<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/NCT03268382</url>
  </required_header>
  <id_info>
    <org_study_id>APR-486</org_study_id>
    <nct_id>NCT03268382</nct_id>
  </id_info>
  <brief_title>p53 Activation in Platinum-Resistant High Grade Serous Ovarian Cancer, a Study of PLD With APR-246</brief_title>
  <official_title>PiSARRO-R: p53 Suppressor Activation in Platinum-Resistant High Grade Serous Ovarian Cancer, a Phase II Study of Systemic Pegylated Liposomal Doxorubicin Chemotherapy With APR-246</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Aprea Therapeutics</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Aprea Therapeutics</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>
      The purpose of this study is to make a preliminary assessment of the efficacy of a combined&#xD;
      APR-246 and PLD chemotherapy regimen in patients with platinum-resistant recurrent high grade&#xD;
      serous ovarian cancer (HGSOC) with mutated TP53. In addition, the study aims to assess the&#xD;
      safety profile of the combined APR-246 and PLD chemotherapy regimen, to evaluate potential&#xD;
      biomarkers, and to assess the biological activity in tumor and surrogate tissues. The trial&#xD;
      will enroll at least 25 evaluable patients.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">July 31, 2017</start_date>
  <completion_date type="Actual">July 10, 2019</completion_date>
  <primary_completion_date type="Actual">July 10, 2019</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>Overall Response Rate (ORR)</measure>
    <time_frame>Up to 18 months</time_frame>
    <description>Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), &gt;=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Treatment-emergent Adverse Events With Combined APR-246 and PLD Regimen</measure>
    <time_frame>Treatment emergent adverse events (TEAEs) were defined as AEs that occurred on or after the first dose of study medication up to and including 30 days after last dose. Median number of 28d Cycles=2.5 (Min = 1, Max = 14)</time_frame>
    <description>Treatment emergent adverse events (TEAEs) were defined as AEs that occurred on or after the first dose of study medication up to and including 30 days after last dose. AEs were graded according to NCI CTCAE (Version 4.0). Patients with multiple TEAEs were only counted once within a summary category: SOC, PT, maximum grade, or relationship to treatment. Patients with events in more than one category were counted once within each category.</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">36</enrollment>
  <condition>High-grade Serous Ovarian Cancer</condition>
  <arm_group>
    <arm_group_label>APR-246 + PLD</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>APR-246</intervention_name>
    <description>Intravenous infusion</description>
    <arm_group_label>APR-246 + PLD</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Pegylated Liposomal Doxorubicin Hydrochloride (PLD)</intervention_name>
    <description>Intravenous infusion</description>
    <arm_group_label>APR-246 + PLD</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Confirmed High Grade Serous Ovarian Cancer, and positive nuclear immunohistochemical&#xD;
             (IHC) staining for p53&#xD;
&#xD;
          -  Disease Progression between 4 weeks - 6 months after the last platinum-based treatment&#xD;
             was administered&#xD;
&#xD;
          -  At least a single measurable lesion&#xD;
&#xD;
          -  Adequate organ function prior to registration&#xD;
&#xD;
          -  Toxicities from previous cancer therapies (excluding alopecia) must have recovered to&#xD;
             grade 1 (defined by National Cancer Institute [NCI] Common Terminology Criteria for&#xD;
             Adverse Events [CTCAE] version 4.0). Chronic stable grade 2 peripheral neuropathy&#xD;
             secondary to neurotoxicity from prior therapies may be considered on a case by case&#xD;
             basis&#xD;
&#xD;
          -  ECOG performance status of 0 to 2&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Prior exposure to cumulative doses of doxorubicin &gt;400 mg/m2 or epirubicin &gt;720 mg/m2&#xD;
&#xD;
          -  Hypersensitivity to PLD or to any of the excipients&#xD;
&#xD;
          -  Unable to undergo imaging by either CT scan or MRI&#xD;
&#xD;
          -  Evidence of any other medical conditions (such as psychiatric illness, infectious&#xD;
             diseases, neurological conditions, physical examination or laboratory findings) that&#xD;
             may interfere with the planned treatment, affect patient compliance or place the&#xD;
             patient at high risk from treatment related complications&#xD;
&#xD;
          -  Concurrent malignancy requiring therapy (excluding non-invasive carcinoma or carcinoma&#xD;
             in situ)&#xD;
&#xD;
          -  Is taking concurrent (or within 4 weeks prior to registration) chemotherapy,&#xD;
             immunotherapy, radiotherapy, or any ancillary therapy that is considered to be&#xD;
             investigational (i.e., used for non-approved indications(s) and in the context of a&#xD;
             research investigation). Supportive care measures are allowed. Palliative limited&#xD;
             radiation therapy for pain reduction is allowed&#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>Charlie Gourley, BSc, MB ChB, PhD, FRCP</last_name>
    <role>Principal Investigator</role>
    <affiliation>Edinburgh Cancer Research Centre, The University of Edinburgh</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Medische oncologie, Universitair Ziekenhuis Gent</name>
      <address>
        <city>Gent</city>
        <zip>9000</zip>
        <country>Belgium</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Leuven University Hospitals</name>
      <address>
        <city>Leuven</city>
        <zip>B-3000</zip>
        <country>Belgium</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Centre Hospitalier Universitaire de Liège</name>
      <address>
        <city>Liège</city>
        <zip>B-4000</zip>
        <country>Belgium</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Institut Català d'Oncologia, Hospital Germans Trias i Pujol</name>
      <address>
        <city>Badalona</city>
        <zip>08916</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Vall d'Hebron</name>
      <address>
        <city>Barcelona</city>
        <zip>08035</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Universitario Fundación Jiménez Díaz</name>
      <address>
        <city>Madrid</city>
        <zip>28040</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Universitario HM Sanchinarro</name>
      <address>
        <city>Madrid</city>
        <zip>28050</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Clinico Universitario de Valencia</name>
      <address>
        <city>Valencia</city>
        <zip>46010</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Cambridge Cancer Trials Centre, Cambridge University Hospitals NHS Foundation Trust, Addenbrooke's Hospital</name>
      <address>
        <city>Cambridge</city>
        <zip>CB2 0QQ</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Edinburgh Cancer Research Centre, The University of Edinburgh</name>
      <address>
        <city>Edinburgh</city>
        <zip>EH4 2XR</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>The Royal Marsden NHS Foundation Trust</name>
      <address>
        <city>London</city>
        <zip>SM2 5PT</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Imperial College London, Hammersmith Hospital Campus</name>
      <address>
        <city>London</city>
        <zip>W12 0NN</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Belgium</country>
    <country>Spain</country>
    <country>United Kingdom</country>
  </location_countries>
  <link>
    <url>http://www.aprea.com</url>
    <description>Aprea Therapeutics AB's website (Sponsor)</description>
  </link>
  <reference>
    <citation>Lehmann S, Bykov VJ, Ali D, Andren O, Cherif H, Tidefelt U, Uggla B, Yachnin J, Juliusson G, Moshfegh A, Paul C, Wiman KG, Andersson PO. Targeting p53 in vivo: a first-in-human study with p53-targeting compound APR-246 in refractory hematologic malignancies and prostate cancer. J Clin Oncol. 2012 Oct 10;30(29):3633-9. doi: 10.1200/JCO.2011.40.7783. Epub 2012 Sep 10.</citation>
    <PMID>22965953</PMID>
  </reference>
  <reference>
    <citation>Deneberg S, Cherif H, Lazarevic V, Andersson PO, von Euler M, Juliusson G, Lehmann S. An open-label phase I dose-finding study of APR-246 in hematological malignancies. Blood Cancer J. 2016 Jul 15;6(7):e447. doi: 10.1038/bcj.2016.60. No abstract available.</citation>
    <PMID>27421096</PMID>
  </reference>
  <verification_date>July 2022</verification_date>
  <study_first_submitted>August 24, 2017</study_first_submitted>
  <study_first_submitted_qc>August 29, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">August 31, 2017</study_first_posted>
  <results_first_submitted>June 1, 2022</results_first_submitted>
  <results_first_submitted_qc>July 19, 2022</results_first_submitted_qc>
  <results_first_posted type="Actual">July 21, 2022</results_first_posted>
  <last_update_submitted>July 19, 2022</last_update_submitted>
  <last_update_submitted_qc>July 19, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">July 21, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Ovarian Cancer</keyword>
  <keyword>Ovarian Carcinoma</keyword>
  <keyword>High Grade Serous Ovarian Cancer</keyword>
  <keyword>Recurrent Cancer</keyword>
  <keyword>Resistant Cancer</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>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Doxorubicin</mesh_term>
    <mesh_term>Liposomal doxorubicin</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>September 12, 2017</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/82/NCT03268382/Prot_SAP_000.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <group_list>
        <group group_id="P1">
          <title>APR-246 (4.5g/6hr) + PLD</title>
          <description>APR-246: Intravenous infusion Pegylated Liposomal Doxorubicin Hydrochloride (PLD): Intravenous infusion</description>
        </group>
        <group group_id="P2">
          <title>APR-246 (4.5g/3hr) +PLD</title>
          <description>APR-246: Intravenous infusion Pegylated Liposomal Doxorubicin Hydrochloride (PLD): Intravenous infusion</description>
        </group>
        <group group_id="P3">
          <title>APR-246 (4.5g/4hr) +PLD</title>
          <description>APR-246: Intravenous infusion Pegylated Liposomal Doxorubicin Hydrochloride (PLD): Intravenous infusion</description>
        </group>
        <group group_id="P4">
          <title>APR-246 (3.7g/4hr) +PLD</title>
          <description>APR-246: Intravenous infusion Pegylated Liposomal Doxorubicin Hydrochloride (PLD): Intravenous infusion</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="28"/>
                <participants group_id="P2" count="3"/>
                <participants group_id="P3" count="2"/>
                <participants group_id="P4" count="3"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="28"/>
                <participants group_id="P2" count="3"/>
                <participants group_id="P3" count="2"/>
                <participants group_id="P4" count="3"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="0"/>
                <participants group_id="P4" count="0"/>
              </participants_list>
            </milestone>
          </milestone_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <population>Patients with Pt-resistant HGSOC with TP53 mutation.</population>
      <group_list>
        <group group_id="B1">
          <title>APR-246 (4.5g/6hr) + PLD</title>
          <description>APR-246: Intravenous infusion Pegylated Liposomal Doxorubicin Hydrochloride (PLD): Intravenous infusion</description>
        </group>
        <group group_id="B2">
          <title>APR-246 (4.5g/3hr) + PLD</title>
          <description>APR-246: Intravenous infusion Pegylated Liposomal Doxorubicin Hydrochloride (PLD): Intravenous infusion</description>
        </group>
        <group group_id="B3">
          <title>APR-246 (4.5g/4hr) + PLD</title>
          <description>APR-246: Intravenous infusion Pegylated Liposomal Doxorubicin Hydrochloride (PLD): Intravenous infusion</description>
        </group>
        <group group_id="B4">
          <title>APR-246 (3.7g/4hr) + PLD</title>
          <description>APR-246: Intravenous infusion Pegylated Liposomal Doxorubicin Hydrochloride (PLD): Intravenous infusion</description>
        </group>
        <group group_id="B5">
          <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="28"/>
            <count group_id="B2" value="3"/>
            <count group_id="B3" value="2"/>
            <count group_id="B4" value="3"/>
            <count group_id="B5" value="36"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>&lt;=18 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                    <measurement group_id="B5" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Between 18 and 65 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="21"/>
                    <measurement group_id="B2" value="2"/>
                    <measurement group_id="B3" value="1"/>
                    <measurement group_id="B4" value="2"/>
                    <measurement group_id="B5" value="26"/>
                  </measurement_list>
                </category>
                <category>
                  <title>&gt;=65 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="7"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="1"/>
                    <measurement group_id="B4" value="1"/>
                    <measurement group_id="B5" value="10"/>
                  </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="28"/>
                    <measurement group_id="B2" value="3"/>
                    <measurement group_id="B3" value="2"/>
                    <measurement group_id="B4" value="3"/>
                    <measurement group_id="B5" value="36"/>
                  </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 group_id="B4" value="0"/>
                    <measurement group_id="B5" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Race/Ethnicity, Customized</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <title>White</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="27"/>
                    <measurement group_id="B2" value="3"/>
                    <measurement group_id="B3" value="2"/>
                    <measurement group_id="B4" value="3"/>
                    <measurement group_id="B5" value="35"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Asian</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                    <measurement group_id="B5" value="1"/>
                  </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>Belgium</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="4"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                    <measurement group_id="B5" value="4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>United Kingdom</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="3"/>
                    <measurement group_id="B2" value="3"/>
                    <measurement group_id="B3" value="2"/>
                    <measurement group_id="B4" value="3"/>
                    <measurement group_id="B5" value="11"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Spain</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="21"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                    <measurement group_id="B5" value="21"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Overall Response Rate (ORR)</title>
        <description>Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), &gt;=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR.</description>
        <time_frame>Up to 18 months</time_frame>
        <population>A total of 36 patients were enrolled in this Phase II study. Of the 36 patients, 28 patients were in the main study, 4.5g/6hr dose cohort; 8 patients were in the sub-study as follows: 3 patients were in the 4.5g/3hr dose cohort; 2 patients were in the 4.5g/4hr dose cohort and 3 patients were in the 3.7g/4hr dose cohort.&#xD;
The 23 Efficacy Evaluable Patients from the Main Study (APR-246 (4.5g/6hr) + PLD) are part of the analysis reported below.</population>
        <group_list>
          <group group_id="O1">
            <title>APR-246 (4.5g/6hr) + PLD</title>
            <description>APR-246: Intravenous infusion Pegylated Liposomal Doxorubicin Hydrochloride (PLD): Intravenous infusion</description>
          </group>
          <group group_id="O2">
            <title>APR-246 (4.5g/3hr) + PLD</title>
            <description>APR-246: Intravenous infusion Pegylated Liposomal Doxorubicin Hydrochloride (PLD): Intravenous infusion</description>
          </group>
          <group group_id="O3">
            <title>APR-246 (4.5g/4hr) + PLD</title>
            <description>APR-246: Intravenous infusion Pegylated Liposomal Doxorubicin Hydrochloride (PLD): Intravenous infusion</description>
          </group>
          <group group_id="O4">
            <title>APR-246 (3.7g/4hr) + PLD</title>
            <description>APR-246: Intravenous infusion Pegylated Liposomal Doxorubicin Hydrochloride (PLD): Intravenous infusion</description>
          </group>
        </group_list>
        <measure>
          <title>Overall Response Rate (ORR)</title>
          <description>Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), &gt;=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR.</description>
          <population>A total of 36 patients were enrolled in this Phase II study. Of the 36 patients, 28 patients were in the main study, 4.5g/6hr dose cohort; 8 patients were in the sub-study as follows: 3 patients were in the 4.5g/3hr dose cohort; 2 patients were in the 4.5g/4hr dose cohort and 3 patients were in the 3.7g/4hr dose cohort.&#xD;
The 23 Efficacy Evaluable Patients from the Main Study (APR-246 (4.5g/6hr) + PLD) are part of the analysis reported below.</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="23"/>
                <count group_id="O2" value="3"/>
                <count group_id="O3" value="2"/>
                <count group_id="O4" value="3"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Partial Response (PR)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                    <measurement group_id="O2" value="0"/>
                    <measurement group_id="O3" value="0"/>
                    <measurement group_id="O4" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Stable Disease (SD)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="15"/>
                    <measurement group_id="O2" value="2"/>
                    <measurement group_id="O3" value="1"/>
                    <measurement group_id="O4" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Progressive Disease (PD)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="7"/>
                    <measurement group_id="O2" value="0"/>
                    <measurement group_id="O3" value="1"/>
                    <measurement group_id="O4" value="2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Not Evaluable</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="1"/>
                    <measurement group_id="O3" value="0"/>
                    <measurement group_id="O4" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Disease Control Rate (CR+PR+SD)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="16"/>
                    <measurement group_id="O2" value="0"/>
                    <measurement group_id="O3" value="0"/>
                    <measurement group_id="O4" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Treatment-emergent Adverse Events With Combined APR-246 and PLD Regimen</title>
        <description>Treatment emergent adverse events (TEAEs) were defined as AEs that occurred on or after the first dose of study medication up to and including 30 days after last dose. AEs were graded according to NCI CTCAE (Version 4.0). Patients with multiple TEAEs were only counted once within a summary category: SOC, PT, maximum grade, or relationship to treatment. Patients with events in more than one category were counted once within each category.</description>
        <time_frame>Treatment emergent adverse events (TEAEs) were defined as AEs that occurred on or after the first dose of study medication up to and including 30 days after last dose. Median number of 28d Cycles=2.5 (Min = 1, Max = 14)</time_frame>
        <group_list>
          <group group_id="O1">
            <title>APR-246 (4.5g/6hr) + PLD</title>
            <description>APR-246: Intravenous infusion Pegylated Liposomal Doxorubicin Hydrochloride (PLD): Intravenous infusion</description>
          </group>
          <group group_id="O2">
            <title>APR-246 (4.5g/3hr) + PLD</title>
            <description>APR-246: Intravenous infusion Pegylated Liposomal Doxorubicin Hydrochloride (PLD): Intravenous infusion</description>
          </group>
          <group group_id="O3">
            <title>APR-246 (4.5g/4hr) + PLD</title>
            <description>APR-246: Intravenous infusion Pegylated Liposomal Doxorubicin Hydrochloride (PLD): Intravenous infusion</description>
          </group>
          <group group_id="O4">
            <title>APR-246 (3.7g/4hr) + PLD</title>
            <description>APR-246: Intravenous infusion Pegylated Liposomal Doxorubicin Hydrochloride (PLD): Intravenous infusion</description>
          </group>
        </group_list>
        <measure>
          <title>Treatment-emergent Adverse Events With Combined APR-246 and PLD Regimen</title>
          <description>Treatment emergent adverse events (TEAEs) were defined as AEs that occurred on or after the first dose of study medication up to and including 30 days after last dose. AEs were graded according to NCI CTCAE (Version 4.0). Patients with multiple TEAEs were only counted once within a summary category: SOC, PT, maximum grade, or relationship to treatment. Patients with events in more than one category were counted once within each category.</description>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="28"/>
                <count group_id="O2" value="3"/>
                <count group_id="O3" value="2"/>
                <count group_id="O4" value="3"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>With Any Treatment-Emergent Adverse Events (TEAEs)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="28"/>
                    <measurement group_id="O2" value="3"/>
                    <measurement group_id="O3" value="2"/>
                    <measurement group_id="O4" value="3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>With APR-246 Related TEAEs</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="25"/>
                    <measurement group_id="O2" value="3"/>
                    <measurement group_id="O3" value="2"/>
                    <measurement group_id="O4" value="3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>With PLD Related TEAEs</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="24"/>
                    <measurement group_id="O2" value="3"/>
                    <measurement group_id="O3" value="2"/>
                    <measurement group_id="O4" value="3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>With Severity Grade &gt;=3</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="14"/>
                    <measurement group_id="O2" value="3"/>
                    <measurement group_id="O3" value="2"/>
                    <measurement group_id="O4" value="3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>With Severity Grade &gt;=3 APR-246 Related TEAEs</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="6"/>
                    <measurement group_id="O2" value="2"/>
                    <measurement group_id="O3" value="2"/>
                    <measurement group_id="O4" value="2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>With Severity Grade &gt;=3 PLD Related TEAEs</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="7"/>
                    <measurement group_id="O2" value="2"/>
                    <measurement group_id="O3" value="0"/>
                    <measurement group_id="O4" value="2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>With Any Serious AEs</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="11"/>
                    <measurement group_id="O2" value="1"/>
                    <measurement group_id="O3" value="1"/>
                    <measurement group_id="O4" value="2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>With Any Serious, APR-246 Related AEs</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="4"/>
                    <measurement group_id="O2" value="1"/>
                    <measurement group_id="O3" value="1"/>
                    <measurement group_id="O4" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>With Any Serious, PLD Related AEs</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2"/>
                    <measurement group_id="O2" value="1"/>
                    <measurement group_id="O3" value="0"/>
                    <measurement group_id="O4" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Who Discontinued APR-246 Due to TEAEs</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2"/>
                    <measurement group_id="O2" value="1"/>
                    <measurement group_id="O3" value="0"/>
                    <measurement group_id="O4" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Who Discontinued PLD Due to TEAEs</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                    <measurement group_id="O3" value="0"/>
                    <measurement group_id="O4" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Who Died Due to any TEAEs</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                    <measurement group_id="O3" value="0"/>
                    <measurement group_id="O4" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>Treatment emergent adverse events (TEAEs) were defined as AEs that occurred on or after the first dose of study medication up to and including 30 days after last dose. Median number of 28d Cycles=2.5 (Min = 1, Max = 14)</time_frame>
      <desc>AEs were graded according to NCI CTCAE (Version 4.0).</desc>
      <group_list>
        <group group_id="E1">
          <title>APR-246 (4.5g/6hr) + PLD</title>
          <description>APR-246: Intravenous infusion Pegylated Liposomal Doxorubicin Hydrochloride (PLD): Intravenous infusion</description>
        </group>
        <group group_id="E2">
          <title>APR-246 (4.5g/3hr) + PLD</title>
          <description>APR-246: Intravenous infusion Pegylated Liposomal Doxorubicin Hydrochloride (PLD): Intravenous infusion</description>
        </group>
        <group group_id="E3">
          <title>APR-246 (4.5g/4hr) + PLD</title>
          <description>APR-246: Intravenous infusion Pegylated Liposomal Doxorubicin Hydrochloride (PLD): Intravenous infusion</description>
        </group>
        <group group_id="E4">
          <title>APR-246 (3.7g/4hr) + PLD</title>
          <description>APR-246: Intravenous infusion Pegylated Liposomal Doxorubicin Hydrochloride (PLD): Intravenous infusion</description>
        </group>
      </group_list>
      <serious_events>
        <default_vocab>MedDRA (17.1)</default_vocab>
        <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="9" subjects_at_risk="28"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="11" subjects_at_risk="28"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="2"/>
                <counts group_id="E4" subjects_affected="2" subjects_at_risk="3"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Blood and lymphatic system disorders</title>
            <event_list>
              <event>
                <sub_title>Thrombocytopenia</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="28"/>
                <counts group_id="E2" events="6" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="3"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Intestinal obstruction</sub_title>
                <counts group_id="E1" events="3" subjects_affected="3" subjects_at_risk="28"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>Nausea</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="28"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>Peritoneal fibrosis</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="28"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>Small intestinal obstruction</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="28"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>Vomiting</sub_title>
                <counts group_id="E1" events="2" subjects_affected="1" subjects_at_risk="28"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="3"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Mucosal inflammation</sub_title>
                <counts group_id="E1" events="3" subjects_affected="1" subjects_at_risk="28"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="3"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Infection</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="28"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>Device related infection</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="28"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>Respiratory tract infection</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="28"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E4" events="2" subjects_affected="1" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>Upper respiratory tract infection</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="28"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>Urinary tract infection</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="28"/>
                <counts group_id="E2" events="2" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E4" 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>Lumbar vertebral fracture</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="28"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>Procedural pain</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="28"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E4" 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>Arthralgia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="28"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="3"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Ataxia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="28"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>Dizziness</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="28"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" events="2" subjects_affected="1" subjects_at_risk="2"/>
                <counts group_id="E4" 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>Renal failure</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="28"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="3"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>5</frequency_threshold>
        <default_vocab>MedDRA (17.1)</default_vocab>
        <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="28" subjects_at_risk="28"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="2" subjects_at_risk="2"/>
                <counts group_id="E4" subjects_affected="3" subjects_at_risk="3"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Blood and lymphatic system disorders</title>
            <event_list>
              <event>
                <sub_title>Anemia</sub_title>
                <counts group_id="E1" subjects_affected="6" subjects_at_risk="28"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="2"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>Neutropenia</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="28"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>Thrombocytopenia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="28"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>Hypophosphatemia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="28"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="3"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Ear and labyrinth disorders</title>
            <event_list>
              <event>
                <sub_title>Ear and labyrinth disorders</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="28"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="3"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Eye disorders</title>
            <event_list>
              <event>
                <sub_title>Blepharitis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="28"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>Lacrimation increased</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="28"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="3"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Nausea</sub_title>
                <counts group_id="E1" subjects_affected="17" subjects_at_risk="28"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="2"/>
                <counts group_id="E4" subjects_affected="3" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>Vomiting</sub_title>
                <counts group_id="E1" subjects_affected="12" subjects_at_risk="28"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="2" subjects_at_risk="2"/>
                <counts group_id="E4" subjects_affected="3" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>Constipation</sub_title>
                <counts group_id="E1" subjects_affected="11" subjects_at_risk="28"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E4" subjects_affected="2" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>Abdominal pain</sub_title>
                <counts group_id="E1" subjects_affected="9" subjects_at_risk="28"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="2"/>
                <counts group_id="E4" subjects_affected="3" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>Diarrhea</sub_title>
                <counts group_id="E1" subjects_affected="6" subjects_at_risk="28"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E4" subjects_affected="2" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>Abdominal distension</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="28"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>Dyspepsia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="28"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>Gastroesophageal reflux disease</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="28"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E4" subjects_affected="2" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>Stomatitis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="28"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>Dry mouth</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="28"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>Dysphagia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="28"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>Gastric ulcer</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="28"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>Ascites</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="28"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>Haemorrhoids</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="28"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>Intestinal obstruction</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="28"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="3"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Fatigue</sub_title>
                <counts group_id="E1" subjects_affected="6" subjects_at_risk="28"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="2"/>
                <counts group_id="E4" subjects_affected="3" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>Asthenia</sub_title>
                <counts group_id="E1" subjects_affected="10" subjects_at_risk="28"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>Mucosal inflammation</sub_title>
                <counts group_id="E1" subjects_affected="7" subjects_at_risk="28"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>Edema peripheral</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="28"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>Gait disturbance</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="28"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>Device occlusion</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="28"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E4" subjects_affected="2" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>Infusion site vesicles</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="28"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>Pyrexia</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="28"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="3"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Immune system disorders</title>
            <event_list>
              <event>
                <sub_title>Hypersensitivity</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="28"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="3"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Urinary tract infection</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="28"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>Conjunctivitis</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="28"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>Infection</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="28"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>Device related infection</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="28"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>Lip infection</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="28"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>Respiratory tract infection</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="28"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="3"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Injury, poisoning and procedural complications</title>
            <event_list>
              <event>
                <sub_title>Vascular access complication</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="28"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="3"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Investigations</title>
            <event_list>
              <event>
                <sub_title>Glomerular filtration rate decreased</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="28"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E4" subjects_affected="1" 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" subjects_affected="7" subjects_at_risk="28"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="2"/>
                <counts group_id="E4" subjects_affected="3" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>Hypoalbuminemia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="28"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E4" subjects_affected="1" 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" subjects_affected="4" subjects_at_risk="28"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>Arthralgia</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="28"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="2"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>Muscular weakness</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="28"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="2"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>Musculoskeletal chest pain</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="28"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>Neck pain</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="28"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>Pain in extremity</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="28"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E4" 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" subjects_affected="5" subjects_at_risk="28"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="2" subjects_at_risk="2"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>Dysgeusia</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="28"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>Ataxia</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="28"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="2"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>Dyskinesia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="28"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>Headache</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="28"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>Balance disorder</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="28"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="2"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>Neuropathy peripheral</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="28"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>Somnolence</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="28"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>Tremor</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="28"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>Akathisia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="28"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="2"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>Aphasia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="28"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="2"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>Apraxia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="28"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="2"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>Dysarthria</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="28"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="2"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>Nystagmus</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="28"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="2"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>Paresthesia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="28"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>Peripheral sensory neuropathy</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="28"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="2"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="3"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Psychiatric disorders</title>
            <event_list>
              <event>
                <sub_title>Hallucination</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="28"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="2"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>Confusional state</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="28"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>Insomnia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="28"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>Irritability</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="28"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>Nightmare</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="28"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="3"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Renal and urinary disorders</title>
            <event_list>
              <event>
                <sub_title>Micturition urgency</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="28"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="2"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>Renal impairment</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="28"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="3"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Dyspnea</sub_title>
                <counts group_id="E1" subjects_affected="5" subjects_at_risk="28"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>Cough</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="28"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>Pulmonary embolism</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="28"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="3"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Skin and subcutaneous tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Alopecia</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="28"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>Dry skin</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="28"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>Rash</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="28"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>Palmar-plantar erythrodysesthesia syndrome</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="28"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>Miliaria</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="28"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>Pruritus</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="28"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>Rash maculo-papular</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="28"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="3"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Vascular disorders</title>
            <event_list>
              <event>
                <sub_title>Vascular disorders</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="28"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E4" 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>
    <point_of_contact>
      <name_or_title>Dr Eyal C Attar, SVP &amp; CMO</name_or_title>
      <organization>Aprea Therapeutics</organization>
      <phone>+1 617 804 6947</phone>
      <email>Eyal.Attar@Aprea.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/NCT03268382
org study id: APR-486
nct id: NCT03268382
lead sponsor: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
The purpose of this study is to make a preliminary assessment of the efficacy of a combined
      APR-246 and PLD chemotherapy regimen in patients with platinum-resistant recurrent high grade
      serous ovarian cancer (HGSOC) with mutated TP53. In addition, the study aims to assess the
      safety profile of the combined APR-246 and PLD chemotherapy regimen, to evaluate potential
      biomarkers, and to assess the biological activity in tumor and surrogate tissues. The trial
      will enroll at least 25 evaluable patients.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Overall Response Rate (ORR)
time frame: Up to 18 months
description: Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR.
measure: Treatment-emergent Adverse Events With Combined APR-246 and PLD Regimen
time frame: Treatment emergent adverse events (TEAEs) were defined as AEs that occurred on or after the first dose of study medication up to and including 30 days after last dose. Median number of 28d Cycles=2.5 (Min = 1, Max = 14)
description: Treatment emergent adverse events (TEAEs) were defined as AEs that occurred on or after the first dose of study medication up to and including 30 days after last dose. AEs were graded according to NCI CTCAE (Version 4.0). Patients with multiple TEAEs were only counted once within a summary category: SOC, PT, maximum grade, or relationship to treatment. Patients with events in more than one category were counted once within each category.
arm group label: APR-246 + PLD
arm group type: Experimental
intervention type: Drug
intervention name: APR-246
description: Intravenous infusion
arm group label: APR-246 + PLD
intervention type: Drug
intervention name: Pegylated Liposomal Doxorubicin Hydrochloride (PLD)
description: Intravenous infusion
arm group label: APR-246 + PLD
criteria: 
gender: Female
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Charlie Gourley, BSc, MB ChB, PhD, FRCP
role: Principal Investigator
affiliation: Edinburgh Cancer Research Centre, The University of Edinburgh
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
country: Belgium
country: Spain
country: United Kingdom
url: http://www.aprea.com
description: Aprea Therapeutics AB's website (Sponsor)
citation: Lehmann S, Bykov VJ, Ali D, Andren O, Cherif H, Tidefelt U, Uggla B, Yachnin J, Juliusson G, Moshfegh A, Paul C, Wiman KG, Andersson PO. Targeting p53 in vivo: a first-in-human study with p53-targeting compound APR-246 in refractory hematologic malignancies and prostate cancer. J Clin Oncol. 2012 Oct 10;30(29):3633-9. doi: 10.1200/JCO.2011.40.7783. Epub 2012 Sep 10.
PMID: 22965953
citation: Deneberg S, Cherif H, Lazarevic V, Andersson PO, von Euler M, Juliusson G, Lehmann S. An open-label phase I dose-finding study of APR-246 in hematological malignancies. Blood Cancer J. 2016 Jul 15;6(7):e447. doi: 10.1038/bcj.2016.60. No abstract available.
PMID: 27421096
responsible party type: Sponsor
mesh term: Ovarian Neoplasms
mesh term: Carcinoma, Ovarian Epithelial
mesh term: Doxorubicin
mesh term: Liposomal doxorubicin
provided document: 
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 