<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/NCT01727089</url>
  </required_header>
  <id_info>
    <org_study_id>NCI-2012-02206</org_study_id>
    <secondary_id>NCI-2012-02206</secondary_id>
    <secondary_id>PHII-121</secondary_id>
    <secondary_id>PhII-121</secondary_id>
    <secondary_id>9144</secondary_id>
    <secondary_id>N01CM00038</secondary_id>
    <secondary_id>N01CM00039</secondary_id>
    <secondary_id>N01CM00071</secondary_id>
    <secondary_id>N01CM00099</secondary_id>
    <secondary_id>P30CA033572</secondary_id>
    <nct_id>NCT01727089</nct_id>
  </id_info>
  <brief_title>Bevacizumab With or Without TRC105 in Treating Patients With Metastatic Kidney Cancer</brief_title>
  <official_title>A Phase II Study of Bevacizumab Alone or in Combination With TRC105 for Advanced Renal Cell Cancer</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>National Cancer Institute (NCI)</agency>
      <agency_class>NIH</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>National Cancer Institute (NCI)</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      This randomized phase II trial studies how well bevacizumab with or without anti-endoglin&#xD;
      monoclonal antibody TRC105 (TRC105) works in treating patients with kidney cancer that has&#xD;
      spread to other parts of the body (metastatic). Monoclonal antibodies, such as bevacizumab&#xD;
      and anti-endoglin monoclonal antibody TRC105, may block tumor growth in different ways by&#xD;
      targeting certain cells.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      PRIMARY OBJECTIVES:&#xD;
&#xD;
      I. To compare the progression-free survival at 12 and 24 weeks for bevacizumab alone or in&#xD;
      combination with TRC105 (anti-endoglin monoclonal antibody TRC105).&#xD;
&#xD;
      SECONDARY OBJECTIVES:&#xD;
&#xD;
      I. Toxicity and Response Evaluation Criteria in Solid Tumors (RECIST) response rate for the&#xD;
      combination compared to single agent bevacizumab.&#xD;
&#xD;
      TERTIARY OBJECTIVES:&#xD;
&#xD;
      I. To evaluate tumor tissue expression of endoglin (CD105), transforming growth factor, beta&#xD;
      receptor II (TGFBR2), activin A receptor type II-like 1 (ACVRL1) and transforming growth&#xD;
      factor, beta receptor 1 (TGFBR1) kinase from pre- and post-treatment tissue samples in order&#xD;
      to determine whether CD105 and stem cell activation occurs after exposure to anti-vascular&#xD;
      endothelial growth factor (VEGF) therapy as predicted by laboratory models, and whether&#xD;
      exposure to anti-endoglin monoclonal antibody TRC105 affects these changes.&#xD;
&#xD;
      II. To compare the soluble CD105 levels at baseline and after treatment between the group&#xD;
      receiving bevacizumab alone and the group receiving bevacizumab in combination with&#xD;
      anti-endoglin monoclonal antibody TRC105.&#xD;
&#xD;
      III. To compare TGFBR2 levels at baseline and after treatment between the group receiving&#xD;
      bevacizumab alone and the group receiving bevacizumab in combination with anti-endoglin&#xD;
      monoclonal antibody TRC105.&#xD;
&#xD;
      IV. To evaluate whether circulating tumor cells (CTCs) can be detected in this patient&#xD;
      population using parylene membrane filter technology, and whether changes in CTC counts and&#xD;
      CD105 expression on CTCs during therapy correspond to imaging and clinical response.&#xD;
&#xD;
      OUTLINE: Patients are randomized to 1 of 2 treatment arms.&#xD;
&#xD;
      ARM I: Patients receive bevacizumab intravenously (IV) over 30-90 minutes on days 1 and 15.&#xD;
&#xD;
      ARM II: Patients receive bevacizumab as in Arm I and anti-endoglin monoclonal antibody TRC105&#xD;
      IV over 1-4 hours on days 1, 8, 15, and 22.&#xD;
&#xD;
      In both arms, treatment repeats every 28 days for up to 12 courses in the absence of disease&#xD;
      progression or unacceptable toxicity.&#xD;
&#xD;
      After completion of study therapy, patients are followed up for 4 weeks.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">November 1, 2012</start_date>
  <completion_date type="Actual">August 8, 2017</completion_date>
  <primary_completion_date type="Actual">August 8, 2017</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>Progression-free Survival at 24 Weeks</measure>
    <time_frame>The duration of time from start of treatment to time of progression or death, assessed at 24 weeks</time_frame>
    <description>Progression-free survival 24 after starting treatment. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Progression-free Survival at 12 Weeks</measure>
    <time_frame>The duration of time from start of treatment to time of progression or death, assessed at 12 weeks</time_frame>
    <description>Progression-free survival 12 after starting treatment. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Number of Participants With Grade 3 and Above Adverse Events (AE) Related to Treatment</measure>
    <time_frame>From time of treatment initiation until 30 days post treatment, assessed every 4 weeks.</time_frame>
    <description>The descriptions and grading scales found in the revised National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0 will be utilized for AE reporting.&#xD;
Grade 1 - Mild; asymptomatic or mild symptoms; clinical or diagnostic observations only; intervention not indicated.&#xD;
Grade 2 - Moderate; minimal, local or noninvasive intervention indicated; limiting age-appropriate instrumental activities of daily living (ADL).&#xD;
Grade 3 - Severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; limiting self care ADL.&#xD;
Grade 4 - Life-threatening consequences; urgent intervention indicated. Grade 5 - Death related adverse event.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of Participants With Overall Response</measure>
    <time_frame>From time of treatment initiation until conclusion of treatment, assessed every 12 weeks.</time_frame>
    <description>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>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">59</enrollment>
  <condition>Clear Cell Renal Cell Carcinoma</condition>
  <condition>Recurrent Renal Cell Carcinoma</condition>
  <condition>Stage IV Renal Cell Cancer</condition>
  <condition>Type 1 Papillary Renal Cell Carcinoma</condition>
  <condition>Type 2 Papillary Renal Cell Carcinoma</condition>
  <arm_group>
    <arm_group_label>Arm I (bevacizumab)</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Patients receive bevacizumab IV over 30-90 minutes on days 1 and 15. Treatment repeats every 28 days for up to 12 courses in the absence of disease progression or unacceptable toxicity.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Arm II (bevacizumab, anti-endoglin monoclonal antibody TRC105)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Patients receive bevacizumab as in Arm I and anti-endoglin monoclonal antibody TRC105 IV over 1-4 hours on days 1, 8, 15, and 22. Treatment repeats every 28 days for up to 12 courses in the absence of disease progression or unacceptable toxicity.</description>
  </arm_group>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>Anti-Endoglin Chimeric Monoclonal Antibody TRC105</intervention_name>
    <description>Given IV</description>
    <arm_group_label>Arm II (bevacizumab, anti-endoglin monoclonal antibody TRC105)</arm_group_label>
    <other_name>TRC105</other_name>
  </intervention>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>Bevacizumab</intervention_name>
    <description>Given IV</description>
    <arm_group_label>Arm I (bevacizumab)</arm_group_label>
    <arm_group_label>Arm II (bevacizumab, anti-endoglin monoclonal antibody TRC105)</arm_group_label>
    <other_name>Anti-VEGF</other_name>
    <other_name>Anti-VEGF Humanized Monoclonal Antibody</other_name>
    <other_name>Anti-VEGF rhuMAb</other_name>
    <other_name>Avastin</other_name>
    <other_name>Bevacizumab Biosimilar BEVZ92</other_name>
    <other_name>Bevacizumab Biosimilar BI 695502</other_name>
    <other_name>Bevacizumab Biosimilar CBT 124</other_name>
    <other_name>Bevacizumab Biosimilar FKB238</other_name>
    <other_name>Immunoglobulin G1 (Human-Mouse Monoclonal rhuMab-VEGF Gamma-Chain Anti-Human Vascular Endothelial Growth Factor), Disulfide With Human-Mouse Monoclonal rhuMab-VEGF Light Chain, Dimer</other_name>
    <other_name>Recombinant Humanized Anti-VEGF Monoclonal Antibody</other_name>
    <other_name>rhuMab-VEGF</other_name>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Laboratory Biomarker Analysis</intervention_name>
    <description>Correlative studies</description>
    <arm_group_label>Arm I (bevacizumab)</arm_group_label>
    <arm_group_label>Arm II (bevacizumab, anti-endoglin monoclonal antibody TRC105)</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Pharmacological Study</intervention_name>
    <description>Correlative studies</description>
    <arm_group_label>Arm II (bevacizumab, anti-endoglin monoclonal antibody TRC105)</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Patients must have histologically or cytologically confirmed renal cancer; all&#xD;
             histologic subtypes will be eligible&#xD;
&#xD;
          -  Patients must have metastatic disease which is measurable, defined as at least one&#xD;
             lesion that can be accurately measured in at least one dimension (longest diameter to&#xD;
             be recorded for non-nodal lesions and short axis for nodal lesions) to &gt;= 20 mm in the&#xD;
             long axis by chest x-ray, &gt;= 10 mm in the long axis by spiral computed tomography&#xD;
             (CT), magnetic resonance imaging (MRI), calipers, or clinical exam, or &gt;= 15 mm in the&#xD;
             short axis for lymph nodes&#xD;
&#xD;
          -  Patients must have received at least 1 prior systemic therapy for renal cancer but no&#xD;
             more than 4 prior therapies; they must have documented intolerance to or progression&#xD;
             despite at least 1 systemic therapy; therapy administered in the adjuvant setting&#xD;
             counts toward the prior systemic therapy total; if adjuvant therapy is the patient's&#xD;
             only prior therapy the disease must have recurred during treatment or within 3 months&#xD;
             of discontinuation&#xD;
&#xD;
          -  Allowable prior therapies include VEGF tyrosine kinase inhibitor (TKIs), mammalian&#xD;
             target of rapamycin (mTOR) inhibitors, and cytokine therapy (example: interleukin-2&#xD;
             [IL2])&#xD;
&#xD;
          -  At least 2 weeks must have elapsed from the last dose of the prior systemic therapy&#xD;
             for biologics and 4 weeks for chemotherapy (6 weeks for nitrosoureas or mitomycin C);&#xD;
             also note that at least 3 weeks should have elapsed since prior TKI administration&#xD;
&#xD;
          -  Eastern Cooperative Oncology Group (ECOG) performance status =&lt; 2&#xD;
&#xD;
          -  Life expectancy of greater than 6 months&#xD;
&#xD;
          -  Leukocytes &gt;= 3,000/mcL&#xD;
&#xD;
          -  Absolute neutrophil count &gt;= 1,500/mcL&#xD;
&#xD;
          -  Platelets &gt;= 100,000/mcL&#xD;
&#xD;
          -  Total bilirubin =&lt; institutional upper limits or normal (except for Gilbert's)&#xD;
&#xD;
          -  Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase&#xD;
             [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT])&#xD;
             =&lt; 2.5 X institutional upper limit of normal (except subjects with liver metastases,&#xD;
             who can have AST/ALT =&lt; 5 x ULN)&#xD;
&#xD;
          -  Creatinine glomerular filtration rate (GFR) (calculated or measured) &gt; 50 mL/min&#xD;
&#xD;
          -  Hemoglobin &gt;= 9 g/dL&#xD;
&#xD;
          -  Women of child-bearing potential and men must agree to use adequate contraception&#xD;
             (hormonal or barrier method of birth control; abstinence) prior to study entry and for&#xD;
             the duration of study participation; should a woman become pregnant or suspect she is&#xD;
             pregnant while she or her partner is participating in this study, she should inform&#xD;
             her treating physician immediately; men treated or enrolled on this protocol must also&#xD;
             agree to use adequate contraception prior to the study, for the duration of study&#xD;
             participation, and 6 months after completion of TRC105 or bevacizumab administration&#xD;
&#xD;
          -  Ability to understand and the willingness to sign a written informed consent document&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Patients who have had systemic biologic therapy or radiotherapy within 2 weeks prior&#xD;
             to entering the study or those who have not recovered from adverse events related to&#xD;
             their prior therapy&#xD;
&#xD;
          -  Patients who have previously been treated with bevacizumab&#xD;
&#xD;
          -  Patients who have previously been treated with TRC105&#xD;
&#xD;
          -  Patients who are receiving any other investigational agents&#xD;
&#xD;
          -  Known central nervous system (CNS) disease except for treated brain metastasis;&#xD;
             treated brain metastases are defined as having no ongoing requirement for steroids and&#xD;
             no evidence of progression or hemorrhage after treatment for at least 3 months, as&#xD;
             ascertained by clinical examination and brain imaging (MRI or CT) (stable dose of&#xD;
             anticonvulsants are allowed); treatment for brain metastases may include whole brain&#xD;
             radiotherapy (WBRT), radiosurgery (RS; gamma knife, linear accelerator [LINAC], or&#xD;
             equivalent) or a combination as deemed appropriate by the treating physician; patients&#xD;
             with CNS metastases treated by neurosurgical resection or brain biopsy performed&#xD;
             within 3 months prior to day 1 will be excluded&#xD;
&#xD;
          -  History of allergic reactions attributed to compounds of similar chemical or biologic&#xD;
             composition to TRC105 or bevacizumab&#xD;
&#xD;
          -  Patients on full-dose anticoagulation will be excluded; antiplatelet therapy will not&#xD;
             be exclusionary&#xD;
&#xD;
          -  Uncontrolled intercurrent illness including, but not limited to, ongoing or active&#xD;
             infection, unhealed wound, gastrointestinal fistula, symptomatic congestive heart&#xD;
             failure, unstable angina pectoris, myocardial infarction, cerebrovascular accident&#xD;
&#xD;
          -  Pregnant women are excluded from this study; breastfeeding should be discontinued if&#xD;
             the mother wishes to participate in the study&#xD;
&#xD;
          -  Patients with a history of bleeding diathesis or inherited coagulopathy are excluded;&#xD;
             in addition, those with a history of deep vein thrombosis (DVT) or pulmonary embolus&#xD;
             within 1 year and still requiring active anticoagulation will be excluded; those with&#xD;
             a more remote history of DVT or pulmonary embolus may be eligible but the risk of&#xD;
             recurrent thrombosis should be considered&#xD;
&#xD;
          -  Patients with history of hereditary hemorrhagic telangiectasis (HHT-1 and HHT-2)&#xD;
&#xD;
          -  Serious or non-healing wound, ulcer, or bone fracture OR history of abdominal fistula,&#xD;
             gastrointestinal perforation or intra-abdominal abscess within 6 months prior to day 1&#xD;
&#xD;
          -  Invasive procedures defined as follows:&#xD;
&#xD;
               -  Major surgical procedure, open biopsy or significant traumatic injury within 28&#xD;
                  days prior to day 1 therapy&#xD;
&#xD;
               -  Anticipation of need for major surgical procedures during the course of the study&#xD;
&#xD;
               -  Core biopsy within 7 days prior to day 1 therapy&#xD;
&#xD;
          -  Patients with clinically significant cardiovascular disease are excluded:&#xD;
&#xD;
               -  Inadequately controlled hypertension (HTN) (systolic blood pressure [SBP] &gt; 160&#xD;
                  mmHg and/or diastolic blood pressure [DBP] &gt; 90 mmHg despite antihypertensive&#xD;
                  medication)&#xD;
&#xD;
               -  History of cerebrovascular accident (CVA) within 6 months&#xD;
&#xD;
               -  Myocardial infarction or unstable angina within 6 months&#xD;
&#xD;
               -  New York Heart Association grade II or greater congestive heart failure&#xD;
&#xD;
               -  Serious and inadequately controlled cardiac arrhythmia&#xD;
&#xD;
               -  Significant vascular disease (e.g. aortic aneurysm, history of aortic dissection)&#xD;
&#xD;
               -  Clinically significant peripheral vascular disease&#xD;
&#xD;
          -  Patients with known hypersensitivity to Chinese hamster ovary cell products or other&#xD;
             recombinant human antibodies&#xD;
&#xD;
          -  Patients with psychiatric illness/social situations that would limit compliance with&#xD;
             study requirements will be excluded&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Tanya Dorff</last_name>
    <role>Principal Investigator</role>
    <affiliation>City of Hope Comprehensive Cancer Center</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>City of Hope Comprehensive Cancer Center</name>
      <address>
        <city>Duarte</city>
        <state>California</state>
        <zip>91010</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>USC / Norris Comprehensive Cancer Center</name>
      <address>
        <city>Los Angeles</city>
        <state>California</state>
        <zip>90033</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of California Davis Comprehensive Cancer Center</name>
      <address>
        <city>Sacramento</city>
        <state>California</state>
        <zip>95817</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>City of Hope South Pasadena</name>
      <address>
        <city>South Pasadena</city>
        <state>California</state>
        <zip>91030</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Colorado Cancer Center - 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 Colorado</name>
      <address>
        <city>Denver</city>
        <state>Colorado</state>
        <zip>80217-3364</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Miami Miller School of Medicine-Sylvester Cancer Center</name>
      <address>
        <city>Miami</city>
        <state>Florida</state>
        <zip>33136</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Moffitt Cancer Center</name>
      <address>
        <city>Tampa</city>
        <state>Florida</state>
        <zip>33612</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Chicago Comprehensive Cancer Center</name>
      <address>
        <city>Chicago</city>
        <state>Illinois</state>
        <zip>60637</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Decatur Memorial Hospital</name>
      <address>
        <city>Decatur</city>
        <state>Illinois</state>
        <zip>62526</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>NorthShore University HealthSystem-Evanston Hospital</name>
      <address>
        <city>Evanston</city>
        <state>Illinois</state>
        <zip>60201</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>NorthShore University HealthSystem-Glenbrook Hospital</name>
      <address>
        <city>Glenview</city>
        <state>Illinois</state>
        <zip>60026</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Ingalls Memorial Hospital</name>
      <address>
        <city>Harvey</city>
        <state>Illinois</state>
        <zip>60426</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Fort Wayne Medical Oncology and Hematology Inc - Jefferson Boulevard</name>
      <address>
        <city>Fort Wayne</city>
        <state>Indiana</state>
        <zip>46804</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Fort Wayne Medical Oncology and Hematology Inc-Parkview</name>
      <address>
        <city>Fort Wayne</city>
        <state>Indiana</state>
        <zip>46845</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Iowa/Holden Comprehensive Cancer Center</name>
      <address>
        <city>Iowa City</city>
        <state>Iowa</state>
        <zip>52242</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Maryland/Greenebaum Cancer Center</name>
      <address>
        <city>Baltimore</city>
        <state>Maryland</state>
        <zip>21201</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Michigan Comprehensive Cancer Center</name>
      <address>
        <city>Ann Arbor</city>
        <state>Michigan</state>
        <zip>48109</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Wayne State University/Karmanos Cancer Institute</name>
      <address>
        <city>Detroit</city>
        <state>Michigan</state>
        <zip>48201</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Mayo Clinic</name>
      <address>
        <city>Rochester</city>
        <state>Minnesota</state>
        <zip>55905</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Metro Minnesota Community Oncology Research Consortium</name>
      <address>
        <city>Saint Louis Park</city>
        <state>Minnesota</state>
        <zip>55416</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Washington University School of Medicine</name>
      <address>
        <city>Saint Louis</city>
        <state>Missouri</state>
        <zip>63110</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Rutgers Cancer Institute of New Jersey</name>
      <address>
        <city>New Brunswick</city>
        <state>New Jersey</state>
        <zip>08903</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Penn State Milton S Hershey Medical Center</name>
      <address>
        <city>Hershey</city>
        <state>Pennsylvania</state>
        <zip>17033-0850</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Pittsburgh Cancer Institute (UPCI)</name>
      <address>
        <city>Pittsburgh</city>
        <state>Pennsylvania</state>
        <zip>15232</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Vanderbilt University/Ingram Cancer Center</name>
      <address>
        <city>Nashville</city>
        <state>Tennessee</state>
        <zip>37232</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>M D Anderson Cancer Center</name>
      <address>
        <city>Houston</city>
        <state>Texas</state>
        <zip>77030</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Virginia Commonwealth University/Massey Cancer Center</name>
      <address>
        <city>Richmond</city>
        <state>Virginia</state>
        <zip>23298</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Royal Prince Alfred Hospital</name>
      <address>
        <city>Camperdown</city>
        <state>New South Wales</state>
        <zip>2050</zip>
        <country>Australia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>National Taiwan University Hospital</name>
      <address>
        <city>Taipei</city>
        <zip>100</zip>
        <country>Taiwan</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Australia</country>
    <country>Taiwan</country>
    <country>United States</country>
  </location_countries>
  <removed_countries>
    <country>Korea, Democratic People's Republic of</country>
  </removed_countries>
  <verification_date>July 2018</verification_date>
  <study_first_submitted>November 12, 2012</study_first_submitted>
  <study_first_submitted_qc>November 12, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">November 15, 2012</study_first_posted>
  <results_first_submitted>April 24, 2018</results_first_submitted>
  <results_first_submitted_qc>May 25, 2018</results_first_submitted_qc>
  <results_first_posted type="Actual">June 26, 2018</results_first_posted>
  <last_update_submitted>July 30, 2018</last_update_submitted>
  <last_update_submitted_qc>July 30, 2018</last_update_submitted_qc>
  <last_update_posted type="Actual">August 28, 2018</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>Carcinoma</mesh_term>
    <mesh_term>Carcinoma, Renal Cell</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Bevacizumab</mesh_term>
    <mesh_term>Antineoplastic Agents, Immunological</mesh_term>
    <mesh_term>Endothelial Growth Factors</mesh_term>
    <mesh_term>Antibodies</mesh_term>
    <mesh_term>Immunoglobulins</mesh_term>
    <mesh_term>Antibodies, Monoclonal</mesh_term>
    <mesh_term>Immunoglobulin G</mesh_term>
  </intervention_browse>
  <provided_document_section>
    <provided_document>
      <document_type>Study Protocol and Statistical Analysis Plan</document_type>
      <document_has_protocol>Yes</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>Yes</document_has_sap>
      <document_date>September 23, 2014</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/89/NCT01727089/Prot_SAP_000.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <group_list>
        <group group_id="P1">
          <title>Arm I (Bevacizumab)</title>
          <description>Patients receive 10 mg/kg bevacizumab IV over 30-90 minutes on days 1 and 15. Treatment repeats every 28 days for up to 12 courses in the absence of disease progression or unacceptable toxicity.&#xD;
Bevacizumab: Given IV&#xD;
Laboratory Biomarker Analysis: Correlative studies</description>
        </group>
        <group group_id="P2">
          <title>Arm II (Bevacizumab, Anti-endoglin Monoclonal Antibody TRC105)</title>
          <description>Patients receive 10 mg\kg bevacizumab as in Arm I and anti-endoglin monoclonal antibody TRC105 10 mg\kg IV over 1-4 hours on days 1, 8, 15, and 22. Treatment repeats every 28 days for up to 12 courses in the absence of disease progression or unacceptable toxicity.&#xD;
Anti-Endoglin Chimeric Monoclonal Antibody TRC105: Given IV&#xD;
Bevacizumab: Given IV&#xD;
Laboratory Biomarker Analysis: Correlative studies&#xD;
Pharmacological Study: Correlative studies</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="29"/>
                <participants group_id="P2" count="30"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="29"/>
                <participants group_id="P2" count="30"/>
              </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>
      <group_list>
        <group group_id="B1">
          <title>Arm I (Bevacizumab)</title>
          <description>Patients receive 10 mg/kg bevacizumab IV over 30-90 minutes on days 1 and 15. Treatment repeats every 28 days for up to 12 courses in the absence of disease progression or unacceptable toxicity.&#xD;
Bevacizumab: Given IV&#xD;
Laboratory Biomarker Analysis: Correlative studies</description>
        </group>
        <group group_id="B2">
          <title>Arm II (Bevacizumab, Anti-endoglin Monoclonal Antibody TRC105)</title>
          <description>Patients receive 10 mg\kg bevacizumab as in Arm I and anti-endoglin monoclonal antibody TRC105 10 mg\kg IV over 1-4 hours on days 1, 8, 15, and 22. Treatment repeats every 28 days for up to 12 courses in the absence of disease progression or unacceptable toxicity.&#xD;
Anti-Endoglin Chimeric Monoclonal Antibody TRC105: Given IV&#xD;
Bevacizumab: Given IV&#xD;
Laboratory Biomarker Analysis: Correlative studies&#xD;
Pharmacological Study: Correlative studies</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="29"/>
            <count group_id="B2" value="30"/>
            <count group_id="B3" value="59"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>years</units>
          <param>Median</param>
          <dispersion>Full Range</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="58" lower_limit="25" upper_limit="82"/>
                    <measurement group_id="B2" value="65" lower_limit="24" upper_limit="78"/>
                    <measurement group_id="B3" value="60" lower_limit="24" upper_limit="82"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Sex: Female, Male</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Female</title>
                  <measurement_list>
                    <measurement group_id="B1" value="9"/>
                    <measurement group_id="B2" value="6"/>
                    <measurement group_id="B3" value="15"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="20"/>
                    <measurement group_id="B2" value="24"/>
                    <measurement group_id="B3" value="44"/>
                  </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="7"/>
                    <measurement group_id="B2" value="3"/>
                    <measurement group_id="B3" value="10"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Not Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="22"/>
                    <measurement group_id="B2" value="27"/>
                    <measurement group_id="B3" value="49"/>
                  </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="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Asian</title>
                  <measurement_list>
                    <measurement group_id="B1" value="3"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="3"/>
                  </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="2"/>
                    <measurement group_id="B3" value="4"/>
                  </measurement_list>
                </category>
                <category>
                  <title>White</title>
                  <measurement_list>
                    <measurement group_id="B1" value="24"/>
                    <measurement group_id="B2" value="28"/>
                    <measurement group_id="B3" value="52"/>
                  </measurement_list>
                </category>
                <category>
                  <title>More than one race</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Region of Enrollment</title>
          <units>participants</units>
          <param>Number</param>
          <class_list>
            <class>
              <title>United States</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="29"/>
                    <measurement group_id="B2" value="30"/>
                    <measurement group_id="B3" value="59"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Progression-free Survival at 24 Weeks</title>
        <description>Progression-free survival 24 after starting treatment. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions.</description>
        <time_frame>The duration of time from start of treatment to time of progression or death, assessed at 24 weeks</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Arm I (Bevacizumab)</title>
            <description>Patients receive 10 mg/kg bevacizumab IV over 30-90 minutes on days 1 and 15. Treatment repeats every 28 days for up to 12 courses in the absence of disease progression or unacceptable toxicity.&#xD;
Bevacizumab: Given IV&#xD;
Laboratory Biomarker Analysis: Correlative studies</description>
          </group>
          <group group_id="O2">
            <title>Arm II (Bevacizumab, Anti-endoglin Monoclonal Antibody TRC105)</title>
            <description>Patients receive 10 mg\kg bevacizumab as in Arm I and anti-endoglin monoclonal antibody TRC105 10 mg\kg IV over 1-4 hours on days 1, 8, 15, and 22. Treatment repeats every 28 days for up to 12 courses in the absence of disease progression or unacceptable toxicity.&#xD;
Anti-Endoglin Chimeric Monoclonal Antibody TRC105: Given IV&#xD;
Bevacizumab: Given IV&#xD;
Laboratory Biomarker Analysis: Correlative studies&#xD;
Pharmacological Study: Correlative studies</description>
          </group>
        </group_list>
        <measure>
          <title>Progression-free Survival at 24 Weeks</title>
          <description>Progression-free survival 24 after starting treatment. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions.</description>
          <units>percentage of participants</units>
          <param>Number</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="29"/>
                <count group_id="O2" value="30"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="52" lower_limit="36" upper_limit="76"/>
                    <measurement group_id="O2" value="27" lower_limit="15" upper_limit="50"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Progression-free Survival at 12 Weeks</title>
        <description>Progression-free survival 12 after starting treatment. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions.</description>
        <time_frame>The duration of time from start of treatment to time of progression or death, assessed at 12 weeks</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Arm I (Bevacizumab)</title>
            <description>Patients receive 10 mg/kg bevacizumab IV over 30-90 minutes on days 1 and 15. Treatment repeats every 28 days for up to 12 courses in the absence of disease progression or unacceptable toxicity.&#xD;
Bevacizumab: Given IV&#xD;
Laboratory Biomarker Analysis: Correlative studies</description>
          </group>
          <group group_id="O2">
            <title>Arm II (Bevacizumab, Anti-endoglin Monoclonal Antibody TRC105)</title>
            <description>Patients receive 10 mg\kg bevacizumab as in Arm I and anti-endoglin monoclonal antibody TRC105 10 mg\kg IV over 1-4 hours on days 1, 8, 15, and 22. Treatment repeats every 28 days for up to 12 courses in the absence of disease progression or unacceptable toxicity.&#xD;
Anti-Endoglin Chimeric Monoclonal Antibody TRC105: Given IV&#xD;
Bevacizumab: Given IV&#xD;
Laboratory Biomarker Analysis: Correlative studies&#xD;
Pharmacological Study: Correlative studies</description>
          </group>
        </group_list>
        <measure>
          <title>Progression-free Survival at 12 Weeks</title>
          <description>Progression-free survival 12 after starting treatment. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions.</description>
          <units>percentage of participants</units>
          <param>Number</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="29"/>
                <count group_id="O2" value="30"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="66" lower_limit="51" upper_limit="86"/>
                    <measurement group_id="O2" value="58" lower_limit="42" upper_limit="71"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Number of Participants With Grade 3 and Above Adverse Events (AE) Related to Treatment</title>
        <description>The descriptions and grading scales found in the revised National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0 will be utilized for AE reporting.&#xD;
Grade 1 - Mild; asymptomatic or mild symptoms; clinical or diagnostic observations only; intervention not indicated.&#xD;
Grade 2 - Moderate; minimal, local or noninvasive intervention indicated; limiting age-appropriate instrumental activities of daily living (ADL).&#xD;
Grade 3 - Severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; limiting self care ADL.&#xD;
Grade 4 - Life-threatening consequences; urgent intervention indicated. Grade 5 - Death related adverse event.</description>
        <time_frame>From time of treatment initiation until 30 days post treatment, assessed every 4 weeks.</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Arm I (Bevacizumab)</title>
            <description>Patients receive 10 mg/kg bevacizumab IV over 30-90 minutes on days 1 and 15. Treatment repeats every 28 days for up to 12 courses in the absence of disease progression or unacceptable toxicity.&#xD;
Bevacizumab: Given IV&#xD;
Laboratory Biomarker Analysis: Correlative studies</description>
          </group>
          <group group_id="O2">
            <title>Arm II (Bevacizumab, Anti-endoglin Monoclonal Antibody TRC105)</title>
            <description>Patients receive 10 mg\kg bevacizumab as in Arm I and anti-endoglin monoclonal antibody TRC105 10 mg\kg IV over 1-4 hours on days 1, 8, 15, and 22. Treatment repeats every 28 days for up to 12 courses in the absence of disease progression or unacceptable toxicity.&#xD;
Anti-Endoglin Chimeric Monoclonal Antibody TRC105: Given IV&#xD;
Bevacizumab: Given IV&#xD;
Laboratory Biomarker Analysis: Correlative studies&#xD;
Pharmacological Study: Correlative studies</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Participants With Grade 3 and Above Adverse Events (AE) Related to Treatment</title>
          <description>The descriptions and grading scales found in the revised National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0 will be utilized for AE reporting.&#xD;
Grade 1 - Mild; asymptomatic or mild symptoms; clinical or diagnostic observations only; intervention not indicated.&#xD;
Grade 2 - Moderate; minimal, local or noninvasive intervention indicated; limiting age-appropriate instrumental activities of daily living (ADL).&#xD;
Grade 3 - Severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; limiting self care ADL.&#xD;
Grade 4 - Life-threatening consequences; urgent intervention indicated. Grade 5 - Death related adverse event.</description>
          <units>participants</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="29"/>
                <count group_id="O2" value="30"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Abdominal pain</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3"/>
                    <measurement group_id="O2" value="3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Anemia</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="4"/>
                    <measurement group_id="O2" value="8"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Anorexia</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>
              <title>Bleeding</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2"/>
                    <measurement group_id="O2" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>bronchopulmonary hemorrhage</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                    <measurement group_id="O2" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Fatigue</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Hypercalcemia</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Hypertension</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="5"/>
                    <measurement group_id="O2" value="4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Hyponatremia</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                    <measurement group_id="O2" value="2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Infusion reaction</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Nausea/vomitting</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Proteinuria</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2"/>
                    <measurement group_id="O2" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Number of Participants With Overall Response</title>
        <description>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 time of treatment initiation until conclusion of treatment, assessed every 12 weeks.</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Arm I (Bevacizumab)</title>
            <description>Patients receive 10 mg/kg bevacizumab IV over 30-90 minutes on days 1 and 15. Treatment repeats every 28 days for up to 12 courses in the absence of disease progression or unacceptable toxicity.&#xD;
Bevacizumab: Given IV&#xD;
Laboratory Biomarker Analysis: Correlative studies</description>
          </group>
          <group group_id="O2">
            <title>Arm II (Bevacizumab, Anti-endoglin Monoclonal Antibody TRC105)</title>
            <description>Patients receive 10 mg\kg bevacizumab as in Arm I and anti-endoglin monoclonal antibody TRC105 10 mg\kg IV over 1-4 hours on days 1, 8, 15, and 22. Treatment repeats every 28 days for up to 12 courses in the absence of disease progression or unacceptable toxicity.&#xD;
Anti-Endoglin Chimeric Monoclonal Antibody TRC105: Given IV&#xD;
Bevacizumab: Given IV&#xD;
Laboratory Biomarker Analysis: Correlative studies&#xD;
Pharmacological Study: Correlative studies</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Participants With Overall Response</title>
          <description>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>
          <units>participants</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="29"/>
                <count group_id="O2" value="30"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                    <measurement group_id="O2" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>Adverse events occurred over a period of 2 years and 7 months.</time_frame>
      <desc>&quot;Other Adverse Events&quot; include all events that were not severe adverse events regardless of grade or relation to treatment.</desc>
      <group_list>
        <group group_id="E1">
          <title>Arm I (Bevacizumab)</title>
          <description>Patients receive 10 mg/kg bevacizumab IV over 30-90 minutes on days 1 and 15. Treatment repeats every 28 days for up to 12 courses in the absence of disease progression or unacceptable toxicity.&#xD;
Bevacizumab: Given IV&#xD;
Laboratory Biomarker Analysis: Correlative studies</description>
        </group>
        <group group_id="E2">
          <title>Arm II (Bevacizumab, Anti-endoglin Monoclonal Antibody TRC105)</title>
          <description>Patients receive 10 mg\kg bevacizumab as in Arm I and anti-endoglin monoclonal antibody TRC105 10 mg\kg IV over 1-4 hours on days 1, 8, 15, and 22. Treatment repeats every 28 days for up to 12 courses in the absence of disease progression or unacceptable toxicity.&#xD;
Anti-Endoglin Chimeric Monoclonal Antibody TRC105: Given IV&#xD;
Bevacizumab: Given IV&#xD;
Laboratory Biomarker Analysis: Correlative studies&#xD;
Pharmacological Study: Correlative studies</description>
        </group>
      </group_list>
      <serious_events>
        <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="4" subjects_at_risk="29"/>
                <counts group_id="E2" subjects_affected="5" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="10" subjects_at_risk="29"/>
                <counts group_id="E2" subjects_affected="14" subjects_at_risk="30"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Blood and lymphatic system disorders</title>
            <event_list>
              <event>
                <sub_title>Anemia</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="29"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="30"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Cardiac disorders</title>
            <event_list>
              <event>
                <sub_title>Heart failure</sub_title>
                <counts group_id="E1" events="3" subjects_affected="2" subjects_at_risk="29"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Left ventricular systolic dysfunction</sub_title>
                <counts group_id="E1" events="2" subjects_affected="1" subjects_at_risk="29"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Restrictive cardiomyopathy</sub_title>
                <counts group_id="E1" events="2" subjects_affected="1" subjects_at_risk="29"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="30"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Abdominal pain</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="29"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Ascites</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="29"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Constipation</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="29"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Duodenal hemorrhage</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="29"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Ileus</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="29"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Nausea</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="29"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Pancreatitis</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="29"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Vomiting</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="29"/>
                <counts group_id="E2" events="3" subjects_affected="3" subjects_at_risk="30"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Death NOS</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="29"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Edema limbs</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="29"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Failure to thrive</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="29"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Fatigue</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="29"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Fever</sub_title>
                <counts group_id="E1" events="2" subjects_affected="1" subjects_at_risk="29"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Infusion related reaction</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="29"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Pain</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="29"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Weakness</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="29"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="30"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Hepatobiliary disorders</title>
            <event_list>
              <event>
                <sub_title>Bile duct stenosis</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="29"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Hepatic failure</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="29"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="30"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Lung infection</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="29"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Skin infection</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="29"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Urinary tract infection</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="29"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="30"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Injury, poisoning and procedural complications</title>
            <event_list>
              <event>
                <sub_title>Fall</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="29"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="30"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Investigations</title>
            <event_list>
              <event>
                <sub_title>Aspartate aminotransferase increased</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="29"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Creatinine increased</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="29"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Lymphocyte count decreased</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="29"/>
                <counts group_id="E2" events="2" subjects_affected="1" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>progression of renal cell cancer</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="29"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="30"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Metabolism and nutrition disorders</title>
            <event_list>
              <event>
                <sub_title>Anorexia</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="29"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Dehydration</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="29"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Hypercalcemia</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="29"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Hyperkalemia</sub_title>
                <counts group_id="E1" events="2" subjects_affected="1" subjects_at_risk="29"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Hyponatremia</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="29"/>
                <counts group_id="E2" events="3" subjects_affected="1" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Hypophosphatemia</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="29"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="30"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Musculoskeletal and connective tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Bone pain</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="29"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Flank pain</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="29"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="30"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Neoplasms benign, malignant and unspecified (incl cysts and polyps)</title>
            <event_list>
              <event>
                <sub_title>Disease progression</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="29"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Progressive Disease</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="29"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>death</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="29"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="30"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Presyncope</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="29"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Somnolence</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="29"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Syncope</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="29"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="30"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Psychiatric disorders</title>
            <event_list>
              <event>
                <sub_title>Anxiety</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="29"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Confusion</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="29"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="30"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Renal and urinary disorders</title>
            <event_list>
              <event>
                <sub_title>Acute kidney injury</sub_title>
                <counts group_id="E1" events="2" subjects_affected="1" subjects_at_risk="29"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Chronic kidney disease</sub_title>
                <counts group_id="E1" events="2" subjects_affected="1" subjects_at_risk="29"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Proteinuria</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="29"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="30"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Bronchopulmonary hemorrhage</sub_title>
                <description>Grade 5, possibly related</description>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="29"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Dyspnea</sub_title>
                <counts group_id="E1" events="4" subjects_affected="3" subjects_at_risk="29"/>
                <counts group_id="E2" events="3" subjects_affected="3" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Hypoxia</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="29"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Pleural effusion</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="29"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Productive cough</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="29"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="30"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Skin and subcutaneous tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Bullous dermatitis</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="29"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>scalp laceration</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="29"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="30"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Vascular disorders</title>
            <event_list>
              <event>
                <sub_title>Hypertension</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="29"/>
                <counts group_id="E2" events="13" subjects_affected="2" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Hypotension</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="29"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="30"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>0</frequency_threshold>
        <default_assessment>Non-systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, other adverse events</sub_title>
                <counts group_id="E1" subjects_affected="29" subjects_at_risk="29"/>
                <counts group_id="E2" subjects_affected="29" subjects_at_risk="30"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Blood and lymphatic system disorders</title>
            <event_list>
              <event>
                <sub_title>Anemia</sub_title>
                <counts group_id="E1" events="29" subjects_affected="10" subjects_at_risk="29"/>
                <counts group_id="E2" events="79" subjects_affected="16" subjects_at_risk="30"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Cardiac disorders</title>
            <event_list>
              <event>
                <sub_title>Sinus bradycardia</sub_title>
                <counts group_id="E1" events="11" subjects_affected="3" subjects_at_risk="29"/>
                <counts group_id="E2" events="9" subjects_affected="5" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Sinus tachycardia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="29"/>
                <counts group_id="E2" events="13" subjects_affected="5" subjects_at_risk="30"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Ear and labyrinth disorders</title>
            <event_list>
              <event>
                <sub_title>Ear pain</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="29"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Vertigo</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="29"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="30"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Eye disorders</title>
            <event_list>
              <event>
                <sub_title>Blurred vision</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="29"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Glaucoma</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="29"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Itchy Eyes</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="29"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Watering eyes</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="29"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>suconjunctival hemorrhage</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="29"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="30"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Abdominal distension</sub_title>
                <counts group_id="E1" events="3" subjects_affected="2" subjects_at_risk="29"/>
                <counts group_id="E2" events="6" subjects_affected="2" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Abdominal pain</sub_title>
                <counts group_id="E1" events="11" subjects_affected="8" subjects_at_risk="29"/>
                <counts group_id="E2" events="14" subjects_affected="4" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Ascites</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="29"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Bloating</sub_title>
                <counts group_id="E1" events="3" subjects_affected="2" subjects_at_risk="29"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Blood in Stool</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="29"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Constipation</sub_title>
                <counts group_id="E1" events="13" subjects_affected="8" subjects_at_risk="29"/>
                <counts group_id="E2" events="10" subjects_affected="8" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Diarrhea</sub_title>
                <counts group_id="E1" events="6" subjects_affected="4" subjects_at_risk="29"/>
                <counts group_id="E2" events="7" subjects_affected="7" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Dry mouth</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="29"/>
                <counts group_id="E2" events="3" subjects_affected="3" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Duodenal hemorrhage</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="29"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Dyspepsia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="29"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Dysphagia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="29"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Flatulence</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="29"/>
                <counts group_id="E2" events="2" subjects_affected="1" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Gastric hemorrhage</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="29"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Gastroesophageal reflux disease</sub_title>
                <counts group_id="E1" events="2" subjects_affected="1" subjects_at_risk="29"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Gingival pain</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="29"/>
                <counts group_id="E2" events="3" subjects_affected="2" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Mucositis oral</sub_title>
                <counts group_id="E1" events="6" subjects_affected="2" subjects_at_risk="29"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Nausea</sub_title>
                <counts group_id="E1" events="9" subjects_affected="7" subjects_at_risk="29"/>
                <counts group_id="E2" events="16" subjects_affected="10" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Oral dysesthesia</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="29"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Oral hemorrhage</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="29"/>
                <counts group_id="E2" events="17" subjects_affected="4" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Oral pain</sub_title>
                <counts group_id="E1" events="2" subjects_affected="1" subjects_at_risk="29"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Periodontal disease</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="29"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Rectal discharge</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="29"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Rectal hemorrhage</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="29"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Stomach pain</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="29"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Tongue Ulcerations</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="29"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Vomiting</sub_title>
                <counts group_id="E1" events="4" subjects_affected="4" subjects_at_risk="29"/>
                <counts group_id="E2" events="9" subjects_affected="7" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>diverticulosis</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="29"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>hiatal hernia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="29"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="30"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Bloody Gums</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="29"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Chills</sub_title>
                <counts group_id="E1" events="6" subjects_affected="4" subjects_at_risk="29"/>
                <counts group_id="E2" events="5" subjects_affected="2" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Cracked Lips</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="29"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Death NOS</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="29"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Edema limbs</sub_title>
                <counts group_id="E1" events="4" subjects_affected="4" subjects_at_risk="29"/>
                <counts group_id="E2" events="6" subjects_affected="5" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Fatigue</sub_title>
                <counts group_id="E1" events="54" subjects_affected="18" subjects_at_risk="29"/>
                <counts group_id="E2" events="79" subjects_affected="23" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Fever</sub_title>
                <counts group_id="E1" events="5" subjects_affected="4" subjects_at_risk="29"/>
                <counts group_id="E2" events="3" subjects_affected="3" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Flu like symptoms</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="29"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Increased Thirst</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="29"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Infusion related reaction</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="29"/>
                <counts group_id="E2" events="6" subjects_affected="5" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Localized edema</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="29"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Malaise</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="29"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Night sweats</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="29"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Non-cardiac chest pain</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="29"/>
                <counts group_id="E2" events="4" subjects_affected="3" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Pain</sub_title>
                <counts group_id="E1" events="7" subjects_affected="2" subjects_at_risk="29"/>
                <counts group_id="E2" events="11" subjects_affected="7" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Rash</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="29"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Swelling of Feet</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="29"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>swelling of feet</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="29"/>
                <counts group_id="E2" events="2" subjects_affected="1" subjects_at_risk="30"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Sinusitis</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="29"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Skin infection</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="29"/>
                <counts group_id="E2" events="4" subjects_affected="3" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Upper respiratory infection</sub_title>
                <counts group_id="E1" events="2" subjects_affected="1" subjects_at_risk="29"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Urinary tract infection</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="29"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="30"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Injury, poisoning and procedural complications</title>
            <event_list>
              <event>
                <sub_title>Bruising</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="29"/>
                <counts group_id="E2" events="14" subjects_affected="2" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Fall</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="29"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="30"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Investigations</title>
            <event_list>
              <event>
                <sub_title>Activated partial thromboplastin time pr</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="29"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Alanine aminotransferase increased</sub_title>
                <counts group_id="E1" events="26" subjects_affected="7" subjects_at_risk="29"/>
                <counts group_id="E2" events="5" subjects_affected="3" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Alkaline phosphatase increased</sub_title>
                <counts group_id="E1" events="13" subjects_affected="7" subjects_at_risk="29"/>
                <counts group_id="E2" events="11" subjects_affected="6" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Aspartate aminotransferase increased</sub_title>
                <counts group_id="E1" events="17" subjects_affected="6" subjects_at_risk="29"/>
                <counts group_id="E2" events="9" subjects_affected="7" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Blood bilirubin increased</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="29"/>
                <counts group_id="E2" events="3" subjects_affected="3" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Cardiac troponin T increased</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="29"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Cholesterol high</sub_title>
                <counts group_id="E1" events="2" subjects_affected="1" subjects_at_risk="29"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Creatinine increased</sub_title>
                <counts group_id="E1" events="15" subjects_affected="7" subjects_at_risk="29"/>
                <counts group_id="E2" events="14" subjects_affected="6" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Elevated BUN</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="29"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Elevated BUN count</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="29"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Elevated Eos Auto</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="29"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Elevated LDH</sub_title>
                <counts group_id="E1" events="3" subjects_affected="1" subjects_at_risk="29"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>GGT increased</sub_title>
                <counts group_id="E1" events="6" subjects_affected="1" subjects_at_risk="29"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Hemoglobin increased</sub_title>
                <counts group_id="E1" events="6" subjects_affected="1" subjects_at_risk="29"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>INCREASED LDH</sub_title>
                <counts group_id="E1" events="3" subjects_affected="1" subjects_at_risk="29"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>INR increased</sub_title>
                <counts group_id="E1" events="3" subjects_affected="1" subjects_at_risk="29"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Lipase increased</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="29"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Low Co2</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="29"/>
                <counts group_id="E2" events="2" subjects_affected="1" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Low LDH</sub_title>
                <counts group_id="E1" events="2" subjects_affected="1" subjects_at_risk="29"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Low chloride count</sub_title>
                <counts group_id="E1" events="3" subjects_affected="1" subjects_at_risk="29"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Lymphocyte count decreased</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="29"/>
                <counts group_id="E2" events="7" subjects_affected="4" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Lymphocyte count increased</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="29"/>
                <counts group_id="E2" events="2" subjects_affected="1" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Platelet count decreased</sub_title>
                <counts group_id="E1" events="22" subjects_affected="6" subjects_at_risk="29"/>
                <counts group_id="E2" events="4" subjects_affected="3" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Weight gain</sub_title>
                <counts group_id="E1" events="3" subjects_affected="2" subjects_at_risk="29"/>
                <counts group_id="E2" events="22" subjects_affected="5" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Weight loss</sub_title>
                <counts group_id="E1" events="7" subjects_affected="3" subjects_at_risk="29"/>
                <counts group_id="E2" events="9" subjects_affected="4" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>White blood cell decreased</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="29"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>creatinine increased</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="29"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="30"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Metabolism and nutrition disorders</title>
            <event_list>
              <event>
                <sub_title>Anorexia</sub_title>
                <counts group_id="E1" events="19" subjects_affected="9" subjects_at_risk="29"/>
                <counts group_id="E2" events="15" subjects_affected="9" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Dehydration</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="29"/>
                <counts group_id="E2" events="8" subjects_affected="7" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>GLUCOSURIA</sub_title>
                <counts group_id="E1" events="2" subjects_affected="1" subjects_at_risk="29"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Glucose intolerance</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="29"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Hypercalcemia</sub_title>
                <counts group_id="E1" events="7" subjects_affected="4" subjects_at_risk="29"/>
                <counts group_id="E2" events="3" subjects_affected="3" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Hyperglycemia</sub_title>
                <counts group_id="E1" events="18" subjects_affected="6" subjects_at_risk="29"/>
                <counts group_id="E2" events="35" subjects_affected="8" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Hyperkalemia</sub_title>
                <counts group_id="E1" events="16" subjects_affected="7" subjects_at_risk="29"/>
                <counts group_id="E2" events="13" subjects_affected="9" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Hypermagnesemia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="29"/>
                <counts group_id="E2" events="3" subjects_affected="3" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Hypernatremia</sub_title>
                <counts group_id="E1" events="6" subjects_affected="3" subjects_at_risk="29"/>
                <counts group_id="E2" events="4" subjects_affected="4" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Hypertriglyceridemia</sub_title>
                <counts group_id="E1" events="4" subjects_affected="1" subjects_at_risk="29"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Hypoalbuminemia</sub_title>
                <counts group_id="E1" events="21" subjects_affected="10" subjects_at_risk="29"/>
                <counts group_id="E2" events="28" subjects_affected="8" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Hypocalcemia</sub_title>
                <counts group_id="E1" events="5" subjects_affected="4" subjects_at_risk="29"/>
                <counts group_id="E2" events="6" subjects_affected="4" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Hypoglycemia</sub_title>
                <counts group_id="E1" events="7" subjects_affected="5" subjects_at_risk="29"/>
                <counts group_id="E2" events="4" subjects_affected="4" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Hypokalemia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="29"/>
                <counts group_id="E2" events="6" subjects_affected="4" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Hypomagnesemia</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="29"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Hyponatremia</sub_title>
                <counts group_id="E1" events="25" subjects_affected="11" subjects_at_risk="29"/>
                <counts group_id="E2" events="29" subjects_affected="11" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Hypophosphatemia</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="29"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Obesity</sub_title>
                <counts group_id="E1" events="5" subjects_affected="3" subjects_at_risk="29"/>
                <counts group_id="E2" events="10" subjects_affected="3" subjects_at_risk="30"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Musculoskeletal and connective tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Arthralgia</sub_title>
                <counts group_id="E1" events="4" subjects_affected="4" subjects_at_risk="29"/>
                <counts group_id="E2" events="7" subjects_affected="3" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Arthritis</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="29"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Back pain</sub_title>
                <counts group_id="E1" events="10" subjects_affected="8" subjects_at_risk="29"/>
                <counts group_id="E2" events="11" subjects_affected="7" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Bone pain</sub_title>
                <counts group_id="E1" events="5" subjects_affected="4" subjects_at_risk="29"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Chest wall pain</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="29"/>
                <counts group_id="E2" events="7" subjects_affected="4" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Generalized muscle weakness</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="29"/>
                <counts group_id="E2" events="2" subjects_affected="1" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Intermittent Chest Wall Tenderness</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="29"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Joint range of motion decreased</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="29"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Muscle Cramps</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="29"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Myalgia</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="29"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Neck pain</sub_title>
                <counts group_id="E1" events="4" subjects_affected="3" subjects_at_risk="29"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Pain in extremity</sub_title>
                <counts group_id="E1" events="7" subjects_affected="3" subjects_at_risk="29"/>
                <counts group_id="E2" events="3" subjects_affected="3" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Scoliosis</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="29"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>anterolisthesis</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="29"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>lumbar disk degeneration</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="29"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="30"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Cognitive disturbance</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="29"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Concentration impairment</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="29"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Dizziness</sub_title>
                <counts group_id="E1" events="7" subjects_affected="5" subjects_at_risk="29"/>
                <counts group_id="E2" events="10" subjects_affected="5" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Dysarthria</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="29"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Dysgeusia</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="29"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Headache</sub_title>
                <counts group_id="E1" events="22" subjects_affected="10" subjects_at_risk="29"/>
                <counts group_id="E2" events="25" subjects_affected="15" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Lethargy</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="29"/>
                <counts group_id="E2" events="2" subjects_affected="1" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Paresthesia</sub_title>
                <counts group_id="E1" events="2" subjects_affected="1" subjects_at_risk="29"/>
                <counts group_id="E2" events="4" subjects_affected="2" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Peripheral motor neuropathy</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="29"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Peripheral sensory neuropathy</sub_title>
                <counts group_id="E1" events="3" subjects_affected="1" subjects_at_risk="29"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Presyncope</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="29"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Rigors</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="29"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Sinus pain</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="29"/>
                <counts group_id="E2" events="9" subjects_affected="1" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Somnolence</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="29"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Tremor</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="29"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="30"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Psychiatric disorders</title>
            <event_list>
              <event>
                <sub_title>Anxiety</sub_title>
                <counts group_id="E1" events="2" subjects_affected="1" subjects_at_risk="29"/>
                <counts group_id="E2" events="3" subjects_affected="3" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Confusion</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="29"/>
                <counts group_id="E2" events="3" subjects_affected="3" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Depression</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="29"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Insomnia</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="29"/>
                <counts group_id="E2" events="4" subjects_affected="4" subjects_at_risk="30"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Renal and urinary disorders</title>
            <event_list>
              <event>
                <sub_title>Burning sensation in urine</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="29"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Chronic kidney disease</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="29"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Hematuria</sub_title>
                <counts group_id="E1" events="8" subjects_affected="4" subjects_at_risk="29"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Hemoglobinuria</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="29"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Hyaline casts &gt;2</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="29"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Leukocyte Esterase 3+</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="29"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Proteinuria</sub_title>
                <counts group_id="E1" events="43" subjects_affected="11" subjects_at_risk="29"/>
                <counts group_id="E2" events="20" subjects_affected="8" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>RBC's &gt; 50</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="29"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Urinary fistula</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="29"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Urinary frequency</sub_title>
                <counts group_id="E1" events="3" subjects_affected="2" subjects_at_risk="29"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Urinary incontinence</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="29"/>
                <counts group_id="E2" events="2" subjects_affected="1" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Urinary retention</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="29"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Urinary urgency</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="29"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Urine discoloration</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="29"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>WBC's &gt; 50</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="29"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>pneumaturia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="29"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="30"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Reproductive system and breast disorders</title>
            <event_list>
              <event>
                <sub_title>Vaginal hemorrhage</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="29"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="30"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Allergic rhinitis</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="29"/>
                <counts group_id="E2" events="3" subjects_affected="3" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Bradypnea</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="29"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Cough</sub_title>
                <counts group_id="E1" events="10" subjects_affected="8" subjects_at_risk="29"/>
                <counts group_id="E2" events="11" subjects_affected="7" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Dyspnea</sub_title>
                <counts group_id="E1" events="8" subjects_affected="4" subjects_at_risk="29"/>
                <counts group_id="E2" events="19" subjects_affected="9" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Epistaxis</sub_title>
                <counts group_id="E1" events="8" subjects_affected="3" subjects_at_risk="29"/>
                <counts group_id="E2" events="56" subjects_affected="16" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Hoarseness</sub_title>
                <counts group_id="E1" events="4" subjects_affected="2" subjects_at_risk="29"/>
                <counts group_id="E2" events="7" subjects_affected="3" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Laryngeal hemorrhage</sub_title>
                <counts group_id="E1" events="3" subjects_affected="1" subjects_at_risk="29"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Nasal congestion</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="29"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Pleural effusion</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="29"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Pleuritic pain</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="29"/>
                <counts group_id="E2" events="2" subjects_affected="1" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Productive cough</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="29"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Pulmonary hypertension</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="29"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Sneezing</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="29"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Sore throat</sub_title>
                <counts group_id="E1" events="3" subjects_affected="2" subjects_at_risk="29"/>
                <counts group_id="E2" events="7" subjects_affected="1" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Tachypnea</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="29"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Wheezing</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="29"/>
                <counts group_id="E2" events="4" subjects_affected="1" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>congestion</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="29"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>hemoptysis</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="29"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>nose bleed</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="29"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="30"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Skin and subcutaneous tissue disorders</title>
            <event_list>
              <event>
                <sub_title>ABRASION LEFT HAND</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="29"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Alopecia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="29"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Dry skin</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="29"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Face and Scalp Skin Lesions</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="29"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Face and scalp lesions</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="29"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Hyperhidrosis</sub_title>
                <counts group_id="E1" events="4" subjects_affected="4" subjects_at_risk="29"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Nail ridging</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="29"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Neck rash</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="29"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Palmar-plantar erythrodysesthesia syndro</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="29"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Periorbital edema</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="29"/>
                <counts group_id="E2" events="3" subjects_affected="1" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Pruritus</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="29"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Rash acneiform</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="29"/>
                <counts group_id="E2" events="3" subjects_affected="2" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Rash maculo-papular</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="29"/>
                <counts group_id="E2" events="33" subjects_affected="5" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Rash on face</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="29"/>
                <counts group_id="E2" events="2" subjects_affected="1" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Skin ulceration</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="29"/>
                <counts group_id="E2" events="2" subjects_affected="1" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Telangiectasia</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="29"/>
                <counts group_id="E2" events="2" subjects_affected="1" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Tenderness/Redness on Hands</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="29"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>cold sores</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="29"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>inflamed skin</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="29"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>pallor</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="29"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>rash</sub_title>
                <counts group_id="E1" events="2" subjects_affected="1" subjects_at_risk="29"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>redness of palm</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="29"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>skin reddened</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="29"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>skin redness: palm</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="29"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="30"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Social circumstances</title>
            <event_list>
              <event>
                <sub_title>hair thinning</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="29"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="30"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Surgical and medical procedures</title>
            <event_list>
              <event>
                <sub_title>Port-A-Cath insertion</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="29"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="30"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Vascular disorders</title>
            <event_list>
              <event>
                <sub_title>Flushing</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="29"/>
                <counts group_id="E2" events="10" subjects_affected="6" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Hot flashes</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="29"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Hypertension</sub_title>
                <counts group_id="E1" events="50" subjects_affected="17" subjects_at_risk="29"/>
                <counts group_id="E2" events="55" subjects_affected="15" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Hypotension</sub_title>
                <counts group_id="E1" events="3" subjects_affected="3" subjects_at_risk="29"/>
                <counts group_id="E2" events="11" subjects_affected="6" subjects_at_risk="30"/>
              </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>Jeff Longmate, Ph.D.</name_or_title>
      <organization>City of Hope</organization>
      <phone>626-218-2478</phone>
      <email>jlongmate@coh.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/NCT01727089
org study id: NCI-2012-02206
secondary id: NCI-2012-02206
secondary id: PHII-121
secondary id: PhII-121
secondary id: 9144
secondary id: N01CM00038
secondary id: N01CM00039
secondary id: N01CM00071
secondary id: N01CM00099
secondary id: P30CA033572
nct id: NCT01727089
lead sponsor: 
has dmc: Yes
This randomized phase II trial studies how well bevacizumab with or without anti-endoglin
      monoclonal antibody TRC105 (TRC105) works in treating patients with kidney cancer that has
      spread to other parts of the body (metastatic). Monoclonal antibodies, such as bevacizumab
      and anti-endoglin monoclonal antibody TRC105, may block tumor growth in different ways by
      targeting certain cells.
PRIMARY OBJECTIVES:

      I. To compare the progression-free survival at 12 and 24 weeks for bevacizumab alone or in
      combination with TRC105 (anti-endoglin monoclonal antibody TRC105).

      SECONDARY OBJECTIVES:

      I. Toxicity and Response Evaluation Criteria in Solid Tumors (RECIST) response rate for the
      combination compared to single agent bevacizumab.

      TERTIARY OBJECTIVES:

      I. To evaluate tumor tissue expression of endoglin (CD105), transforming growth factor, beta
      receptor II (TGFBR2), activin A receptor type II-like 1 (ACVRL1) and transforming growth
      factor, beta receptor 1 (TGFBR1) kinase from pre- and post-treatment tissue samples in order
      to determine whether CD105 and stem cell activation occurs after exposure to anti-vascular
      endothelial growth factor (VEGF) therapy as predicted by laboratory models, and whether
      exposure to anti-endoglin monoclonal antibody TRC105 affects these changes.

      II. To compare the soluble CD105 levels at baseline and after treatment between the group
      receiving bevacizumab alone and the group receiving bevacizumab in combination with
      anti-endoglin monoclonal antibody TRC105.

      III. To compare TGFBR2 levels at baseline and after treatment between the group receiving
      bevacizumab alone and the group receiving bevacizumab in combination with anti-endoglin
      monoclonal antibody TRC105.

      IV. To evaluate whether circulating tumor cells (CTCs) can be detected in this patient
      population using parylene membrane filter technology, and whether changes in CTC counts and
      CD105 expression on CTCs during therapy correspond to imaging and clinical response.

      OUTLINE: Patients are randomized to 1 of 2 treatment arms.

      ARM I: Patients receive bevacizumab intravenously (IV) over 30-90 minutes on days 1 and 15.

      ARM II: Patients receive bevacizumab as in Arm I and anti-endoglin monoclonal antibody TRC105
      IV over 1-4 hours on days 1, 8, 15, and 22.

      In both arms, treatment repeats every 28 days for up to 12 courses in the absence of disease
      progression or unacceptable toxicity.

      After completion of study therapy, patients are followed up for 4 weeks.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Progression-free Survival at 24 Weeks
time frame: The duration of time from start of treatment to time of progression or death, assessed at 24 weeks
description: Progression-free survival 24 after starting treatment. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions.
measure: Progression-free Survival at 12 Weeks
time frame: The duration of time from start of treatment to time of progression or death, assessed at 12 weeks
description: Progression-free survival 12 after starting treatment. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions.
measure: Number of Participants With Grade 3 and Above Adverse Events (AE) Related to Treatment
time frame: From time of treatment initiation until 30 days post treatment, assessed every 4 weeks.
description: The descriptions and grading scales found in the revised National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0 will be utilized for AE reporting.
Grade 1 - Mild; asymptomatic or mild symptoms; clinical or diagnostic observations only; intervention not indicated.
Grade 2 - Moderate; minimal, local or noninvasive intervention indicated; limiting age-appropriate instrumental activities of daily living (ADL).
Grade 3 - Severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; limiting self care ADL.
Grade 4 - Life-threatening consequences; urgent intervention indicated. Grade 5 - Death related adverse event.
measure: Number of Participants With Overall Response
time frame: From time of treatment initiation until conclusion of treatment, assessed every 12 weeks.
description: 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
arm group label: Arm I (bevacizumab)
arm group type: Active Comparator
description: Patients receive bevacizumab IV over 30-90 minutes on days 1 and 15. Treatment repeats every 28 days for up to 12 courses in the absence of disease progression or unacceptable toxicity.
arm group label: Arm II (bevacizumab, anti-endoglin monoclonal antibody TRC105)
arm group type: Experimental
description: Patients receive bevacizumab as in Arm I and anti-endoglin monoclonal antibody TRC105 IV over 1-4 hours on days 1, 8, 15, and 22. Treatment repeats every 28 days for up to 12 courses in the absence of disease progression or unacceptable toxicity.
intervention type: Biological
intervention name: Anti-Endoglin Chimeric Monoclonal Antibody TRC105
description: Given IV
arm group label: Arm II (bevacizumab, anti-endoglin monoclonal antibody TRC105)
other name: TRC105
intervention type: Biological
intervention name: Bevacizumab
description: Given IV
arm group label: Arm I (bevacizumab)
arm group label: Arm II (bevacizumab, anti-endoglin monoclonal antibody TRC105)
other name: Anti-VEGF
other name: Anti-VEGF Humanized Monoclonal Antibody
other name: Anti-VEGF rhuMAb
other name: Avastin
other name: Bevacizumab Biosimilar BEVZ92
other name: Bevacizumab Biosimilar BI 695502
other name: Bevacizumab Biosimilar CBT 124
other name: Bevacizumab Biosimilar FKB238
other name: Immunoglobulin G1 (Human-Mouse Monoclonal rhuMab-VEGF Gamma-Chain Anti-Human Vascular Endothelial Growth Factor), Disulfide With Human-Mouse Monoclonal rhuMab-VEGF Light Chain, Dimer
other name: Recombinant Humanized Anti-VEGF Monoclonal Antibody
other name: rhuMab-VEGF
intervention type: Other
intervention name: Laboratory Biomarker Analysis
description: Correlative studies
arm group label: Arm I (bevacizumab)
arm group label: Arm II (bevacizumab, anti-endoglin monoclonal antibody TRC105)
intervention type: Other
intervention name: Pharmacological Study
description: Correlative studies
arm group label: Arm II (bevacizumab, anti-endoglin monoclonal antibody TRC105)
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Tanya Dorff
role: Principal Investigator
affiliation: City of Hope Comprehensive Cancer Center
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country: Australia
country: Taiwan
country: United States
country: Korea, Democratic People's Republic of
responsible party type: Sponsor
mesh term: Carcinoma
mesh term: Carcinoma, Renal Cell
mesh term: Bevacizumab
mesh term: Antineoplastic Agents, Immunological
mesh term: Endothelial Growth Factors
mesh term: Antibodies
mesh term: Immunoglobulins
mesh term: Antibodies, Monoclonal
mesh term: Immunoglobulin G
provided document: 
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 