately post-cytoreductive surgery, followed by standard of care intravenous chemotherapy.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Standard of Care Intravenous Chemotherapy</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Standard of care intravenous chemotherapy (with platinum and taxane agents) administered per institutional standards.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>NanoPac® 100 mg/m2</intervention_name>
    <description>Single intraperitoneal injection of 100 mg/m2 NanoPac® during cytoreductive surgery, followed by standard-of-care IV carboplatin and IV paclitaxel treatment</description>
    <arm_group_label>NanoPac® 100 mg/m2</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>NanoPac® 200 mg/m2</intervention_name>
    <description>Single intraperitoneal injection of 200 mg/m2 NanoPac® during cytoreductive surgery, followed by standard-of-care IV carboplatin and IV paclitaxel treatment</description>
    <arm_group_label>NanoPac® 200 mg/m2</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>NanoPac® 300 mg/m2</intervention_name>
    <description>Single intraperitoneal injection of 300 mg/m2 NanoPac® during cytoreductive surgery, followed by standard-of-care IV carboplatin and IV paclitaxel treatment</description>
    <arm_group_label>NanoPac® 300 mg/m2</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>NanoPac® 400 mg/m2</intervention_name>
    <description>Single intraperitoneal injection of 400 mg/m2 NanoPac® during cytoreductive surgery, followed by standard-of-care IV carboplatin and IV paclitaxel treatment</description>
    <arm_group_label>NanoPac® 400 mg/m2</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Standard of Care Intravenous Chemotherapy</intervention_name>
    <description>Cytoreductive surgery followed by standard-of-care IV carboplatin and IV paclitaxel treatment</description>
    <arm_group_label>NanoPac® 100 mg/m2</arm_group_label>
    <arm_group_label>NanoPac® 200 mg/m2</arm_group_label>
    <arm_group_label>NanoPac® 300 mg/m2</arm_group_label>
    <arm_group_label>NanoPac® 400 mg/m2</arm_group_label>
    <arm_group_label>Standard of Care Intravenous Chemotherapy</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Epithelial ovarian cancer which is contained within the abdomen, but may include&#xD;
             pleural effusion if that is the limit of non-peritoneal cavity disease. If subject has&#xD;
             recurrent epithelial ovarian cancer, the disease must be platinum sensitive&#xD;
             (recurrence &gt;6 months from prior chemotherapy regimen that included a platinum agent&#xD;
             and cytoreductive surgery)&#xD;
&#xD;
          -  Subject appropriate for cytoreductive surgery and treatment with IV platinum and&#xD;
             paclitaxel&#xD;
&#xD;
          -  Minimal or non-symptomatic ascites&#xD;
&#xD;
          -  ≥18 years old&#xD;
&#xD;
          -  Signed informed consent&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Epithelial ovarian cancer outside of the peritoneal cavity, with the exception of&#xD;
             pleural effusions&#xD;
&#xD;
          -  Anticipated use of concomitant chemotherapy (other than the protocol-specified&#xD;
             agents), immunotherapy, or radiation therapy&#xD;
&#xD;
          -  Treatment with a prior investigational agent within 30 days of planned instillation of&#xD;
             NanoPac®, with the exception of subjects participating in poly (ADP-ribose) polymerase&#xD;
             (PARP) inhibitor trials. These subjects must discontinue the investigational agent&#xD;
             prior to surgery&#xD;
&#xD;
          -  Known sensitivity to any of the study medication components or the chemotherapy&#xD;
             regimen&#xD;
&#xD;
          -  History of prior malignancy other than ovarian that has not been in remission for &gt;5&#xD;
             years, with the exception of basal cell or squamous cell carcinoma or cervical&#xD;
             carcinoma in situ on biopsy&#xD;
&#xD;
          -  Ileostomy or hepatic resection during current cytoreductive surgery&#xD;
&#xD;
          -  Women of childbearing potential not practicing adequate forms of birth control&#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>Joan Walker, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>University of Oklahoma</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Gere diZerega, MD</last_name>
    <role>Study Chair</role>
    <affiliation>US Biotest, Inc./NanOlogy, LLC</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>University of Chicago</name>
      <address>
        <city>Chicago</city>
        <state>Illinois</state>
        <zip>60637</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Greater Baltimore Medical Center</name>
      <address>
        <city>Baltimore</city>
        <state>Maryland</state>
        <zip>21204</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Minnesota</name>
      <address>
        <city>Minneapolis</city>
        <state>Minnesota</state>
        <zip>55455</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>SUNY Downstate</name>
      <address>
        <city>Brooklyn</city>
        <state>New York</state>
        <zip>11203</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Magee-Womens Hospital of UPMC</name>
      <address>
        <city>Pittsburgh</city>
        <state>Pennsylvania</state>
        <zip>15213</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Women &amp; Infants Hospital of Rhode Island</name>
      <address>
        <city>Providence</city>
        <state>Rhode Island</state>
        <zip>02905</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Texas Southwestern</name>
      <address>
        <city>Dallas</city>
        <state>Texas</state>
        <zip>75390</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>March 2021</verification_date>
  <study_first_submitted>January 20, 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>March 8, 2021</results_first_submitted>
  <results_first_submitted_qc>March 31, 2021</results_first_submitted_qc>
  <results_first_posted type="Actual">April 27, 2021</results_first_posted>
  <last_update_submitted>March 31, 2021</last_update_submitted>
  <last_update_submitted_qc>March 31, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">April 27, 2021</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>ovarian carcinoma</keyword>
  <keyword>ovarian cancer</keyword>
  <keyword>ovarian neoplasms</keyword>
  <keyword>ovarian diseases</keyword>
  <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>
  </condition_browse>
  <patient_data>
    <sharing_ipd>Undecided</sharing_ipd>
  </patient_data>
  <provided_document_section>
    <provided_document>
      <document_type>Study Protocol</document_type>
      <document_has_protocol>Yes</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>No</document_has_sap>
      <document_date>April 19, 2019</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/85/NCT03029585/Prot_000.pdf</document_url>
    </provided_document>
    <provided_document>
      <document_type>Statistical Analysis Plan</document_type>
      <document_has_protocol>No</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>Yes</document_has_sap>
      <document_date>January 29, 2020</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/85/NCT03029585/SAP_001.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <group_list>
        <group group_id="P1">
          <title>NanoPac® 100 mg/m2</title>
          <description>Intraperitoneal NanoPac® 100 mg/m2 applied immediately post-cytoreductive surgery, followed by standard of care intravenous chemotherapy.&#xD;
NanoPac® 100 mg/m2: Single intraperitoneal injection of 100 mg/m2 NanoPac® during cytoreductive surgery, followed by standard-of-care IV carboplatin and IV paclitaxel treatment&#xD;
Standard of Care Intravenous Chemotherapy: Cytoreductive surgery followed by standard-of-care IV carboplatin and IV paclitaxel treatment</description>
        </group>
        <group group_id="P2">
          <title>NanoPac® 200 mg/m2</title>
          <description>Intraperitoneal NanoPac® 200 mg/m2 applied immediately post-cytoreductive surgery, followed by standard of care intravenous chemotherapy.&#xD;
NanoPac® 200 mg/m2: Single intraperitoneal injection of 200 mg/m2 NanoPac® during cytoreductive surgery, followed by standard-of-care IV carboplatin and IV paclitaxel treatment&#xD;
Standard of Care Intravenous Chemotherapy: Cytoreductive surgery followed by standard-of-care IV carboplatin and IV paclitaxel treatment</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="7"/>
                <participants group_id="P2" count="3"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="5"/>
                <participants group_id="P2" count="2"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="2"/>
                <participants group_id="P2" count="1"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Death</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Withdrawal by Subject</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>NanoPac® 100 mg/m2</title>
          <description>Intraperitoneal NanoPac® 100 mg/m2 applied immediately post-cytoreductive surgery, followed by standard of care intravenous chemotherapy.&#xD;
NanoPac® 100 mg/m2: Single intraperitoneal injection of 100 mg/m2 NanoPac® during cytoreductive surgery, followed by standard-of-care IV carboplatin and IV paclitaxel treatment&#xD;
Standard of Care Intravenous Chemotherapy: Cytoreductive surgery followed by standard-of-care IV carboplatin and IV paclitaxel treatment</description>
        </group>
        <group group_id="B2">
          <title>NanoPac® 200 mg/m2</title>
          <description>Intraperitoneal NanoPac® 200 mg/m2 applied immediately post-cytoreductive surgery, followed by standard of care intravenous chemotherapy.&#xD;
NanoPac® 200 mg/m2: Single intraperitoneal injection of 200 mg/m2 NanoPac® during cytoreductive surgery, followed by standard-of-care IV carboplatin and IV paclitaxel treatment&#xD;
Standard of Care Intravenous Chemotherapy: Cytoreductive surgery followed by standard-of-care IV carboplatin and IV paclitaxel treatment</description>
        </group>
        <group group_id="B3">
          <title>Total</title>
          <description>Total of all reporting groups</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="7"/>
            <count group_id="B2" value="3"/>
            <count group_id="B3" value="10"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>years</units>
          <param>Median</param>
          <dispersion>Full Range</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="68" lower_limit="50" upper_limit="72"/>
                    <measurement group_id="B2" value="62" lower_limit="56" upper_limit="71"/>
                    <measurement group_id="B3" value="67" lower_limit="50" upper_limit="72"/>
                  </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="7"/>
                    <measurement group_id="B2" value="3"/>
                    <measurement group_id="B3" value="10"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
              </category_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 group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Asian</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Native Hawaiian or Other Pacific Islander</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Black or African American</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="1"/>
                  </measurement_list>
                </category>
                <category>
                  <title>White</title>
                  <measurement_list>
                    <measurement group_id="B1" value="6"/>
                    <measurement group_id="B2" value="3"/>
                    <measurement group_id="B3" value="9"/>
                  </measurement_list>
                </category>
                <category>
                  <title>More than one race</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Disease Status</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Primary</title>
                  <measurement_list>
                    <measurement group_id="B1" value="4"/>
                    <measurement group_id="B2" value="2"/>
                    <measurement group_id="B3" value="6"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Recurrent</title>
                  <measurement_list>
                    <measurement group_id="B1" value="3"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>ECOG Status</title>
          <description>ECOG Performance Scale:&#xD;
0 Fully active, able to carry on all pre-disease performance without restriction&#xD;
Restricted in physically strenuous activity but ambulatory and able to carry out work of a light or sedentary nature, e.g., light house work, office work&#xD;
Ambulatory and capable of all selfcare but unable to carry out any work activities; up and about more than 50% of waking hours&#xD;
Capable of only limited selfcare; confined to bed or chair more than 50% of waking hours&#xD;
Completely disabled; cannot carry on any selfcare; totally confined to bed or chair&#xD;
Dead</description>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>ECOG 0</title>
                  <measurement_list>
                    <measurement group_id="B1" value="5"/>
                    <measurement group_id="B2" value="2"/>
                    <measurement group_id="B3" value="7"/>
                  </measurement_list>
                </category>
                <category>
                  <title>ECOG 1</title>
                  <measurement_list>
                    <measurement group_id="B1" value="2"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Status of Ovarian Cancer at Screening</title>
          <description>Ovarian cancer stages range from stage I (1) through IV (4). As a rule, the lower the number, the less the cancer has spread. A higher number, such as stage IV, means cancer has spread more.</description>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>IIIA2</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="1"/>
                  </measurement_list>
                </category>
                <category>
                  <title>IIIB</title>
                  <measurement_list>
                    <measurement group_id="B1" value="2"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="2"/>
                  </measurement_list>
                </category>
                <category>
                  <title>IIIC</title>
                  <measurement_list>
                    <measurement group_id="B1" value="4"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="5"/>
                  </measurement_list>
                </category>
                <category>
                  <title>IVB</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Treatment-emergent Adverse Events</title>
        <description>Adverse events will include any clinically relevant changes in laboratory values, vital signs, and physical examination. Treatment-emergent adverse events occur when the date and time of the adverse event onset is on or after the first application of the investigational agent and any time up to when the intravenous chemotherapy commences. Treatment-emergent adverse events will be summarized for each treatment group. The summaries will include an overall summary of the number of subjects reporting and the number of events reported, summaries of adverse events leading to termination or death, and summaries by severity and relatedness (separately and combined). Of greatest interest will be post-surgery signs of toxicity (e.g., severe abdominal pain after 5-7 days, neutropenia, thrombocytopenia, bowel dehiscence, prolonged ileus).</description>
        <time_frame>12 months</time_frame>
        <group_list>
          <group group_id="O1">
            <title>NanoPac® 100 mg/m2</title>
            <description>Intraperitoneal NanoPac® 100 mg/m2 applied immediately post-cytoreductive surgery, followed by standard of care intravenous chemotherapy.&#xD;
NanoPac® 100 mg/m2: Single intraperitoneal injection of 100 mg/m2 NanoPac® during cytoreductive surgery, followed by standard-of-care IV carboplatin and IV paclitaxel treatment&#xD;
Standard of Care Intravenous Chemotherapy: Cytoreductive surgery followed by standard-of-care IV carboplatin and IV paclitaxel treatment</description>
          </group>
          <group group_id="O2">
            <title>NanoPac® 200 mg/m2</title>
            <description>Intraperitoneal NanoPac® 200 mg/m2 applied immediately post-cytoreductive surgery, followed by standard of care intravenous chemotherapy.&#xD;
NanoPac® 200 mg/m2: Single intraperitoneal injection of 200 mg/m2 NanoPac® during cytoreductive surgery, followed by standard-of-care IV carboplatin and IV paclitaxel treatment&#xD;
Standard of Care Intravenous Chemotherapy: Cytoreductive surgery followed by standard-of-care IV carboplatin and IV paclitaxel treatment</description>
          </group>
        </group_list>
        <measure>
          <title>Treatment-emergent Adverse Events</title>
          <description>Adverse events will include any clinically relevant changes in laboratory values, vital signs, and physical examination. Treatment-emergent adverse events occur when the date and time of the adverse event onset is on or after the first application of the investigational agent and any time up to when the intravenous chemotherapy commences. Treatment-emergent adverse events will be summarized for each treatment group. The summaries will include an overall summary of the number of subjects reporting and the number of events reported, summaries of adverse events leading to termination or death, and summaries by severity and relatedness (separately and combined). Of greatest interest will be post-surgery signs of toxicity (e.g., severe abdominal pain after 5-7 days, neutropenia, thrombocytopenia, bowel dehiscence, prolonged ileus).</description>
          <units>Treatment Emergent Adverse Events</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="7"/>
                <count group_id="O2" value="3"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="80"/>
                    <measurement group_id="O2" value="28"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Maximum Plasma Concentration of Paclitaxel (Cmax)</title>
        <description>Plasma samples will be taken on Day 1 at 1, 2, 4, 8, and 24 hours post-intraperitoneal administration of NanoPac® and weekly thereafter until IV chemotherapy begins. Additionally, a pharmacokinetics (PK) sample will be collected from every subject prior to each cycle of IV chemotherapy for determination of paclitaxel concentrations to assess potential NanoPac® persistence. PK levels of paclitaxel in the plasma will be summarized descriptively.</description>
        <time_frame>12 months</time_frame>
        <group_list>
          <group group_id="O1">
            <title>NanoPac® 100 mg/m2</title>
            <description>Intraperitoneal NanoPac® 100 mg/m2 applied immediately post-cytoreductive surgery, followed by standard of care intravenous chemotherapy.&#xD;
NanoPac® 100 mg/m2: Single intraperitoneal injection of 100 mg/m2 NanoPac® during cytoreductive surgery, followed by standard-of-care IV carboplatin and IV paclitaxel treatment&#xD;
Standard of Care Intravenous Chemotherapy: Cytoreductive surgery followed by standard-of-care IV carboplatin and IV paclitaxel treatment</description>
          </group>
          <group group_id="O2">
            <title>NanoPac® 200 mg/m2</title>
            <description>Intraperitoneal NanoPac® 200 mg/m2 applied immediately post-cytoreductive surgery, followed by standard of care intravenous chemotherapy.&#xD;
NanoPac® 200 mg/m2: Single intraperitoneal injection of 200 mg/m2 NanoPac® during cytoreductive surgery, followed by standard-of-care IV carboplatin and IV paclitaxel treatment&#xD;
Standard of Care Intravenous Chemotherapy: Cytoreductive surgery followed by standard-of-care IV carboplatin and IV paclitaxel treatment</description>
          </group>
        </group_list>
        <measure>
          <title>Maximum Plasma Concentration of Paclitaxel (Cmax)</title>
          <description>Plasma samples will be taken on Day 1 at 1, 2, 4, 8, and 24 hours post-intraperitoneal administration of NanoPac® and weekly thereafter until IV chemotherapy begins. Additionally, a pharmacokinetics (PK) sample will be collected from every subject prior to each cycle of IV chemotherapy for determination of paclitaxel concentrations to assess potential NanoPac® persistence. PK levels of paclitaxel in the plasma will be summarized descriptively.</description>
          <units>ng/mL</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="7"/>
                <count group_id="O2" value="3"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="12.56" spread="10.98"/>
                    <measurement group_id="O2" value="26.50" spread="13.56"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Progression Free Survival (PFS) at 12 Months</title>
        <description>Progression free survival (PFS) was assessed every 3 months until the end of the 12-month follow-up period, and every 6 months thereafter until progression or the last subject in the trial has completed 12 months of follow-up. Factors taken into account to determine time-to-progression included CA-125 levels, tumor burden as assessed by imaging and utilizing RECIST version 1.1 for assessment of response, and cancer-related symptoms such as bowel obstruction and ascites.</description>
        <time_frame>12 months post-treatment</time_frame>
        <population>Of the 10 subjects enrolled, four subjects were not evaluable for PFS at 12 months post-NanoPac instillation. For one subject, no imaging was performed over the course of the study; one subject was deceased due to leptomeningeal carcinomatosis; one subject was deceased due to a respiratory arrest; and one subject withdrew consent from the study. Both deaths were considered not related to study medication by the Investigator and the Medical Monitor.</population>
        <group_list>
          <group group_id="O1">
            <title>NanoPac® 100 mg/m2</title>
            <description>Intraperitoneal NanoPac® 100 mg/m2 applied immediately post-cytoreductive surgery, followed by standard of care intravenous chemotherapy.&#xD;
NanoPac® 100 mg/m2: Single intraperitoneal injection of 100 mg/m2 NanoPac® during cytoreductive surgery, followed by standard-of-care IV carboplatin and IV paclitaxel treatment&#xD;
Standard of Care Intravenous Chemotherapy: Cytoreductive surgery followed by standard-of-care IV carboplatin and IV paclitaxel treatment</description>
          </group>
          <group group_id="O2">
            <title>NanoPac® 200 mg/m2</title>
            <description>Intraperitoneal NanoPac® 200 mg/m2 applied immediately post-cytoreductive surgery, followed by standard of care intravenous chemotherapy.&#xD;
NanoPac® 200 mg/m2: Single intraperitoneal injection of 200 mg/m2 NanoPac® during cytoreductive surgery, followed by standard-of-care IV carboplatin and IV paclitaxel treatment&#xD;
Standard of Care Intravenous Chemotherapy: Cytoreductive surgery followed by standard-of-care IV carboplatin and IV paclitaxel treatment</description>
          </group>
        </group_list>
        <measure>
          <title>Progression Free Survival (PFS) at 12 Months</title>
          <description>Progression free survival (PFS) was assessed every 3 months until the end of the 12-month follow-up period, and every 6 months thereafter until progression or the last subject in the trial has completed 12 months of follow-up. Factors taken into account to determine time-to-progression included CA-125 levels, tumor burden as assessed by imaging and utilizing RECIST version 1.1 for assessment of response, and cancer-related symptoms such as bowel obstruction and ascites.</description>
          <population>Of the 10 subjects enrolled, four subjects were not evaluable for PFS at 12 months post-NanoPac instillation. For one subject, no imaging was performed over the course of the study; one subject was deceased due to leptomeningeal carcinomatosis; one subject was deceased due to a respiratory arrest; and one subject withdrew consent from the study. Both deaths were considered not related to study medication by the Investigator and the Medical Monitor.</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="4"/>
                <count group_id="O2" value="2"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>PFS at 12 months</title>
                  <measurement_list>
                    <measurement group_id="O1" value="4"/>
                    <measurement group_id="O2" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Disease Progression</title>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>AEs were collected at all study visits from the time of dosing until end of study, for a planned 30-month collection period for each subject.</time_frame>
      <group_list>
        <group group_id="E1">
          <title>NanoPac® 100 mg/m2</title>
          <description>Intraperitoneal NanoPac® 100 mg/m2 applied immediately post-cytoreductive surgery, followed by standard of care intravenous chemotherapy.&#xD;
NanoPac® 100 mg/m2: Single intraperitoneal injection of 100 mg/m2 NanoPac® during cytoreductive surgery, followed by standard-of-care IV carboplatin and IV paclitaxel treatment&#xD;
Standard of Care Intravenous Chemotherapy: Cytoreductive surgery followed by standard-of-care IV carboplatin and IV paclitaxel treatment</description>
        </group>
        <group group_id="E2">
          <title>NanoPac® 200 mg/m2</title>
          <description>Intraperitoneal NanoPac® 200 mg/m2 applied immediately post-cytoreductive surgery, followed by standard of care intravenous chemotherapy.&#xD;
NanoPac® 200 mg/m2: Single intraperitoneal injection of 200 mg/m2 NanoPac® during cytoreductive surgery, followed by standard-of-care IV carboplatin and IV paclitaxel treatment&#xD;
Standard of Care Intravenous Chemotherapy: Cytoreductive surgery followed by standard-of-care IV carboplatin and IV paclitaxel treatment</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="1" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="3"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Pyelonephritis</sub_title>
                <assessment>Non-systematic Assessment</assessment>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="7"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>Cellulitis</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>Pelvic abscess</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="7"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>Cystitis</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="7"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Injury, poisoning and procedural complications</title>
            <event_list>
              <event>
                <sub_title>Wound dehiscence</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="7"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>Wound necrosis</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="3"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Metabolism and nutrition disorders</title>
            <event_list>
              <event>
                <sub_title>Hyperglycaemia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="7"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Neoplasms benign, malignant and unspecified (incl cysts and polyps)</title>
            <event_list>
              <event>
                <sub_title>Metastases to meninges</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="3"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Psychiatric disorders</title>
            <event_list>
              <event>
                <sub_title>Major depression</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="3"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Reproductive system and breast disorders</title>
            <event_list>
              <event>
                <sub_title>Pelvic fluid collection</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E2" events="2" subjects_affected="1" subjects_at_risk="3"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Respiratory arrest</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="7"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
              </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="7" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="3"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Blood and lymphatic system disorders</title>
            <event_list>
              <event>
                <sub_title>Anaemia</sub_title>
                <assessment>Non-systematic Assessment</assessment>
                <counts group_id="E1" events="5" subjects_affected="1" subjects_at_risk="7"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>Leukocytosis</sub_title>
                <counts group_id="E1" events="3" subjects_affected="2" subjects_at_risk="7"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>Thrombocytosis</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="7"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Cardiac disorders</title>
            <event_list>
              <event>
                <sub_title>Arrhythmia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="7"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>Palpitations</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="7"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>Tachycardia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="7"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Abdominal distension</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="7"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>Abdominal pain</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>Ascites</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="7"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>Constipation</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="7"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>Diarrhoea</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="7"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>Gastrooesophageal Reflux</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="7"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>Ileus</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>Ileus paralytic</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="7"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>Nausea</sub_title>
                <counts group_id="E1" events="5" subjects_affected="3" subjects_at_risk="7"/>
                <counts group_id="E2" events="3" subjects_affected="3" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>Vomiting</sub_title>
                <counts group_id="E1" events="3" subjects_affected="2" subjects_at_risk="7"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="3"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Administration site extravasation</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="7"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>Fatigue</sub_title>
                <counts group_id="E1" events="5" subjects_affected="3" subjects_at_risk="7"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>Pain</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>Pyrexia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="7"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="3"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Pneumonia</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>Pyelonephritis</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="7"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>Urinary tract infection</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="7"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="3"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Injury, poisoning and procedural complications</title>
            <event_list>
              <event>
                <sub_title>Incision site pain</sub_title>
                <counts group_id="E1" events="3" subjects_affected="1" subjects_at_risk="7"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>Procedural pain</sub_title>
                <counts group_id="E1" events="4" subjects_affected="4" subjects_at_risk="7"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="3"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Investigations</title>
            <event_list>
              <event>
                <sub_title>Blood albumin decreased</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="7"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>Blood chloride decreased</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="7"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>Blood urea decreased</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="7"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>Glomerular filtration rate decreased</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="7"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>Haematocrit decreased</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="7"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>Heart rate irregular</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="7"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>Lymphocyte count</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>Platelet count decreased</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="7"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>Protein total decreased</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="7"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>White blood cell count increased</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="7"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Metabolism and nutrition disorders</title>
            <event_list>
              <event>
                <sub_title>Decreased appetite</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>Hyperglycaemia</sub_title>
                <counts group_id="E1" events="4" subjects_affected="2" subjects_at_risk="7"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>Hypermagnesaemia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="7"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>Hypoalbuminaemia</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>Hypocalcaemia</sub_title>
                <counts group_id="E1" events="2" subjects_affected="1" subjects_at_risk="7"/>
                <counts group_id="E2" events="2" subjects_affected="1" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>Hypokalacaemia</sub_title>
                <assessment>Non-systematic Assessment</assessment>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="7"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>Hyponatraemia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="7"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>Hypophosphataemia</sub_title>
                <counts group_id="E1" events="3" subjects_affected="2" subjects_at_risk="7"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Musculoskeletal and connective tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Back pain</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="7"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>Flank pain</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="7"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>Muscular weakness</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="7"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>Pain in extremity</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="7"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Dizziness</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="7"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>Hypoaesthesia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="7"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Renal and urinary disorders</title>
            <event_list>
              <event>
                <sub_title>Haematuria</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="7"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>Hydronephrosis</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>Urinary incontinence</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="7"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Reproductive system and breast disorders</title>
            <event_list>
              <event>
                <sub_title>Pelvic fluid collection</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>Pelvic pain</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="3"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Cough</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="7"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>Nasal congestion</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="7"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>Oropharyngeal pain</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="7"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Vascular disorders</title>
            <event_list>
              <event>
                <sub_title>Hypotension</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="7"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </other_events>
    </reported_events>

    <certain_agreements>
      <pi_employee>Principal Investigators are NOT 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>
    <limitations_and_caveats>Early termination leading to small numbers of subjects analyzed.</limitations_and_caveats>
    <point_of_contact>
      <name_or_title>Gere S. diZerega, MD, Responsible Medical Officer</name_or_title>
      <organization>US Biotest, Inc.</organization>
      <phone>1-805-595-1300</phone>
      <email>gere.dizerega@usbiotest.com</email>
    </point_of_contact>
  </clinical_results>
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT03029585
org study id: NANOPAC-2016-01
nct id: NCT03029585
lead sponsor: 
collaborator: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
This study will evaluate NanoPac® administered intraperitoneally (IP) immediately
      post-cytoreductive surgery, followed by standard of care (SOC) intravenous (IV) chemotherapy,
      in women with ovarian cancer. The study will compare IP NanoPac® (plus IV chemotherapy) with
      SOC IV chemotherapy alone.
Research has shown that the administration of chemotherapy directly into the peritoneal
      cavity (intraperitoneal [IP] chemotherapy) may provide a significant survival benefit to
      women with ovarian cancer when combined with cytoreductive surgery and IV chemotherapy.

      This study will include a dose-finding phase and an efficacy phase to evaluate IP NanoPac®
      administered immediately post-cytoreductive surgery in women with ovarian cancer. In the
      dose-finding phase, subjects will be enrolled in dose-escalated cohorts of three subjects and
      receive IP NanoPac® at 100, 200, 300, or 400 mg/m2 plus standard of care (SOC) IV
      chemotherapy. Subjects will be followed for disease status for 12 months. The two best doses
      from the dose-finding phase will be determined. In the efficacy phase, subjects will be
      randomized 1:1:1 to one of the two best doses plus SOC IV chemotherapy or SOC alone.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Treatment-emergent Adverse Events
time frame: 12 months
description: Adverse events will include any clinically relevant changes in laboratory values, vital signs, and physical examination. Treatment-emergent adverse events occur when the date and time of the adverse event onset is on or after the first application of the investigational agent and any time up to when the intravenous chemotherapy commences. Treatment-emergent adverse events will be summarized for each treatment group. The summaries will include an overall summary of the number of subjects reporting and the number of events reported, summaries of adverse events leading to termination or death, and summaries by severity and relatedness (separately and combined). Of greatest interest will be post-surgery signs of toxicity (e.g., severe abdominal pain after 5-7 days, neutropenia, thrombocytopenia, bowel dehiscence, prolonged ileus).
measure: Maximum Plasma Concentration of Paclitaxel (Cmax)
time frame: 12 months
description: Plasma samples will be taken on Day 1 at 1, 2, 4, 8, and 24 hours post-intraperitoneal administration of NanoPac® and weekly thereafter until IV chemotherapy begins. Additionally, a pharmacokinetics (PK) sample will be collected from every subject prior to each cycle of IV chemotherapy for determination of paclitaxel concentrations to assess potential NanoPac® persistence. PK levels of paclitaxel in the plasma will be summarized descriptively.
measure: Progression Free Survival (PFS) at 12 Months
time frame: 12 months post-treatment
description: Progression free survival (PFS) was assessed every 3 months until the end of the 12-month follow-up period, and every 6 months thereafter until progression or the last subject in the trial has completed 12 months of follow-up. Factors taken into account to determine time-to-progression included CA-125 levels, tumor burden as assessed by imaging and utilizing RECIST version 1.1 for assessment of response, and cancer-related symptoms such as bowel obstruction and ascites.
arm group label: NanoPac® 100 mg/m2
arm group type: Experimental
description: Intraperitoneal NanoPac® 100 mg/m2 applied immediately post-cytoreductive surgery, followed by standard of care intravenous chemotherapy.
arm group label: NanoPac® 200 mg/m2
arm group type: Experimental
description: Intraperitoneal NanoPac® 200 mg/m2 applied immediately post-cytoreductive surgery, followed by standard of care intravenous chemotherapy.
arm group label: NanoPac® 300 mg/m2
arm group type: Experimental
description: Intraperitoneal NanoPac® 300 mg/m2 applied immediately post-cytoreductive surgery, followed by standard of care intravenous chemotherapy.
arm group label: NanoPac® 400 mg/m2
arm group type: Experimental
description: Intraperitoneal NanoPac® 400 mg/m2 applied immediately post-cytoreductive surgery, followed by standard of care intravenous chemotherapy.
arm group label: Standard of Care Intravenous Chemotherapy
arm group type: Active Comparator
description: Standard of care intravenous chemotherapy (with platinum and taxane agents) administered per institutional standards.
intervention type: Drug
intervention name: NanoPac® 100 mg/m2
description: Single intraperitoneal injection of 100 mg/m2 NanoPac® during cytoreductive surgery, followed by standard-of-care IV carboplatin and IV paclitaxel treatment
arm group label: NanoPac® 100 mg/m2
intervention type: Drug
intervention name: NanoPac® 200 mg/m2
description: Single intraperitoneal injection of 200 mg/m2 NanoPac® during cytoreductive surgery, followed by standard-of-care IV carboplatin and IV paclitaxel treatment
arm group label: NanoPac® 200 mg/m2
intervention type: Drug
intervention name: NanoPac® 300 mg/m2
description: Single intraperitoneal injection of 300 mg/m2 NanoPac® during cytoreductive surgery, followed by standard-of-care IV carboplatin and IV paclitaxel treatment
arm group label: NanoPac® 300 mg/m2
intervention type: Drug
intervention name: NanoPac® 400 mg/m2
description: Single intraperitoneal injection of 400 mg/m2 NanoPac® during cytoreductive surgery, followed by standard-of-care IV carboplatin and IV paclitaxel treatment
arm group label: NanoPac® 400 mg/m2
intervention type: Drug
intervention name: Standard of Care Intravenous Chemotherapy
description: Cytoreductive surgery followed by standard-of-care IV carboplatin and IV paclitaxel treatment
arm group label: NanoPac® 100 mg/m2
arm group label: NanoPac® 200 mg/m2
arm group label: NanoPac® 300 mg/m2
arm group label: NanoPac® 400 mg/m2
arm group label: Standard of Care Intravenous Chemotherapy
criteria: 
gender: Female
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Joan Walker, MD
role: Principal Investigator
affiliation: University of Oklahoma
last name: Gere diZerega, MD
role: Study Chair
affiliation: US Biotest, Inc./NanOlogy, LLC
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
country: United States
responsible party type: Sponsor
mesh term: Ovarian Neoplasms
mesh term: Carcinoma, Ovarian Epithelial
sharing ipd: Undecided
provided document: 
provided document: 
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
limitations and caveats: Early termination leading to small numbers of subjects analyzed.
point of contact: 