<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/NCT02228681</url>
  </required_header>
  <id_info>
    <org_study_id>GOG-3007</org_study_id>
    <secondary_id>CRAD001CUS236T</secondary_id>
    <nct_id>NCT02228681</nct_id>
  </id_info>
  <brief_title>Everolimus and Letrozole or Hormonal Therapy to Treat Endometrial Cancer</brief_title>
  <official_title>A Randomized Phase II Trial of Everolimus and Letrozole or Hormonal Therapy (Tamoxifen/Medroxyprogesterone Acetate) in Women With Advanced, Recurrent, or Persistent Endometria Carcinoma</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Gynecologic Oncology Group</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Novartis Pharmaceuticals</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>GOG Foundation</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The main purpose of this study is to evaluate the effectiveness of the combination of the&#xD;
      drugs Everolimus and Letrozole compared to Tamoxifen and Medroxyprogesterone acetate in&#xD;
      treating endometrial cancer and to determine the types and severity of side effects caused by&#xD;
      treatment with these drug combinations.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Active, not recruiting</last_known_status>
  <start_date>February 2015</start_date>
  <primary_completion_date type="Actual">January 2018</primary_completion_date>
  <phase>Phase 2</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Frequency of Response</measure>
    <time_frame>From date of randomization until the date of first documented progression or date of death , up to 3 years.</time_frame>
    <description>A confirmed complete or partial response as defined by RECIST 1.1 was considered a response. &quot;Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), &gt;=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Median Progression-free Survival</measure>
    <time_frame>Tumor measurements were done at 8 and 16 weeks after initiating treatment and then every 12 weeks and compared with baseline measurements prior to treatment. Measurements are continued until disease progression is documented or death.</time_frame>
    <description>Progression-free Survival is defined as the duration alive from study entry until progression is documented, or death; whichever comes sooner. Progressive disease is defined as at least a 5 mm absolute increase and a 20% relative increase in the sum of measurable target lesions' longest dimensions relative to the smallest sum at baseline or on study or the appearance of new lesions or unequivocal progression of existing non-target lesions.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Frequency and Severity of CTCAE (Common Toxicity Criteria for Adverse Events) Version 4</measure>
    <time_frame>Assessed throughout the treatment period and for 30 days after discontinuation of treatment. Treatment continues until progression of disease.</time_frame>
    <description>Maximum grade of physician assessed adverse events graded and categorized using Common Toxicity Criteria for Adverse Events (CTCAE) version 4</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Median Survival</measure>
    <time_frame>Following treatment discontinuation, patients are followed quarterly for 2 years, semi-annually for 3 more years, annually thereafter.</time_frame>
    <description>Survival is defined as the duration alive from study entry until death.</description>
  </secondary_outcome>
  <other_outcome>
    <measure>Hormone Receptor Immunohistochemistry</measure>
    <time_frame>At study entry</time_frame>
    <description>To determine if relevant biomarkers correlate with response to treatment in each of the two arms. Unstained sections of tumor tissue will be used for hormone receptor (estrogen receptor-alpha, estrogen receptor-beta, progesterone receptor-A, progesterone receptor B and the G protein-coupled estrogen receptor, GPR-30) immunohistochemistry.</description>
  </other_outcome>
  <other_outcome>
    <measure>mTOR Pathway Immunohistochemistry</measure>
    <time_frame>At study entry</time_frame>
    <description>To determine if relevant biomarkers correlate with response to treatment in each of the two arms. Unstained sections of tumor tissue will be used for mTOR pathway (including phosphorylated S6 ribosomal protein, PTEN, total and phosphorylated AKT, total and phosphorylated mTOR, and phospho-ERK1/2) immunohistochemistry</description>
  </other_outcome>
  <other_outcome>
    <measure>Mutation Analysis</measure>
    <time_frame>At study entry</time_frame>
    <description>To determine if relevant biomarkers correlate with response to treatment in each of the two arms. Unstained sections of tumor tissue and DNA extracted from whole blood will be used for mutational analysis (including PTEN, PIK3CA, KRAS, and CTNNB1 (beta-catenin) performed using a sequencing panel assay.</description>
  </other_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">74</enrollment>
  <condition>Advanced, Persistent, or Recurrent Endometrial Cancer</condition>
  <arm_group>
    <arm_group_label>Everolimus and Letrozole</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Everolimus 10 mg daily and Letrozole 2.5 mg PO daily</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Hormonal Therapy</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Tamoxifen 20 mg PO BID; on alternating weeks (even numbered) weeks, Medroxyprogesterone Acetate 200 mg PO daily with Tamoxifen 20 mg PO BID</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Everolimus</intervention_name>
    <description>10mg daily by mouth</description>
    <arm_group_label>Everolimus and Letrozole</arm_group_label>
    <other_name>RAD001</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Tamoxifen</intervention_name>
    <description>20 mg daily by mouth on alternating weeks (even numbered) weeks</description>
    <arm_group_label>Hormonal Therapy</arm_group_label>
    <other_name>Nolvadex®</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Letrozole</intervention_name>
    <description>2.5mg once a day by mouth</description>
    <arm_group_label>Everolimus and Letrozole</arm_group_label>
    <other_name>Femara®</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Medroxyprogesterone Acetate</intervention_name>
    <description>200 mg daily by mouth</description>
    <arm_group_label>Hormonal Therapy</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Patients must have histologically confirmed advanced (FIGO Stage III or IV),&#xD;
             persistent, or recurrent endometrial carcinoma, which is not likely to be curable by&#xD;
             surgery or radiotherapy. Histologic documentation of the recurrence is not required.&#xD;
&#xD;
          -  All patients must have measurable disease. Measurable disease is defined by RECIST&#xD;
             version 1.1). Measurable disease is defined as at least one lesion that can be&#xD;
             accurately measured in at least one dimension (longest diameter to be recorded). Each&#xD;
             lesion must be greater than or equal to 10 mm when measured by CT, MRI or caliper&#xD;
             measurement by clinical exam; or greater than or equal to 20 mm when measured by chest&#xD;
             x-ray. Lymph nodes must be greater than or equal to 15 mm in short axis when measured&#xD;
             by CT or MRI (See section 8).&#xD;
&#xD;
          -  Patients must have at least one &quot;target lesion&quot; to be used to assess response on this&#xD;
             protocol as defined by RECIST 1.1 (Section 8.1). Tumors within a previously irradiated&#xD;
             field will be designated as &quot;non-target&quot; lesions unless progression is documented or a&#xD;
             biopsy is obtained to confirm persistence at least 90 days following completion of&#xD;
             radiation therapy.&#xD;
&#xD;
          -  Prior chemoradiotherapy for a pelvic recurrence is permitted. Prior chemotherapy in&#xD;
             the adjuvant setting for Stage I, II or III disease is permitted.&#xD;
&#xD;
        Note: No prior chemotherapy in the setting of Stage IV disease is permitted unless the&#xD;
        patient was without evidence of disease at the completion of chemotherapy and had at least&#xD;
        six months of progression-free survival since the completion of chemotherapy.&#xD;
&#xD;
        Regardless of circumstances, no more than one prior chemotherapy regimen (including&#xD;
        chemo-radiotherapy) is permitted.&#xD;
&#xD;
          -  Patient must be able to take p.o. medications.&#xD;
&#xD;
          -  Performance status must be 0-1.&#xD;
&#xD;
          -  Patients must have adequate organ and marrow function as defined below:&#xD;
&#xD;
        NOTE: Institutional/laboratory upper limit of normal = ULN Institutional/laboratory lower&#xD;
        limit of normal = LLN&#xD;
&#xD;
          -  Bone marrow function:&#xD;
&#xD;
               -  Absolute neutrophil count (ANC) greater than or equal to 1,500/mcl&#xD;
&#xD;
               -  Platelets greater than or equal to 100,000 cells/mcl&#xD;
&#xD;
               -  Hemoglobin greater than or equal to 9 g/dL&#xD;
&#xD;
          -  Coagulation&#xD;
&#xD;
             • INR less than or equal to 1.5 x ULN (or in range INR, usually between 2 and 3, if a&#xD;
             patient is on a stable dose of therapeutic warfarin).&#xD;
&#xD;
          -  Renal function:&#xD;
&#xD;
             • Creatinine less than or equal to 1.5 x ULN&#xD;
&#xD;
          -  Hepatic function:&#xD;
&#xD;
               -  Bilirubin less than or equal to 1.5 x ULN&#xD;
&#xD;
               -  ALT and AST less than or equal to 3 x ULN&#xD;
&#xD;
               -  Alkaline phosphatase less than or equal to 2.5 x ULN&#xD;
&#xD;
               -  Albumin greater than or equal to 2.8 g/dL&#xD;
&#xD;
          -  Lipid panel:&#xD;
&#xD;
               -  Fasting serum cholesterol less than or equal to 300 mg/dL&#xD;
&#xD;
               -  Fasting triglycerides less than or equal to 300 mg/&#xD;
&#xD;
          -  At least 4 weeks must have elapsed since the patient underwent any major surgery&#xD;
             (e.g., major: hysterectomy, resection of a lung nodule; minor: central venous access&#xD;
             catheter placement).&#xD;
&#xD;
          -  At least 4 weeks must have elapsed since the patient received any radiation therapy.&#xD;
&#xD;
          -  Patients who have met the pre-entry requirements specified in Section 7.0&#xD;
&#xD;
          -  Patients must have signed an approved informed consent and authorization permitting&#xD;
             release of personal health information.&#xD;
&#xD;
          -  All patients must be at least 18 years of age&#xD;
&#xD;
          -  Patients of childbearing potential must have a negative serum pregnancy test prior to&#xD;
             the study entry and be practicing a highly effective form of contraception.&#xD;
&#xD;
        During the study treatment and for 8 weeks after stopping the treatment. Highly effective&#xD;
        contraception methods include combination of any two of the following:&#xD;
&#xD;
          -  Use of oral, injected or implanted hormonal methods of contraception or;&#xD;
&#xD;
          -  Placement of an intrauterine device (IUD) or intrauterine system (IUS);&#xD;
&#xD;
          -  Barrier methods of contraception: condom or occlusive cap (diaphragm or cervical/vault&#xD;
             caps) with spermicidal foam/gel/film/cream/ vaginal suppository;&#xD;
&#xD;
          -  Total abstinence or;&#xD;
&#xD;
          -  Male/female sterilization. Women are considered post-menopausal and not of&#xD;
             child-bearing potential if they have had 12 months of natural (spontaneous) amenorrhea&#xD;
             with an appropriate clinical profile (e.g. age appropriate, history of vasomotor&#xD;
             symptoms) or have had surgical bilateral oophorectomy (with or without hysterectomy)&#xD;
             or tubal ligation at least six weeks prior to randomization. In the case of&#xD;
             oophorectomy alone, only when the reproductive status of the woman has been confirmed&#xD;
             by follow up hormone level assessment is she considered not of child-bearing&#xD;
             potential.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Patients who have previously received everolimus, any another mTOR inhibitor or any&#xD;
             agent targeting the PI3K/AKT/mTOR pathway.&#xD;
&#xD;
          -  Known intolerance or hypersensitivity to Everolimus or other rapamycin analogs (e.g.&#xD;
             sirolimus, temsirolimus)&#xD;
&#xD;
          -  Patients who have previously received hormonal therapy for endometrial cancer.&#xD;
&#xD;
          -  Patients with concomitant invasive malignancy or a history of other invasive&#xD;
             malignancies, with the exception of non-melanoma skin cancer, are excluded if there is&#xD;
             any evidence of other malignancy being present within the past five years. Patients&#xD;
             are also excluded if their previous cancer treatment contraindicates this protocol.&#xD;
&#xD;
          -  Patients receiving chronic treatment with systemic steroids or another&#xD;
             immunosuppressive agent.&#xD;
&#xD;
          -  Patients with active or uncontrolled systemic infection.&#xD;
&#xD;
          -  Uncontrolled diabetes mellitus as defined by HbA1c &gt;8% despite adequate therapy.&#xD;
             Patients with a known history of impaired fasting glucose or diabetes mellitus (DM)&#xD;
             may be included, however blood glucose and anti-diabetic treatment must be monitored&#xD;
             closely throughout the trial and adjusted as necessary.&#xD;
&#xD;
          -  Known severely impaired lung function, including:&#xD;
&#xD;
             • CTCAE grade 2 (or greater) hypoxia (decreased oxygen saturation with exercise [e.g.,&#xD;
             pulse oximeter &lt;88%]; intermittent supplemental oxygen)&#xD;
&#xD;
          -  Patients with a known history of cardiac disease. This includes:&#xD;
&#xD;
          -  Uncontrolled hypertension, defined as systolic greater than 150 mm Hg or diastolic&#xD;
             greater than 90 mm Hg despite antihypertensive medications.&#xD;
&#xD;
          -  Myocardial infarction or unstable angina within 6 months prior to registration.&#xD;
&#xD;
          -  New York Heart Association (NYHA) Class II or greater congestive heart failure.&#xD;
&#xD;
          -  History of serious ventricular arrhythmia (i.e., ventricular tachycardia or&#xD;
             ventricular fibrillation) or serious cardiac arrhythmia requiring medication. This&#xD;
             does not include asymptomatic atrial fibrillation with controlled ventricular rate.&#xD;
&#xD;
          -  Cerebrovascular accident (CVA, stroke), transient ischemic attack (TIA) within 6&#xD;
             months prior to the first date of study therapy.&#xD;
&#xD;
          -  Patients who are pregnant or breast-feeding.&#xD;
&#xD;
          -  Patients with known central nervous system metastases.&#xD;
&#xD;
          -  Patients with known human immunodeficiency virus (HIV) infection.&#xD;
&#xD;
          -  Patients with an impairment of gastrointestinal function or gastrointestinal disease&#xD;
             that may significantly alter the absorption of everolimus (e.g., ulcerative disease;&#xD;
             uncontrolled nausea, vomiting and/or diarrhea; malabsorption syndrome; clinical signs&#xD;
             and symptoms of gastrointestinal obstruction; and/or patients who require parenteral&#xD;
             hydration and/or nutrition).&#xD;
&#xD;
          -  Patients who plan to receive live attenuated vaccines within 1 week of start of&#xD;
             everolimus and during the study. Patient should also avoid close contact with others&#xD;
             who have received live attenuated vaccines. Examples of live attenuated vaccines&#xD;
             include intranasal influenza, measles, mumps, rubella, oral polio, BCG, yellow fever,&#xD;
             varicella and TY21a typhoid vaccines.&#xD;
&#xD;
          -  Patients with active bleeding or pathologic conditions that carry high risk of&#xD;
             bleeding, such as known bleeding disorder or coagulopathy.&#xD;
&#xD;
          -  Patients who are currently part of or have participated in any clinical investigation&#xD;
             with an investigational drug within 30 days prior to dosing.&#xD;
&#xD;
          -  Patients must be able to follow concomitant medication restrictions:&#xD;
&#xD;
               -  Avoid the use of strong CYP3A/PgP inhibitors (e.g., ketoconazole, itraconazole,&#xD;
                  clarithromycin, atazanavir, nefazodone, saquinavir, telithromycin, ritonavir,&#xD;
                  indinavir, nelfinavir, voriconazole).&#xD;
&#xD;
               -  Use caution when co-administered with moderate CYP3A4/PgP inhibitors (e.g.,&#xD;
                  amprenavir, fosamprenavir, aprepitant, erythromycin, fluconazole, verapamil,&#xD;
                  diltiazem).&#xD;
&#xD;
               -  Grapefruit, grapefruit juice, and other foods known to inhibit cytochrome P450&#xD;
                  and PgP activity may increase everolimus exposures and should be avoided during&#xD;
                  treatment.&#xD;
&#xD;
               -  Avoid the use of concomitant strong CYP3A4/PgP inducers (e.g., phenytoin,&#xD;
                  carbamazepine, rifampin, rifabutin, rifapentine, and phenobarbital).&#xD;
&#xD;
               -  St. John's Wort may decrease everolimus exposure unpredictably and should be&#xD;
                  avoided.&#xD;
&#xD;
          -  Patients with active hepatitis B or C. Screening for hepatitis B&#xD;
&#xD;
        Prior to randomization/start of everolimus, the following three categories of patients&#xD;
        should be tested for hepatitis B viral load and serologic markers, that is, HBsAg, HBcAb,&#xD;
        HBsAb and quantitative hepatitis B DNA PCR (HBV-DNA):&#xD;
&#xD;
        • All patients who currently live in (or have lived in) Asia, Africa, Central and South&#xD;
        America, Eastern Europe, Spain, Portugal and Greece.&#xD;
&#xD;
        [http://wwwnc.cdc.gov/travel/yellowbook/2012/chapter-3-infectious-diseases-related-to-trave&#xD;
        l/hepatitis-b.htm]&#xD;
&#xD;
          -  Patients with any of the following risk factors:&#xD;
&#xD;
          -  known or suspected past hepatitis B infection,&#xD;
&#xD;
          -  blood transfusion(s) prior to 1990,&#xD;
&#xD;
          -  current or prior IV drug users,&#xD;
&#xD;
          -  current or prior dialysis,&#xD;
&#xD;
          -  household contact with hepatitis B infected patient(s),&#xD;
&#xD;
          -  current or prior high-risk sexual activity,&#xD;
&#xD;
          -  body piercing or tattoos,&#xD;
&#xD;
          -  mother known to have hepatitis B&#xD;
&#xD;
          -  history suggestive of hepatitis B infection, e.g., dark urine, jaundice, right upper&#xD;
             quadrant pain.&#xD;
&#xD;
          -  Additional patients at the discretion of the investigator The management guidelines,&#xD;
             in Section 6, are provided according to the results of the baseline assessment of&#xD;
             viral load and serological markers for hepatitis B.&#xD;
&#xD;
        Screening for hepatitis C&#xD;
&#xD;
        Patients with any of the following risk factors for hepatitis C should be tested using&#xD;
        quantitative RNA-PCR:&#xD;
&#xD;
          -  known or suspected past hepatitis C infection (including patients with past interferon&#xD;
             'curative' treatment),&#xD;
&#xD;
          -  blood transfusions prior to 1990,&#xD;
&#xD;
          -  current or prior IV drug users,&#xD;
&#xD;
          -  current or prior dialysis,&#xD;
&#xD;
          -  household contact of hepatitis C infected patient(s),&#xD;
&#xD;
          -  current or prior high-risk sexual activity,&#xD;
&#xD;
          -  body piercing or tattoos. At the discretion of the investigator, additional patients&#xD;
             may also be tested for hepatitis C.&#xD;
&#xD;
        The management guidelines, in Section 6 are provided according to the results of the&#xD;
        baseline assessment of hepatitis C viral load.&#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>Brian Slomovitz, MD</last_name>
    <role>Study Chair</role>
    <affiliation>Gynecologic Oncology Group</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>University of Colorado - Anschutz Cancer Pavilion</name>
      <address>
        <city>Aurora</city>
        <state>Colorado</state>
        <zip>80045</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Miami - Sylvester Comprehensive Cancer Center</name>
      <address>
        <city>Miami</city>
        <state>Florida</state>
        <zip>33136</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>John B. Amos Cancer Center</name>
      <address>
        <city>Columbus</city>
        <state>Georgia</state>
        <zip>31904</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>Maine Medical Center</name>
      <address>
        <city>Scarborough</city>
        <state>Maine</state>
        <zip>04074</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Johns Hopkins</name>
      <address>
        <city>Baltimore</city>
        <state>Maryland</state>
        <zip>21287</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Massachusetts Memorial Center</name>
      <address>
        <city>Worcester</city>
        <state>Massachusetts</state>
        <zip>01605</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Sanford Clinic North - Bemidji</name>
      <address>
        <city>Bemidji</city>
        <state>Minnesota</state>
        <zip>56601</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>39215</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>Women's Cancer 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>New Mexico Cancer Alliance</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-Cancer Center</name>
      <address>
        <city>Albuquerque</city>
        <state>New Mexico</state>
        <zip>87131</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>Sanford Roger Maris Cancer Center</name>
      <address>
        <city>Fargo</city>
        <state>North Dakota</state>
        <zip>58122</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University Hospital Case Medical Center</name>
      <address>
        <city>Cleveland</city>
        <state>Ohio</state>
        <zip>44106</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Ohio State University</name>
      <address>
        <city>Columbus</city>
        <state>Ohio</state>
        <zip>43210</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Oklahoma</name>
      <address>
        <city>Oklahoma City</city>
        <state>Oklahoma</state>
        <zip>73104</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Abington Memorial Hospital</name>
      <address>
        <city>Abington</city>
        <state>Pennsylvania</state>
        <zip>19001-3788</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>The University of Pennsylvania</name>
      <address>
        <city>Philadelphia</city>
        <state>Pennsylvania</state>
        <zip>19104</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Magee Women's Hospital of UPMC</name>
      <address>
        <city>Pittsburgh</city>
        <state>Pennsylvania</state>
        <zip>15213</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Women &amp; Infants Hospital of Rhode Island</name>
      <address>
        <city>Providence</city>
        <state>Rhode Island</state>
        <zip>02905</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Sanford Medical Center - Sioux Falls</name>
      <address>
        <city>Sioux Falls</city>
        <state>South Dakota</state>
        <zip>57104</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Texas 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>Huntsman Cancer Institute</name>
      <address>
        <city>Salt Lake City</city>
        <state>Utah</state>
        <zip>84112</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>September 2021</verification_date>
  <study_first_submitted>August 14, 2014</study_first_submitted>
  <study_first_submitted_qc>August 27, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">August 29, 2014</study_first_posted>
  <results_first_submitted>September 20, 2018</results_first_submitted>
  <results_first_submitted_qc>May 23, 2019</results_first_submitted_qc>
  <results_first_posted type="Actual">May 24, 2019</results_first_posted>
  <last_update_submitted>September 28, 2021</last_update_submitted>
  <last_update_submitted_qc>September 28, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">September 30, 2021</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Endometrial Neoplasms</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Tamoxifen</mesh_term>
    <mesh_term>Everolimus</mesh_term>
    <mesh_term>Letrozole</mesh_term>
    <mesh_term>Medroxyprogesterone Acetate</mesh_term>
    <mesh_term>Medroxyprogesterone</mesh_term>
  </intervention_browse>
  <provided_document_section>
    <provided_document>
      <document_type>Study Protocol and Statistical Analysis Plan</document_type>
      <document_has_protocol>Yes</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>Yes</document_has_sap>
      <document_date>June 25, 2015</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/81/NCT02228681/Prot_SAP_000.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <recruitment_details>The study was activated on 02/19/2015 and closed to accrual on 04/18/2016. All patients underwent disease evaluation and were found to have measurable histologically confirmed advanced stage, persistent or recurrent endometrial carcinoma. After obtaining informed consent and verification of eligibility, patients were enrolled and treated.</recruitment_details>
      <group_list>
        <group group_id="P1">
          <title>Everolimus and Letrozole</title>
          <description>Everolimus 10 mg daily plus letrozole 2.5 mg PO daily in a 28 day cycle.</description>
        </group>
        <group group_id="P2">
          <title>Tamoxifen and Medroxyprogesterone Acetate</title>
          <description>Tamoxifen 20 mg PO bid days 1-28 plus medroxyprogesterone acetate 200 mg PO days 8-14 and 22-28 repeating in a 28 day cycle.</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="37"/>
                <participants group_id="P2" count="37"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="37"/>
                <participants group_id="P2" count="37"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="0"/>
              </participants_list>
            </milestone>
          </milestone_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <population>Eligible and evaluable patients</population>
      <group_list>
        <group group_id="B1">
          <title>Everolimus and Letrozole</title>
          <description>Everolimus 10 mg daily plus letrozole 2.5 mg PO daily in a 28 day cycle.</description>
        </group>
        <group group_id="B2">
          <title>Tamoxifen and Medroxyprogesterone Acetate</title>
          <description>Tamoxifen 20 mg PO bid days 1-28 plus medroxyprogesterone acetate 200 mg PO days 8-14 and 22-28 repeating in a 28 day cycle.</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="37"/>
            <count group_id="B2" value="37"/>
            <count group_id="B3" value="74"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>years</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="63.3" spread="9.1"/>
                    <measurement group_id="B2" value="66.8" spread="7.3"/>
                    <measurement group_id="B3" value="65" spread="8.4"/>
                  </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="37"/>
                    <measurement group_id="B2" value="37"/>
                    <measurement group_id="B3" value="74"/>
                  </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="4"/>
                    <measurement group_id="B3" value="8"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Not Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="33"/>
                    <measurement group_id="B2" value="33"/>
                    <measurement group_id="B3" value="66"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>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="2"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="3"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Asian</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="1"/>
                  </measurement_list>
                </category>
                <category>
                  <title>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="2"/>
                    <measurement group_id="B2" value="5"/>
                    <measurement group_id="B3" value="7"/>
                  </measurement_list>
                </category>
                <category>
                  <title>White</title>
                  <measurement_list>
                    <measurement group_id="B1" value="32"/>
                    <measurement group_id="B2" value="31"/>
                    <measurement group_id="B3" value="63"/>
                  </measurement_list>
                </category>
                <category>
                  <title>More than one race</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Frequency of Response</title>
        <description>A confirmed complete or partial response as defined by RECIST 1.1 was considered a response. &quot;Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), &gt;=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR</description>
        <time_frame>From date of randomization until the date of first documented progression or date of death , up to 3 years.</time_frame>
        <population>Eligible and treated participants. One participant in arm II was not treated. Participant flow contains all eligible participants.</population>
        <group_list>
          <group group_id="O1">
            <title>Everolimus and Letrozole</title>
            <description>Everolimus 10 mg daily plus letrozole 2.5 mg PO daily in a 28 day cycle.</description>
          </group>
          <group group_id="O2">
            <title>Tamoxifen and Medroxyprogesterone Acetate</title>
            <description>Tamoxifen 20 mg PO bid days 1-28 plus medroxyprogesterone acetate 200 mg PO days 8-14 and 22-28 repeating in a 28 day cycle.</description>
          </group>
        </group_list>
        <measure>
          <title>Frequency of Response</title>
          <description>A confirmed complete or partial response as defined by RECIST 1.1 was considered a response. &quot;Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), &gt;=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR</description>
          <population>Eligible and treated participants. One participant in arm II was not treated. Participant flow contains all eligible participants.</population>
          <units>Number of participants</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="37"/>
                <count group_id="O2" value="36"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="9"/>
                    <measurement group_id="O2" value="8"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Median Progression-free Survival</title>
        <description>Progression-free Survival is defined as the duration alive from study entry until progression is documented, or death; whichever comes sooner. Progressive disease is defined as at least a 5 mm absolute increase and a 20% relative increase in the sum of measurable target lesions' longest dimensions relative to the smallest sum at baseline or on study or the appearance of new lesions or unequivocal progression of existing non-target lesions.</description>
        <time_frame>Tumor measurements were done at 8 and 16 weeks after initiating treatment and then every 12 weeks and compared with baseline measurements prior to treatment. Measurements are continued until disease progression is documented or death.</time_frame>
        <population>Eligible Patients</population>
        <group_list>
          <group group_id="O1">
            <title>Everolimus and Letrozole</title>
            <description>Everolimus 10 mg daily plus letrozole 2.5 mg PO daily in a 28 day cycle.</description>
          </group>
          <group group_id="O2">
            <title>Tamoxifen and Medroxyprogesterone Acetate</title>
            <description>Tamoxifen 20 mg PO bid days 1-28 plus medroxyprogesterone acetate 200 mg PO days 8-14 and 22-28 repeating in a 28 day cycle.</description>
          </group>
        </group_list>
        <measure>
          <title>Median Progression-free Survival</title>
          <description>Progression-free Survival is defined as the duration alive from study entry until progression is documented, or death; whichever comes sooner. Progressive disease is defined as at least a 5 mm absolute increase and a 20% relative increase in the sum of measurable target lesions' longest dimensions relative to the smallest sum at baseline or on study or the appearance of new lesions or unequivocal progression of existing non-target lesions.</description>
          <population>Eligible Patients</population>
          <units>months</units>
          <param>Median</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="37"/>
                <count group_id="O2" value="37"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="6.4" lower_limit="3.8" upper_limit="17.7"/>
                    <measurement group_id="O2" value="3.7" lower_limit="2.5" upper_limit="8.9"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Frequency and Severity of CTCAE (Common Toxicity Criteria for Adverse Events) Version 4</title>
        <description>Maximum grade of physician assessed adverse events graded and categorized using Common Toxicity Criteria for Adverse Events (CTCAE) version 4</description>
        <time_frame>Assessed throughout the treatment period and for 30 days after discontinuation of treatment. Treatment continues until progression of disease.</time_frame>
        <population>Eligible and Treated Patients</population>
        <group_list>
          <group group_id="O1">
            <title>Everolimus and Letrozole</title>
            <description>Everolimus 10 mg daily plus letrozole 2.5 mg PO daily in a 28 day cycle.</description>
          </group>
          <group group_id="O2">
            <title>Tamoxifen and Medroxyprogesterone Acetate</title>
            <description>Tamoxifen 20 mg PO bid days 1-28 plus medroxyprogesterone acetate 200 mg PO days 8-14 and 22-28 repeating in a 28 day cycle.</description>
          </group>
        </group_list>
        <measure>
          <title>Frequency and Severity of CTCAE (Common Toxicity Criteria for Adverse Events) Version 4</title>
          <description>Maximum grade of physician assessed adverse events graded and categorized using Common Toxicity Criteria for Adverse Events (CTCAE) version 4</description>
          <population>Eligible and Treated Patients</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="37"/>
                <count group_id="O2" value="36"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Grade 1</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2"/>
                    <measurement group_id="O2" value="2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Grade 2</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="6"/>
                    <measurement group_id="O2" value="14"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Grade 3</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="27"/>
                    <measurement group_id="O2" value="17"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Grade 4</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2"/>
                    <measurement group_id="O2" value="2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Grade 5</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Median Survival</title>
        <description>Survival is defined as the duration alive from study entry until death.</description>
        <time_frame>Following treatment discontinuation, patients are followed quarterly for 2 years, semi-annually for 3 more years, annually thereafter.</time_frame>
        <population>Eligible patients</population>
        <group_list>
          <group group_id="O1">
            <title>Everolimus and Letrozole</title>
            <description>Everolimus 10 mg daily plus letrozole 2.5 mg PO daily in a 28 day cycle.</description>
          </group>
          <group group_id="O2">
            <title>Tamoxifen and Medroxyprogesterone Acetate</title>
            <description>Tamoxifen 20 mg PO bid days 1-28 plus medroxyprogesterone acetate 200 mg PO days 8-14 and 22-28 repeating in a 28 day cycle.</description>
          </group>
        </group_list>
        <measure>
          <title>Median Survival</title>
          <description>Survival is defined as the duration alive from study entry until death.</description>
          <population>Eligible patients</population>
          <units>Months</units>
          <param>Median</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="37"/>
                <count group_id="O2" value="37"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="NA" lower_limit="14.2" upper_limit="NA">No upper limit or median estimate can be provided as the median survival time has not been reached.</measurement>
                    <measurement group_id="O2" value="16.6" lower_limit="7.6" upper_limit="NA">No upper limit or median estimate can be provided as the median survival time has not been reached.</measurement>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Other Pre-specified</type>
        <title>Hormone Receptor Immunohistochemistry</title>
        <description>To determine if relevant biomarkers correlate with response to treatment in each of the two arms. Unstained sections of tumor tissue will be used for hormone receptor (estrogen receptor-alpha, estrogen receptor-beta, progesterone receptor-A, progesterone receptor B and the G protein-coupled estrogen receptor, GPR-30) immunohistochemistry.</description>
        <time_frame>At study entry</time_frame>
      </outcome>
      <outcome>
        <type>Other Pre-specified</type>
        <title>mTOR Pathway Immunohistochemistry</title>
        <description>To determine if relevant biomarkers correlate with response to treatment in each of the two arms. Unstained sections of tumor tissue will be used for mTOR pathway (including phosphorylated S6 ribosomal protein, PTEN, total and phosphorylated AKT, total and phosphorylated mTOR, and phospho-ERK1/2) immunohistochemistry</description>
        <time_frame>At study entry</time_frame>
      </outcome>
      <outcome>
        <type>Other Pre-specified</type>
        <title>Mutation Analysis</title>
        <description>To determine if relevant biomarkers correlate with response to treatment in each of the two arms. Unstained sections of tumor tissue and DNA extracted from whole blood will be used for mutational analysis (including PTEN, PIK3CA, KRAS, and CTNNB1 (beta-catenin) performed using a sequencing panel assay.</description>
        <time_frame>At study entry</time_frame>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>up to 30 days after the last cycle.</time_frame>
      <desc>Collected on a 28 day cycle while treatment continues and then up to 30 days after the last cycle.</desc>
      <group_list>
        <group group_id="E1">
          <title>Everolimus and Letrozole</title>
          <description>Everolimus 10 mg daily plus letrozole 2.5 mg PO daily in a 28 day cycle.</description>
        </group>
        <group group_id="E2">
          <title>Tamoxifen and Medroxyprogesterone Acetate</title>
          <description>Tamoxifen 20 mg PO bid days 1-28 plus medroxyprogesterone acetate 200 mg PO days 8-14 and 22-28 repeating in a 28 day cycle.</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, all-cause mortality</sub_title>
                <counts group_id="E1" subjects_affected="13" subjects_at_risk="37"/>
                <counts group_id="E2" subjects_affected="20" subjects_at_risk="36"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="13" subjects_at_risk="37"/>
                <counts group_id="E2" subjects_affected="10" subjects_at_risk="36"/>
              </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="0" subjects_at_risk="37"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="36"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Cardiac disorders</title>
            <event_list>
              <event>
                <sub_title>Pericardial Effusion</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="37"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="36"/>
              </event>
              <event>
                <sub_title>Supraventricular Tachycardia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="37"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="36"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Ascites</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="37"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="36"/>
              </event>
              <event>
                <sub_title>Diarrhea</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="37"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="36"/>
              </event>
              <event>
                <sub_title>Ileus</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="37"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="36"/>
              </event>
              <event>
                <sub_title>Nausea</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="37"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="36"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Fever</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="37"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="36"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Hepatobiliary disorders</title>
            <event_list>
              <event>
                <sub_title>Cholecystitis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="37"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="36"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Kidney Infection</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="37"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="36"/>
              </event>
              <event>
                <sub_title>Lung Infection</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="37"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="36"/>
              </event>
              <event>
                <sub_title>Sepsis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="37"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="36"/>
              </event>
              <event>
                <sub_title>Urinary Tract Infection</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="37"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="36"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Investigations</title>
            <event_list>
              <event>
                <sub_title>Creatinine Increased</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="37"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="36"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Musculoskeletal and connective tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Back Pain</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="37"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="36"/>
              </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 (including cysts and polyps)</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="37"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="36"/>
              </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="37"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="36"/>
              </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="0" subjects_at_risk="37"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="36"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Pleural Effusion</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="37"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="36"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Skin and subcutaneous tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Skin and Subcutaneous Tissue Disorder</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="37"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="36"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Vascular disorders</title>
            <event_list>
              <event>
                <sub_title>Thromboembolic Event</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="37"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="36"/>
              </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="37" subjects_at_risk="37"/>
                <counts group_id="E2" subjects_affected="36" subjects_at_risk="36"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Blood and lymphatic system disorders</title>
            <event_list>
              <event>
                <sub_title>Blood And Lymphatic System Disorders - Other</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="37"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="36"/>
              </event>
              <event>
                <sub_title>Anemia</sub_title>
                <counts group_id="E1" subjects_affected="25" subjects_at_risk="37"/>
                <counts group_id="E2" subjects_affected="20" subjects_at_risk="36"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Cardiac disorders</title>
            <event_list>
              <event>
                <sub_title>Atrial Fibrillation</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="37"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="36"/>
              </event>
              <event>
                <sub_title>Supraventricular Tachycardia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="37"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="36"/>
              </event>
              <event>
                <sub_title>Palpitations</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="37"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="36"/>
              </event>
              <event>
                <sub_title>Heart Failure</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="37"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="36"/>
              </event>
              <event>
                <sub_title>Cardiac Disorders - Other</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="37"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="36"/>
              </event>
              <event>
                <sub_title>Pericardial Effusion</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="37"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="36"/>
              </event>
              <event>
                <sub_title>Sinus Tachycardia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="37"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="36"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Ear and labyrinth disorders</title>
            <event_list>
              <event>
                <sub_title>Vertigo</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="37"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="36"/>
              </event>
              <event>
                <sub_title>Tinnitus</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="37"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="36"/>
              </event>
              <event>
                <sub_title>Hearing Impaired</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="37"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="36"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Endocrine disorders</title>
            <event_list>
              <event>
                <sub_title>Hyperthyroidism</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="37"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="36"/>
              </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="1" subjects_at_risk="37"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="36"/>
              </event>
              <event>
                <sub_title>Blurred Vision</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="37"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="36"/>
              </event>
              <event>
                <sub_title>Vitreous Hemorrhage</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="37"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="36"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Dysphagia</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="37"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="36"/>
              </event>
              <event>
                <sub_title>Dyspepsia</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="37"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="36"/>
              </event>
              <event>
                <sub_title>Dry Mouth</sub_title>
                <counts group_id="E1" subjects_affected="5" subjects_at_risk="37"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="36"/>
              </event>
              <event>
                <sub_title>Constipation</sub_title>
                <counts group_id="E1" subjects_affected="13" subjects_at_risk="37"/>
                <counts group_id="E2" subjects_affected="12" subjects_at_risk="36"/>
              </event>
              <event>
                <sub_title>Diarrhea</sub_title>
                <counts group_id="E1" subjects_affected="18" subjects_at_risk="37"/>
                <counts group_id="E2" subjects_affected="7" subjects_at_risk="36"/>
              </event>
              <event>
                <sub_title>Cheilitis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="37"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="36"/>
              </event>
              <event>
                <sub_title>Vomiting</sub_title>
                <counts group_id="E1" subjects_affected="9" subjects_at_risk="37"/>
                <counts group_id="E2" subjects_affected="5" subjects_at_risk="36"/>
              </event>
              <event>
                <sub_title>Bloating</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="37"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="36"/>
              </event>
              <event>
                <sub_title>Stomach Pain</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="37"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="36"/>
              </event>
              <event>
                <sub_title>Salivary Duct Inflammation</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="37"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="36"/>
              </event>
              <event>
                <sub_title>Rectal Mucositis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="37"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="36"/>
              </event>
              <event>
                <sub_title>Abdominal Pain</sub_title>
                <counts group_id="E1" subjects_affected="7" subjects_at_risk="37"/>
                <counts group_id="E2" subjects_affected="9" subjects_at_risk="36"/>
              </event>
              <event>
                <sub_title>Proctitis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="37"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="36"/>
              </event>
              <event>
                <sub_title>Rectal Hemorrhage</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="37"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="36"/>
              </event>
              <event>
                <sub_title>Mucositis Oral</sub_title>
                <counts group_id="E1" subjects_affected="24" subjects_at_risk="37"/>
                <counts group_id="E2" subjects_affected="4" subjects_at_risk="36"/>
              </event>
              <event>
                <sub_title>Gastrointestinal Disorders - Other</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="37"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="36"/>
              </event>
              <event>
                <sub_title>Oral Hemorrhage</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="37"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="36"/>
              </event>
              <event>
                <sub_title>Ileus</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="37"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="36"/>
              </event>
              <event>
                <sub_title>Gastrointestinal Pain</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="37"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="36"/>
              </event>
              <event>
                <sub_title>Oral Pain</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="37"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="36"/>
              </event>
              <event>
                <sub_title>Abdominal Distension</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="37"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="36"/>
              </event>
              <event>
                <sub_title>Nausea</sub_title>
                <counts group_id="E1" subjects_affected="19" subjects_at_risk="37"/>
                <counts group_id="E2" subjects_affected="12" subjects_at_risk="36"/>
              </event>
              <event>
                <sub_title>Gastroesophageal Reflux Disease</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="37"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="36"/>
              </event>
              <event>
                <sub_title>Lip Pain</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="37"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="36"/>
              </event>
              <event>
                <sub_title>Fecal Incontinence</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="37"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="36"/>
              </event>
              <event>
                <sub_title>Hemorrhoids</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="37"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="36"/>
              </event>
              <event>
                <sub_title>Ascites</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="37"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="36"/>
              </event>
              <event>
                <sub_title>Toothache</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="37"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="36"/>
              </event>
              <event>
                <sub_title>Flatulence</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="37"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="36"/>
              </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="0" subjects_at_risk="37"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="36"/>
              </event>
              <event>
                <sub_title>Pain</sub_title>
                <counts group_id="E1" subjects_affected="10" subjects_at_risk="37"/>
                <counts group_id="E2" subjects_affected="6" subjects_at_risk="36"/>
              </event>
              <event>
                <sub_title>Malaise</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="37"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="36"/>
              </event>
              <event>
                <sub_title>Localized Edema</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="37"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="36"/>
              </event>
              <event>
                <sub_title>Flu Like Symptoms</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="37"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="36"/>
              </event>
              <event>
                <sub_title>Non-Cardiac Chest Pain</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="37"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="36"/>
              </event>
              <event>
                <sub_title>Edema Limbs</sub_title>
                <counts group_id="E1" subjects_affected="15" subjects_at_risk="37"/>
                <counts group_id="E2" subjects_affected="9" subjects_at_risk="36"/>
              </event>
              <event>
                <sub_title>Edema Face</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="37"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="36"/>
              </event>
              <event>
                <sub_title>Fatigue</sub_title>
                <counts group_id="E1" subjects_affected="22" subjects_at_risk="37"/>
                <counts group_id="E2" subjects_affected="15" subjects_at_risk="36"/>
              </event>
              <event>
                <sub_title>Fever</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="37"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="36"/>
              </event>
              <event>
                <sub_title>Chills</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="37"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="36"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Hepatobiliary disorders</title>
            <event_list>
              <event>
                <sub_title>Portal Vein Thrombosis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="37"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="36"/>
              </event>
              <event>
                <sub_title>Cholecystitis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="37"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="36"/>
              </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="1" subjects_at_risk="37"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="36"/>
              </event>
              <event>
                <sub_title>Wound Infection</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="37"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="36"/>
              </event>
              <event>
                <sub_title>Upper Respiratory Infection</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="37"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="36"/>
              </event>
              <event>
                <sub_title>Tooth Infection</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="37"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="36"/>
              </event>
              <event>
                <sub_title>Vulval Infection</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="37"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="36"/>
              </event>
              <event>
                <sub_title>Skin Infection</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="37"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="36"/>
              </event>
              <event>
                <sub_title>Sinusitis</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="37"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="36"/>
              </event>
              <event>
                <sub_title>Sepsis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="37"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="36"/>
              </event>
              <event>
                <sub_title>Otitis Media</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="37"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="36"/>
              </event>
              <event>
                <sub_title>Papulopustular Rash</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="37"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="36"/>
              </event>
              <event>
                <sub_title>Nail Infection</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="37"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="36"/>
              </event>
              <event>
                <sub_title>Mucosal Infection</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="37"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="36"/>
              </event>
              <event>
                <sub_title>Lung Infection</sub_title>
                <counts group_id="E1" subjects_affected="5" subjects_at_risk="37"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="36"/>
              </event>
              <event>
                <sub_title>Kidney Infection</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="37"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="36"/>
              </event>
              <event>
                <sub_title>Eye Infection</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="37"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="36"/>
              </event>
              <event>
                <sub_title>Vaginal Infection</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="37"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="36"/>
              </event>
              <event>
                <sub_title>Urinary Tract Infection</sub_title>
                <counts group_id="E1" subjects_affected="6" subjects_at_risk="37"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="36"/>
              </event>
              <event>
                <sub_title>Bronchial Infection</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="37"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="36"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Injury, poisoning and procedural complications</title>
            <event_list>
              <event>
                <sub_title>Wrist Fracture</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="37"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="36"/>
              </event>
              <event>
                <sub_title>Fracture</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="37"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="36"/>
              </event>
              <event>
                <sub_title>Fall</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="37"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="36"/>
              </event>
              <event>
                <sub_title>Burn</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="37"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="36"/>
              </event>
              <event>
                <sub_title>Bruising</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="37"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="36"/>
              </event>
              <event>
                <sub_title>Ankle Fracture</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="37"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="36"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Investigations</title>
            <event_list>
              <event>
                <sub_title>Investigations - Other</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="37"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="36"/>
              </event>
              <event>
                <sub_title>Weight Loss</sub_title>
                <counts group_id="E1" subjects_affected="7" subjects_at_risk="37"/>
                <counts group_id="E2" subjects_affected="5" subjects_at_risk="36"/>
              </event>
              <event>
                <sub_title>Weight Gain</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="37"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="36"/>
              </event>
              <event>
                <sub_title>Platelet Count Decreased</sub_title>
                <counts group_id="E1" subjects_affected="15" subjects_at_risk="37"/>
                <counts group_id="E2" subjects_affected="4" subjects_at_risk="36"/>
              </event>
              <event>
                <sub_title>Lymphocyte Count Decreased</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="37"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="36"/>
              </event>
              <event>
                <sub_title>Lipase Increased</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="37"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="36"/>
              </event>
              <event>
                <sub_title>Inr Increased</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="37"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="36"/>
              </event>
              <event>
                <sub_title>Creatinine Increased</sub_title>
                <counts group_id="E1" subjects_affected="6" subjects_at_risk="37"/>
                <counts group_id="E2" subjects_affected="8" subjects_at_risk="36"/>
              </event>
              <event>
                <sub_title>Cholesterol High</sub_title>
                <counts group_id="E1" subjects_affected="16" subjects_at_risk="37"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="36"/>
              </event>
              <event>
                <sub_title>Neutrophil Count Decreased</sub_title>
                <counts group_id="E1" subjects_affected="12" subjects_at_risk="37"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="36"/>
              </event>
              <event>
                <sub_title>Cd4 Lymphocytes Decreased</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="37"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="36"/>
              </event>
              <event>
                <sub_title>Blood Bilirubin Increased</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="37"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="36"/>
              </event>
              <event>
                <sub_title>White Blood Cell Decreased</sub_title>
                <counts group_id="E1" subjects_affected="17" subjects_at_risk="37"/>
                <counts group_id="E2" subjects_affected="4" subjects_at_risk="36"/>
              </event>
              <event>
                <sub_title>Aspartate Aminotransferase Increased</sub_title>
                <counts group_id="E1" subjects_affected="14" subjects_at_risk="37"/>
                <counts group_id="E2" subjects_affected="8" subjects_at_risk="36"/>
              </event>
              <event>
                <sub_title>Alkaline Phosphatase Increased</sub_title>
                <counts group_id="E1" subjects_affected="7" subjects_at_risk="37"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="36"/>
              </event>
              <event>
                <sub_title>Alanine Aminotransferase Increased</sub_title>
                <counts group_id="E1" subjects_affected="11" subjects_at_risk="37"/>
                <counts group_id="E2" subjects_affected="9" subjects_at_risk="36"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Metabolism and nutrition disorders</title>
            <event_list>
              <event>
                <sub_title>Hypophosphatemia</sub_title>
                <counts group_id="E1" subjects_affected="5" subjects_at_risk="37"/>
                <counts group_id="E2" subjects_affected="7" subjects_at_risk="36"/>
              </event>
              <event>
                <sub_title>Hyponatremia</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="37"/>
                <counts group_id="E2" subjects_affected="5" subjects_at_risk="36"/>
              </event>
              <event>
                <sub_title>Hypomagnesemia</sub_title>
                <counts group_id="E1" subjects_affected="8" subjects_at_risk="37"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="36"/>
              </event>
              <event>
                <sub_title>Hypokalemia</sub_title>
                <counts group_id="E1" subjects_affected="13" subjects_at_risk="37"/>
                <counts group_id="E2" subjects_affected="8" subjects_at_risk="36"/>
              </event>
              <event>
                <sub_title>Hypoglycemia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="37"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="36"/>
              </event>
              <event>
                <sub_title>Hypocalcemia</sub_title>
                <counts group_id="E1" subjects_affected="8" subjects_at_risk="37"/>
                <counts group_id="E2" subjects_affected="9" subjects_at_risk="36"/>
              </event>
              <event>
                <sub_title>Hypoalbuminemia</sub_title>
                <counts group_id="E1" subjects_affected="16" subjects_at_risk="37"/>
                <counts group_id="E2" subjects_affected="12" subjects_at_risk="36"/>
              </event>
              <event>
                <sub_title>Hypertriglyceridemia</sub_title>
                <counts group_id="E1" subjects_affected="20" subjects_at_risk="37"/>
                <counts group_id="E2" subjects_affected="8" subjects_at_risk="36"/>
              </event>
              <event>
                <sub_title>Hypernatremia</sub_title>
                <counts group_id="E1" subjects_affected="5" subjects_at_risk="37"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="36"/>
              </event>
              <event>
                <sub_title>Hypermagnesemia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="37"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="36"/>
              </event>
              <event>
                <sub_title>Hyperkalemia</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="37"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="36"/>
              </event>
              <event>
                <sub_title>Hyperglycemia</sub_title>
                <counts group_id="E1" subjects_affected="23" subjects_at_risk="37"/>
                <counts group_id="E2" subjects_affected="11" subjects_at_risk="36"/>
              </event>
              <event>
                <sub_title>Hypercalcemia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="37"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="36"/>
              </event>
              <event>
                <sub_title>Dehydration</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="37"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="36"/>
              </event>
              <event>
                <sub_title>Anorexia</sub_title>
                <counts group_id="E1" subjects_affected="13" subjects_at_risk="37"/>
                <counts group_id="E2" subjects_affected="8" subjects_at_risk="36"/>
              </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="8" subjects_at_risk="37"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="36"/>
              </event>
              <event>
                <sub_title>Osteoporosis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="37"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="36"/>
              </event>
              <event>
                <sub_title>Neck Pain</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="37"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="36"/>
              </event>
              <event>
                <sub_title>Myalgia</sub_title>
                <counts group_id="E1" subjects_affected="8" subjects_at_risk="37"/>
                <counts group_id="E2" subjects_affected="4" subjects_at_risk="36"/>
              </event>
              <event>
                <sub_title>Muscle Weakness Lower Limb</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="37"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="36"/>
              </event>
              <event>
                <sub_title>Generalized Muscle Weakness</sub_title>
                <counts group_id="E1" subjects_affected="5" subjects_at_risk="37"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="36"/>
              </event>
              <event>
                <sub_title>Trismus</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="37"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="36"/>
              </event>
              <event>
                <sub_title>Bone Pain</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="37"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="36"/>
              </event>
              <event>
                <sub_title>Back Pain</sub_title>
                <counts group_id="E1" subjects_affected="7" subjects_at_risk="37"/>
                <counts group_id="E2" subjects_affected="4" subjects_at_risk="36"/>
              </event>
              <event>
                <sub_title>Arthritis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="37"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="36"/>
              </event>
              <event>
                <sub_title>Arthralgia</sub_title>
                <counts group_id="E1" subjects_affected="8" subjects_at_risk="37"/>
                <counts group_id="E2" subjects_affected="5" subjects_at_risk="36"/>
              </event>
              <event>
                <sub_title>Musculoskeletal And Connective Tissue Disorder -</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="37"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="36"/>
              </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="1" subjects_at_risk="37"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="36"/>
              </event>
              <event>
                <sub_title>Tumor Pain</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="37"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="36"/>
              </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="1" subjects_at_risk="37"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="36"/>
              </event>
              <event>
                <sub_title>Tremor</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="37"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="36"/>
              </event>
              <event>
                <sub_title>Stroke</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="37"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="36"/>
              </event>
              <event>
                <sub_title>Peripheral Sensory Neuropathy</sub_title>
                <counts group_id="E1" subjects_affected="7" subjects_at_risk="37"/>
                <counts group_id="E2" subjects_affected="5" subjects_at_risk="36"/>
              </event>
              <event>
                <sub_title>Paresthesia</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="37"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="36"/>
              </event>
              <event>
                <sub_title>Memory Impairment</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="37"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="36"/>
              </event>
              <event>
                <sub_title>Lethargy</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="37"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="36"/>
              </event>
              <event>
                <sub_title>Headache</sub_title>
                <counts group_id="E1" subjects_affected="15" subjects_at_risk="37"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="36"/>
              </event>
              <event>
                <sub_title>Dysgeusia</sub_title>
                <counts group_id="E1" subjects_affected="8" subjects_at_risk="37"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="36"/>
              </event>
              <event>
                <sub_title>Syncope</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="37"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="36"/>
              </event>
              <event>
                <sub_title>Dizziness</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="37"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="36"/>
              </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="1" subjects_at_risk="37"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="36"/>
              </event>
              <event>
                <sub_title>Suicidal Ideation</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="37"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="36"/>
              </event>
              <event>
                <sub_title>Restlessness</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="37"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="36"/>
              </event>
              <event>
                <sub_title>Insomnia</sub_title>
                <counts group_id="E1" subjects_affected="9" subjects_at_risk="37"/>
                <counts group_id="E2" subjects_affected="4" subjects_at_risk="36"/>
              </event>
              <event>
                <sub_title>Hallucinations</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="37"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="36"/>
              </event>
              <event>
                <sub_title>Depression</sub_title>
                <counts group_id="E1" subjects_affected="8" subjects_at_risk="37"/>
                <counts group_id="E2" subjects_affected="4" subjects_at_risk="36"/>
              </event>
              <event>
                <sub_title>Delirium</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="37"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="36"/>
              </event>
              <event>
                <sub_title>Confusion</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="37"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="36"/>
              </event>
              <event>
                <sub_title>Anxiety</sub_title>
                <counts group_id="E1" subjects_affected="5" subjects_at_risk="37"/>
                <counts group_id="E2" subjects_affected="4" subjects_at_risk="36"/>
              </event>
              <event>
                <sub_title>Agitation</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="37"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="36"/>
              </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="0" subjects_at_risk="37"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="36"/>
              </event>
              <event>
                <sub_title>Urinary Urgency</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="37"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="36"/>
              </event>
              <event>
                <sub_title>Urinary Tract Obstruction</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="37"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="36"/>
              </event>
              <event>
                <sub_title>Urinary Retention</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="37"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="36"/>
              </event>
              <event>
                <sub_title>Urinary Incontinence</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="37"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="36"/>
              </event>
              <event>
                <sub_title>Urinary Tract Pain</sub_title>
                <counts group_id="E1" subjects_affected="5" subjects_at_risk="37"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="36"/>
              </event>
              <event>
                <sub_title>Urinary Frequency</sub_title>
                <counts group_id="E1" subjects_affected="6" subjects_at_risk="37"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="36"/>
              </event>
              <event>
                <sub_title>Renal Calculi</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="37"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="36"/>
              </event>
              <event>
                <sub_title>Proteinuria</sub_title>
                <counts group_id="E1" subjects_affected="7" subjects_at_risk="37"/>
                <counts group_id="E2" subjects_affected="5" subjects_at_risk="36"/>
              </event>
              <event>
                <sub_title>Hematuria</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="37"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="36"/>
              </event>
              <event>
                <sub_title>Acute Kidney Injury</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="37"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="36"/>
              </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="37"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="36"/>
              </event>
              <event>
                <sub_title>Vaginal Pain</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="37"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="36"/>
              </event>
              <event>
                <sub_title>Vaginal Hemorrhage</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="37"/>
                <counts group_id="E2" subjects_affected="6" subjects_at_risk="36"/>
              </event>
              <event>
                <sub_title>Perineal Pain</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="37"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="36"/>
              </event>
              <event>
                <sub_title>Pelvic Pain</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="37"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="36"/>
              </event>
              <event>
                <sub_title>Vaginal Discharge</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="37"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="36"/>
              </event>
              <event>
                <sub_title>Breast Pain</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="37"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="36"/>
              </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="37"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="36"/>
              </event>
              <event>
                <sub_title>Sore Throat</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="37"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="36"/>
              </event>
              <event>
                <sub_title>Pulmonary Edema</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="37"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="36"/>
              </event>
              <event>
                <sub_title>Postnasal Drip</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="37"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="36"/>
              </event>
              <event>
                <sub_title>Pneumothorax</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="37"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="36"/>
              </event>
              <event>
                <sub_title>Pneumonitis</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="37"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="36"/>
              </event>
              <event>
                <sub_title>Pleural Effusion</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="37"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="36"/>
              </event>
              <event>
                <sub_title>Nasal Congestion</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="37"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="36"/>
              </event>
              <event>
                <sub_title>Pleuritic Pain</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="37"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="36"/>
              </event>
              <event>
                <sub_title>Productive Cough</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="37"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="36"/>
              </event>
              <event>
                <sub_title>Hypoxia</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="37"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="36"/>
              </event>
              <event>
                <sub_title>Epistaxis</sub_title>
                <counts group_id="E1" subjects_affected="11" subjects_at_risk="37"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="36"/>
              </event>
              <event>
                <sub_title>Dyspnea</sub_title>
                <counts group_id="E1" subjects_affected="15" subjects_at_risk="37"/>
                <counts group_id="E2" subjects_affected="11" subjects_at_risk="36"/>
              </event>
              <event>
                <sub_title>Cough</sub_title>
                <counts group_id="E1" subjects_affected="18" subjects_at_risk="37"/>
                <counts group_id="E2" subjects_affected="7" subjects_at_risk="36"/>
              </event>
              <event>
                <sub_title>Allergic Rhinitis</sub_title>
                <counts group_id="E1" subjects_affected="6" subjects_at_risk="37"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="36"/>
              </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="2" subjects_at_risk="37"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="36"/>
              </event>
              <event>
                <sub_title>Rash Acneiform</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="37"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="36"/>
              </event>
              <event>
                <sub_title>Pruritus</sub_title>
                <counts group_id="E1" subjects_affected="7" subjects_at_risk="37"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="36"/>
              </event>
              <event>
                <sub_title>Periorbital Edema</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="37"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="36"/>
              </event>
              <event>
                <sub_title>Pain Of Skin</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="37"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="36"/>
              </event>
              <event>
                <sub_title>Rash Maculo-Papular</sub_title>
                <counts group_id="E1" subjects_affected="8" subjects_at_risk="37"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="36"/>
              </event>
              <event>
                <sub_title>Nail Ridging</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="37"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="36"/>
              </event>
              <event>
                <sub_title>Nail Discoloration</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="37"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="36"/>
              </event>
              <event>
                <sub_title>Dry Skin</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="37"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="36"/>
              </event>
              <event>
                <sub_title>Alopecia</sub_title>
                <counts group_id="E1" subjects_affected="8" subjects_at_risk="37"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="36"/>
              </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="37"/>
                <counts group_id="E2" subjects_affected="5" subjects_at_risk="36"/>
              </event>
              <event>
                <sub_title>Lymphedema</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="37"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="36"/>
              </event>
              <event>
                <sub_title>Hypertension</sub_title>
                <counts group_id="E1" subjects_affected="13" subjects_at_risk="37"/>
                <counts group_id="E2" subjects_affected="8" subjects_at_risk="36"/>
              </event>
              <event>
                <sub_title>Hot Flashes</sub_title>
                <counts group_id="E1" subjects_affected="9" subjects_at_risk="37"/>
                <counts group_id="E2" subjects_affected="8" subjects_at_risk="36"/>
              </event>
              <event>
                <sub_title>Flushing</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="37"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="36"/>
              </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>The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.</restrictive_agreement>
    </certain_agreements>
    <point_of_contact>
      <name_or_title>Linda Gedeon for Virginia Filiaci, PhD</name_or_title>
      <organization>GOG Foundation</organization>
      <phone>716-845-1169</phone>
      <email>lgedeon@gogstats.org</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/NCT02228681
org study id: GOG-3007
secondary id: CRAD001CUS236T
nct id: NCT02228681
lead sponsor: 
collaborator: 
has dmc: No
The main purpose of this study is to evaluate the effectiveness of the combination of the
      drugs Everolimus and Letrozole compared to Tamoxifen and Medroxyprogesterone acetate in
      treating endometrial cancer and to determine the types and severity of side effects caused by
      treatment with these drug combinations.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Frequency of Response
time frame: From date of randomization until the date of first documented progression or date of death , up to 3 years.
description: A confirmed complete or partial response as defined by RECIST 1.1 was considered a response. "Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR
measure: Median Progression-free Survival
time frame: Tumor measurements were done at 8 and 16 weeks after initiating treatment and then every 12 weeks and compared with baseline measurements prior to treatment. Measurements are continued until disease progression is documented or death.
description: Progression-free Survival is defined as the duration alive from study entry until progression is documented, or death; whichever comes sooner. Progressive disease is defined as at least a 5 mm absolute increase and a 20% relative increase in the sum of measurable target lesions' longest dimensions relative to the smallest sum at baseline or on study or the appearance of new lesions or unequivocal progression of existing non-target lesions.
measure: Frequency and Severity of CTCAE (Common Toxicity Criteria for Adverse Events) Version 4
time frame: Assessed throughout the treatment period and for 30 days after discontinuation of treatment. Treatment continues until progression of disease.
description: Maximum grade of physician assessed adverse events graded and categorized using Common Toxicity Criteria for Adverse Events (CTCAE) version 4
measure: Median Survival
time frame: Following treatment discontinuation, patients are followed quarterly for 2 years, semi-annually for 3 more years, annually thereafter.
description: Survival is defined as the duration alive from study entry until death.
measure: Hormone Receptor Immunohistochemistry
time frame: At study entry
description: To determine if relevant biomarkers correlate with response to treatment in each of the two arms. Unstained sections of tumor tissue will be used for hormone receptor (estrogen receptor-alpha, estrogen receptor-beta, progesterone receptor-A, progesterone receptor B and the G protein-coupled estrogen receptor, GPR-30) immunohistochemistry.
measure: mTOR Pathway Immunohistochemistry
time frame: At study entry
description: To determine if relevant biomarkers correlate with response to treatment in each of the two arms. Unstained sections of tumor tissue will be used for mTOR pathway (including phosphorylated S6 ribosomal protein, PTEN, total and phosphorylated AKT, total and phosphorylated mTOR, and phospho-ERK1/2) immunohistochemistry
measure: Mutation Analysis
time frame: At study entry
description: To determine if relevant biomarkers correlate with response to treatment in each of the two arms. Unstained sections of tumor tissue and DNA extracted from whole blood will be used for mutational analysis (including PTEN, PIK3CA, KRAS, and CTNNB1 (beta-catenin) performed using a sequencing panel assay.
arm group label: Everolimus and Letrozole
arm group type: Experimental
description: Everolimus 10 mg daily and Letrozole 2.5 mg PO daily
arm group label: Hormonal Therapy
arm group type: Active Comparator
description: Tamoxifen 20 mg PO BID; on alternating weeks (even numbered) weeks, Medroxyprogesterone Acetate 200 mg PO daily with Tamoxifen 20 mg PO BID
intervention type: Drug
intervention name: Everolimus
description: 10mg daily by mouth
arm group label: Everolimus and Letrozole
other name: RAD001
intervention type: Drug
intervention name: Tamoxifen
description: 20 mg daily by mouth on alternating weeks (even numbered) weeks
arm group label: Hormonal Therapy
other name: Nolvadex®
intervention type: Drug
intervention name: Letrozole
description: 2.5mg once a day by mouth
arm group label: Everolimus and Letrozole
other name: Femara®
intervention type: Drug
intervention name: Medroxyprogesterone Acetate
description: 200 mg daily by mouth
arm group label: Hormonal Therapy
criteria: 
gender: Female
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Brian Slomovitz, MD
role: Study Chair
affiliation: Gynecologic Oncology Group
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country: United States
responsible party type: Sponsor
mesh term: Endometrial Neoplasms
mesh term: Tamoxifen
mesh term: Everolimus
mesh term: Letrozole
mesh term: Medroxyprogesterone Acetate
mesh term: Medroxyprogesterone
provided document: 
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 