<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/NCT02207439</url>
  </required_header>
  <id_info>
    <org_study_id>UPCC 15313</org_study_id>
    <nct_id>NCT02207439</nct_id>
  </id_info>
  <brief_title>Phase II Trial of Nelfinavir With Concurrent Chemoradiotherapy in Squamous Cell Carcinoma of the Head and Neck</brief_title>
  <official_title>A Phase II Trial of a Protease Inhibitor, Nelfinavir (NFV), Given With Definitive, Concurrent Chemoradiotherapy (CTRT) in Patients With Locally-Advanced, Human Papilloma Virus (HPV) Negative, Squamous Cell Carcinoma of the Head and Neck</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Abramson Cancer Center at Penn Medicine</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Abramson Cancer Center at Penn Medicine</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      This is a Phase II trial of definitive chemoradiotherapy (CTRT) given with the protease&#xD;
      inhibitor,Nelfinavir (NFV), in patients with locally advanced head and neck. Eligible&#xD;
      patients will receive a &quot;lead-in&quot; period of Nelfinavir (1250 mg po bid) for 7-14 days prior&#xD;
      to initiation of CTRT. Nelfinavir will then be given concurrently with platinum-based&#xD;
      chemotherapy and radiation therapy (planned total dose of 70 Gy over 7 weeks).&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This is a single-arm Phase II study of organ-preservation chemoradiotherapy given in&#xD;
      combination with the protease inhibitor, Nelfinavir, in patients with stage II, IVa, or IVb&#xD;
      (per AJCC version 7) squamous cell carcinoma of the oral cavity, oropharynx, larynx, or&#xD;
      hypopharynx. Patients start treatment with Nelfinvir at a dose of 1250 mg twice daily for&#xD;
      7-14 days, before continuing Nelfinvir at this dose concurrent with chemotherapy and&#xD;
      radiation therapy (for a total dose of 70 Gy over a period of 7 weeks).&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">July 2014</start_date>
  <completion_date type="Actual">May 2022</completion_date>
  <primary_completion_date type="Actual">May 2021</primary_completion_date>
  <phase>Phase 2</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>N/A</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <primary_purpose>Diagnostic</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Locoregional Control</measure>
    <time_frame>5 years</time_frame>
    <description>locoregional control determined via diagnostic imaging and clinical examination.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Decrease in Hypoxia From Nelfinavir</measure>
    <time_frame>7-14 days</time_frame>
    <description>Decrease in Hypoxia from Nelfinavir was determined by change in uptake and volume as assessed via 18f-FMISO or 18f-EF5 PET/CT pre-Nelfinavir versus post Nelfnavir lead-in</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in Glucose Metabolism From Nelfinavir</measure>
    <time_frame>From the initiation of any study procedures to 30 days following the completion of 7 chemoradiation</time_frame>
    <description>Change in Glucose Metabolism from Nelfinavir was determined by change in glucose uptake as assessed via FDG-PET/CT pre-Nelfinavir versus post Nelfnavir lead-in</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">18</enrollment>
  <condition>Head and Neck Squamous Cell Carcinoma</condition>
  <arm_group>
    <arm_group_label>Single Arm Phase 2</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Single Arm, Phase II study of Nelfinavir Lead-In (Period 1) Followed by Concurrent Chemoradiation with Nelfinavir (Period 2)</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Nelfinavir (Viracept®) 1250 mg</intervention_name>
    <description>Period 1: Nelfinavir Lead-In (1250 mg bid, 7-14 days).</description>
    <arm_group_label>Single Arm Phase 2</arm_group_label>
    <other_name>Nelfinavir Lead-In</other_name>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Chemoradiation</intervention_name>
    <description>Period 2: Concurrent Chemoradiation (70 Gy over 7 weeks) with Nelfinavir (1250 mg bid)</description>
    <arm_group_label>Single Arm Phase 2</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Patients ≥ 18 years old.&#xD;
&#xD;
          -  Histologically confirmed diagnosis of squamous cell carcinoma of the oral cavity,&#xD;
             oropharynx, larynx, or hypopharynx stages III, IVa, or IVb, p16-negative on&#xD;
             immunohistochemistry&#xD;
&#xD;
          -  Determined by the treating physician to be a candidate for organ preserving,&#xD;
             concurrent standard chemotherapy and radiation therapy to the head and neck with&#xD;
             definitive intent.&#xD;
&#xD;
          -  ECOG Performance Status 0-2&#xD;
&#xD;
          -  Patients must sign an informed consent document that indicates they are aware of the&#xD;
             investigational nature of the treatment in this protocol as well as the potential&#xD;
             risks and benefits.&#xD;
&#xD;
          -  The effects of EF5 on the developing human fetus are unknown. For this reason, women&#xD;
             of childbearing potential and men must agree to use adequate contraception (hormonal&#xD;
             or barrier method of birth control) prior to study entry, during study, until 1 month&#xD;
             after completion of the final FMISO PET/CT scan. Should a woman become pregnant or&#xD;
             suspect she is pregnant while participating in this study, she should inform her&#xD;
             treating physician immediately. Serum pregnancy testing will be required for women of&#xD;
             childbearing potential.&#xD;
&#xD;
          -  Ability to understand and the willingness to sign a written informed consent.&#xD;
&#xD;
        Exclusion Criteria&#xD;
&#xD;
          -  Prior radiation therapy to the head and neck&#xD;
&#xD;
          -  Prior chemotherapy within the past 5 years&#xD;
&#xD;
          -  Previous therapy with a human immunodeficiency virus (HIV) protease inhibitor&#xD;
&#xD;
          -  Pregnant or lactating patients.&#xD;
&#xD;
          -  Patients with known HIV disease. These patients have a high probability of treatment&#xD;
             with anti-retroviral therapy which may interact with the nelfinavir.&#xD;
&#xD;
          -  Absolute Neutrophil Count ≤ 1500 per mm3&#xD;
&#xD;
          -  Platelet count ≤ 100,000 per mm3&#xD;
&#xD;
          -  Serum creatinine &gt; 1.5 times the upper limit of normal&#xD;
&#xD;
          -  Serum AST or ALT &gt; 2 times the upper limit of normal&#xD;
&#xD;
          -  Serum bilirubin &gt; 1.2 mg/dl&#xD;
&#xD;
          -  Weight loss of &gt; 10% over the past 6 months which is due to tumor wasting syndrome&#xD;
&#xD;
          -  Distant metastases&#xD;
&#xD;
          -  Patients receiving the following drugs that are contraindicated with NFV will be&#xD;
             excluded: Antiarrhythmics:amiodarone, quinidine, Antimycobacterial: rifampin, Ergot&#xD;
             Derivatives:dihydroergotamine, ergonovine, ergotamine, methylergonovine, Herbal&#xD;
             Products: St.John's wort (hypericum perforatum), HMG-CoA Reductase Inhibitors:&#xD;
             lovastatin,simvastatin, Neuroleptic:pimozide, Proton Pump Inhibitors,&#xD;
             Sedative/Hypnotics: midazolam, triazolam,&#xD;
&#xD;
          -  Patients receiving the following drugs will be clinically evaluated as to whether&#xD;
             dosage/medication can be changed to permit patient on study: Anti-Convulsants:&#xD;
             carbamazepine, Phenobarbital, Anti-Convulsant:phenytoin, Anti-Mycobacterial:rifabutin,&#xD;
             PDE5 Inhibitors: sildenafil, vardenafil, tadalafil, HMG-CoA: Reductase Inhibitors:&#xD;
             atorvastatin, rosuvastatin, Immuno-suppressants: cyclosporine,tacrolimus, sirolimus,&#xD;
             Narcotic Analgesic: methadone, Oral Contraceptive:ethinyl estradiol, Macrolide&#xD;
             Antibiotic:azithromycin, Inhaled/nasal steroid fluticasone, Antidepressant: trazodone.&#xD;
&#xD;
          -  Women of childbearing potential who have a positive result on screening urine&#xD;
             pregnancy test.&#xD;
&#xD;
          -  Subjects with moderate-severe renal disease.&#xD;
&#xD;
          -  History of allergic reactionsattributed to Flagyl (metronidazole), which has a&#xD;
             chemical structure similar to FMISO.&#xD;
&#xD;
          -  Uncontrolled intercurrent illness including, but not limited to symptomatic congestive&#xD;
             heart failure, unstable angina pectoris, or psychiatric illness/social situations that&#xD;
             would limit compliance with study requirements.&#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>Alexander Lin, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Abramson Cancer Center at Penn Medicine</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Abramson Cancer Center of the University of Pennsylvania</name>
      <address>
        <city>Philadelphia</city>
        <state>Pennsylvania</state>
        <zip>19104</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>June 2023</verification_date>
  <study_first_submitted>July 31, 2014</study_first_submitted>
  <study_first_submitted_qc>August 1, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">August 4, 2014</study_first_posted>
  <results_first_submitted>October 6, 2022</results_first_submitted>
  <results_first_submitted_qc>June 30, 2023</results_first_submitted_qc>
  <results_first_posted type="Actual">July 25, 2023</results_first_posted>
  <last_update_submitted>June 30, 2023</last_update_submitted>
  <last_update_submitted_qc>June 30, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">July 25, 2023</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, Squamous Cell</mesh_term>
    <mesh_term>Squamous Cell Carcinoma of Head and Neck</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Nelfinavir</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>April 3, 2020</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/39/NCT02207439/Prot_SAP_000.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <group_list>
        <group group_id="P1">
          <title>Single Arm, 2 Period, Phase 2 Trial</title>
          <description>Period 1: Nelfinavir Lead-In (1250 mg bid, 7-14 days)&#xD;
Period 2: Definitive Chemoradiotherapy with Nelfinavir (70 Gy radiotherapy over 7 weeks)</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Nelfinavir Lead-In</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="17"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="17"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
              </participants_list>
            </milestone>
          </milestone_list>
        </period>
        <period>
          <title>Chemoradiotherapy With Nelfinavir</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="17"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="17"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
              </participants_list>
            </milestone>
          </milestone_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>Single Arm Phase 2</title>
          <description>Nelfinavir (Viracept®) 1250 mg&#xD;
FMISO</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="17"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>&lt;=18 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Between 18 and 65 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="15"/>
                  </measurement_list>
                </category>
                <category>
                  <title>&gt;=65 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Age</title>
          <units>years</units>
          <param>Median</param>
          <dispersion>Full Range</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="61" lower_limit="43" upper_limit="74"/>
                  </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="3"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="14"/>
                  </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_list>
                </category>
                <category>
                  <title>Asian</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Native Hawaiian or Other Pacific Islander</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Black or African American</title>
                  <measurement_list>
                    <measurement group_id="B1" value="3"/>
                  </measurement_list>
                </category>
                <category>
                  <title>White</title>
                  <measurement_list>
                    <measurement group_id="B1" value="14"/>
                  </measurement_list>
                </category>
                <category>
                  <title>More than one race</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" 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="17"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Locoregional head and neck cancer</title>
          <units>participants</units>
          <param>Number</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="17"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Locoregional Control</title>
        <description>locoregional control determined via diagnostic imaging and clinical examination.</description>
        <time_frame>5 years</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Single Arm Phase 2</title>
            <description>Locoregional Control</description>
          </group>
        </group_list>
        <measure>
          <title>Locoregional Control</title>
          <description>locoregional control determined via diagnostic imaging and clinical examination.</description>
          <units>participants</units>
          <param>Number</param>
          <dispersion>64.7% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="17"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="17" lower_limit="11" upper_limit="17"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Decrease in Hypoxia From Nelfinavir</title>
        <description>Decrease in Hypoxia from Nelfinavir was determined by change in uptake and volume as assessed via 18f-FMISO or 18f-EF5 PET/CT pre-Nelfinavir versus post Nelfnavir lead-in</description>
        <time_frame>7-14 days</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Single Arm, 2 Period, Phase 2 Trial</title>
            <description>Period 1: Nelfinavir Lead-In (1250 mg bid, 7-14 days)&#xD;
Period 2: Definitive Chemoradiotherapy with Nelfinavir (70 Gy radiotherapy over 7 weeks)</description>
          </group>
        </group_list>
        <measure>
          <title>Decrease in Hypoxia From Nelfinavir</title>
          <description>Decrease in Hypoxia from Nelfinavir was determined by change in uptake and volume as assessed via 18f-FMISO or 18f-EF5 PET/CT pre-Nelfinavir versus post Nelfnavir lead-in</description>
          <units>participants</units>
          <param>Number</param>
          <dispersion>67% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="12"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="12" lower_limit="8" upper_limit="12"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change in Glucose Metabolism From Nelfinavir</title>
        <description>Change in Glucose Metabolism from Nelfinavir was determined by change in glucose uptake as assessed via FDG-PET/CT pre-Nelfinavir versus post Nelfnavir lead-in</description>
        <time_frame>From the initiation of any study procedures to 30 days following the completion of 7 chemoradiation</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Single Arm, 2 Period, Phase 2 Trial</title>
            <description>Period 1: Nelfinavir Lead-In (1250 mg bid, 7-14 days)&#xD;
Period 2: Definitive Chemoradiotherapy with Nelfinavir (70 Gy radiotherapy over 7 weeks)</description>
          </group>
        </group_list>
        <measure>
          <title>Change in Glucose Metabolism From Nelfinavir</title>
          <description>Change in Glucose Metabolism from Nelfinavir was determined by change in glucose uptake as assessed via FDG-PET/CT pre-Nelfinavir versus post Nelfnavir lead-in</description>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="17"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="17"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>Start: at initiation of first study procedure (baseline PET/CT imaging) Ends: 30 days after last day of chemoradiation</time_frame>
      <group_list>
        <group group_id="E1">
          <title>Single Arm Phase 2</title>
          <description>Nelfinavir (Viracept®) 1250 mg&#xD;
FMISO</description>
        </group>
      </group_list>
      <serious_events>
        <default_vocab>CTCAE (5.0)</default_vocab>
        <default_assessment>Systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, all-cause mortality</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="17"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="17" subjects_at_risk="17"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Blood and lymphatic system disorders</title>
            <event_list>
              <event>
                <sub_title>Anemia</sub_title>
                <description>A disorder characterized by an reduction in the amount of hemoglobin in 100 ml of blood.</description>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="17"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Cardiac disorders</title>
            <event_list>
              <event>
                <sub_title>Sinus bradycardia</sub_title>
                <description>A disorder characterized by a dysrhythmia with a heart rate less than 60 beats per minute that originates in the sinus node.</description>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="17"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Dysphagia</sub_title>
                <description>A disorder characterized by difficulty in swallowing.</description>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="17"/>
              </event>
              <event>
                <sub_title>Esophagitis</sub_title>
                <description>A disorder characterized by inflammation of the esophageal wall.</description>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="17"/>
              </event>
              <event>
                <sub_title>Mucositis oral</sub_title>
                <description>A disorder characterized by inflammation of the oral mucosal.</description>
                <counts group_id="E1" events="3" subjects_affected="3" subjects_at_risk="17"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Hepatobiliary disorders</title>
            <event_list>
              <event>
                <sub_title>Cholecystitis</sub_title>
                <description>A disorder characterized by inflammation involving the gallbladder. It may be associated with the presence of gallstones.</description>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="17"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Immune system disorders</title>
            <event_list>
              <event>
                <sub_title>Allergic reaction</sub_title>
                <description>A disorder characterized by an adverse local or general response from exposure to an allergen.</description>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="17"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Investigations</title>
            <event_list>
              <event>
                <sub_title>Aspartate aminotransferase increased</sub_title>
                <description>A finding based on laboratory test results that indicate an increase in the level of aspartate aminotransferase (AST or SGOT) in a blood specimen.</description>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="17"/>
              </event>
              <event>
                <sub_title>Lymphocyte count decreased</sub_title>
                <description>A finding based on laboratory test results that indicate a decrease in number of lymphocytes in a blood specimen.</description>
                <counts group_id="E1" events="9" subjects_affected="5" subjects_at_risk="17"/>
              </event>
              <event>
                <sub_title>Neutrophil count decreased</sub_title>
                <description>A finding based on laboratory test results that indicate a decrease in number of neutrophils in a blood specimen.</description>
                <counts group_id="E1" events="3" subjects_affected="1" subjects_at_risk="17"/>
              </event>
              <event>
                <sub_title>Platelet count decreased</sub_title>
                <description>A finding based on laboratory test results that indicate a decrease in number of platelets in a blood specimen.</description>
                <counts group_id="E1" events="2" subjects_affected="1" subjects_at_risk="17"/>
              </event>
              <event>
                <sub_title>White blood cell decreased</sub_title>
                <description>A finding based on laboratory test results that indicate an decrease in number of white blood cells in a blood specimen.</description>
                <counts group_id="E1" events="46" subjects_affected="1" subjects_at_risk="17"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Metabolism and nutrition disorders</title>
            <event_list>
              <event>
                <sub_title>Anorexia</sub_title>
                <description>A disorder characterized by a loss of appetite.</description>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="17"/>
              </event>
              <event>
                <sub_title>Hyperglycemia</sub_title>
                <description>A disorder characterized by laboratory test results that indicate an elevation in the concentration of blood sugar.</description>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="17"/>
              </event>
              <event>
                <sub_title>Hypokalemia</sub_title>
                <description>A disorder characterized by laboratory test results that indicate a low concentration of potassium in the blood.</description>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="17"/>
              </event>
              <event>
                <sub_title>Hyponatremia</sub_title>
                <description>A disorder characterized by laboratory test results that indicate a low concentration of sodium in the blood.</description>
                <counts group_id="E1" events="3" subjects_affected="3" subjects_at_risk="17"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Dysgeusia</sub_title>
                <description>A disorder characterized by abnormal sensual experience with the taste of foodstuffs; it can be related to a decrease in the sense of smell.</description>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="17"/>
              </event>
              <event>
                <sub_title>Headache</sub_title>
                <description>A disorder characterized by a sensation of marked discomfort in various parts of the head, not confined to the area of distribution of any nerve.</description>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="17"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Aspiration</sub_title>
                <description>A disorder characterized by inhalation of solids or liquids into the lungs.</description>
                <counts group_id="E1" events="5" subjects_affected="2" subjects_at_risk="17"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Vascular disorders</title>
            <event_list>
              <event>
                <sub_title>Hypertension</sub_title>
                <description>A disorder characterized by a pathological increase in blood pressure</description>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="17"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>0</frequency_threshold>
        <default_vocab>CTCAE (5.0)</default_vocab>
        <default_assessment>Systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, other adverse events</sub_title>
                <counts group_id="E1" subjects_affected="17" subjects_at_risk="17"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Blood and lymphatic system disorders</title>
            <event_list>
              <event>
                <sub_title>Anemia</sub_title>
                <description>A disorder characterized by an reduction in the amount of hemoglobin in 100 ml of blood.</description>
                <counts group_id="E1" events="17" subjects_affected="8" subjects_at_risk="17"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Ear and labyrinth disorders</title>
            <event_list>
              <event>
                <sub_title>Ear pain</sub_title>
                <description>A disorder characterized by a sensation of marked discomfort in the ear.</description>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="17"/>
              </event>
              <event>
                <sub_title>Middle ear inflammation</sub_title>
                <description>A disorder characterized by inflammation (physiologic response to irritation), swelling and redness to the middle ear.</description>
                <counts group_id="E1" events="2" subjects_affected="1" subjects_at_risk="17"/>
              </event>
              <event>
                <sub_title>Tinnitus</sub_title>
                <description>A disorder characterized by noise in the ears, such as ringing, buzzing, roaring or clicking.</description>
                <counts group_id="E1" events="3" subjects_affected="3" subjects_at_risk="17"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Constipation</sub_title>
                <description>A disorder characterized by irregular and infrequent or difficult evacuation of the bowels.</description>
                <counts group_id="E1" events="9" subjects_affected="8" subjects_at_risk="17"/>
              </event>
              <event>
                <sub_title>Diarrhea</sub_title>
                <description>A disorder characterized by frequent and watery bowel movements.</description>
                <counts group_id="E1" events="8" subjects_affected="8" subjects_at_risk="17"/>
              </event>
              <event>
                <sub_title>Dry mouth</sub_title>
                <description>A disorder characterized by reduced salivary flow in the oral cavity.</description>
                <counts group_id="E1" events="8" subjects_affected="8" subjects_at_risk="17"/>
              </event>
              <event>
                <sub_title>Dysphagia</sub_title>
                <description>A disorder characterized by difficulty in swallowing.</description>
                <counts group_id="E1" events="17" subjects_affected="11" subjects_at_risk="17"/>
              </event>
              <event>
                <sub_title>Gastroesophageal reflux disease</sub_title>
                <description>A disorder characterized by reflux of the gastric and/or duodenal contents into the distal esophagus.</description>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="17"/>
              </event>
              <event>
                <sub_title>Gastroparesis</sub_title>
                <description>A disorder characterized by an incomplete paralysis of the muscles of the stomach wall resulting in delayed emptying of the gastric contents into the small intestine.</description>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="17"/>
              </event>
              <event>
                <sub_title>Hemorrhoids</sub_title>
                <description>A disorder characterized by the presence of dilated veins in the rectum and surrounding area.</description>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="17"/>
              </event>
              <event>
                <sub_title>Mucositis oral</sub_title>
                <description>A disorder characterized by inflammation of the oral mucosal.</description>
                <counts group_id="E1" events="13" subjects_affected="9" subjects_at_risk="17"/>
              </event>
              <event>
                <sub_title>Nausea</sub_title>
                <description>A disorder characterized by a queasy sensation and/or the urge to vomit.</description>
                <counts group_id="E1" events="7" subjects_affected="7" subjects_at_risk="17"/>
              </event>
              <event>
                <sub_title>Oral pain</sub_title>
                <description>A disorder characterized by a sensation of marked discomfort in the mouth, tongue or lips.</description>
                <counts group_id="E1" events="3" subjects_affected="3" subjects_at_risk="17"/>
              </event>
              <event>
                <sub_title>Salivary duct inflammation</sub_title>
                <description>A disorder characterized by inflammation of the salivary duct.</description>
                <counts group_id="E1" events="14" subjects_affected="10" subjects_at_risk="17"/>
              </event>
              <event>
                <sub_title>Stomach pain</sub_title>
                <description>A disorder characterized by a sensation of marked discomfort in the stomach.</description>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="17"/>
              </event>
              <event>
                <sub_title>Vomiting</sub_title>
                <description>A disorder characterized by the reflexive act of ejecting the contents of the stomach through the mouth.</description>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="17"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Edema face</sub_title>
                <description>A disorder characterized by swelling due to excessive fluid accumulation in facial tissues.</description>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="17"/>
              </event>
              <event>
                <sub_title>Edema limbs</sub_title>
                <description>A disorder characterized by swelling due to excessive fluid accumulation in the upper or lower extremities.</description>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="17"/>
              </event>
              <event>
                <sub_title>Fatigue</sub_title>
                <description>A disorder characterized by a state of generalized weakness with a pronounced inability to summon sufficient energy to accomplish daily activities.</description>
                <counts group_id="E1" events="17" subjects_affected="11" subjects_at_risk="17"/>
              </event>
              <event>
                <sub_title>Fever</sub_title>
                <description>A disorder characterized by elevation of the body's temperature above the upper limit of normal.</description>
                <counts group_id="E1" events="3" subjects_affected="2" subjects_at_risk="17"/>
              </event>
              <event>
                <sub_title>Localized edema</sub_title>
                <description>A disorder characterized by swelling due to excessive fluid accumulation at a specific anatomic site.</description>
                <counts group_id="E1" events="2" subjects_affected="1" subjects_at_risk="17"/>
              </event>
              <event>
                <sub_title>Neck edema</sub_title>
                <description>A disorder characterized by swelling due to an accumulation of excessive fluid in the neck.</description>
                <counts group_id="E1" events="8" subjects_affected="7" subjects_at_risk="17"/>
              </event>
              <event>
                <sub_title>Pain</sub_title>
                <description>A disorder characterized by the sensation of marked discomfort, distress or agony.</description>
                <counts group_id="E1" events="8" subjects_affected="5" subjects_at_risk="17"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Immune system disorders</title>
            <event_list>
              <event>
                <sub_title>Allergic reaction</sub_title>
                <description>A disorder characterized by an adverse local or general response from exposure to an allergen.</description>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="17"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Infections and infestations</sub_title>
                <description>Infections and infestations</description>
                <counts group_id="E1" events="3" subjects_affected="2" subjects_at_risk="17"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Injury, poisoning and procedural complications</title>
            <event_list>
              <event>
                <sub_title>Dermatitis radiation</sub_title>
                <description>A finding of cutaneous inflammatory reaction occurring as a result of exposure to biologically effective levels of ionizing radiation.</description>
                <counts group_id="E1" events="21" subjects_affected="14" subjects_at_risk="17"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Investigations</title>
            <event_list>
              <event>
                <sub_title>Alanine aminotransferase increased</sub_title>
                <description>A finding based on laboratory test results that indicate an increase in the level of alanine aminotransferase (ALT or SGPT) in the blood specimen.</description>
                <counts group_id="E1" events="4" subjects_affected="3" subjects_at_risk="17"/>
              </event>
              <event>
                <sub_title>Alkaline phosphatase increased</sub_title>
                <description>A finding based on laboratory test results that indicate an increase in the level of alkaline phosphatase in a blood specimen.</description>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="17"/>
              </event>
              <event>
                <sub_title>Aspartate aminotransferase increased</sub_title>
                <description>A finding based on laboratory test results that indicate an increase in the level of aspartate aminotransferase (AST or SGOT) in a blood specimen.</description>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="17"/>
              </event>
              <event>
                <sub_title>Creatinine increased</sub_title>
                <description>A finding based on laboratory test results that indicate increased levels of creatinine in a biological specimen.</description>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="17"/>
              </event>
              <event>
                <sub_title>Lymphocyte count decreased</sub_title>
                <description>A finding based on laboratory test results that indicate a decrease in number of lymphocytes in a blood specimen.</description>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="17"/>
              </event>
              <event>
                <sub_title>Lymphocyte count increased</sub_title>
                <description>A finding based on laboratory test results that indicate an abnormal increase in the number of lymphocytes in the blood, effusions or bone marrow.</description>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="17"/>
              </event>
              <event>
                <sub_title>Platelet count decreased</sub_title>
                <description>A finding based on laboratory test results that indicate a decrease in number of platelets in a blood specimen.</description>
                <counts group_id="E1" events="5" subjects_affected="2" subjects_at_risk="17"/>
              </event>
              <event>
                <sub_title>Weight loss</sub_title>
                <description>A finding characterized by a decrease in overall body weight; for pediatrics, less than the baseline growth curve.</description>
                <counts group_id="E1" events="6" subjects_affected="4" subjects_at_risk="17"/>
              </event>
              <event>
                <sub_title>White blood cell decreased</sub_title>
                <description>A finding based on laboratory test results that indicate an decrease in number of white blood cells in a blood specimen.</description>
                <counts group_id="E1" events="332" subjects_affected="17" subjects_at_risk="17"/>
              </event>
              <event>
                <sub_title>Investigations</sub_title>
                <description>Investigations</description>
                <counts group_id="E1" events="8" subjects_affected="2" subjects_at_risk="17"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Metabolism and nutrition disorders</title>
            <event_list>
              <event>
                <sub_title>Anorexia</sub_title>
                <description>A disorder characterized by a loss of appetite.</description>
                <counts group_id="E1" events="17" subjects_affected="9" subjects_at_risk="17"/>
              </event>
              <event>
                <sub_title>Dehydration</sub_title>
                <description>A disorder characterized by excessive loss of water from the body. It is usually caused by severe diarrhea, vomiting or diaphoresis.</description>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="17"/>
              </event>
              <event>
                <sub_title>Hyperglycemia</sub_title>
                <description>A disorder characterized by laboratory test results that indicate an elevation in the concentration of blood sugar.</description>
                <counts group_id="E1" events="2" subjects_affected="1" subjects_at_risk="17"/>
              </event>
              <event>
                <sub_title>Hyperkalemia</sub_title>
                <description>A disorder characterized by laboratory test results that indicate an elevation in the concentration of potassium in the blood; associated with kidney failure or sometimes with the use of diuretic drugs.</description>
                <counts group_id="E1" events="2" subjects_affected="1" subjects_at_risk="17"/>
              </event>
              <event>
                <sub_title>Hypoalbuminemia</sub_title>
                <description>A disorder characterized by laboratory test results that indicate a low concentration of albumin in the blood.</description>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="17"/>
              </event>
              <event>
                <sub_title>Hypocalcemia</sub_title>
                <description>A disorder characterized by laboratory test results that indicate a low concentration of calcium in the blood.</description>
                <counts group_id="E1" events="6" subjects_affected="4" subjects_at_risk="17"/>
              </event>
              <event>
                <sub_title>Hypokalemia</sub_title>
                <description>A disorder characterized by laboratory test results that indicate a low concentration of potassium in the blood.</description>
                <counts group_id="E1" events="5" subjects_affected="2" subjects_at_risk="17"/>
              </event>
              <event>
                <sub_title>Hypomagnesemia</sub_title>
                <description>A disorder characterized by laboratory test results that indicate a low concentration of magnesium in the blood.</description>
                <counts group_id="E1" events="6" subjects_affected="4" subjects_at_risk="17"/>
              </event>
              <event>
                <sub_title>Hyponatremia</sub_title>
                <description>A disorder characterized by laboratory test results that indicate a low concentration of sodium in the blood.</description>
                <counts group_id="E1" events="8" subjects_affected="5" subjects_at_risk="17"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Musculoskeletal and connective tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Back pain</sub_title>
                <description>A disorder characterized by marked discomfort sensation in the back region.</description>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="17"/>
              </event>
              <event>
                <sub_title>Neck pain</sub_title>
                <description>A disorder characterized by marked discomfort sensation in the neck area.</description>
                <counts group_id="E1" events="3" subjects_affected="3" subjects_at_risk="17"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Dizziness</sub_title>
                <description>A disorder characterized by a disturbing sensation of lightheadedness, unsteadiness, giddiness, spinning or rocking.</description>
                <counts group_id="E1" events="3" subjects_affected="3" subjects_at_risk="17"/>
              </event>
              <event>
                <sub_title>Dysgeusia</sub_title>
                <description>A disorder characterized by abnormal sensual experience with the taste of foodstuffs; it can be related to a decrease in the sense of smell.</description>
                <counts group_id="E1" events="22" subjects_affected="15" subjects_at_risk="17"/>
              </event>
              <event>
                <sub_title>Headache</sub_title>
                <description>A disorder characterized by a sensation of marked discomfort in various parts of the head, not confined to the area of distribution of any nerve.</description>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="17"/>
              </event>
              <event>
                <sub_title>Somnolence</sub_title>
                <description>A disorder characterized by characterized by excessive sleepiness and drowsiness.</description>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="17"/>
              </event>
              <event>
                <sub_title>Tremor</sub_title>
                <description>A disorder characterized by the uncontrolled shaking movement of the whole body or individual parts.</description>
                <counts group_id="E1" events="3" subjects_affected="3" subjects_at_risk="17"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Psychiatric disorders</title>
            <event_list>
              <event>
                <sub_title>Agitation</sub_title>
                <description>A disorder characterized by a state of restlessness associated with unpleasant feelings of irritability and tension.</description>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="17"/>
              </event>
              <event>
                <sub_title>Anxiety</sub_title>
                <description>A disorder characterized by apprehension of danger and dread accompanied by restlessness, tension, tachycardia, and dyspnea unattached to a clearly identifiable stimulus.</description>
                <counts group_id="E1" events="4" subjects_affected="3" subjects_at_risk="17"/>
              </event>
              <event>
                <sub_title>Depression</sub_title>
                <description>A disorder characterized by melancholic feelings of grief or unhappiness.</description>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="17"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Reproductive system and breast disorders</title>
            <event_list>
              <event>
                <sub_title>Prostatic pain</sub_title>
                <description>A disorder characterized by a sensation of marked discomfort in the prostate gland.</description>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="17"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Aspiration</sub_title>
                <description>A disorder characterized by inhalation of solids or liquids into the lungs.</description>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="17"/>
              </event>
              <event>
                <sub_title>Cough</sub_title>
                <description>A disorder characterized by sudden, often repetitive, spasmodic contraction of the thoracic cavity, resulting in violent release of air from the lungs and usually accompanied by a distinctive sound.</description>
                <counts group_id="E1" events="4" subjects_affected="4" subjects_at_risk="17"/>
              </event>
              <event>
                <sub_title>Dyspnea</sub_title>
                <description>A disorder characterized by an uncomfortable sensation of difficulty breathing.</description>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="17"/>
              </event>
              <event>
                <sub_title>Hiccups</sub_title>
                <description>A disorder characterized by repeated gulp sounds that result from an involuntary opening and closing of the glottis. This is attributed to a spasm of the diaphragm.</description>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="17"/>
              </event>
              <event>
                <sub_title>Hoarseness</sub_title>
                <description>A disorder characterized by harsh and raspy voice arising from or spreading to the larynx.</description>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="17"/>
              </event>
              <event>
                <sub_title>Laryngeal edema</sub_title>
                <description>A disorder characterized by swelling due to an excessive accumulation of fluid in the larynx.</description>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="17"/>
              </event>
              <event>
                <sub_title>Sore throat</sub_title>
                <description>A disorder characterized by of marked discomfort in the throat</description>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="17"/>
              </event>
              <event>
                <sub_title>Voice alteration</sub_title>
                <description>A disorder characterized by a change in the sound and/or speed of the voice.</description>
                <counts group_id="E1" events="7" subjects_affected="6" subjects_at_risk="17"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Skin and subcutaneous tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Alopecia</sub_title>
                <description>A disorder characterized by a decrease in density of hair compared to normal for a given individual at a given age and body location</description>
                <counts group_id="E1" events="3" subjects_affected="3" subjects_at_risk="17"/>
              </event>
              <event>
                <sub_title>Bullous dermatitis</sub_title>
                <description>A disorder characterized by inflammation of the skin characterized by the presence of bullae which are filled with fluid.</description>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="17"/>
              </event>
              <event>
                <sub_title>Erythema multiforme</sub_title>
                <description>A disorder characterized by target lesions (a pink-red ring around a pale center).</description>
                <counts group_id="E1" events="4" subjects_affected="4" subjects_at_risk="17"/>
              </event>
              <event>
                <sub_title>Esophageal pain</sub_title>
                <description>A disorder characterized by a sensation of marked discomfort in the esophageal region.</description>
                <counts group_id="E1" events="2" subjects_affected="1" subjects_at_risk="17"/>
              </event>
              <event>
                <sub_title>Rash maculo-papular</sub_title>
                <description>A disorder characterized by the presence of macules (flat) and papules (elevated)</description>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="17"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Vascular disorders</title>
            <event_list>
              <event>
                <sub_title>Hypotension</sub_title>
                <description>A disorder characterized by a blood pressure that is below the normal expected for an individual in a given environment.</description>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="17"/>
              </event>
              <event>
                <sub_title>Thromboembolic event</sub_title>
                <description>A disorder characterized by occlusion of a vessel by a thrombus that has migrated from a distal site via the blood stream.</description>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="17"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </other_events>
    </reported_events>

    <certain_agreements>
      <pi_employee>Principal Investigators are NOT employed by the organization sponsoring the study.</pi_employee>
      <restrictive_agreement>There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed. </restrictive_agreement>
    </certain_agreements>
    <point_of_contact>
      <name_or_title>Alexander Lin, MD</name_or_title>
      <organization>University of Pennsylvania</organization>
      <phone>215-662-3198</phone>
      <email>alexander.lin2@pennmedicine.upenn.edu</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/NCT02207439
org study id: UPCC 15313
nct id: NCT02207439
lead sponsor: 
has dmc: Yes
This is a Phase II trial of definitive chemoradiotherapy (CTRT) given with the protease
      inhibitor,Nelfinavir (NFV), in patients with locally advanced head and neck. Eligible
      patients will receive a "lead-in" period of Nelfinavir (1250 mg po bid) for 7-14 days prior
      to initiation of CTRT. Nelfinavir will then be given concurrently with platinum-based
      chemotherapy and radiation therapy (planned total dose of 70 Gy over 7 weeks).
This is a single-arm Phase II study of organ-preservation chemoradiotherapy given in
      combination with the protease inhibitor, Nelfinavir, in patients with stage II, IVa, or IVb
      (per AJCC version 7) squamous cell carcinoma of the oral cavity, oropharynx, larynx, or
      hypopharynx. Patients start treatment with Nelfinvir at a dose of 1250 mg twice daily for
      7-14 days, before continuing Nelfinvir at this dose concurrent with chemotherapy and
      radiation therapy (for a total dose of 70 Gy over a period of 7 weeks).
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Diagnostic
masking: None (Open Label)
measure: Locoregional Control
time frame: 5 years
description: locoregional control determined via diagnostic imaging and clinical examination.
measure: Decrease in Hypoxia From Nelfinavir
time frame: 7-14 days
description: Decrease in Hypoxia from Nelfinavir was determined by change in uptake and volume as assessed via 18f-FMISO or 18f-EF5 PET/CT pre-Nelfinavir versus post Nelfnavir lead-in
measure: Change in Glucose Metabolism From Nelfinavir
time frame: From the initiation of any study procedures to 30 days following the completion of 7 chemoradiation
description: Change in Glucose Metabolism from Nelfinavir was determined by change in glucose uptake as assessed via FDG-PET/CT pre-Nelfinavir versus post Nelfnavir lead-in
arm group label: Single Arm Phase 2
arm group type: Experimental
description: Single Arm, Phase II study of Nelfinavir Lead-In (Period 1) Followed by Concurrent Chemoradiation with Nelfinavir (Period 2)
intervention type: Drug
intervention name: Nelfinavir (Viracept®) 1250 mg
description: Period 1: Nelfinavir Lead-In (1250 mg bid, 7-14 days).
arm group label: Single Arm Phase 2
other name: Nelfinavir Lead-In
intervention type: Other
intervention name: Chemoradiation
description: Period 2: Concurrent Chemoradiation (70 Gy over 7 weeks) with Nelfinavir (1250 mg bid)
arm group label: Single Arm Phase 2
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Alexander Lin, MD
role: Principal Investigator
affiliation: Abramson Cancer Center at Penn Medicine
facility: 
country: United States
responsible party type: Sponsor
mesh term: Carcinoma
mesh term: Carcinoma, Squamous Cell
mesh term: Squamous Cell Carcinoma of Head and Neck
mesh term: Nelfinavir
provided document: 
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 