<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/NCT01666444</url>
  </required_header>
  <id_info>
    <org_study_id>GOG-3003</org_study_id>
    <nct_id>NCT01666444</nct_id>
  </id_info>
  <brief_title>VTX-2337 and Pegylated Liposomal Doxorubicin (PLD) in Patients With Recurrent or Persistent Epithelial Ovarian, Fallopian Tube or Primary Peritoneal Cancer</brief_title>
  <official_title>A Randomized, Double-Blind, Placebo-Controlled Phase II Study of VTX-2337 in Combination With Pegylated Liposomal Doxorubicin (PLD) in Patients With Recurrent or Persistent Epithelial Ovarian, Fallopian Tube or Primary Peritoneal Cancer</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Celgene</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Gynecologic Oncology Group</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Celgene</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The purpose of this study is to compare the overall survival of patients treated with&#xD;
      VTX-2337 + pegylated liposomal doxorubicin (PLD) versus those treated with PLD alone in women&#xD;
      with recurrent or persistent, epithelial ovarian, fallopian tube or primary peritoneal&#xD;
      cancer.&#xD;
&#xD;
      VTX-2337, a small molecule agonist of Toll-like Receptor 8 (TLR8), activates multiple&#xD;
      components of the innate immune system and is being developed as a novel therapeutic agent&#xD;
      for use in oncology. Experimental data obtained in an animal model of ovarian cancer supports&#xD;
      the combination of VTX-2337 with PLD. In this model, the combination of VTX-2337 and PLD&#xD;
      resulted in a significant reduction in tumor growth compared to either agent alone and an&#xD;
      increase in the number of T lymphocytes infiltrating the tumor. The combination of PLD and&#xD;
      VTX-2337 has been tested in a small number of women with ovarian cancer in a Phase 1b study&#xD;
      and appears to be generally well-tolerated.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      OBJECTIVES&#xD;
&#xD;
      Primary Objectives:&#xD;
&#xD;
        -  To compare the overall survival (OS) of patients treated with VTX-2337 + PLD versus&#xD;
           those treated with PLD alone in women with recurrent or persistent, epithelial ovarian,&#xD;
           fallopian tube or primary peritoneal cancer.&#xD;
&#xD;
        -  To compare the progression-free survival (PFS) between the two treatment groups using&#xD;
           Immune-Related Response Evaluation Criteria in Solid Tumors (irRECIST).&#xD;
&#xD;
      Secondary Objectives:&#xD;
&#xD;
        -  To compare the progression-free survival (PFS) between the two treatment groups using&#xD;
           Response Evaluation Criteria In Solid Tumors (RECIST 1.1).&#xD;
&#xD;
        -  To compare the nature, frequency and severity of drug-related adverse events (AEs)&#xD;
           between the two treatment groups.&#xD;
&#xD;
      Exploratory Objectives:&#xD;
&#xD;
        -  To compare the best overall response rate (ORR) and duration of response (based on the&#xD;
           probability of being in response function [PBRF]) between the two treatment groups using&#xD;
           irRECIST and RECIST 1.1.&#xD;
&#xD;
        -  To compare the disease control rate (DCR) between the two treatment groups using&#xD;
           irRECIST and RECIST 1.1.&#xD;
&#xD;
        -  To assess the impact of immune status and response on the clinical effects (OS, PFS,&#xD;
           DCR, ORR, PBRF, AEs) of study treatment.&#xD;
&#xD;
        -  To assess the effect of TLR8 polymorphisms and BRCA1/BRCA2 mutations on the clinical&#xD;
           effects (OS, PFS, DCR, ORR, PBRF, AEs) of study treatment.&#xD;
&#xD;
        -  To assess the effect of immune cell subsets, as measured by immunohistochemistry and&#xD;
           micro RNA in primary tumor tissue (e.g. immune score), on the clinical effects (OS, PFS,&#xD;
           DCR, ORR, PBRF, AEs) of study treatment.&#xD;
&#xD;
        -  To assess whether the presence of autoantibodies to tumor-derived proteins are&#xD;
           predictive of the clinical effects (OS, PFS, DCR, ORR, PBRF, AEs) of study treatment.&#xD;
&#xD;
      OUTLINE:&#xD;
&#xD;
      This is Phase 2 multicenter clinical study to evaluate the efficacy and safety of the&#xD;
      combination of VTX-2337 + PLD compared to PLD + Placebo.&#xD;
&#xD;
      The dosing schedule will be the same for both treatment arms, and will be based on a 28-day&#xD;
      cycle. The starting dose schedule is PLD on Day 1 plus VTX-2337 or placebo on Day 3, Day 10,&#xD;
      and Day 17 for the first 4 cycles. Starting with cycle 5, the dose regimen will be PLD on Day&#xD;
      1 plus VTX-2337 or placebo on Day 3.&#xD;
&#xD;
      Blood samples are collected periodically during cycle 1 for pharmacodynamics,&#xD;
      pharmacogenomics, and other research studies.&#xD;
&#xD;
      Patients will receive therapy until disease progression based on Immune-Related RECIST or&#xD;
      until adverse effects prohibit further therapy. Following treatment completion, all patients&#xD;
      will be followed with physical exams and histories every three months for the first two&#xD;
      years, and then every six months for the next three years, and then&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">October 31, 2012</start_date>
  <completion_date type="Actual">July 31, 2016</completion_date>
  <primary_completion_date type="Actual">July 31, 2016</primary_completion_date>
  <phase>Phase 2</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Overall Survival</measure>
    <time_frame>Survival is measured from date of enrollment and randomization on the study until death from any cause, or if alive at last contact, date of last contact.</time_frame>
    <description>Comparison of duration of survival between the 2 treatment groups</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Progression-free Survival (PFS)</measure>
    <time_frame>Progression-free survival is measured from enrollment and randomization on the study until first indication of progression based on irRECIST criteria or death from any cause, or if progression-free at last contact, the date of last disease assessment.</time_frame>
    <description>Comparison of PFS between the 2 treatment groups</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Frequency and Severity of Adverse Events (AEs)</measure>
    <time_frame>Assessed during each cycle of therapy and within 30 days after the last cycle of therapy</time_frame>
    <description>An AE is any untoward medical occurrence associated with the use of a drug in humans, whether or not considered drug-related. An AE can be unfavorable and unintended sign, symptom, or disease which is temporally associated with the use of investigational product (IP), whether or not considered related to the IP. A serious AE = an AE occurring at any dose that: • Results in death • Is life- threatening • Requires or prolongs existing inpatient hospitalization • Results in persistent or significant disability/incapacity • Is a congenital anomaly/birth defect; • Constitutes an important medical event. The Investigator assessed the relationship of each AE to IP and graded the severity according to the National Cancer Institute Common Terminology Criteria for Adverse Events, Version 4.0: Grade (GR) 1 = Mild; asymptomatic or mild symptoms; GR 2 = Moderate (minimal, local or noninvasive intervention indicated); GR 3 = Severe or medically significant; GR 4 = Life-threatening; GR 5 = Death</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">297</enrollment>
  <condition>Epithelial Ovarian Cancer</condition>
  <condition>Fallopian Tube Cancer</condition>
  <condition>Primary Peritoneal Cancer</condition>
  <arm_group>
    <arm_group_label>PLD 40 mg/m2 plus VTX-2337</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>The dosing schedule will be be based on a 28-day cycle. The starting dose schedule is PLD on Day 1 plus VTX-2337 on Day 3, Day 10, and Day 17 for the first 4 cycles. Starting with cycle 5, the dose regimen will be PLD on Day 1 plus VTX-2337 on Day 3 only, without additional doses of VTX-2337 on Days 10 and Day 17.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>PLD 40 mg/m2 plus placebo</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>The dosing schedule will be based on a 28-day cycle. The starting dose schedule is PLD on Day 1 plus placebo on Day 3, Day 10, and Day 17 for the first 4 cycles. Starting with cycle 5, the dose regimen will be PLD on Day 1 plus placebo on Day 3 only.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>pegylated liposomal doxorubicin (PLD)</intervention_name>
    <arm_group_label>PLD 40 mg/m2 plus VTX-2337</arm_group_label>
    <arm_group_label>PLD 40 mg/m2 plus placebo</arm_group_label>
    <other_name>Doxil</other_name>
    <other_name>Lipodox</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>VTX-2337</intervention_name>
    <description>TLR8 Agonist</description>
    <arm_group_label>PLD 40 mg/m2 plus VTX-2337</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <arm_group_label>PLD 40 mg/m2 plus placebo</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Patients must have recurrent or persistent epithelial ovarian, fallopian tube, or&#xD;
             primary peritoneal carcinoma.&#xD;
&#xD;
          2. Patients with the following histologic cell types are eligible: serous adenocarcinoma,&#xD;
             endometrioid adenocarcinoma, mucinous adenocarcinoma, undifferentiated carcinoma,&#xD;
             clear cell adenocarcinoma, mixed epithelial adenocarcinoma, transitional cell&#xD;
             carcinoma, malignant Brenner's tumor or adenocarcinoma not otherwise specified.&#xD;
&#xD;
          3. Patient must have measurable disease as defined by RECIST 1.1.&#xD;
&#xD;
          4. Patients must have received treatment with a platinum-based chemotherapeutic regimen&#xD;
             for management of primary disease containing carboplatin, cisplatin or another&#xD;
             organoplatinum compound. This initial treatment may have included intraperitoneal&#xD;
             therapy, consolidation, non-cytotoxic agents or extended therapy administered after&#xD;
             surgical or non-surgical assessment.&#xD;
&#xD;
             Patients are allowed to receive, but are not required to receive, one additional&#xD;
             cytotoxic regimen for management of recurrent or persistent disease.&#xD;
&#xD;
             Patients are allowed to have received, but are not required to have received,&#xD;
             biologic/targeted therapy (e.g., bevacizumab and/or PARP inhibitor) as part of their&#xD;
             primary treatment regimen or for management of recurrent or persistent disease.&#xD;
&#xD;
          5. Patients must have platinum-resistant disease, defined as having a platinum-free&#xD;
             interval (PFI) of &lt; 12 months after first- or second-line platinum-based chemotherapy,&#xD;
             or having disease progression while receiving second-line platinum-based chemotherapy.&#xD;
&#xD;
          6. Patients must have adequate bone marrow, renal, hepatic, and neurologic functions as&#xD;
             defined by the following:&#xD;
&#xD;
               -  Bone marrow function: absolute neutrophil count (ANC) ≥ 1,500/mm3. This ANC&#xD;
                  cannot have been induced or supported by granulocyte colony stimulating factors.&#xD;
                  Platelets ≥ 100,000/mm3. Hemoglobin ≥ 9 g/dL.&#xD;
&#xD;
               -  Renal function: creatinine ≤ 1.5 x institutional upper limit normal (ULN).&#xD;
&#xD;
               -  Hepatic function: bilirubin &lt; 1.2 mg/dL, SGOT (AST) and SGPT (ALT) ≤ 3.0 x ULN&#xD;
                  and alkaline phosphatase ≤ 2.5 x ULN.&#xD;
&#xD;
          7. Patients must have recovered from effects of recent surgery, radiotherapy or&#xD;
             chemotherapy:&#xD;
&#xD;
               -  Patients should be free of active infection requiring parenteral antibiotics.&#xD;
&#xD;
               -  Any hormonal therapy directed at the malignant tumor must be discontinued at&#xD;
                  least one week prior to registration. Continuation of hormone replacement therapy&#xD;
                  is permitted.&#xD;
&#xD;
               -  Any other prior therapy directed at the malignant tumor, including chemotherapy,&#xD;
                  biologic/targeted agents and immunologic agents, must be discontinued at least&#xD;
                  three weeks prior to registration.&#xD;
&#xD;
               -  Any prior radiation therapy must be completed at least four weeks prior to&#xD;
                  registration.&#xD;
&#xD;
          8. Patients must have a GOG performance status of 0 or 1.&#xD;
&#xD;
          9. Patients of childbearing potential must have a negative pregnancy test prior to the&#xD;
             study entry and be practicing an effective form of contraception. If applicable,&#xD;
             patients must discontinue breastfeeding prior to study entry.&#xD;
&#xD;
         10. Patients must meet the entry requirements and undergo the baseline procedures.&#xD;
&#xD;
         11. Patients must have signed an IRB-approved informed consent form and authorization&#xD;
             permitting release of personal health information.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Patients who have had treatment with VTX-2337, doxorubicin, PLD, or any other&#xD;
             anthracycline.&#xD;
&#xD;
          2. Patients who have received an investigational agent &lt; 30 days prior to registration.&#xD;
&#xD;
          3. Patients who have received oral or parenteral corticosteroids &lt; 2 weeks prior to&#xD;
             registration or who require ongoing systemic immunosuppressive therapy for any reason.&#xD;
&#xD;
          4. Patients with active autoimmune disease. &quot;Active&quot; refers to any condition currently&#xD;
             requiring therapy. Examples of autoimmune disease include systemic lupus&#xD;
             erythematosus, multiple sclerosis, inflammatory bowel disease and rheumatoid&#xD;
             arthritis.&#xD;
&#xD;
          5. Patients with a history of other invasive malignancies, with the exception of&#xD;
             non-melanoma skin cancer, are excluded if there is any evidence of the other&#xD;
             malignancy being present within the last three years.&#xD;
&#xD;
          6. Patients who have received prior radiotherapy OTHER THAN for the treatment of ovarian,&#xD;
             fallopian tube or primary peritoneal cancer within the last three years are excluded.&#xD;
&#xD;
          7. Patients who have received prior chemotherapy OTHER THAN for the treatment of ovarian,&#xD;
             fallopian tube or primary peritoneal cancer within the last three years are excluded.&#xD;
&#xD;
          8. Patients with history or evidence upon physical examination of CNS disease, including&#xD;
             primary brain tumor, seizures not controlled with standard medical therapy, any brain&#xD;
             metastases, or history of cerebrovascular accident (CVA, stroke), transient ischemic&#xD;
             attack (TIA) or subarachnoid hemorrhage within six months of the first date of&#xD;
             treatment on this study.&#xD;
&#xD;
          9. Patients with clinically significant cardiovascular disease.&#xD;
&#xD;
         10. Patients who are pregnant or nursing.&#xD;
&#xD;
         11. Patients under the age of 18.&#xD;
&#xD;
         12. Patients with clinical symptoms or signs of gastrointestinal obstruction and/or who&#xD;
             require parenteral hydration or nutrition.&#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>Bradley J. Monk, MD</last_name>
    <role>Study Chair</role>
    <affiliation>St. Joseph's Hospital and Medical Center, Phoenix AZ</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Amar Patel, MD</last_name>
    <role>Study Director</role>
    <affiliation>Celgene</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>St. Joseph's Hospital and Medical Center</name>
      <address>
        <city>Phoenix</city>
        <state>Arizona</state>
        <zip>85013</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Winthrop P. Rockefeller Cancer Institute - University of Arkansas</name>
      <address>
        <city>Little Rock</city>
        <state>Arkansas</state>
        <zip>72205</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Providence Saint Joseph Medical Center</name>
      <address>
        <city>Burbank</city>
        <state>California</state>
        <zip>91505</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Kaiser Permanente Medical Center</name>
      <address>
        <city>Hayward</city>
        <state>California</state>
        <zip>94545</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Long Beach Memorial Medical Center</name>
      <address>
        <city>Long Beach</city>
        <state>California</state>
        <zip>90806</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Kaiser Permanente Medical Center</name>
      <address>
        <city>Oakland</city>
        <state>California</state>
        <zip>94611</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Kaiser Permanente Medical Center</name>
      <address>
        <city>Roseville</city>
        <state>California</state>
        <zip>95661</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Sutter Cancer Center</name>
      <address>
        <city>Sacramento</city>
        <state>California</state>
        <zip>95816</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Kaiser Permanente Medical Center</name>
      <address>
        <city>Sacramento</city>
        <state>California</state>
        <zip>95825</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Kaiser Permanente Medical Center</name>
      <address>
        <city>San Francisco</city>
        <state>California</state>
        <zip>94115</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Kaiser Permanente Medical Center</name>
      <address>
        <city>San Jose</city>
        <state>California</state>
        <zip>95119</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Kaiser Permanente Medical Center</name>
      <address>
        <city>Santa Clara</city>
        <state>California</state>
        <zip>95051</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Kaiser Permanente Medical Center</name>
      <address>
        <city>South San Francisco</city>
        <state>California</state>
        <zip>94080</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Stanford University School of Medicine</name>
      <address>
        <city>Stanford</city>
        <state>California</state>
        <zip>94305</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Kaiser Permanente Medical Center</name>
      <address>
        <city>Vallejo</city>
        <state>California</state>
        <zip>94586</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Kaiser Permanente Medical Center</name>
      <address>
        <city>Walnut Creek</city>
        <state>California</state>
        <zip>94596</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Colorado Cancer Center</name>
      <address>
        <city>Aurora</city>
        <state>Colorado</state>
        <zip>80045</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hartford Hospital</name>
      <address>
        <city>Hartford</city>
        <state>Connecticut</state>
        <zip>06102</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>St. Francis Hospital and Medical Center</name>
      <address>
        <city>Hartford</city>
        <state>Connecticut</state>
        <zip>06105</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>The Hospital of Central Connecticut</name>
      <address>
        <city>New Britain</city>
        <state>Connecticut</state>
        <zip>06050</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Yale - New Haven Hospital</name>
      <address>
        <city>New Haven</city>
        <state>Connecticut</state>
        <zip>06520</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>MD Anderson Cancer Center - Orlando</name>
      <address>
        <city>Orlando</city>
        <state>Florida</state>
        <zip>32806</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Women's Cancer Associates</name>
      <address>
        <city>Saint Petersburg</city>
        <state>Florida</state>
        <zip>33701</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Northside Hospital</name>
      <address>
        <city>Atlanta</city>
        <state>Georgia</state>
        <zip>30342</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Georgia Regents University</name>
      <address>
        <city>Augusta</city>
        <state>Georgia</state>
        <zip>30912</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Northeast Georgia Medical Center</name>
      <address>
        <city>Gainesville</city>
        <state>Georgia</state>
        <zip>30501</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Central Georgia Gynecologic Oncology</name>
      <address>
        <city>Macon</city>
        <state>Georgia</state>
        <zip>31201</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Memorial Health University Medical Center</name>
      <address>
        <city>Savannah</city>
        <state>Georgia</state>
        <zip>31404</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>St. Joseph's - Candler Gynecologic Oncology</name>
      <address>
        <city>Savannah</city>
        <state>Georgia</state>
        <zip>31405</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Kapiolani Medical Center for Women and Children</name>
      <address>
        <city>Honolulu</city>
        <state>Hawaii</state>
        <zip>96826</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Northwestern University - Robert H. Lurie Comprehensive Cancer Center</name>
      <address>
        <city>Chicago</city>
        <state>Illinois</state>
        <zip>60611</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Rush University Medical Center</name>
      <address>
        <city>Chicago</city>
        <state>Illinois</state>
        <zip>60612</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Sudarshan K. Sharma, MD, LTD</name>
      <address>
        <city>Hinsdale</city>
        <state>Illinois</state>
        <zip>60521</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Carle Cancer Center</name>
      <address>
        <city>Urbana</city>
        <state>Illinois</state>
        <zip>61801</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Indiana University Medical Center</name>
      <address>
        <city>Indianapolis</city>
        <state>Indiana</state>
        <zip>46202</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>St. Vincent Gynecologic Oncology</name>
      <address>
        <city>Indianapolis</city>
        <state>Indiana</state>
        <zip>46260</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>McFarland Clinic</name>
      <address>
        <city>Ames</city>
        <state>Iowa</state>
        <zip>50010</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Iowa Hospitals and Clinics</name>
      <address>
        <city>Iowa City</city>
        <state>Iowa</state>
        <zip>52242</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Kansas Medical Center</name>
      <address>
        <city>Westwood</city>
        <state>Kansas</state>
        <zip>66205</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Maine Medical Partners Women's Health</name>
      <address>
        <city>Scarborough</city>
        <state>Maine</state>
        <zip>04074</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Maryland Medical Center</name>
      <address>
        <city>Baltimore</city>
        <state>Maryland</state>
        <zip>21201</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Greater Baltimore Medical Center</name>
      <address>
        <city>Baltimore</city>
        <state>Maryland</state>
        <zip>21204</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Sinai Hospital of Baltimore</name>
      <address>
        <city>Baltimore</city>
        <state>Maryland</state>
        <zip>21215</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Johns Hopkins Medical Institution</name>
      <address>
        <city>Baltimore</city>
        <state>Maryland</state>
        <zip>21287</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Lahey Hospital &amp; Medical Center</name>
      <address>
        <city>Burlington</city>
        <state>Massachusetts</state>
        <zip>01805</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Massachusetts Memorial Healthcare</name>
      <address>
        <city>Worcester</city>
        <state>Massachusetts</state>
        <zip>01605</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>St. Joseph Mercy Hospital</name>
      <address>
        <city>Ann Arbor</city>
        <state>Michigan</state>
        <zip>48106</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Bronson Battle Creek</name>
      <address>
        <city>Battle Creek</city>
        <state>Michigan</state>
        <zip>49017</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Karmanos Cancer Institute - Wayne State University</name>
      <address>
        <city>Detroit</city>
        <state>Michigan</state>
        <zip>48201</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Henry Ford Health System</name>
      <address>
        <city>Detroit</city>
        <state>Michigan</state>
        <zip>48202</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Grand Rapids Clinical Oncology</name>
      <address>
        <city>Grand Rapids</city>
        <state>Michigan</state>
        <zip>49503</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Saint Mary's Health Care</name>
      <address>
        <city>Grand Rapids</city>
        <state>Michigan</state>
        <zip>49503</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Spectrum Health at Butterworth Campus</name>
      <address>
        <city>Grand Rapids</city>
        <state>Michigan</state>
        <zip>49503</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Gynecologic Oncology of West Michigan</name>
      <address>
        <city>Grand Rapids</city>
        <state>Michigan</state>
        <zip>49546</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>West Michigan Cancer Center</name>
      <address>
        <city>Kalamazoo</city>
        <state>Michigan</state>
        <zip>49007</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Mercy Health Partners - Mercy Campus</name>
      <address>
        <city>Muskegon</city>
        <state>Michigan</state>
        <zip>49444</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Reed City Hospital - Spectrum Health</name>
      <address>
        <city>Reed City</city>
        <state>Michigan</state>
        <zip>49677</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Munson Medical Center</name>
      <address>
        <city>Traverse City</city>
        <state>Michigan</state>
        <zip>49684</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Minnesota Oncology Coon Rapids Clinic</name>
      <address>
        <city>Coon Rapids</city>
        <state>Minnesota</state>
        <zip>55433</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Fairview Southdale Hospital</name>
      <address>
        <city>Edina</city>
        <state>Minnesota</state>
        <zip>55435</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Abbott Northwestern Hospital</name>
      <address>
        <city>Minneapolis</city>
        <state>Minnesota</state>
        <zip>55404</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Metro Minnesota Clinical Oncology Program</name>
      <address>
        <city>Saint Louis Park</city>
        <state>Minnesota</state>
        <zip>55416</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Park Nicollet Frauenshuh Cancer Center</name>
      <address>
        <city>Saint Louis Park</city>
        <state>Minnesota</state>
        <zip>55426</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Minnesota Oncology Hematology - St. Paul Cancer Center</name>
      <address>
        <city>Saint Paul</city>
        <state>Minnesota</state>
        <zip>55102</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Woodbury Clinic - CornerStone Medical Specialty Centre</name>
      <address>
        <city>Woodbury</city>
        <state>Minnesota</state>
        <zip>55125</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>St. Dominic-Jackson Memorial Hospital</name>
      <address>
        <city>Jackson</city>
        <state>Mississippi</state>
        <zip>32916</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Mississippi Medical Center</name>
      <address>
        <city>Jackson</city>
        <state>Mississippi</state>
        <zip>39216</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Ellis Fischel Cancer Center - University of Missouri</name>
      <address>
        <city>Columbia</city>
        <state>Missouri</state>
        <zip>65211</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Women's Cancer Care Center of Nevada</name>
      <address>
        <city>Las Vegas</city>
        <state>Nevada</state>
        <zip>89169</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Dartmouth-Hitchcock Medical Center</name>
      <address>
        <city>Lebanon</city>
        <state>New Hampshire</state>
        <zip>03756</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Cooper University Hospital</name>
      <address>
        <city>Camden</city>
        <state>New Jersey</state>
        <zip>08103</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hackensack University Medical Center</name>
      <address>
        <city>Hackensack</city>
        <state>New Jersey</state>
        <zip>07601</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Southwest Gynecologic Oncology Associates</name>
      <address>
        <city>Albuquerque</city>
        <state>New Mexico</state>
        <zip>87016</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of New Mexico Cancer Center</name>
      <address>
        <city>Albuquerque</city>
        <state>New Mexico</state>
        <zip>87106</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Memorial Medical Center</name>
      <address>
        <city>Las Cruces</city>
        <state>New Mexico</state>
        <zip>88011</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Women's Cancer Care Associates</name>
      <address>
        <city>Albany</city>
        <state>New York</state>
        <zip>12208</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>SUNY Downstate Medical Center</name>
      <address>
        <city>Brooklyn</city>
        <state>New York</state>
        <zip>11203</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Roswell Park Cancer Institute</name>
      <address>
        <city>Buffalo</city>
        <state>New York</state>
        <zip>14263</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Monter Cancer Center</name>
      <address>
        <city>Lake Success</city>
        <state>New York</state>
        <zip>11042</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>North Shore University Hospital</name>
      <address>
        <city>Manhasset</city>
        <state>New York</state>
        <zip>11030</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Long Island Jewish Medical Center</name>
      <address>
        <city>New Hyde Park</city>
        <state>New York</state>
        <zip>11040</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>NYU Langone Medical Center - Cancer Institute</name>
      <address>
        <city>New York</city>
        <state>New York</state>
        <zip>10016</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Columbia University Medical Center</name>
      <address>
        <city>New York</city>
        <state>New York</state>
        <zip>10032</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Memorial Sloan Kettering Cancer Center</name>
      <address>
        <city>New York</city>
        <state>New York</state>
        <zip>10065</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Gynecologic Oncology of Central New York - SUNY Upstate</name>
      <address>
        <city>Syracuse</city>
        <state>New York</state>
        <zip>13057</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hope Women's Cancer Center</name>
      <address>
        <city>Asheville</city>
        <state>North Carolina</state>
        <zip>28806</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Alamance Regional Cancer Center</name>
      <address>
        <city>Burlington</city>
        <state>North Carolina</state>
        <zip>27215</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Carolinas Medical Center / Levine Cancer Institute</name>
      <address>
        <city>Charlotte</city>
        <state>North Carolina</state>
        <zip>28204</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Carolinas Medical Center - Northeast</name>
      <address>
        <city>Concord</city>
        <state>North Carolina</state>
        <zip>28025</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Wake Forest University Health Science</name>
      <address>
        <city>Winston-Salem</city>
        <state>North Carolina</state>
        <zip>27157</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Summa Health System</name>
      <address>
        <city>Akron</city>
        <state>Ohio</state>
        <zip>44304</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Cincinnati</name>
      <address>
        <city>Cincinnati</city>
        <state>Ohio</state>
        <zip>45267</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University Hospitals of Cleveland</name>
      <address>
        <city>Cleveland</city>
        <state>Ohio</state>
        <zip>44106</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Fairview Hospital Moll Pavilion Cancer Center</name>
      <address>
        <city>Cleveland</city>
        <state>Ohio</state>
        <zip>44111</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Cleveland Clinic Foundation</name>
      <address>
        <city>Cleveland</city>
        <state>Ohio</state>
        <zip>44195</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Ohio State University Medical Center</name>
      <address>
        <city>Columbus</city>
        <state>Ohio</state>
        <zip>43210</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Women's Cancer Center at Kettering Medical Center</name>
      <address>
        <city>Kettering</city>
        <state>Ohio</state>
        <zip>45429</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hillcrest Hospital - Cleveland Clinic</name>
      <address>
        <city>Mayfield Heights</city>
        <state>Ohio</state>
        <zip>44124</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Lake University Seidman Cancer Center</name>
      <address>
        <city>Mentor</city>
        <state>Ohio</state>
        <zip>44060</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Peggy and Charles Stephenson Cancer Center</name>
      <address>
        <city>Oklahoma City</city>
        <state>Oklahoma</state>
        <zip>73104</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Tulsa Cancer Institute</name>
      <address>
        <city>Tulsa</city>
        <state>Oklahoma</state>
        <zip>74146</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Abington Memorial Hospital; Hanjani Institute for Gynecologic Oncology</name>
      <address>
        <city>Abington</city>
        <state>Pennsylvania</state>
        <zip>19001</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Geisinger Medical Center</name>
      <address>
        <city>Danville</city>
        <state>Pennsylvania</state>
        <zip>17822</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Pennsylvania Medical Center</name>
      <address>
        <city>Philadelphia</city>
        <state>Pennsylvania</state>
        <zip>19104</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Fox Chase Cancer Center</name>
      <address>
        <city>Philadelphia</city>
        <state>Pennsylvania</state>
        <zip>19111</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hillman Cancer Center - University of Pittsburgh</name>
      <address>
        <city>Pittsburgh</city>
        <state>Pennsylvania</state>
        <zip>15213</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Western Pennsylvania Hospital</name>
      <address>
        <city>Pittsburgh</city>
        <state>Pennsylvania</state>
        <zip>15224</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Reading Hospital (McGlinn Family Regional Cancer Center)</name>
      <address>
        <city>West Reading</city>
        <state>Pennsylvania</state>
        <zip>19611</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Women and Infants Hospital of Rhode Island</name>
      <address>
        <city>Providence</city>
        <state>Rhode Island</state>
        <zip>02905</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Medical University of South Carolina</name>
      <address>
        <city>Charleston</city>
        <state>South Carolina</state>
        <zip>29425</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Bon Secours St. Francis Hospital</name>
      <address>
        <city>Greenville</city>
        <state>South Carolina</state>
        <zip>29601</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Gibbs Cancer Center</name>
      <address>
        <city>Spartanburg</city>
        <state>South Carolina</state>
        <zip>29303</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Avera Cancer Institute</name>
      <address>
        <city>Sioux Falls</city>
        <state>South Dakota</state>
        <zip>57105</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>UT Southwestern Medical Center</name>
      <address>
        <city>Dallas</city>
        <state>Texas</state>
        <zip>75390</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Texas Medical Branch</name>
      <address>
        <city>Galveston</city>
        <state>Texas</state>
        <zip>77555</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>MD Anderson Cancer Center</name>
      <address>
        <city>Houston</city>
        <state>Texas</state>
        <zip>77030</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>The Methodist Hospital</name>
      <address>
        <city>Houston</city>
        <state>Texas</state>
        <zip>77030</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Huntsman Cancer Institute, University of Utah</name>
      <address>
        <city>Salt Lake City</city>
        <state>Utah</state>
        <zip>84112</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Mid Atlantic Pelvic Surgery Associates</name>
      <address>
        <city>Annandale</city>
        <state>Virginia</state>
        <zip>22003</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Virginia Gynecology Oncology</name>
      <address>
        <city>Richmond</city>
        <state>Virginia</state>
        <zip>23229</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Carilion Clinic Gynecological Oncology</name>
      <address>
        <city>Roanoke</city>
        <state>Virginia</state>
        <zip>24016</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Pacific Gynecology Specialists</name>
      <address>
        <city>Seattle</city>
        <state>Washington</state>
        <zip>98104</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Seattle Cancer Care Alliance</name>
      <address>
        <city>Seattle</city>
        <state>Washington</state>
        <zip>98109</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Northwest Hospital - UW Medicine</name>
      <address>
        <city>Seattle</city>
        <state>Washington</state>
        <zip>98133</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Women's Cancer Care of Seattle</name>
      <address>
        <city>Seattle</city>
        <state>Washington</state>
        <zip>98133</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Washington Medical Center</name>
      <address>
        <city>Seattle</city>
        <state>Washington</state>
        <zip>98195</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Green Bay Oncology at St. Vincent's Hospital</name>
      <address>
        <city>Green Bay</city>
        <state>Wisconsin</state>
        <zip>54301</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>St Vincent Hospital</name>
      <address>
        <city>Green Bay</city>
        <state>Wisconsin</state>
        <zip>54301</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Green Bay Oncology at St. Mary's Hospital</name>
      <address>
        <city>Green Bay</city>
        <state>Wisconsin</state>
        <zip>54303</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Wisconsin-Madison</name>
      <address>
        <city>Madison</city>
        <state>Wisconsin</state>
        <zip>53792</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Holy Family Memorial Medical Center</name>
      <address>
        <city>Manitowoc</city>
        <state>Wisconsin</state>
        <zip>54221</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Bay Area Medical Center</name>
      <address>
        <city>Marinette</city>
        <state>Wisconsin</state>
        <zip>54143</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Marshfield Clinic</name>
      <address>
        <city>Marshfield</city>
        <state>Wisconsin</state>
        <zip>54449</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Aurora St. Luke's Medical Center Gynecologic Oncology</name>
      <address>
        <city>Milwaukee</city>
        <state>Wisconsin</state>
        <zip>53215</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Medical College of Wisconsin</name>
      <address>
        <city>Milwaukee</city>
        <state>Wisconsin</state>
        <zip>53226</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Aspirus Regional Cancer Center</name>
      <address>
        <city>Wausau</city>
        <state>Wisconsin</state>
        <zip>54401</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>September 2019</verification_date>
  <study_first_submitted>August 10, 2012</study_first_submitted>
  <study_first_submitted_qc>August 13, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">August 16, 2012</study_first_posted>
  <results_first_submitted>March 5, 2017</results_first_submitted>
  <results_first_submitted_qc>September 24, 2019</results_first_submitted_qc>
  <results_first_posted type="Actual">September 26, 2019</results_first_posted>
  <last_update_submitted>September 24, 2019</last_update_submitted>
  <last_update_submitted_qc>September 24, 2019</last_update_submitted_qc>
  <last_update_posted type="Actual">September 26, 2019</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>recurrent epithelial ovarian cancer</keyword>
  <keyword>recurrent fallopian tube cancer</keyword>
  <keyword>recurrent primary peritoneal cavity cancer</keyword>
  <keyword>ovarian serous cystadenocarcinoma</keyword>
  <keyword>ovarian endometrioid adenocarcinoma</keyword>
  <keyword>ovarian mucinous cystadenocarcinoma</keyword>
  <keyword>ovarian undifferentiated adenocarcinoma</keyword>
  <keyword>ovarian clear cell cystadenocarcinoma</keyword>
  <keyword>ovarian mixed epithelial carcinoma</keyword>
  <keyword>Brenner tumor</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>
    <mesh_term>Fallopian Tube Neoplasms</mesh_term>
    <mesh_term>Peritoneal Neoplasms</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Doxorubicin</mesh_term>
    <mesh_term>Liposomal doxorubicin</mesh_term>
  </intervention_browse>

  <clinical_results>

    <participant_flow>
      <recruitment_details>Enrollment was initiated on 2012-Aug-13 and terminated on 2014-Apr-11. During this time, 297 patients were enrolled.</recruitment_details>
      <pre_assignment_details>Prior to enrollment and treatment assignment, a completed eligibility checklist was electronically checked for completeness and compliance with eligibility criteria. Prior to treatment assignment, patients were stratified by prior platinum free interval (&lt;6 months or &gt;6-12 months) and performance status (0 or 1). Treatments were double-blinded.</pre_assignment_details>
      <group_list>
        <group group_id="P1">
          <title>Pegylated Liposomal Doxorubicin (PLD) + Placebo</title>
          <description>Pegylated Liposomal Doxorubicin (PLD) 40 mg/m2 plus placebo</description>
        </group>
        <group group_id="P2">
          <title>Pegylated Liposomal Doxorubicin (PLD)+VTX-2337 (VTX)</title>
          <description>Pegylated Liposomal Doxorubicin (PLD) 40 mg/m2 plus VTX-2337 3.0 mg/m2</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="149"/>
                <participants group_id="P2" count="148"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="147"/>
                <participants group_id="P2" count="147"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="2"/>
                <participants group_id="P2" count="1"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Did not initiate treatment</title>
              <participants_list>
                <participants group_id="P1" count="2"/>
                <participants group_id="P2" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <population>All enrolled patients</population>
      <group_list>
        <group group_id="B1">
          <title>Pegylated Liposomal Doxorubicin (PLD) + Placebo</title>
          <description>Pegylated Liposomal Doxorubicin (PLD) 40 mg/m2 plus placebo</description>
        </group>
        <group group_id="B2">
          <title>Pegylated Liposomal Doxorubicin (PLD)+VTX-2337 (VTX)</title>
          <description>Pegylated Liposomal Doxorubicin (PLD) 40 mg/m2 plus VTX-2337 3.0 mg/m2</description>
        </group>
        <group group_id="B3">
          <title>Total</title>
          <description>Total of all reporting groups</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="149"/>
            <count group_id="B2" value="148"/>
            <count group_id="B3" value="297"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>years</units>
          <param>Median</param>
          <dispersion>Full Range</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="61.6" lower_limit="29.7" upper_limit="91.1"/>
                    <measurement group_id="B2" value="63.5" lower_limit="39.6" upper_limit="84.8"/>
                    <measurement group_id="B3" value="62.7" lower_limit="29.7" upper_limit="91.1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Age, Customized</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <title>&lt;40 years</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="4"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>40-49 years</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="22"/>
                    <measurement group_id="B2" value="11"/>
                    <measurement group_id="B3" value="33"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>50-59 years</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="39"/>
                    <measurement group_id="B2" value="42"/>
                    <measurement group_id="B3" value="81"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>60-69 years</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="50"/>
                    <measurement group_id="B2" value="51"/>
                    <measurement group_id="B3" value="101"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>70-79 years</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="31"/>
                    <measurement group_id="B2" value="38"/>
                    <measurement group_id="B3" value="69"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>&gt; 79 years</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="3"/>
                    <measurement group_id="B2" value="5"/>
                    <measurement group_id="B3" value="8"/>
                  </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="149"/>
                    <measurement group_id="B2" value="148"/>
                    <measurement group_id="B3" value="297"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Ethnicity (NIH/OMB)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="4"/>
                    <measurement group_id="B2" value="3"/>
                    <measurement group_id="B3" value="7"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Not Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="143"/>
                    <measurement group_id="B2" value="145"/>
                    <measurement group_id="B3" value="288"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="2"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Race (NIH/OMB)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>American Indian or Alaska Native</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="2"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Asian</title>
                  <measurement_list>
                    <measurement group_id="B1" value="3"/>
                    <measurement group_id="B2" value="3"/>
                    <measurement group_id="B3" value="6"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Native Hawaiian or Other Pacific Islander</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Black or African American</title>
                  <measurement_list>
                    <measurement group_id="B1" value="4"/>
                    <measurement group_id="B2" value="6"/>
                    <measurement group_id="B3" value="10"/>
                  </measurement_list>
                </category>
                <category>
                  <title>White</title>
                  <measurement_list>
                    <measurement group_id="B1" value="141"/>
                    <measurement group_id="B2" value="137"/>
                    <measurement group_id="B3" value="278"/>
                  </measurement_list>
                </category>
                <category>
                  <title>More than one race</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Eastern Cooperative Oncology Group (ECOG) Performance Status</title>
          <description>ECOG performance status is used to describe a patient's level of functioning in terms of their ability to care for themselves, daily activity, and physical ability (walking, working, etc.).&#xD;
The scale ranges from 0 to 5:&#xD;
0 = Fully active, no restrictions;&#xD;
= Restricted activity but ambulatory, able to carry out work of a light nature;&#xD;
= Ambulatory and capable of all self-care but unable to carry out work activities;&#xD;
= Limited self-care, confined to bed or chair more than 50% of waking hours;&#xD;
= Completely disabled, no self-care, confined to bed or chair;&#xD;
= Dead</description>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>0 = Fully active, no restrictions</title>
                  <measurement_list>
                    <measurement group_id="B1" value="104"/>
                    <measurement group_id="B2" value="105"/>
                    <measurement group_id="B3" value="209"/>
                  </measurement_list>
                </category>
                <category>
                  <title>1=Restricted activity;ambulatory;can do light work</title>
                  <measurement_list>
                    <measurement group_id="B1" value="45"/>
                    <measurement group_id="B2" value="43"/>
                    <measurement group_id="B3" value="88"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Prior Platinum-Free Interval as per Case Report Forms</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>&lt;= 6 months</title>
                  <measurement_list>
                    <measurement group_id="B1" value="79"/>
                    <measurement group_id="B2" value="72"/>
                    <measurement group_id="B3" value="151"/>
                  </measurement_list>
                </category>
                <category>
                  <title>&gt; 6 months</title>
                  <measurement_list>
                    <measurement group_id="B1" value="70"/>
                    <measurement group_id="B2" value="76"/>
                    <measurement group_id="B3" value="146"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Prior Chemotherapy Regimens</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <title>1</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="81"/>
                    <measurement group_id="B2" value="69"/>
                    <measurement group_id="B3" value="150"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>2</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="64"/>
                    <measurement group_id="B2" value="74"/>
                    <measurement group_id="B3" value="138"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>3</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="4"/>
                    <measurement group_id="B2" value="5"/>
                    <measurement group_id="B3" value="9"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Overall Survival</title>
        <description>Comparison of duration of survival between the 2 treatment groups</description>
        <time_frame>Survival is measured from date of enrollment and randomization on the study until death from any cause, or if alive at last contact, date of last contact.</time_frame>
        <population>All enrolled patients</population>
        <group_list>
          <group group_id="O1">
            <title>Pegylated Liposomal Doxorubicin (PLD) + Placebo</title>
            <description>Pegylated Liposomal Doxorubicin (PLD) 40 mg/m2 plus placebo</description>
          </group>
          <group group_id="O2">
            <title>Pegylated Liposomal Doxorubicin (PLD)+VTX-2337 (VTX)</title>
            <description>Pegylated Liposomal Doxorubicin (PLD) 40 mg/m2 plus VTX-2337 3.0 mg/m2</description>
          </group>
        </group_list>
        <measure>
          <title>Overall Survival</title>
          <description>Comparison of duration of survival between the 2 treatment groups</description>
          <population>All enrolled patients</population>
          <units>days</units>
          <param>Median</param>
          <dispersion>Inter-Quartile Range</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="149"/>
                <count group_id="O2" value="148"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="574" lower_limit="242" upper_limit="1141"/>
                    <measurement group_id="O2" value="552" lower_limit="240" upper_limit="869"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>The null hypothesis is that the hazards of death are equal for both treatment groups. The primary assessment of this hypothesis was done with a stratified logrank test and the study was to be considered sufficiently mature to assess this hypothesis when at least 211 deaths had occurred among all individuals enrolled. Type I error was to be set to 0.08 for a one-sided test and the power for detecting a 30% reduction in the hazard (hazard ratio=0.70) due to VTX-2337 was 88.2%.</groups_desc>
            <non_inferiority_type>Superiority or Other (legacy)</non_inferiority_type>
            <p_value>0.923</p_value>
            <p_value_desc>P-value is for a one-sided hypothesis test.</p_value_desc>
            <method>Log Rank</method>
            <method_desc>The logrank test is stratified for platinum-free interval (&lt;= 6 months vs &gt; 6 months), and performance status (0 vs 1).</method_desc>
            <param_type>Hazard Ratio (HR)</param_type>
            <param_value>1.22</param_value>
            <ci_percent>92</ci_percent>
            <ci_n_sides>1-Sided</ci_n_sides>
            <ci_upper_limit>1.48</ci_upper_limit>
            <estimate_desc>Treatment Hazard ratio for overall survival (PLD+VTX relative to PLD+placebo). Survival is measured from date of enrollment and randomization on the study until death from any cause, or date of last contact.</estimate_desc>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Progression-free Survival (PFS)</title>
        <description>Comparison of PFS between the 2 treatment groups</description>
        <time_frame>Progression-free survival is measured from enrollment and randomization on the study until first indication of progression based on irRECIST criteria or death from any cause, or if progression-free at last contact, the date of last disease assessment.</time_frame>
        <population>All enrolled patients.</population>
        <group_list>
          <group group_id="O1">
            <title>Pegylated Liposomal Doxorubicin (PLD) + Placebo</title>
            <description>Pegylated Liposomal Doxorubicin (PLD) 40 mg/m2 plus placebo</description>
          </group>
          <group group_id="O2">
            <title>Pegylated Liposomal Doxorubicin (PLD)+VTX-2337 (VTX)</title>
            <description>Pegylated Liposomal Doxorubicin (PLD) 40 mg/m2 plus VTX-2337 3.0 mg/m2</description>
          </group>
        </group_list>
        <measure>
          <title>Progression-free Survival (PFS)</title>
          <description>Comparison of PFS between the 2 treatment groups</description>
          <population>All enrolled patients.</population>
          <units>days</units>
          <param>Median</param>
          <dispersion>Inter-Quartile Range</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="149"/>
                <count group_id="O2" value="148"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="159" lower_limit="87" upper_limit="351"/>
                    <measurement group_id="O2" value="147" lower_limit="85" upper_limit="267"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>The null hypothesis is that the hazards of first progression or death are equal for both treatment groups. The primary assessment was to use a stratified logrank test and the study was to be considered sufficiently mature when survival is mature for analysis. Type I error was to be set to 0.02 for a one-sided test and the power for detecting a 31% reduction in the hazard (hazard ratio=0.69) due to VTX-2337 was expected to be approximately 83%.</groups_desc>
            <non_inferiority_type>Superiority or Other (legacy)</non_inferiority_type>
            <p_value>0.943</p_value>
            <p_value_desc>P-value is for a one-sided hypothesis test.</p_value_desc>
            <method>Log Rank</method>
            <method_desc>The logrank test is stratified for platinum-free interval (&lt;= 6 months vs &gt; 6 months), and performance status (0 vs 1).</method_desc>
            <param_type>Hazard Ratio (HR)</param_type>
            <param_value>1.21</param_value>
            <ci_percent>98</ci_percent>
            <ci_n_sides>1-Sided</ci_n_sides>
            <ci_upper_limit>1.56</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Frequency and Severity of Adverse Events (AEs)</title>
        <description>An AE is any untoward medical occurrence associated with the use of a drug in humans, whether or not considered drug-related. An AE can be unfavorable and unintended sign, symptom, or disease which is temporally associated with the use of investigational product (IP), whether or not considered related to the IP. A serious AE = an AE occurring at any dose that: • Results in death • Is life- threatening • Requires or prolongs existing inpatient hospitalization • Results in persistent or significant disability/incapacity • Is a congenital anomaly/birth defect; • Constitutes an important medical event. The Investigator assessed the relationship of each AE to IP and graded the severity according to the National Cancer Institute Common Terminology Criteria for Adverse Events, Version 4.0: Grade (GR) 1 = Mild; asymptomatic or mild symptoms; GR 2 = Moderate (minimal, local or noninvasive intervention indicated); GR 3 = Severe or medically significant; GR 4 = Life-threatening; GR 5 = Death</description>
        <time_frame>Assessed during each cycle of therapy and within 30 days after the last cycle of therapy</time_frame>
        <population>All patients who initiated study treatment. There were 147 patients who initiated treatment on each arm.</population>
        <group_list>
          <group group_id="O1">
            <title>Pegylated Liposomal Doxorubicin (PLD) + Placebo</title>
            <description>Pegylated Liposomal Doxorubicin (PLD) 40 mg/m2 plus placebo</description>
          </group>
          <group group_id="O2">
            <title>Pegylated Liposomal Doxorubicin (PLD)+VTX-2337 (VTX)</title>
            <description>Pegylated Liposomal Doxorubicin (PLD) 40 mg/m2 plus VTX-2337 3.0 mg/m2</description>
          </group>
        </group_list>
        <measure>
          <title>Frequency and Severity of Adverse Events (AEs)</title>
          <description>An AE is any untoward medical occurrence associated with the use of a drug in humans, whether or not considered drug-related. An AE can be unfavorable and unintended sign, symptom, or disease which is temporally associated with the use of investigational product (IP), whether or not considered related to the IP. A serious AE = an AE occurring at any dose that: • Results in death • Is life- threatening • Requires or prolongs existing inpatient hospitalization • Results in persistent or significant disability/incapacity • Is a congenital anomaly/birth defect; • Constitutes an important medical event. The Investigator assessed the relationship of each AE to IP and graded the severity according to the National Cancer Institute Common Terminology Criteria for Adverse Events, Version 4.0: Grade (GR) 1 = Mild; asymptomatic or mild symptoms; GR 2 = Moderate (minimal, local or noninvasive intervention indicated); GR 3 = Severe or medically significant; GR 4 = Life-threatening; GR 5 = Death</description>
          <population>All patients who initiated study treatment. There were 147 patients who initiated treatment on each arm.</population>
          <units>participants</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="147"/>
                <count group_id="O2" value="147"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Grade 1</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="8"/>
                    <measurement group_id="O2" value="3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Grade 2</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="40"/>
                    <measurement group_id="O2" value="44"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Grade 3</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="83"/>
                    <measurement group_id="O2" value="90"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Grade 4</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="10"/>
                    <measurement group_id="O2" value="3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Grade 5</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="6"/>
                    <measurement group_id="O2" value="7"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>Adverse Event assessments began with initiation of any study treatment up until 30 days following the last cycle of treatment.</time_frame>
      <group_list>
        <group group_id="E1">
          <title>Pegylated Liposomal Doxorubicin (PLD) + Placebo</title>
          <description>Pegylated Liposomal Doxorubicin (PLD) 40 mg/m2 plus placebo</description>
        </group>
        <group group_id="E2">
          <title>Pegylated Liposomal Doxorubicin (PLD)+VTX-2337 (VTX)</title>
          <description>Pegylated Liposomal Doxorubicin (PLD) 40 mg/m2 plus VTX-2337 3.0 mg/m2</description>
        </group>
      </group_list>
      <serious_events>
        <default_vocab>CTCAE (4.0)</default_vocab>
        <default_assessment>Non-systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="30" subjects_at_risk="147"/>
                <counts group_id="E2" subjects_affected="36" subjects_at_risk="147"/>
              </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="3" subjects_at_risk="147"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="147"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Cardiac disorders</title>
            <event_list>
              <event>
                <sub_title>Atrial Fibrillation</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="147"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="147"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Constipation</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="147"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="147"/>
              </event>
              <event>
                <sub_title>Diarrhea</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="147"/>
                <counts group_id="E2" subjects_affected="4" subjects_at_risk="147"/>
              </event>
              <event>
                <sub_title>Vomiting</sub_title>
                <counts group_id="E1" subjects_affected="5" subjects_at_risk="147"/>
                <counts group_id="E2" subjects_affected="7" subjects_at_risk="147"/>
              </event>
              <event>
                <sub_title>Upper Gastrointestinal Hemorrhage</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="147"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="147"/>
              </event>
              <event>
                <sub_title>Bloating</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="147"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="147"/>
              </event>
              <event>
                <sub_title>Small Intestinal Obstruction</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="147"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="147"/>
              </event>
              <event>
                <sub_title>Abdominal Pain</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="147"/>
                <counts group_id="E2" subjects_affected="6" subjects_at_risk="147"/>
              </event>
              <event>
                <sub_title>Mucositis Oral</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="147"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="147"/>
              </event>
              <event>
                <sub_title>Gastrointestinal Disorders - Other</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="147"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="147"/>
              </event>
              <event>
                <sub_title>Ileus</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="147"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="147"/>
              </event>
              <event>
                <sub_title>Abdominal Distension</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="147"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="147"/>
              </event>
              <event>
                <sub_title>Nausea</sub_title>
                <counts group_id="E1" subjects_affected="8" subjects_at_risk="147"/>
                <counts group_id="E2" subjects_affected="9" subjects_at_risk="147"/>
              </event>
              <event>
                <sub_title>Esophageal Ulcer</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="147"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="147"/>
              </event>
              <event>
                <sub_title>Esophagitis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="147"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="147"/>
              </event>
              <event>
                <sub_title>Ascites</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="147"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="147"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Pain</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="147"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="147"/>
              </event>
              <event>
                <sub_title>Malaise</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="147"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="147"/>
              </event>
              <event>
                <sub_title>Injection Site Reaction</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="147"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="147"/>
              </event>
              <event>
                <sub_title>Non-Cardiac Chest Pain</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="147"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="147"/>
              </event>
              <event>
                <sub_title>Edema Limbs</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="147"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="147"/>
              </event>
              <event>
                <sub_title>Fatigue</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="147"/>
                <counts group_id="E2" subjects_affected="4" subjects_at_risk="147"/>
              </event>
              <event>
                <sub_title>Death Nos</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="147"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="147"/>
              </event>
              <event>
                <sub_title>Fever</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="147"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="147"/>
              </event>
              <event>
                <sub_title>Chills</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="147"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="147"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Sinusitis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="147"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="147"/>
              </event>
              <event>
                <sub_title>Sepsis</sub_title>
                <counts group_id="E1" subjects_affected="5" subjects_at_risk="147"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="147"/>
              </event>
              <event>
                <sub_title>Lung Infection</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="147"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="147"/>
              </event>
              <event>
                <sub_title>Cecal Infection</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="147"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="147"/>
              </event>
              <event>
                <sub_title>Urinary Tract Infection</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="147"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="147"/>
              </event>
              <event>
                <sub_title>Enterocolitis Infectious</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="147"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="147"/>
              </event>
              <event>
                <sub_title>Biliary Tract Infection</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="147"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="147"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Injury, poisoning and procedural complications</title>
            <event_list>
              <event>
                <sub_title>Spinal Fracture</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="147"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="147"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Investigations</title>
            <event_list>
              <event>
                <sub_title>Lymphocyte Count Decreased</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="147"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="147"/>
              </event>
              <event>
                <sub_title>Inr Increased</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="147"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="147"/>
              </event>
              <event>
                <sub_title>Creatinine Increased</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="147"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="147"/>
              </event>
              <event>
                <sub_title>Neutrophil Count Decreased</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="147"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="147"/>
              </event>
              <event>
                <sub_title>Blood Bilirubin Increased</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="147"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="147"/>
              </event>
              <event>
                <sub_title>White Blood Cell Decreased</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="147"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="147"/>
              </event>
              <event>
                <sub_title>Aspartate Aminotransferase Increased</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="147"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="147"/>
              </event>
              <event>
                <sub_title>Alkaline Phosphatase Increased</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="147"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="147"/>
              </event>
              <event>
                <sub_title>Alanine Aminotransferase Increased</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="147"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="147"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Metabolism and nutrition disorders</title>
            <event_list>
              <event>
                <sub_title>Hyponatremia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="147"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="147"/>
              </event>
              <event>
                <sub_title>Hypomagnesemia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="147"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="147"/>
              </event>
              <event>
                <sub_title>Hypokalemia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="147"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="147"/>
              </event>
              <event>
                <sub_title>Hypocalcemia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="147"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="147"/>
              </event>
              <event>
                <sub_title>Hypoalbuminemia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="147"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="147"/>
              </event>
              <event>
                <sub_title>Hyperglycemia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="147"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="147"/>
              </event>
              <event>
                <sub_title>Dehydration</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="147"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="147"/>
              </event>
              <event>
                <sub_title>Anorexia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="147"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="147"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Musculoskeletal and connective tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Pain In Extremity</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="147"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="147"/>
              </event>
              <event>
                <sub_title>Generalized Muscle Weakness</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="147"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="147"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Neoplasms benign, malignant and unspecified (incl cysts and polyps)</title>
            <event_list>
              <event>
                <sub_title>Neoplasms Benign, Malignant And Unspecified (Incl</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="147"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="147"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Stroke</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="147"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="147"/>
              </event>
              <event>
                <sub_title>Dysarthria</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="147"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="147"/>
              </event>
              <event>
                <sub_title>Cognitive Disturbance</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="147"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="147"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Psychiatric disorders</title>
            <event_list>
              <event>
                <sub_title>Confusion</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="147"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="147"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Renal and urinary disorders</title>
            <event_list>
              <event>
                <sub_title>Urinary Tract Obstruction</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="147"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="147"/>
              </event>
              <event>
                <sub_title>Acute Kidney Injury</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="147"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="147"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Respiratory, Thoracic And Mediastinal Disorders -</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="147"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="147"/>
              </event>
              <event>
                <sub_title>Respiratory Failure</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="147"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="147"/>
              </event>
              <event>
                <sub_title>Pleural Effusion</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="147"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="147"/>
              </event>
              <event>
                <sub_title>Hypoxia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="147"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="147"/>
              </event>
              <event>
                <sub_title>Dyspnea</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="147"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="147"/>
              </event>
              <event>
                <sub_title>Aspiration</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="147"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="147"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Vascular disorders</title>
            <event_list>
              <event>
                <sub_title>Thromboembolic Event</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="147"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="147"/>
              </event>
              <event>
                <sub_title>Hypotension</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="147"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="147"/>
              </event>
              <event>
                <sub_title>Hypertension</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="147"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="147"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>0</frequency_threshold>
        <default_vocab>CTCAE (4.0)</default_vocab>
        <default_assessment>Non-systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, other adverse events</sub_title>
                <counts group_id="E1" subjects_affected="147" subjects_at_risk="147"/>
                <counts group_id="E2" subjects_affected="147" subjects_at_risk="147"/>
              </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="103" subjects_at_risk="147"/>
                <counts group_id="E2" subjects_affected="105" subjects_at_risk="147"/>
              </event>
              <event>
                <sub_title>Febrile Neutropenia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="147"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="147"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Cardiac disorders</title>
            <event_list>
              <event>
                <sub_title>Atrial Fibrillation</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="147"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="147"/>
              </event>
              <event>
                <sub_title>Ventricular Tachycardia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="147"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="147"/>
              </event>
              <event>
                <sub_title>Sinus Bradycardia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="147"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="147"/>
              </event>
              <event>
                <sub_title>Palpitations</sub_title>
                <counts group_id="E1" subjects_affected="8" subjects_at_risk="147"/>
                <counts group_id="E2" subjects_affected="6" subjects_at_risk="147"/>
              </event>
              <event>
                <sub_title>Heart Failure</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="147"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="147"/>
              </event>
              <event>
                <sub_title>Atrial Flutter</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="147"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="147"/>
              </event>
              <event>
                <sub_title>Cardiac Disorders - Other</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="147"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="147"/>
              </event>
              <event>
                <sub_title>Pericardial Effusion</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="147"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="147"/>
              </event>
              <event>
                <sub_title>Sinus Tachycardia</sub_title>
                <counts group_id="E1" subjects_affected="11" subjects_at_risk="147"/>
                <counts group_id="E2" subjects_affected="6" subjects_at_risk="147"/>
              </event>
              <event>
                <sub_title>Chest Pain - Cardiac</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="147"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="147"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Ear and labyrinth disorders</title>
            <event_list>
              <event>
                <sub_title>Middle Ear Inflammation</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="147"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="147"/>
              </event>
              <event>
                <sub_title>Ear And Labyrinth Disorders - Other</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="147"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="147"/>
              </event>
              <event>
                <sub_title>Vertigo</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="147"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="147"/>
              </event>
              <event>
                <sub_title>Tinnitus</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="147"/>
                <counts group_id="E2" subjects_affected="5" subjects_at_risk="147"/>
              </event>
              <event>
                <sub_title>Hearing Impaired</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="147"/>
                <counts group_id="E2" subjects_affected="4" subjects_at_risk="147"/>
              </event>
              <event>
                <sub_title>Ear Pain</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="147"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="147"/>
              </event>
              <event>
                <sub_title>External Ear Inflammation</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="147"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="147"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Endocrine disorders</title>
            <event_list>
              <event>
                <sub_title>Hyperthyroidism</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="147"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="147"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Eye disorders</title>
            <event_list>
              <event>
                <sub_title>Eye Disorders - Other</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="147"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="147"/>
              </event>
              <event>
                <sub_title>Watering Eyes</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="147"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="147"/>
              </event>
              <event>
                <sub_title>Flashing Lights</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="147"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="147"/>
              </event>
              <event>
                <sub_title>Eye Pain</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="147"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="147"/>
              </event>
              <event>
                <sub_title>Cataract</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="147"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="147"/>
              </event>
              <event>
                <sub_title>Conjunctivitis</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="147"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="147"/>
              </event>
              <event>
                <sub_title>Blurred Vision</sub_title>
                <counts group_id="E1" subjects_affected="6" subjects_at_risk="147"/>
                <counts group_id="E2" subjects_affected="5" subjects_at_risk="147"/>
              </event>
              <event>
                <sub_title>Dry Eye</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="147"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="147"/>
              </event>
              <event>
                <sub_title>Floaters</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="147"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="147"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Enterocolitis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="147"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="147"/>
              </event>
              <event>
                <sub_title>Dysphagia</sub_title>
                <counts group_id="E1" subjects_affected="17" subjects_at_risk="147"/>
                <counts group_id="E2" subjects_affected="12" subjects_at_risk="147"/>
              </event>
              <event>
                <sub_title>Dyspepsia</sub_title>
                <counts group_id="E1" subjects_affected="13" subjects_at_risk="147"/>
                <counts group_id="E2" subjects_affected="22" subjects_at_risk="147"/>
              </event>
              <event>
                <sub_title>Duodenal Obstruction</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="147"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="147"/>
              </event>
              <event>
                <sub_title>Dry Mouth</sub_title>
                <counts group_id="E1" subjects_affected="10" subjects_at_risk="147"/>
                <counts group_id="E2" subjects_affected="7" subjects_at_risk="147"/>
              </event>
              <event>
                <sub_title>Colonic Obstruction</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="147"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="147"/>
              </event>
              <event>
                <sub_title>Colitis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="147"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="147"/>
              </event>
              <event>
                <sub_title>Constipation</sub_title>
                <counts group_id="E1" subjects_affected="75" subjects_at_risk="147"/>
                <counts group_id="E2" subjects_affected="79" subjects_at_risk="147"/>
              </event>
              <event>
                <sub_title>Diarrhea</sub_title>
                <counts group_id="E1" subjects_affected="52" subjects_at_risk="147"/>
                <counts group_id="E2" subjects_affected="45" subjects_at_risk="147"/>
              </event>
              <event>
                <sub_title>Cheilitis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="147"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="147"/>
              </event>
              <event>
                <sub_title>Vomiting</sub_title>
                <counts group_id="E1" subjects_affected="48" subjects_at_risk="147"/>
                <counts group_id="E2" subjects_affected="70" subjects_at_risk="147"/>
              </event>
              <event>
                <sub_title>Upper Gastrointestinal Hemorrhage</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="147"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="147"/>
              </event>
              <event>
                <sub_title>Bloating</sub_title>
                <counts group_id="E1" subjects_affected="26" subjects_at_risk="147"/>
                <counts group_id="E2" subjects_affected="24" subjects_at_risk="147"/>
              </event>
              <event>
                <sub_title>Small Intestinal Perforation</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="147"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="147"/>
              </event>
              <event>
                <sub_title>Stomach Pain</sub_title>
                <counts group_id="E1" subjects_affected="7" subjects_at_risk="147"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="147"/>
              </event>
              <event>
                <sub_title>Small Intestinal Obstruction</sub_title>
                <counts group_id="E1" subjects_affected="13" subjects_at_risk="147"/>
                <counts group_id="E2" subjects_affected="12" subjects_at_risk="147"/>
              </event>
              <event>
                <sub_title>Anal Hemorrhage</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="147"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="147"/>
              </event>
              <event>
                <sub_title>Anal Mucositis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="147"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="147"/>
              </event>
              <event>
                <sub_title>Abdominal Pain</sub_title>
                <counts group_id="E1" subjects_affected="54" subjects_at_risk="147"/>
                <counts group_id="E2" subjects_affected="61" subjects_at_risk="147"/>
              </event>
              <event>
                <sub_title>Periodontal Disease</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="147"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="147"/>
              </event>
              <event>
                <sub_title>Rectal Hemorrhage</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="147"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="147"/>
              </event>
              <event>
                <sub_title>Obstruction Gastric</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="147"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="147"/>
              </event>
              <event>
                <sub_title>Small Intestinal Mucositis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="147"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="147"/>
              </event>
              <event>
                <sub_title>Mucositis Oral</sub_title>
                <counts group_id="E1" subjects_affected="57" subjects_at_risk="147"/>
                <counts group_id="E2" subjects_affected="56" subjects_at_risk="147"/>
              </event>
              <event>
                <sub_title>Lower Gastrointestinal Hemorrhage</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="147"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="147"/>
              </event>
              <event>
                <sub_title>Gastrointestinal Disorders - Other</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="147"/>
                <counts group_id="E2" subjects_affected="5" subjects_at_risk="147"/>
              </event>
              <event>
                <sub_title>Anal Pain</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="147"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="147"/>
              </event>
              <event>
                <sub_title>Oral Hemorrhage</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="147"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="147"/>
              </event>
              <event>
                <sub_title>Ileus</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="147"/>
                <counts group_id="E2" subjects_affected="5" subjects_at_risk="147"/>
              </event>
              <event>
                <sub_title>Ileal Obstruction</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="147"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="147"/>
              </event>
              <event>
                <sub_title>Gastrointestinal Pain</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="147"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="147"/>
              </event>
              <event>
                <sub_title>Gastric Hemorrhage</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="147"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="147"/>
              </event>
              <event>
                <sub_title>Oral Pain</sub_title>
                <counts group_id="E1" subjects_affected="10" subjects_at_risk="147"/>
                <counts group_id="E2" subjects_affected="10" subjects_at_risk="147"/>
              </event>
              <event>
                <sub_title>Abdominal Distension</sub_title>
                <counts group_id="E1" subjects_affected="15" subjects_at_risk="147"/>
                <counts group_id="E2" subjects_affected="15" subjects_at_risk="147"/>
              </event>
              <event>
                <sub_title>Nausea</sub_title>
                <counts group_id="E1" subjects_affected="93" subjects_at_risk="147"/>
                <counts group_id="E2" subjects_affected="97" subjects_at_risk="147"/>
              </event>
              <event>
                <sub_title>Gastroparesis</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="147"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="147"/>
              </event>
              <event>
                <sub_title>Gastric Ulcer</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="147"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="147"/>
              </event>
              <event>
                <sub_title>Gastroesophageal Reflux Disease</sub_title>
                <counts group_id="E1" subjects_affected="12" subjects_at_risk="147"/>
                <counts group_id="E2" subjects_affected="15" subjects_at_risk="147"/>
              </event>
              <event>
                <sub_title>Rectal Pain</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="147"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="147"/>
              </event>
              <event>
                <sub_title>Lip Pain</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="147"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="147"/>
              </event>
              <event>
                <sub_title>Esophageal Ulcer</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="147"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="147"/>
              </event>
              <event>
                <sub_title>Esophagitis</sub_title>
                <counts group_id="E1" subjects_affected="7" subjects_at_risk="147"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="147"/>
              </event>
              <event>
                <sub_title>Fecal Incontinence</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="147"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="147"/>
              </event>
              <event>
                <sub_title>Hemorrhoidal Hemorrhage</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="147"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="147"/>
              </event>
              <event>
                <sub_title>Hemorrhoids</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="147"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="147"/>
              </event>
              <event>
                <sub_title>Ascites</sub_title>
                <counts group_id="E1" subjects_affected="15" subjects_at_risk="147"/>
                <counts group_id="E2" subjects_affected="8" subjects_at_risk="147"/>
              </event>
              <event>
                <sub_title>Toothache</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="147"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="147"/>
              </event>
              <event>
                <sub_title>Esophageal Pain</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="147"/>
                <counts group_id="E2" subjects_affected="5" subjects_at_risk="147"/>
              </event>
              <event>
                <sub_title>Dental Caries</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="147"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="147"/>
              </event>
              <event>
                <sub_title>Flatulence</sub_title>
                <counts group_id="E1" subjects_affected="6" subjects_at_risk="147"/>
                <counts group_id="E2" subjects_affected="6" subjects_at_risk="147"/>
              </event>
              <event>
                <sub_title>Gastritis</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="147"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="147"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>General Disorders And Administration Site Conditio</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="147"/>
                <counts group_id="E2" subjects_affected="7" subjects_at_risk="147"/>
              </event>
              <event>
                <sub_title>Pain</sub_title>
                <counts group_id="E1" subjects_affected="23" subjects_at_risk="147"/>
                <counts group_id="E2" subjects_affected="26" subjects_at_risk="147"/>
              </event>
              <event>
                <sub_title>Malaise</sub_title>
                <counts group_id="E1" subjects_affected="7" subjects_at_risk="147"/>
                <counts group_id="E2" subjects_affected="6" subjects_at_risk="147"/>
              </event>
              <event>
                <sub_title>Localized Edema</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="147"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="147"/>
              </event>
              <event>
                <sub_title>Irritability</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="147"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="147"/>
              </event>
              <event>
                <sub_title>Injection Site Reaction</sub_title>
                <counts group_id="E1" subjects_affected="13" subjects_at_risk="147"/>
                <counts group_id="E2" subjects_affected="107" subjects_at_risk="147"/>
              </event>
              <event>
                <sub_title>Infusion Site Extravasation</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="147"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="147"/>
              </event>
              <event>
                <sub_title>Flu Like Symptoms</sub_title>
                <counts group_id="E1" subjects_affected="8" subjects_at_risk="147"/>
                <counts group_id="E2" subjects_affected="45" subjects_at_risk="147"/>
              </event>
              <event>
                <sub_title>Edema Trunk</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="147"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="147"/>
              </event>
              <event>
                <sub_title>Non-Cardiac Chest Pain</sub_title>
                <counts group_id="E1" subjects_affected="6" subjects_at_risk="147"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="147"/>
              </event>
              <event>
                <sub_title>Edema Limbs</sub_title>
                <counts group_id="E1" subjects_affected="19" subjects_at_risk="147"/>
                <counts group_id="E2" subjects_affected="37" subjects_at_risk="147"/>
              </event>
              <event>
                <sub_title>Facial Pain</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="147"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="147"/>
              </event>
              <event>
                <sub_title>Edema Face</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="147"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="147"/>
              </event>
              <event>
                <sub_title>Fatigue</sub_title>
                <counts group_id="E1" subjects_affected="109" subjects_at_risk="147"/>
                <counts group_id="E2" subjects_affected="127" subjects_at_risk="147"/>
              </event>
              <event>
                <sub_title>Fever</sub_title>
                <counts group_id="E1" subjects_affected="19" subjects_at_risk="147"/>
                <counts group_id="E2" subjects_affected="70" subjects_at_risk="147"/>
              </event>
              <event>
                <sub_title>Gait Disturbance</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="147"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="147"/>
              </event>
              <event>
                <sub_title>Chills</sub_title>
                <counts group_id="E1" subjects_affected="25" subjects_at_risk="147"/>
                <counts group_id="E2" subjects_affected="92" subjects_at_risk="147"/>
              </event>
              <event>
                <sub_title>Infusion Related Reaction</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="147"/>
                <counts group_id="E2" subjects_affected="5" subjects_at_risk="147"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Hepatobiliary disorders</title>
            <event_list>
              <event>
                <sub_title>Hepatobiliary Disorders - Other</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="147"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="147"/>
              </event>
              <event>
                <sub_title>Cholecystitis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="147"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="147"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Immune system disorders</title>
            <event_list>
              <event>
                <sub_title>Anaphylaxis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="147"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="147"/>
              </event>
              <event>
                <sub_title>Allergic Reaction</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="147"/>
                <counts group_id="E2" subjects_affected="4" subjects_at_risk="147"/>
              </event>
              <event>
                <sub_title>Cytokine Release Syndrome</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="147"/>
                <counts group_id="E2" subjects_affected="24" subjects_at_risk="147"/>
              </event>
              <event>
                <sub_title>Immune System Disorders - Other</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="147"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="147"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Infections And Infestations - Other</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="147"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="147"/>
              </event>
              <event>
                <sub_title>Wound Infection</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="147"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="147"/>
              </event>
              <event>
                <sub_title>Upper Respiratory Infection</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="147"/>
                <counts group_id="E2" subjects_affected="4" subjects_at_risk="147"/>
              </event>
              <event>
                <sub_title>Tooth Infection</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="147"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="147"/>
              </event>
              <event>
                <sub_title>Stoma Site Infection</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="147"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="147"/>
              </event>
              <event>
                <sub_title>Vulval Infection</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="147"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="147"/>
              </event>
              <event>
                <sub_title>Soft Tissue Infection</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="147"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="147"/>
              </event>
              <event>
                <sub_title>Skin Infection</sub_title>
                <counts group_id="E1" subjects_affected="6" subjects_at_risk="147"/>
                <counts group_id="E2" subjects_affected="16" subjects_at_risk="147"/>
              </event>
              <event>
                <sub_title>Sinusitis</sub_title>
                <counts group_id="E1" subjects_affected="6" subjects_at_risk="147"/>
                <counts group_id="E2" subjects_affected="4" subjects_at_risk="147"/>
              </event>
              <event>
                <sub_title>Sepsis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="147"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="147"/>
              </event>
              <event>
                <sub_title>Salivary Gland Infection</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="147"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="147"/>
              </event>
              <event>
                <sub_title>Rash Pustular</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="147"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="147"/>
              </event>
              <event>
                <sub_title>Peripheral Nerve Infection</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="147"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="147"/>
              </event>
              <event>
                <sub_title>Papulopustular Rash</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="147"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="147"/>
              </event>
              <event>
                <sub_title>Nail Infection</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="147"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="147"/>
              </event>
              <event>
                <sub_title>Mucosal Infection</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="147"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="147"/>
              </event>
              <event>
                <sub_title>Lymph Gland Infection</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="147"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="147"/>
              </event>
              <event>
                <sub_title>Lung Infection</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="147"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="147"/>
              </event>
              <event>
                <sub_title>Eye Infection</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="147"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="147"/>
              </event>
              <event>
                <sub_title>Device Related Infection</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="147"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="147"/>
              </event>
              <event>
                <sub_title>Gum Infection</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="147"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="147"/>
              </event>
              <event>
                <sub_title>Vaginal Infection</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="147"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="147"/>
              </event>
              <event>
                <sub_title>Urinary Tract Infection</sub_title>
                <counts group_id="E1" subjects_affected="12" subjects_at_risk="147"/>
                <counts group_id="E2" subjects_affected="12" subjects_at_risk="147"/>
              </event>
              <event>
                <sub_title>Catheter Related Infection</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="147"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="147"/>
              </event>
              <event>
                <sub_title>Joint Infection</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="147"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="147"/>
              </event>
              <event>
                <sub_title>Bronchial Infection</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="147"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="147"/>
              </event>
              <event>
                <sub_title>Bone Infection</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="147"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="147"/>
              </event>
              <event>
                <sub_title>Bladder Infection</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="147"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="147"/>
              </event>
              <event>
                <sub_title>Lip Infection</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="147"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="147"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Injury, poisoning and procedural complications</title>
            <event_list>
              <event>
                <sub_title>Wound Dehiscence</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="147"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="147"/>
              </event>
              <event>
                <sub_title>Vascular Access Complication</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="147"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="147"/>
              </event>
              <event>
                <sub_title>Vaginal Anastomotic Leak</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="147"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="147"/>
              </event>
              <event>
                <sub_title>Urostomy Obstruction</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="147"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="147"/>
              </event>
              <event>
                <sub_title>Spinal Fracture</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="147"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="147"/>
              </event>
              <event>
                <sub_title>Radiation Recall Reaction (Dermatologic)</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="147"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="147"/>
              </event>
              <event>
                <sub_title>Fracture</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="147"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="147"/>
              </event>
              <event>
                <sub_title>Fall</sub_title>
                <counts group_id="E1" subjects_affected="6" subjects_at_risk="147"/>
                <counts group_id="E2" subjects_affected="7" subjects_at_risk="147"/>
              </event>
              <event>
                <sub_title>Wound Complication</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="147"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="147"/>
              </event>
              <event>
                <sub_title>Burn</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="147"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="147"/>
              </event>
              <event>
                <sub_title>Bruising</sub_title>
                <counts group_id="E1" subjects_affected="6" subjects_at_risk="147"/>
                <counts group_id="E2" subjects_affected="8" subjects_at_risk="147"/>
              </event>
              <event>
                <sub_title>Ankle Fracture</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="147"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="147"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Investigations</title>
            <event_list>
              <event>
                <sub_title>Investigations - Other</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="147"/>
                <counts group_id="E2" subjects_affected="4" subjects_at_risk="147"/>
              </event>
              <event>
                <sub_title>Weight Loss</sub_title>
                <counts group_id="E1" subjects_affected="19" subjects_at_risk="147"/>
                <counts group_id="E2" subjects_affected="25" subjects_at_risk="147"/>
              </event>
              <event>
                <sub_title>Weight Gain</sub_title>
                <counts group_id="E1" subjects_affected="5" subjects_at_risk="147"/>
                <counts group_id="E2" subjects_affected="4" subjects_at_risk="147"/>
              </event>
              <event>
                <sub_title>Platelet Count Decreased</sub_title>
                <counts group_id="E1" subjects_affected="30" subjects_at_risk="147"/>
                <counts group_id="E2" subjects_affected="18" subjects_at_risk="147"/>
              </event>
              <event>
                <sub_title>Lymphocyte Count Decreased</sub_title>
                <counts group_id="E1" subjects_affected="10" subjects_at_risk="147"/>
                <counts group_id="E2" subjects_affected="15" subjects_at_risk="147"/>
              </event>
              <event>
                <sub_title>Inr Increased</sub_title>
                <counts group_id="E1" subjects_affected="5" subjects_at_risk="147"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="147"/>
              </event>
              <event>
                <sub_title>Hemoglobin Increased</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="147"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="147"/>
              </event>
              <event>
                <sub_title>Ggt Increased</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="147"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="147"/>
              </event>
              <event>
                <sub_title>Electrocardiogram Qt Corrected Interval Prolonged</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="147"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="147"/>
              </event>
              <event>
                <sub_title>Ejection Fraction Decreased</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="147"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="147"/>
              </event>
              <event>
                <sub_title>Creatinine Increased</sub_title>
                <counts group_id="E1" subjects_affected="9" subjects_at_risk="147"/>
                <counts group_id="E2" subjects_affected="11" subjects_at_risk="147"/>
              </event>
              <event>
                <sub_title>Cholesterol High</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="147"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="147"/>
              </event>
              <event>
                <sub_title>Neutrophil Count Decreased</sub_title>
                <counts group_id="E1" subjects_affected="60" subjects_at_risk="147"/>
                <counts group_id="E2" subjects_affected="54" subjects_at_risk="147"/>
              </event>
              <event>
                <sub_title>Urine Output Decreased</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="147"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="147"/>
              </event>
              <event>
                <sub_title>Cd4 Lymphocytes Decreased</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="147"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="147"/>
              </event>
              <event>
                <sub_title>Blood Bilirubin Increased</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="147"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="147"/>
              </event>
              <event>
                <sub_title>White Blood Cell Decreased</sub_title>
                <counts group_id="E1" subjects_affected="83" subjects_at_risk="147"/>
                <counts group_id="E2" subjects_affected="74" subjects_at_risk="147"/>
              </event>
              <event>
                <sub_title>Aspartate Aminotransferase Increased</sub_title>
                <counts group_id="E1" subjects_affected="14" subjects_at_risk="147"/>
                <counts group_id="E2" subjects_affected="17" subjects_at_risk="147"/>
              </event>
              <event>
                <sub_title>Alkaline Phosphatase Increased</sub_title>
                <counts group_id="E1" subjects_affected="18" subjects_at_risk="147"/>
                <counts group_id="E2" subjects_affected="18" subjects_at_risk="147"/>
              </event>
              <event>
                <sub_title>Alanine Aminotransferase Increased</sub_title>
                <counts group_id="E1" subjects_affected="12" subjects_at_risk="147"/>
                <counts group_id="E2" subjects_affected="9" subjects_at_risk="147"/>
              </event>
              <event>
                <sub_title>Activated Partial Thromboplastin Time Prolonged</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="147"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="147"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Metabolism and nutrition disorders</title>
            <event_list>
              <event>
                <sub_title>Metabolism And Nutrition Disorders - Other</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="147"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="147"/>
              </event>
              <event>
                <sub_title>Hypophosphatemia</sub_title>
                <counts group_id="E1" subjects_affected="10" subjects_at_risk="147"/>
                <counts group_id="E2" subjects_affected="6" subjects_at_risk="147"/>
              </event>
              <event>
                <sub_title>Hyponatremia</sub_title>
                <counts group_id="E1" subjects_affected="18" subjects_at_risk="147"/>
                <counts group_id="E2" subjects_affected="21" subjects_at_risk="147"/>
              </event>
              <event>
                <sub_title>Hypomagnesemia</sub_title>
                <counts group_id="E1" subjects_affected="28" subjects_at_risk="147"/>
                <counts group_id="E2" subjects_affected="24" subjects_at_risk="147"/>
              </event>
              <event>
                <sub_title>Hypokalemia</sub_title>
                <counts group_id="E1" subjects_affected="28" subjects_at_risk="147"/>
                <counts group_id="E2" subjects_affected="12" subjects_at_risk="147"/>
              </event>
              <event>
                <sub_title>Hypoglycemia</sub_title>
                <counts group_id="E1" subjects_affected="7" subjects_at_risk="147"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="147"/>
              </event>
              <event>
                <sub_title>Hypocalcemia</sub_title>
                <counts group_id="E1" subjects_affected="14" subjects_at_risk="147"/>
                <counts group_id="E2" subjects_affected="15" subjects_at_risk="147"/>
              </event>
              <event>
                <sub_title>Hypoalbuminemia</sub_title>
                <counts group_id="E1" subjects_affected="27" subjects_at_risk="147"/>
                <counts group_id="E2" subjects_affected="23" subjects_at_risk="147"/>
              </event>
              <event>
                <sub_title>Hypertriglyceridemia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="147"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="147"/>
              </event>
              <event>
                <sub_title>Hypernatremia</sub_title>
                <counts group_id="E1" subjects_affected="5" subjects_at_risk="147"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="147"/>
              </event>
              <event>
                <sub_title>Hypermagnesemia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="147"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="147"/>
              </event>
              <event>
                <sub_title>Hyperkalemia</sub_title>
                <counts group_id="E1" subjects_affected="8" subjects_at_risk="147"/>
                <counts group_id="E2" subjects_affected="4" subjects_at_risk="147"/>
              </event>
              <event>
                <sub_title>Hyperglycemia</sub_title>
                <counts group_id="E1" subjects_affected="28" subjects_at_risk="147"/>
                <counts group_id="E2" subjects_affected="19" subjects_at_risk="147"/>
              </event>
              <event>
                <sub_title>Hypercalcemia</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="147"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="147"/>
              </event>
              <event>
                <sub_title>Glucose Intolerance</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="147"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="147"/>
              </event>
              <event>
                <sub_title>Dehydration</sub_title>
                <counts group_id="E1" subjects_affected="9" subjects_at_risk="147"/>
                <counts group_id="E2" subjects_affected="11" subjects_at_risk="147"/>
              </event>
              <event>
                <sub_title>Anorexia</sub_title>
                <counts group_id="E1" subjects_affected="46" subjects_at_risk="147"/>
                <counts group_id="E2" subjects_affected="48" subjects_at_risk="147"/>
              </event>
              <event>
                <sub_title>Alkalosis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="147"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="147"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Musculoskeletal and connective tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Pain In Extremity</sub_title>
                <counts group_id="E1" subjects_affected="15" subjects_at_risk="147"/>
                <counts group_id="E2" subjects_affected="23" subjects_at_risk="147"/>
              </event>
              <event>
                <sub_title>Osteoporosis</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="147"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="147"/>
              </event>
              <event>
                <sub_title>Neck Pain</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="147"/>
                <counts group_id="E2" subjects_affected="5" subjects_at_risk="147"/>
              </event>
              <event>
                <sub_title>Myalgia</sub_title>
                <counts group_id="E1" subjects_affected="24" subjects_at_risk="147"/>
                <counts group_id="E2" subjects_affected="20" subjects_at_risk="147"/>
              </event>
              <event>
                <sub_title>Muscle Weakness Upper Limb</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="147"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="147"/>
              </event>
              <event>
                <sub_title>Muscle Weakness Lower Limb</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="147"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="147"/>
              </event>
              <event>
                <sub_title>Muscle Weakness Left-Sided</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="147"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="147"/>
              </event>
              <event>
                <sub_title>Joint Range Of Motion Decreased</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="147"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="147"/>
              </event>
              <event>
                <sub_title>Joint Effusion</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="147"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="147"/>
              </event>
              <event>
                <sub_title>Generalized Muscle Weakness</sub_title>
                <counts group_id="E1" subjects_affected="12" subjects_at_risk="147"/>
                <counts group_id="E2" subjects_affected="16" subjects_at_risk="147"/>
              </event>
              <event>
                <sub_title>Flank Pain</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="147"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="147"/>
              </event>
              <event>
                <sub_title>Chest Wall Pain</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="147"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="147"/>
              </event>
              <event>
                <sub_title>Buttock Pain</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="147"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="147"/>
              </event>
              <event>
                <sub_title>Bone Pain</sub_title>
                <counts group_id="E1" subjects_affected="8" subjects_at_risk="147"/>
                <counts group_id="E2" subjects_affected="6" subjects_at_risk="147"/>
              </event>
              <event>
                <sub_title>Back Pain</sub_title>
                <counts group_id="E1" subjects_affected="26" subjects_at_risk="147"/>
                <counts group_id="E2" subjects_affected="30" subjects_at_risk="147"/>
              </event>
              <event>
                <sub_title>Avascular Necrosis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="147"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="147"/>
              </event>
              <event>
                <sub_title>Arthritis</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="147"/>
                <counts group_id="E2" subjects_affected="4" subjects_at_risk="147"/>
              </event>
              <event>
                <sub_title>Arthralgia</sub_title>
                <counts group_id="E1" subjects_affected="23" subjects_at_risk="147"/>
                <counts group_id="E2" subjects_affected="17" subjects_at_risk="147"/>
              </event>
              <event>
                <sub_title>Abdominal Soft Tissue Necrosis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="147"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="147"/>
              </event>
              <event>
                <sub_title>Musculoskeletal And Connective Tissue Disorder -</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="147"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="147"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Neoplasms benign, malignant and unspecified (incl cysts and polyps)</title>
            <event_list>
              <event>
                <sub_title>Neoplasms Benign, Malignant And Unspecified (Incl</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="147"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="147"/>
              </event>
              <event>
                <sub_title>Tumor Pain</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="147"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="147"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Nervous System Disorders - Other</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="147"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="147"/>
              </event>
              <event>
                <sub_title>Tremor</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="147"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="147"/>
              </event>
              <event>
                <sub_title>Transient Ischemic Attacks</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="147"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="147"/>
              </event>
              <event>
                <sub_title>Somnolence</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="147"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="147"/>
              </event>
              <event>
                <sub_title>Seizure</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="147"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="147"/>
              </event>
              <event>
                <sub_title>Presyncope</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="147"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="147"/>
              </event>
              <event>
                <sub_title>Peripheral Sensory Neuropathy</sub_title>
                <counts group_id="E1" subjects_affected="47" subjects_at_risk="147"/>
                <counts group_id="E2" subjects_affected="45" subjects_at_risk="147"/>
              </event>
              <event>
                <sub_title>Peripheral Motor Neuropathy</sub_title>
                <counts group_id="E1" subjects_affected="6" subjects_at_risk="147"/>
                <counts group_id="E2" subjects_affected="5" subjects_at_risk="147"/>
              </event>
              <event>
                <sub_title>Paresthesia</sub_title>
                <counts group_id="E1" subjects_affected="5" subjects_at_risk="147"/>
                <counts group_id="E2" subjects_affected="7" subjects_at_risk="147"/>
              </event>
              <event>
                <sub_title>Neuralgia</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="147"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="147"/>
              </event>
              <event>
                <sub_title>Memory Impairment</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="147"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="147"/>
              </event>
              <event>
                <sub_title>Lethargy</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="147"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="147"/>
              </event>
              <event>
                <sub_title>Hypersomnia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="147"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="147"/>
              </event>
              <event>
                <sub_title>Headache</sub_title>
                <counts group_id="E1" subjects_affected="34" subjects_at_risk="147"/>
                <counts group_id="E2" subjects_affected="27" subjects_at_risk="147"/>
              </event>
              <event>
                <sub_title>Facial Nerve Disorder</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="147"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="147"/>
              </event>
              <event>
                <sub_title>Dysphasia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="147"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="147"/>
              </event>
              <event>
                <sub_title>Dysgeusia</sub_title>
                <counts group_id="E1" subjects_affected="13" subjects_at_risk="147"/>
                <counts group_id="E2" subjects_affected="7" subjects_at_risk="147"/>
              </event>
              <event>
                <sub_title>Dysarthria</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="147"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="147"/>
              </event>
              <event>
                <sub_title>Syncope</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="147"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="147"/>
              </event>
              <event>
                <sub_title>Dizziness</sub_title>
                <counts group_id="E1" subjects_affected="14" subjects_at_risk="147"/>
                <counts group_id="E2" subjects_affected="24" subjects_at_risk="147"/>
              </event>
              <event>
                <sub_title>Depressed Level Of Consciousness</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="147"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="147"/>
              </event>
              <event>
                <sub_title>Concentration Impairment</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="147"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="147"/>
              </event>
              <event>
                <sub_title>Cognitive Disturbance</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="147"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="147"/>
              </event>
              <event>
                <sub_title>Ataxia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="147"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="147"/>
              </event>
              <event>
                <sub_title>Akathisia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="147"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="147"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Psychiatric disorders</title>
            <event_list>
              <event>
                <sub_title>Psychiatric Disorders - Other</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="147"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="147"/>
              </event>
              <event>
                <sub_title>Suicidal Ideation</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="147"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="147"/>
              </event>
              <event>
                <sub_title>Psychosis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="147"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="147"/>
              </event>
              <event>
                <sub_title>Insomnia</sub_title>
                <counts group_id="E1" subjects_affected="16" subjects_at_risk="147"/>
                <counts group_id="E2" subjects_affected="27" subjects_at_risk="147"/>
              </event>
              <event>
                <sub_title>Hallucinations</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="147"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="147"/>
              </event>
              <event>
                <sub_title>Depression</sub_title>
                <counts group_id="E1" subjects_affected="24" subjects_at_risk="147"/>
                <counts group_id="E2" subjects_affected="24" subjects_at_risk="147"/>
              </event>
              <event>
                <sub_title>Confusion</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="147"/>
                <counts group_id="E2" subjects_affected="6" subjects_at_risk="147"/>
              </event>
              <event>
                <sub_title>Anxiety</sub_title>
                <counts group_id="E1" subjects_affected="24" subjects_at_risk="147"/>
                <counts group_id="E2" subjects_affected="32" subjects_at_risk="147"/>
              </event>
              <event>
                <sub_title>Agitation</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="147"/>
                <counts group_id="E2" subjects_affected="6" subjects_at_risk="147"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Renal and urinary disorders</title>
            <event_list>
              <event>
                <sub_title>Renal And Urinary Disorders - Other</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="147"/>
                <counts group_id="E2" subjects_affected="6" subjects_at_risk="147"/>
              </event>
              <event>
                <sub_title>Urine Discoloration</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="147"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="147"/>
              </event>
              <event>
                <sub_title>Urinary Urgency</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="147"/>
                <counts group_id="E2" subjects_affected="5" subjects_at_risk="147"/>
              </event>
              <event>
                <sub_title>Urinary Tract Obstruction</sub_title>
                <counts group_id="E1" subjects_affected="5" subjects_at_risk="147"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="147"/>
              </event>
              <event>
                <sub_title>Urinary Retention</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="147"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="147"/>
              </event>
              <event>
                <sub_title>Urinary Incontinence</sub_title>
                <counts group_id="E1" subjects_affected="5" subjects_at_risk="147"/>
                <counts group_id="E2" subjects_affected="11" subjects_at_risk="147"/>
              </event>
              <event>
                <sub_title>Urinary Tract Pain</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="147"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="147"/>
              </event>
              <event>
                <sub_title>Urinary Frequency</sub_title>
                <counts group_id="E1" subjects_affected="7" subjects_at_risk="147"/>
                <counts group_id="E2" subjects_affected="13" subjects_at_risk="147"/>
              </event>
              <event>
                <sub_title>Proteinuria</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="147"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="147"/>
              </event>
              <event>
                <sub_title>Hemoglobinuria</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="147"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="147"/>
              </event>
              <event>
                <sub_title>Hematuria</sub_title>
                <counts group_id="E1" subjects_affected="5" subjects_at_risk="147"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="147"/>
              </event>
              <event>
                <sub_title>Chronic Kidney Disease</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="147"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="147"/>
              </event>
              <event>
                <sub_title>Acute Kidney Injury</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="147"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="147"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Reproductive system and breast disorders</title>
            <event_list>
              <event>
                <sub_title>Reproductive System And Breast Disorders - Other</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="147"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="147"/>
              </event>
              <event>
                <sub_title>Vaginal Pain</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="147"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="147"/>
              </event>
              <event>
                <sub_title>Vaginal Hemorrhage</sub_title>
                <counts group_id="E1" subjects_affected="6" subjects_at_risk="147"/>
                <counts group_id="E2" subjects_affected="5" subjects_at_risk="147"/>
              </event>
              <event>
                <sub_title>Vaginal Dryness</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="147"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="147"/>
              </event>
              <event>
                <sub_title>Pelvic Pain</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="147"/>
                <counts group_id="E2" subjects_affected="5" subjects_at_risk="147"/>
              </event>
              <event>
                <sub_title>Vaginal Discharge</sub_title>
                <counts group_id="E1" subjects_affected="8" subjects_at_risk="147"/>
                <counts group_id="E2" subjects_affected="5" subjects_at_risk="147"/>
              </event>
              <event>
                <sub_title>Vaginal Inflammation</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="147"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="147"/>
              </event>
              <event>
                <sub_title>Breast Pain</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="147"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="147"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Respiratory, Thoracic And Mediastinal Disorders -</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="147"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="147"/>
              </event>
              <event>
                <sub_title>Sore Throat</sub_title>
                <counts group_id="E1" subjects_affected="6" subjects_at_risk="147"/>
                <counts group_id="E2" subjects_affected="6" subjects_at_risk="147"/>
              </event>
              <event>
                <sub_title>Sneezing</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="147"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="147"/>
              </event>
              <event>
                <sub_title>Sinus Disorder</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="147"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="147"/>
              </event>
              <event>
                <sub_title>Postnasal Drip</sub_title>
                <counts group_id="E1" subjects_affected="5" subjects_at_risk="147"/>
                <counts group_id="E2" subjects_affected="4" subjects_at_risk="147"/>
              </event>
              <event>
                <sub_title>Pneumothorax</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="147"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="147"/>
              </event>
              <event>
                <sub_title>Pneumonitis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="147"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="147"/>
              </event>
              <event>
                <sub_title>Pleural Effusion</sub_title>
                <counts group_id="E1" subjects_affected="7" subjects_at_risk="147"/>
                <counts group_id="E2" subjects_affected="9" subjects_at_risk="147"/>
              </event>
              <event>
                <sub_title>Pharyngolaryngeal Pain</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="147"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="147"/>
              </event>
              <event>
                <sub_title>Pharyngeal Mucositis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="147"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="147"/>
              </event>
              <event>
                <sub_title>Nasal Congestion</sub_title>
                <counts group_id="E1" subjects_affected="10" subjects_at_risk="147"/>
                <counts group_id="E2" subjects_affected="12" subjects_at_risk="147"/>
              </event>
              <event>
                <sub_title>Pleuritic Pain</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="147"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="147"/>
              </event>
              <event>
                <sub_title>Productive Cough</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="147"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="147"/>
              </event>
              <event>
                <sub_title>Hypoxia</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="147"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="147"/>
              </event>
              <event>
                <sub_title>Hoarseness</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="147"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="147"/>
              </event>
              <event>
                <sub_title>Sleep Apnea</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="147"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="147"/>
              </event>
              <event>
                <sub_title>Hiccups</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="147"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="147"/>
              </event>
              <event>
                <sub_title>Epistaxis</sub_title>
                <counts group_id="E1" subjects_affected="5" subjects_at_risk="147"/>
                <counts group_id="E2" subjects_affected="4" subjects_at_risk="147"/>
              </event>
              <event>
                <sub_title>Dyspnea</sub_title>
                <counts group_id="E1" subjects_affected="40" subjects_at_risk="147"/>
                <counts group_id="E2" subjects_affected="39" subjects_at_risk="147"/>
              </event>
              <event>
                <sub_title>Cough</sub_title>
                <counts group_id="E1" subjects_affected="29" subjects_at_risk="147"/>
                <counts group_id="E2" subjects_affected="36" subjects_at_risk="147"/>
              </event>
              <event>
                <sub_title>Wheezing</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="147"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="147"/>
              </event>
              <event>
                <sub_title>Atelectasis</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="147"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="147"/>
              </event>
              <event>
                <sub_title>Aspiration</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="147"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="147"/>
              </event>
              <event>
                <sub_title>Allergic Rhinitis</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="147"/>
                <counts group_id="E2" subjects_affected="5" subjects_at_risk="147"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Skin and subcutaneous tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Skin And Subcutaneous Tissue Disorders - Other</sub_title>
                <counts group_id="E1" subjects_affected="8" subjects_at_risk="147"/>
                <counts group_id="E2" subjects_affected="15" subjects_at_risk="147"/>
              </event>
              <event>
                <sub_title>Urticaria</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="147"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="147"/>
              </event>
              <event>
                <sub_title>Stevens-Johnson Syndrome</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="147"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="147"/>
              </event>
              <event>
                <sub_title>Skin Ulceration</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="147"/>
                <counts group_id="E2" subjects_affected="5" subjects_at_risk="147"/>
              </event>
              <event>
                <sub_title>Skin Induration</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="147"/>
                <counts group_id="E2" subjects_affected="7" subjects_at_risk="147"/>
              </event>
              <event>
                <sub_title>Skin Hyperpigmentation</sub_title>
                <counts group_id="E1" subjects_affected="20" subjects_at_risk="147"/>
                <counts group_id="E2" subjects_affected="21" subjects_at_risk="147"/>
              </event>
              <event>
                <sub_title>Scalp Pain</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="147"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="147"/>
              </event>
              <event>
                <sub_title>Rash Acneiform</sub_title>
                <counts group_id="E1" subjects_affected="7" subjects_at_risk="147"/>
                <counts group_id="E2" subjects_affected="9" subjects_at_risk="147"/>
              </event>
              <event>
                <sub_title>Purpura</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="147"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="147"/>
              </event>
              <event>
                <sub_title>Pruritus</sub_title>
                <counts group_id="E1" subjects_affected="24" subjects_at_risk="147"/>
                <counts group_id="E2" subjects_affected="20" subjects_at_risk="147"/>
              </event>
              <event>
                <sub_title>Photosensitivity</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="147"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="147"/>
              </event>
              <event>
                <sub_title>Palmar-Plantar Erythrodysesthesia Syndrome</sub_title>
                <counts group_id="E1" subjects_affected="55" subjects_at_risk="147"/>
                <counts group_id="E2" subjects_affected="54" subjects_at_risk="147"/>
              </event>
              <event>
                <sub_title>Pain Of Skin</sub_title>
                <counts group_id="E1" subjects_affected="6" subjects_at_risk="147"/>
                <counts group_id="E2" subjects_affected="4" subjects_at_risk="147"/>
              </event>
              <event>
                <sub_title>Rash Maculo-Papular</sub_title>
                <counts group_id="E1" subjects_affected="58" subjects_at_risk="147"/>
                <counts group_id="E2" subjects_affected="53" subjects_at_risk="147"/>
              </event>
              <event>
                <sub_title>Nail Ridging</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="147"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="147"/>
              </event>
              <event>
                <sub_title>Nail Loss</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="147"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="147"/>
              </event>
              <event>
                <sub_title>Nail Discoloration</sub_title>
                <counts group_id="E1" subjects_affected="8" subjects_at_risk="147"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="147"/>
              </event>
              <event>
                <sub_title>Hyperhidrosis</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="147"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="147"/>
              </event>
              <event>
                <sub_title>Erythema Multiforme</sub_title>
                <counts group_id="E1" subjects_affected="5" subjects_at_risk="147"/>
                <counts group_id="E2" subjects_affected="8" subjects_at_risk="147"/>
              </event>
              <event>
                <sub_title>Dry Skin</sub_title>
                <counts group_id="E1" subjects_affected="21" subjects_at_risk="147"/>
                <counts group_id="E2" subjects_affected="24" subjects_at_risk="147"/>
              </event>
              <event>
                <sub_title>Bullous Dermatitis</sub_title>
                <counts group_id="E1" subjects_affected="6" subjects_at_risk="147"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="147"/>
              </event>
              <event>
                <sub_title>Alopecia</sub_title>
                <counts group_id="E1" subjects_affected="14" subjects_at_risk="147"/>
                <counts group_id="E2" subjects_affected="20" subjects_at_risk="147"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Surgical and medical procedures</title>
            <event_list>
              <event>
                <sub_title>Surgical And Medical Procedures - Other</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="147"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="147"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Vascular disorders</title>
            <event_list>
              <event>
                <sub_title>Vascular Disorders - Other</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="147"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="147"/>
              </event>
              <event>
                <sub_title>Thromboembolic Event</sub_title>
                <counts group_id="E1" subjects_affected="7" subjects_at_risk="147"/>
                <counts group_id="E2" subjects_affected="5" subjects_at_risk="147"/>
              </event>
              <event>
                <sub_title>Superficial Thrombophlebitis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="147"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="147"/>
              </event>
              <event>
                <sub_title>Lymphedema</sub_title>
                <counts group_id="E1" subjects_affected="5" subjects_at_risk="147"/>
                <counts group_id="E2" subjects_affected="4" subjects_at_risk="147"/>
              </event>
              <event>
                <sub_title>Hypotension</sub_title>
                <counts group_id="E1" subjects_affected="6" subjects_at_risk="147"/>
                <counts group_id="E2" subjects_affected="11" subjects_at_risk="147"/>
              </event>
              <event>
                <sub_title>Hypertension</sub_title>
                <counts group_id="E1" subjects_affected="13" subjects_at_risk="147"/>
                <counts group_id="E2" subjects_affected="18" subjects_at_risk="147"/>
              </event>
              <event>
                <sub_title>Hot Flashes</sub_title>
                <counts group_id="E1" subjects_affected="13" subjects_at_risk="147"/>
                <counts group_id="E2" subjects_affected="7" subjects_at_risk="147"/>
              </event>
              <event>
                <sub_title>Hematoma</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="147"/>
                <counts group_id="E2" subjects_affected="4" subjects_at_risk="147"/>
              </event>
              <event>
                <sub_title>Flushing</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="147"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="147"/>
              </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>Kristi Manjarrez</name_or_title>
      <organization>Vice President, Clinical Affairs</organization>
      <phone>206-689-2256</phone>
      <email>kmanjarrez@ventirx.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/NCT01666444
org study id: GOG-3003
nct id: NCT01666444
lead sponsor: 
collaborator: 
has dmc: Yes
The purpose of this study is to compare the overall survival of patients treated with
      VTX-2337 + pegylated liposomal doxorubicin (PLD) versus those treated with PLD alone in women
      with recurrent or persistent, epithelial ovarian, fallopian tube or primary peritoneal
      cancer.

      VTX-2337, a small molecule agonist of Toll-like Receptor 8 (TLR8), activates multiple
      components of the innate immune system and is being developed as a novel therapeutic agent
      for use in oncology. Experimental data obtained in an animal model of ovarian cancer supports
      the combination of VTX-2337 with PLD. In this model, the combination of VTX-2337 and PLD
      resulted in a significant reduction in tumor growth compared to either agent alone and an
      increase in the number of T lymphocytes infiltrating the tumor. The combination of PLD and
      VTX-2337 has been tested in a small number of women with ovarian cancer in a Phase 1b study
      and appears to be generally well-tolerated.
OBJECTIVES

      Primary Objectives:

        -  To compare the overall survival (OS) of patients treated with VTX-2337 + PLD versus
           those treated with PLD alone in women with recurrent or persistent, epithelial ovarian,
           fallopian tube or primary peritoneal cancer.

        -  To compare the progression-free survival (PFS) between the two treatment groups using
           Immune-Related Response Evaluation Criteria in Solid Tumors (irRECIST).

      Secondary Objectives:

        -  To compare the progression-free survival (PFS) between the two treatment groups using
           Response Evaluation Criteria In Solid Tumors (RECIST 1.1).

        -  To compare the nature, frequency and severity of drug-related adverse events (AEs)
           between the two treatment groups.

      Exploratory Objectives:

        -  To compare the best overall response rate (ORR) and duration of response (based on the
           probability of being in response function [PBRF]) between the two treatment groups using
           irRECIST and RECIST 1.1.

        -  To compare the disease control rate (DCR) between the two treatment groups using
           irRECIST and RECIST 1.1.

        -  To assess the impact of immune status and response on the clinical effects (OS, PFS,
           DCR, ORR, PBRF, AEs) of study treatment.

        -  To assess the effect of TLR8 polymorphisms and BRCA1/BRCA2 mutations on the clinical
           effects (OS, PFS, DCR, ORR, PBRF, AEs) of study treatment.

        -  To assess the effect of immune cell subsets, as measured by immunohistochemistry and
           micro RNA in primary tumor tissue (e.g. immune score), on the clinical effects (OS, PFS,
           DCR, ORR, PBRF, AEs) of study treatment.

        -  To assess whether the presence of autoantibodies to tumor-derived proteins are
           predictive of the clinical effects (OS, PFS, DCR, ORR, PBRF, AEs) of study treatment.

      OUTLINE:

      This is Phase 2 multicenter clinical study to evaluate the efficacy and safety of the
      combination of VTX-2337 + PLD compared to PLD + Placebo.

      The dosing schedule will be the same for both treatment arms, and will be based on a 28-day
      cycle. The starting dose schedule is PLD on Day 1 plus VTX-2337 or placebo on Day 3, Day 10,
      and Day 17 for the first 4 cycles. Starting with cycle 5, the dose regimen will be PLD on Day
      1 plus VTX-2337 or placebo on Day 3.

      Blood samples are collected periodically during cycle 1 for pharmacodynamics,
      pharmacogenomics, and other research studies.

      Patients will receive therapy until disease progression based on Immune-Related RECIST or
      until adverse effects prohibit further therapy. Following treatment completion, all patients
      will be followed with physical exams and histories every three months for the first two
      years, and then every six months for the next three years, and then
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
measure: Overall Survival
time frame: Survival is measured from date of enrollment and randomization on the study until death from any cause, or if alive at last contact, date of last contact.
description: Comparison of duration of survival between the 2 treatment groups
measure: Progression-free Survival (PFS)
time frame: Progression-free survival is measured from enrollment and randomization on the study until first indication of progression based on irRECIST criteria or death from any cause, or if progression-free at last contact, the date of last disease assessment.
description: Comparison of PFS between the 2 treatment groups
measure: Frequency and Severity of Adverse Events (AEs)
time frame: Assessed during each cycle of therapy and within 30 days after the last cycle of therapy
description: An AE is any untoward medical occurrence associated with the use of a drug in humans, whether or not considered drug-related. An AE can be unfavorable and unintended sign, symptom, or disease which is temporally associated with the use of investigational product (IP), whether or not considered related to the IP. A serious AE = an AE occurring at any dose that: • Results in death • Is life- threatening • Requires or prolongs existing inpatient hospitalization • Results in persistent or significant disability/incapacity • Is a congenital anomaly/birth defect; • Constitutes an important medical event. The Investigator assessed the relationship of each AE to IP and graded the severity according to the National Cancer Institute Common Terminology Criteria for Adverse Events, Version 4.0: Grade (GR) 1 = Mild; asymptomatic or mild symptoms; GR 2 = Moderate (minimal, local or noninvasive intervention indicated); GR 3 = Severe or medically significant; GR 4 = Life-threatening; GR 5 = Death
arm group label: PLD 40 mg/m2 plus VTX-2337
arm group type: Experimental
description: The dosing schedule will be be based on a 28-day cycle. The starting dose schedule is PLD on Day 1 plus VTX-2337 on Day 3, Day 10, and Day 17 for the first 4 cycles. Starting with cycle 5, the dose regimen will be PLD on Day 1 plus VTX-2337 on Day 3 only, without additional doses of VTX-2337 on Days 10 and Day 17.
arm group label: PLD 40 mg/m2 plus placebo
arm group type: Active Comparator
description: The dosing schedule will be based on a 28-day cycle. The starting dose schedule is PLD on Day 1 plus placebo on Day 3, Day 10, and Day 17 for the first 4 cycles. Starting with cycle 5, the dose regimen will be PLD on Day 1 plus placebo on Day 3 only.
intervention type: Drug
intervention name: pegylated liposomal doxorubicin (PLD)
arm group label: PLD 40 mg/m2 plus VTX-2337
arm group label: PLD 40 mg/m2 plus placebo
other name: Doxil
other name: Lipodox
intervention type: Drug
intervention name: VTX-2337
description: TLR8 Agonist
arm group label: PLD 40 mg/m2 plus VTX-2337
intervention type: Drug
intervention name: Placebo
arm group label: PLD 40 mg/m2 plus placebo
criteria: 
gender: Female
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Bradley J. Monk, MD
role: Study Chair
affiliation: St. Joseph's Hospital and Medical Center, Phoenix AZ
last name: Amar Patel, MD
role: Study Director
affiliation: Celgene
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country: United States
responsible party type: Sponsor
mesh term: Ovarian Neoplasms
mesh term: Carcinoma, Ovarian Epithelial
mesh term: Fallopian Tube Neoplasms
mesh term: Peritoneal Neoplasms
mesh term: Doxorubicin
mesh term: Liposomal doxorubicin
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 