<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/NCT01711658</url>
  </required_header>
  <id_info>
    <org_study_id>RF-3501</org_study_id>
    <secondary_id>LAP116153</secondary_id>
    <nct_id>NCT01711658</nct_id>
  </id_info>
  <brief_title>TRYHARD: Radiation Therapy Plus Cisplatin With or Without Lapatinib in Treating Patients With Head and Neck Cancer.</brief_title>
  <acronym>TRYHARD</acronym>
  <official_title>TRYHARD: A Phase II, Randomized, Double Blind, Placebo-Controlled Study of Lapatinib (Tykerb®) for Non-HPV Locally Advanced Head and Neck Cancer With Concurrent Chemoradiation</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Radiation Therapy Oncology Group</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>GlaxoSmithKline</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
    <collaborator>
      <agency>Novartis</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>Radiation Therapy Oncology Group</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      PURPOSE: This trial is studying if and how well lapatinib adds to the effectiveness of&#xD;
      radiation therapy plus cisplatin in patients who have head and neck cancer that is not&#xD;
      related to the human papillomavirus (HPV).&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Active, not recruiting</overall_status>
  <start_date type="Actual">March 15, 2013</start_date>
  <completion_date type="Anticipated">January 1, 2026</completion_date>
  <primary_completion_date type="Actual">December 1, 2020</primary_completion_date>
  <phase>Phase 2</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Percentage of Participants Alive Without Progression (Progression-free Survival)</measure>
    <time_frame>From randomization to last follow-up. Maximum follow-up at time of analysis was 7.1 years.</time_frame>
    <description>An event for progression-free survival is local, regional, or distant disease progression or death due to any cause. Progression-free survival time is defined as time from randomization to the date of progression/death or last known follow-up (censored). Rates are estimated by the Kaplan-Meier method. The protocol specifies that the distributions of survival times be compared between the arms, which is reported in the statistical analysis results. Five-year rates are provided. Analysis occurred after 67 progressions or deaths were reported.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Percentage of Participants Alive (Overall Survival)</measure>
    <time_frame>From randomization to last follow-up. Maximum follow-up at time of analysis was 7.1 years.</time_frame>
    <description>An event for overall survival is death due to any cause. Overall survival time is defined as time from randomization to the date of death or last known follow-up (censored). Rates are estimated by the Kaplan-Meier method. The protocol specifies that the distributions of survival times be compared between the arms, which is reported in the statistical analysis results. Five-year rates are provided.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percentage of Participants With Distant Metastases</measure>
    <time_frame>From randomization to last follow-up. Maximum follow-up at time of analysis was 7.1 years.</time_frame>
    <description>Failure for distant metastasis endpoint was defined as distant progression; local-regional failure and death due to any cause were considered competing risks. Distant metastasis time is defined as time from randomization to the date of progression/death or last known follow-up (censored). Rates are estimated by the cumulative incidence method. The protocol specifies that the distributions of failure times be compared between the arms, which is reported in the statistical analysis results. Five-year rates are provided.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percentage of Participants With Treatment-related Grade 3 or Higher Adverse Events</measure>
    <time_frame>From start of treatment to last follow-up. Maximum follow-up at time of analysis was 7.1 years.</time_frame>
    <description>Adverse events (AE) were graded using the Common Terminology Criteria for Adverse Events (CTCAE) v4.0. Grade refers to the severity of the AE. The CTCAE v4.0 assigns Grades 1 through 5 with unique clinical descriptions of severity for each AE based on this general guideline: Grade 1 Mild, Grade 2 Moderate, Grade 3 Severe, Grade 4 Life-threatening or disabling, Grade 5 Death related to adverse event. &quot;Treatment-related&quot; is defined definitely, probably, or possibly related to treatment.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percentage of Participants Who Complied With Protocol Treatment</measure>
    <time_frame>From start of treatment to end of treatment (approximately 5 months from randomization).</time_frame>
    <description>Compliance with protocol treatment is defined as &quot;per protocol&quot; or &quot;acceptable variation&quot; per study chair review for IMRT, cisplatin, pre-IMRT lapatinib/placebo, concurrent lapatinib/placebo, and maintenance lapatinib/placebo. Rates of treatment compliance were compared between groups by a 2-sided Fisher's exact test.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percentage of Participants With Local-regional Progression</measure>
    <time_frame>From randomization to last follow-up. Maximum follow-up at time of analysis was 7.1 years.</time_frame>
    <description>Failure for local-regional control endpoint was defined as local or regional progression, salvage surgery of the primary tumor with tumor present/unknown, salvage neck dissection with tumor present/unknown &gt; 20 weeks after the end of radiation therapy, death due to study cancer without documented progression, or death due to unknown causes without documented progression; distant metastasis and death due to other causes were considered competing risks. Local-regional failure time is defined as time from randomization to the date of progression/death or last known follow-up (censored). Failure rates are estimated by the cumulative incidence method. The protocol specifies that the distributions of failure times be compared between the arms, which is reported in the statistical analysis results. Five-year rates are provided.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Performance Status Scale for Head &amp; Neck Cancer.</measure>
    <time_frame>3 months, 1 year, and 2 years</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Functional Assessment of Cancer Therapy - Head &amp; Neck.</measure>
    <time_frame>3 months, 1 year, and 2 years.</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>University of Michigan Xerostomia-Related Quality of Life Scale.</measure>
    <time_frame>3 months, 1 year, and 2 years.</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>HER2, EGFR, EMT as Biomarkers of Response.</measure>
    <time_frame>End of Study</time_frame>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">142</enrollment>
  <condition>Non-HPV Locally Advanced Head and Neck Cancer</condition>
  <arm_group>
    <arm_group_label>IMRT + cisplatin + placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Intensity Modulated Radiation Therapy (IMRT) with cisplatin and placebo</description>
  </arm_group>
  <arm_group>
    <arm_group_label>IMRT + cisplatin + lapatinib</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>IMRT with cisplatin and lapatinib</description>
  </arm_group>
  <intervention>
    <intervention_type>Radiation</intervention_type>
    <intervention_name>IMRT</intervention_name>
    <description>Intensity modulated radiation therapy (IMRT), 35 fractions over 6 weeks, 6 fractions per week for 5 weeks and 5 fractions per week for 1 week, 2 Gy per fraction to total dose of 70 Gy</description>
    <arm_group_label>IMRT + cisplatin + lapatinib</arm_group_label>
    <arm_group_label>IMRT + cisplatin + placebo</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Cisplatin</intervention_name>
    <description>100 mg/m^2 administered intravenously on days 8 and 29</description>
    <arm_group_label>IMRT + cisplatin + lapatinib</arm_group_label>
    <arm_group_label>IMRT + cisplatin + placebo</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>placebo</intervention_name>
    <description>1500 mg placebo daily by mouth or by feeding tube starting 7 days before IMRT for 7 weeks prior to and during IMRT and 3 months after completion of IMRT</description>
    <arm_group_label>IMRT + cisplatin + placebo</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Lapatinib</intervention_name>
    <description>1500 mg lapatinib by mouth or by feeding tube daily starting 7 days before IMRT for 7 weeks prior to and during IMRT and 3 months after completion of IMRT</description>
    <arm_group_label>IMRT + cisplatin + lapatinib</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion criteria:&#xD;
&#xD;
          -  Patients must have histologically or cytologically confirmed diagnosis (from primary&#xD;
             lesion and/or lymph nodes) of Squamous Cell Cancer of the oropharynx, hypopharynx or&#xD;
             larynx (For patients with oropharynx primary, the tumor must be negative for p16 by&#xD;
             immunohistochemistry).&#xD;
&#xD;
          -  Patients with selected Stage III or IV disease (T2 N2-3 M0, T3-4 any N M0, T1 N2b, N2c&#xD;
             or N3 p16 negative oropharynx cancer or T1-2 any N+ hypopharynx cancer) including no&#xD;
             distant metastases.&#xD;
&#xD;
          -  History/Physical examination by a Radiation Oncologist and Medical oncologist prior to&#xD;
             entering the study.&#xD;
&#xD;
          -  Examination by an ears, nose, throat (ENT) or Head &amp; Neck Surgeon including&#xD;
             laryngopharyngoscopy prior to entering the study.&#xD;
&#xD;
          -  Patients must have a chest CT scan, or positron emission tomography (PET)/CT scan to&#xD;
             rule out metastatic disease&#xD;
&#xD;
          -  Patients must have a contrast enhanced CT scan or MRI or PET/CT scan of the tumor site&#xD;
             and neck nodes prior to entering the study.&#xD;
&#xD;
          -  Patients must have an EKG and echocardiogram (ECHO) or multigated acquisition (MUGA)&#xD;
             scan prior to entering the study.&#xD;
&#xD;
          -  Patients must have Zubrod Performance Status of 0-1.&#xD;
&#xD;
          -  Patients must be ≥ 18 years of age.&#xD;
&#xD;
          -  Patients must have normal organ and marrow function as defined below:&#xD;
&#xD;
               -  Absolute neutrophil count (ANC) ≥ 1,500 cells/mm3&#xD;
&#xD;
               -  Platelets ≥ 100,000 cells/mm3&#xD;
&#xD;
               -  Hemoglobin ≥ 8.0 g/dl&#xD;
&#xD;
               -  Serum creatinine &lt; 1.5 mg/dl or creatinine clearance (CC) ≥ 50 ml/min&#xD;
&#xD;
               -  Total bilirubin &lt; 2 x the institutional upper limit of normal&#xD;
&#xD;
               -  Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) ≤ 3 x the&#xD;
                  institutional upper limit of normal&#xD;
&#xD;
          -  Patient must have magnesium, calcium, glucose, potassium and sodium levels within&#xD;
             normal limits&#xD;
&#xD;
          -  Women of childbearing potential must have a negative pregnancy test prior to&#xD;
             registration.&#xD;
&#xD;
          -  Patients of reproductive potential must practice effective contraception while on&#xD;
             study and for at least 60 calendar days following treatment.&#xD;
&#xD;
          -  All patients must sign an informed consent prior to enrollment.&#xD;
&#xD;
          -  Patients must comply with the treatment plan and follow-up schedule.&#xD;
&#xD;
        Exclusion criteria:&#xD;
&#xD;
          -  Patients with simultaneous primaries or bilateral tumors.&#xD;
&#xD;
          -  Patients who have had gross total excision of the primary tumor.&#xD;
&#xD;
          -  Patients with initial surgical treatment, radical or modified neck dissection.&#xD;
&#xD;
          -  Patients who received prior systemic chemotherapy for the study cancer.&#xD;
&#xD;
          -  Patients who received prior radiotherapy to the region of the study cancer that would&#xD;
             result in overlap of radiation therapy fields.&#xD;
&#xD;
          -  Patients with primary tumor of oral cavity, nasopharynx, sinuses or salivary glands.&#xD;
&#xD;
          -  Prior allergic reaction to the study drugs.&#xD;
&#xD;
          -  Patients who have had prior therapy that specifically and directly targets the&#xD;
             epidermal growth factor receptor (EGFR)/human epidermal growth factor receptor 2&#xD;
             (HER2) pathway.&#xD;
&#xD;
          -  Patients who have current active hepatic or biliary disease (with exception of&#xD;
             patients with Gilbert's syndrome, asymptomatic gallstones, or stable chronic liver&#xD;
             disease per investigator assessment);&#xD;
&#xD;
          -  Pregnant women or sexually active patients not willing or able to use medically&#xD;
             acceptable forms of contraceptive method while on treatment.&#xD;
&#xD;
          -  Patients with severe, active co-morbidity, defined as follows:&#xD;
&#xD;
               -  Uncontrolled cardiac disease, such as uncontrolled hypertension, unstable angina,&#xD;
                  and/or congestive heart failure requiring hospitalization within the last 6&#xD;
                  months&#xD;
&#xD;
               -  Transmural myocardial infarction within the last 6 months&#xD;
&#xD;
               -  Left ventricular ejection fraction &lt; 45%&#xD;
&#xD;
               -  Acute bacterial or fungal infection requiring intravenous antibiotics at the time&#xD;
                  of registration&#xD;
&#xD;
               -  Chronic Obstructive Pulmonary Disease exacerbation or other respiratory illness&#xD;
                  requiring hospitalization or precluding study therapy within 30 calendar days&#xD;
                  prior to registration&#xD;
&#xD;
               -  Hepatic insufficiency resulting in clinical jaundice and/or Coagulation defects&#xD;
&#xD;
               -  Acquired Immune Deficiency Syndrome (AIDS) based upon current Centers for Disease&#xD;
                  Control and Prevention (CDC) definition&#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>Stuart Wong, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Medical College of Wisconsin</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>University of Alabama at Birmingham Comprehensive Cancer Center</name>
      <address>
        <city>Birmingham</city>
        <state>Alabama</state>
        <zip>35294</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of California, San Diego</name>
      <address>
        <city>La Jolla</city>
        <state>California</state>
        <zip>92093</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Sutter General Hospital</name>
      <address>
        <city>Sacramento</city>
        <state>California</state>
        <zip>95816</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of California San Francisco</name>
      <address>
        <city>San Francisco</city>
        <state>California</state>
        <zip>94143</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Yale University</name>
      <address>
        <city>New Haven</city>
        <state>Connecticut</state>
        <zip>06520</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Emory University</name>
      <address>
        <city>Atlanta</city>
        <state>Georgia</state>
        <zip>30308</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>James Graham Brown Cancer Center at University of Louisville</name>
      <address>
        <city>Louisville</city>
        <state>Kentucky</state>
        <zip>40202</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University Hospitals of Cleveland</name>
      <address>
        <city>Cleveland</city>
        <state>Ohio</state>
        <zip>44106</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Ohio State University Medical Center</name>
      <address>
        <city>Columbus</city>
        <state>Ohio</state>
        <zip>43210</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Oklahoma Health Sciences Center</name>
      <address>
        <city>Oklahoma City</city>
        <state>Oklahoma</state>
        <zip>73190</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Fox Chase Cancer Center Buckingham</name>
      <address>
        <city>Furlong</city>
        <state>Pennsylvania</state>
        <zip>18925</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Texas Southwestern Medical School</name>
      <address>
        <city>Dallas</city>
        <state>Texas</state>
        <zip>75390</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Texas - MD Anderson Cancer Center</name>
      <address>
        <city>Houston</city>
        <state>Texas</state>
        <zip>77030-4009</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Wisconsin Comprehensive Cancer Center</name>
      <address>
        <city>Madison</city>
        <state>Wisconsin</state>
        <zip>53792</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Medical College of Wisconsin</name>
      <address>
        <city>Milwaukee</city>
        <state>Wisconsin</state>
        <zip>53226</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>McGill Cancer Centre at McGill University</name>
      <address>
        <city>Montreal</city>
        <state>Quebec</state>
        <zip>H2W 1S6</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Canada</country>
    <country>United States</country>
  </location_countries>
  <reference>
    <citation>Ang KK, Harris J, Wheeler R, Weber R, Rosenthal DI, Nguyen-Tan PF, Westra WH, Chung CH, Jordan RC, Lu C, Kim H, Axelrod R, Silverman CC, Redmond KP, Gillison ML. Human papillomavirus and survival of patients with oropharyngeal cancer. N Engl J Med. 2010 Jul 1;363(1):24-35. doi: 10.1056/NEJMoa0912217. Epub 2010 Jun 7.</citation>
    <PMID>20530316</PMID>
  </reference>
  <reference>
    <citation>Harrington K. et al. Phase II study of oral Lapatinib, a dual-tyrosine kinase inhibitor, combined with chemoradiotherapy (CRT) in patients with advanced squamous cell carcinoma of the head and neck (SCCHN). J Clin Oncol. 28:15s, 2010 suppl. Abstract 5505. GSK study 884</citation>
  </reference>
  <verification_date>October 2021</verification_date>
  <study_first_submitted>October 16, 2012</study_first_submitted>
  <study_first_submitted_qc>October 18, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">October 22, 2012</study_first_posted>
  <results_first_submitted>October 29, 2021</results_first_submitted>
  <results_first_submitted_qc>October 29, 2021</results_first_submitted_qc>
  <results_first_posted type="Actual">November 29, 2021</results_first_posted>
  <last_update_submitted>October 29, 2021</last_update_submitted>
  <last_update_submitted_qc>October 29, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">November 29, 2021</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Head and Neck Neoplasms</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Lapatinib</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 27, 2016</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/58/NCT01711658/Prot_SAP_000.pdf</document_url>
    </provided_document>
    <provided_document>
      <document_type>Informed Consent Form</document_type>
      <document_has_protocol>No</document_has_protocol>
      <document_has_icf>Yes</document_has_icf>
      <document_has_sap>No</document_has_sap>
      <document_date>September 27, 2016</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/58/NCT01711658/ICF_001.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <pre_assignment_details>After first step registration and prior to randomization, patients with oropharyngeal cancer were tested for p16. Only patients with p16-negative tumors continued to randomization. Patients with larynx or hypopharynx cancer did not require p16 testing. In total, 142 patients were enrolled and 127 were randomized.</pre_assignment_details>
      <group_list>
        <group group_id="P1">
          <title>IMRT + Cisplatin + Placebo</title>
          <description>Intensity Modulated Radiation Therapy (IMRT), 35 fractions over 6 weeks, 6 fractions per week for 5 weeks and 5 fractions per week for 1 week, 2 Gy per fraction to total dose of 70 Gy&#xD;
Cisplatin: 100 mg/m^2 administered intravenously on days 8 and 29&#xD;
Placebo: 1500 mg placebo daily by mouth or by feeding tube starting 7 days before IMRT for 7 weeks prior to and during IMRT and 3 months after completion of IMRT</description>
        </group>
        <group group_id="P2">
          <title>IMRT + Cisplatin + Lapatinib</title>
          <description>IMRT: IMRT, 35 fractions over 6 weeks, 6 fractions per week for 5 weeks and 5 fractions per week for 1 week, 2 Gy per fraction to total dose of 70 Gy&#xD;
Cisplatin: 100 mg/m^2 administered intravenously on days 8 and 29&#xD;
Lapatinib: 1500 mg lapatinib by mouth or by feeding tube daily starting 7 days before IMRT for 7 weeks prior to and during IMRT and 3 months after completion of IMRT</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="64"/>
                <participants group_id="P2" count="63"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>Participants Who Started Protocol Treatment</title>
              <participants_list>
                <participants group_id="P1" count="59"/>
                <participants group_id="P2" count="60"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="64"/>
                <participants group_id="P2" count="63"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="0"/>
              </participants_list>
            </milestone>
          </milestone_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <population>All randomized patients</population>
      <group_list>
        <group group_id="B1">
          <title>IMRT + Cisplatin + Placebo</title>
          <description>IMRT: IMRT, 35 fractions over 6 weeks, 6 fractions per week for 5 weeks and 5 fractions per week for 1 week, 2 Gy per fraction to total dose of 70 Gy&#xD;
Cisplatin: 100 mg/m^2 administered intravenously on days 8 and 29&#xD;
Placebo: 1500 mg placebo daily by mouth or by feeding tube starting 7 days before IMRT for 7 weeks prior to and during IMRT and 3 months after completion of IMRT</description>
        </group>
        <group group_id="B2">
          <title>IMRT + Cisplatin + Lapatinib</title>
          <description>IMRT: IMRT, 35 fractions over 6 weeks, 6 fractions per week for 5 weeks and 5 fractions per week for 1 week, 2 Gy per fraction to total dose of 70 Gy&#xD;
Cisplatin: 100 mg/m^2 administered intravenously on days 8 and 29&#xD;
Lapatinib: 1500 mg lapatinib by mouth or by feeding tube daily starting 7 days before IMRT for 7 weeks prior to and during IMRT and 3 months after completion of IMRT</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="64"/>
            <count group_id="B2" value="63"/>
            <count group_id="B3" value="127"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>years</units>
          <param>Median</param>
          <dispersion>Full Range</dispersion>
          <class_list>
            <class>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="64"/>
                    <count group_id="B2" value="63"/>
                    <count group_id="B3" value="127"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="58" lower_limit="42" upper_limit="80"/>
                    <measurement group_id="B2" value="57" lower_limit="33" upper_limit="75"/>
                    <measurement group_id="B3" value="58" lower_limit="33" upper_limit="80"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Age, Customized</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="64"/>
                    <count group_id="B2" value="63"/>
                    <count group_id="B3" value="127"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <title>&lt;=65</title>
                  <measurement_list>
                    <measurement group_id="B1" value="54"/>
                    <measurement group_id="B2" value="56"/>
                    <measurement group_id="B3" value="110"/>
                  </measurement_list>
                </category>
                <category>
                  <title>&gt;65</title>
                  <measurement_list>
                    <measurement group_id="B1" value="10"/>
                    <measurement group_id="B2" value="7"/>
                    <measurement group_id="B3" value="17"/>
                  </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>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="64"/>
                    <count group_id="B2" value="63"/>
                    <count group_id="B3" value="127"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <title>Female</title>
                  <measurement_list>
                    <measurement group_id="B1" value="13"/>
                    <measurement group_id="B2" value="16"/>
                    <measurement group_id="B3" value="29"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="51"/>
                    <measurement group_id="B2" value="47"/>
                    <measurement group_id="B3" value="98"/>
                  </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>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="64"/>
                    <count group_id="B2" value="63"/>
                    <count group_id="B3" value="127"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <title>Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="3"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="4"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Not Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="60"/>
                    <measurement group_id="B2" value="61"/>
                    <measurement group_id="B3" value="121"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Race (NIH/OMB)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="64"/>
                    <count group_id="B2" value="63"/>
                    <count group_id="B3" value="127"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <title>American Indian or Alaska Native</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="2"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Asian</title>
                  <measurement_list>
                    <measurement group_id="B1" value="2"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="2"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Native Hawaiian or Other Pacific Islander</title>
                  <measurement_list>
                    <measurement group_id="B1" value="2"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="2"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Black or African American</title>
                  <measurement_list>
                    <measurement group_id="B1" value="9"/>
                    <measurement group_id="B2" value="10"/>
                    <measurement group_id="B3" value="19"/>
                  </measurement_list>
                </category>
                <category>
                  <title>White</title>
                  <measurement_list>
                    <measurement group_id="B1" value="49"/>
                    <measurement group_id="B2" value="50"/>
                    <measurement group_id="B3" value="99"/>
                  </measurement_list>
                </category>
                <category>
                  <title>More than one race</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="1"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Zubrod performance status</title>
          <description>0 = Asymptomatic; 1 = Symptomatic but completely ambulatory; 2 = Symptomatic, &lt;50% in bed during the day; 3 = Symptomatic, &gt;50% in bed, but not bedbound; 4 = Bedbound; 5 = Death</description>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="64"/>
                    <count group_id="B2" value="63"/>
                    <count group_id="B3" value="127"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <title>0</title>
                  <measurement_list>
                    <measurement group_id="B1" value="33"/>
                    <measurement group_id="B2" value="27"/>
                    <measurement group_id="B3" value="60"/>
                  </measurement_list>
                </category>
                <category>
                  <title>1</title>
                  <measurement_list>
                    <measurement group_id="B1" value="31"/>
                    <measurement group_id="B2" value="36"/>
                    <measurement group_id="B3" value="67"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Smoking history: pack-years</title>
          <description>Smoking history as measured in pack-years. It is calculated by multiplying the number of packs of cigarettes smoked per day by the number of years the person has smoked.</description>
          <population>Two patients are missing smoking history data.</population>
          <units>pack-years</units>
          <param>Median</param>
          <dispersion>Full Range</dispersion>
          <class_list>
            <class>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="63"/>
                    <count group_id="B2" value="62"/>
                    <count group_id="B3" value="125"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="38" lower_limit="0" upper_limit="126"/>
                    <measurement group_id="B2" value="29.5" lower_limit="0" upper_limit="168"/>
                    <measurement group_id="B3" value="30" lower_limit="0" upper_limit="168"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Smoking history: pack-years</title>
          <description>Smoking history as measured in pack-years. It is calculated by multiplying the number of packs of cigarettes smoked per day by the number of years the person has smoked.</description>
          <population>Two patients are missing smoking history data.</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="63"/>
                    <count group_id="B2" value="62"/>
                    <count group_id="B3" value="125"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <title>&lt;=10</title>
                  <measurement_list>
                    <measurement group_id="B1" value="13"/>
                    <measurement group_id="B2" value="17"/>
                    <measurement group_id="B3" value="30"/>
                  </measurement_list>
                </category>
                <category>
                  <title>&gt;10</title>
                  <measurement_list>
                    <measurement group_id="B1" value="50"/>
                    <measurement group_id="B2" value="45"/>
                    <measurement group_id="B3" value="95"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Primary site</title>
          <description>Primary location of tumor.</description>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="64"/>
                    <count group_id="B2" value="63"/>
                    <count group_id="B3" value="127"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <title>Oropharynx, p16-negative (central review)</title>
                  <measurement_list>
                    <measurement group_id="B1" value="15"/>
                    <measurement group_id="B2" value="16"/>
                    <measurement group_id="B3" value="31"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Oropharynx, unknown p16 (central review)</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="1"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Hypopharynx</title>
                  <measurement_list>
                    <measurement group_id="B1" value="16"/>
                    <measurement group_id="B2" value="7"/>
                    <measurement group_id="B3" value="23"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Larynx</title>
                  <measurement_list>
                    <measurement group_id="B1" value="33"/>
                    <measurement group_id="B2" value="39"/>
                    <measurement group_id="B3" value="72"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>T stage (stratification factor)</title>
          <description>Tumor stage per the American Joint Committee on Cancer (AJCC) 7th ed. refers to the size and/or extent of the main tumor. The higher the number after the T, the larger the tumor or the more it has grown into nearby tissues.</description>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="64"/>
                    <count group_id="B2" value="63"/>
                    <count group_id="B3" value="127"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <title>T1</title>
                  <measurement_list>
                    <measurement group_id="B1" value="2"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="2"/>
                  </measurement_list>
                </category>
                <category>
                  <title>T2</title>
                  <measurement_list>
                    <measurement group_id="B1" value="9"/>
                    <measurement group_id="B2" value="7"/>
                    <measurement group_id="B3" value="16"/>
                  </measurement_list>
                </category>
                <category>
                  <title>T3</title>
                  <measurement_list>
                    <measurement group_id="B1" value="35"/>
                    <measurement group_id="B2" value="38"/>
                    <measurement group_id="B3" value="73"/>
                  </measurement_list>
                </category>
                <category>
                  <title>T4</title>
                  <measurement_list>
                    <measurement group_id="B1" value="18"/>
                    <measurement group_id="B2" value="18"/>
                    <measurement group_id="B3" value="36"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>N stage (stratification factor)</title>
          <description>Regional lymph nodes staging per American Joint Committee on Cancer (AJCC) 7th ed. refers to the number and/or extent of spread of lymph nodes that contain cancer. N0 means lymph nodes aren't involved. A higher number means the cancer is in more lymph nodes, farther away from the original tumor.</description>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="64"/>
                    <count group_id="B2" value="63"/>
                    <count group_id="B3" value="127"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <title>N0</title>
                  <measurement_list>
                    <measurement group_id="B1" value="18"/>
                    <measurement group_id="B2" value="20"/>
                    <measurement group_id="B3" value="38"/>
                  </measurement_list>
                </category>
                <category>
                  <title>N1</title>
                  <measurement_list>
                    <measurement group_id="B1" value="7"/>
                    <measurement group_id="B2" value="8"/>
                    <measurement group_id="B3" value="15"/>
                  </measurement_list>
                </category>
                <category>
                  <title>N2a</title>
                  <measurement_list>
                    <measurement group_id="B1" value="3"/>
                    <measurement group_id="B2" value="2"/>
                    <measurement group_id="B3" value="5"/>
                  </measurement_list>
                </category>
                <category>
                  <title>N2b</title>
                  <measurement_list>
                    <measurement group_id="B1" value="19"/>
                    <measurement group_id="B2" value="19"/>
                    <measurement group_id="B3" value="38"/>
                  </measurement_list>
                </category>
                <category>
                  <title>N2c</title>
                  <measurement_list>
                    <measurement group_id="B1" value="15"/>
                    <measurement group_id="B2" value="13"/>
                    <measurement group_id="B3" value="28"/>
                  </measurement_list>
                </category>
                <category>
                  <title>N3</title>
                  <measurement_list>
                    <measurement group_id="B1" value="2"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Overall stage</title>
          <description>Overall cancer stage per American Joint Committee on Cancer (AJCC) 7th ed. combines tumor (T), regional lymph node (N), and distant metastasis (M) staging to determine an overall stage of II, III, or IV, ranging from least to most advanced, respectively. Stage II: T2/N0/M0; Stage III: T3/N0/M0 or T1-3/N1/M0; Stage IV: T4a/N0-1/M0 or T4b/any N/M0 or any T/N2-3/M0. The higher the number after the T, the larger the tumor or the more it has grown into nearby tissues. The higher the number after the N, the greater the involvement of regional lymph nodes. M0 indicates no distant metastasis.</description>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="64"/>
                    <count group_id="B2" value="63"/>
                    <count group_id="B3" value="127"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <title>II</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="1"/>
                  </measurement_list>
                </category>
                <category>
                  <title>III</title>
                  <measurement_list>
                    <measurement group_id="B1" value="18"/>
                    <measurement group_id="B2" value="20"/>
                    <measurement group_id="B3" value="38"/>
                  </measurement_list>
                </category>
                <category>
                  <title>IV</title>
                  <measurement_list>
                    <measurement group_id="B1" value="45"/>
                    <measurement group_id="B2" value="43"/>
                    <measurement group_id="B3" value="88"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Percentage of Participants Alive Without Progression (Progression-free Survival)</title>
        <description>An event for progression-free survival is local, regional, or distant disease progression or death due to any cause. Progression-free survival time is defined as time from randomization to the date of progression/death or last known follow-up (censored). Rates are estimated by the Kaplan-Meier method. The protocol specifies that the distributions of survival times be compared between the arms, which is reported in the statistical analysis results. Five-year rates are provided. Analysis occurred after 67 progressions or deaths were reported.</description>
        <time_frame>From randomization to last follow-up. Maximum follow-up at time of analysis was 7.1 years.</time_frame>
        <population>All randomized participants</population>
        <group_list>
          <group group_id="O1">
            <title>IMRT + Cisplatin + Placebo</title>
            <description>IMRT: IMRT, 35 fractions over 6 weeks, 6 fractions per week for 5 weeks and 5 fractions per week for 1 week, 2 Gy per fraction to total dose of 70 Gy&#xD;
Cisplatin: 100 mg/m^2 administered intravenously on days 8 and 29&#xD;
Placebo: 1500 mg placebo daily by mouth or by feeding tube starting 7 days before IMRT for 7 weeks prior to and during IMRT and 3 months after completion of IMRT</description>
          </group>
          <group group_id="O2">
            <title>IMRT + Cisplatin + Lapatinib</title>
            <description>IMRT: IMRT, 35 fractions over 6 weeks, 6 fractions per week for 5 weeks and 5 fractions per week for 1 week, 2 Gy per fraction to total dose of 70 Gy&#xD;
Cisplatin: 100 mg/m^2 administered intravenously on days 8 and 29&#xD;
Lapatinib: 1500 mg lapatinib by mouth or by feeding tube daily starting 7 days before IMRT for 7 weeks prior to and during IMRT and 3 months after completion of IMRT</description>
          </group>
        </group_list>
        <measure>
          <title>Percentage of Participants Alive Without Progression (Progression-free Survival)</title>
          <description>An event for progression-free survival is local, regional, or distant disease progression or death due to any cause. Progression-free survival time is defined as time from randomization to the date of progression/death or last known follow-up (censored). Rates are estimated by the Kaplan-Meier method. The protocol specifies that the distributions of survival times be compared between the arms, which is reported in the statistical analysis results. Five-year rates are provided. Analysis occurred after 67 progressions or deaths were reported.</description>
          <population>All randomized participants</population>
          <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="64"/>
                <count group_id="O2" value="63"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="34.6" lower_limit="21.2" upper_limit="48.0"/>
                    <measurement group_id="O2" value="43.1" lower_limit="30.1" upper_limit="56.1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>Hazard ratio (lapatinib/placebo) set at 0.65 (35% reduction), 1-sided alpha 0.20 (final test at 0.1803 accounting for 1 interim analysis), logrank test, 80% power, 69 events in 128 randomized (142 total enrolled) patients required. Final analysis at 67 (of 69) events drops power to 79%.</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.3436</p_value>
            <method>Log Rank</method>
            <method_desc>One-sided significance level = 0.1803</method_desc>
            <param_type>Hazard Ratio (HR)</param_type>
            <param_value>0.91</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>0.56</ci_lower_limit>
            <ci_upper_limit>1.46</ci_upper_limit>
            <estimate_desc>Reference level = IMRT + cisplatin + placebo</estimate_desc>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Percentage of Participants Alive (Overall Survival)</title>
        <description>An event for overall survival is death due to any cause. Overall survival time is defined as time from randomization to the date of death or last known follow-up (censored). Rates are estimated by the Kaplan-Meier method. The protocol specifies that the distributions of survival times be compared between the arms, which is reported in the statistical analysis results. Five-year rates are provided.</description>
        <time_frame>From randomization to last follow-up. Maximum follow-up at time of analysis was 7.1 years.</time_frame>
        <population>All randomized participants</population>
        <group_list>
          <group group_id="O1">
            <title>IMRT + Cisplatin + Placebo</title>
            <description>IMRT: IMRT, 35 fractions over 6 weeks, 6 fractions per week for 5 weeks and 5 fractions per week for 1 week, 2 Gy per fraction to total dose of 70 Gy&#xD;
Cisplatin: 100 mg/m^2 administered intravenously on days 8 and 29&#xD;
Placebo: 1500 mg placebo daily by mouth or by feeding tube starting 7 days before IMRT for 7 weeks prior to and during IMRT and 3 months after completion of IMRT</description>
          </group>
          <group group_id="O2">
            <title>IMRT + Cisplatin + Lapatinib</title>
            <description>IMRT: IMRT, 35 fractions over 6 weeks, 6 fractions per week for 5 weeks and 5 fractions per week for 1 week, 2 Gy per fraction to total dose of 70 Gy&#xD;
Cisplatin: 100 mg/m^2 administered intravenously on days 8 and 29&#xD;
Lapatinib: 1500 mg lapatinib by mouth or by feeding tube daily starting 7 days before IMRT for 7 weeks prior to and during IMRT and 3 months after completion of IMRT</description>
          </group>
        </group_list>
        <measure>
          <title>Percentage of Participants Alive (Overall Survival)</title>
          <description>An event for overall survival is death due to any cause. Overall survival time is defined as time from randomization to the date of death or last known follow-up (censored). Rates are estimated by the Kaplan-Meier method. The protocol specifies that the distributions of survival times be compared between the arms, which is reported in the statistical analysis results. Five-year rates are provided.</description>
          <population>All randomized participants</population>
          <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="64"/>
                <count group_id="O2" value="63"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="55.1" lower_limit="40.6" upper_limit="69.5"/>
                    <measurement group_id="O2" value="49.9" lower_limit="35.5" upper_limit="64.3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.5836</p_value>
            <method>Log Rank</method>
            <method_desc>One-sided significance level = 0.05</method_desc>
            <param_type>Hazard Ratio (HR)</param_type>
            <param_value>1.06</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>0.61</ci_lower_limit>
            <ci_upper_limit>1.86</ci_upper_limit>
            <estimate_desc>Reference level = IMRT + cisplatin + placebo</estimate_desc>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Percentage of Participants With Distant Metastases</title>
        <description>Failure for distant metastasis endpoint was defined as distant progression; local-regional failure and death due to any cause were considered competing risks. Distant metastasis time is defined as time from randomization to the date of progression/death or last known follow-up (censored). Rates are estimated by the cumulative incidence method. The protocol specifies that the distributions of failure times be compared between the arms, which is reported in the statistical analysis results. Five-year rates are provided.</description>
        <time_frame>From randomization to last follow-up. Maximum follow-up at time of analysis was 7.1 years.</time_frame>
        <population>All randomized participants</population>
        <group_list>
          <group group_id="O1">
            <title>IMRT + Cisplatin + Placebo</title>
            <description>IMRT: IMRT, 35 fractions over 6 weeks, 6 fractions per week for 5 weeks and 5 fractions per week for 1 week, 2 Gy per fraction to total dose of 70 Gy&#xD;
Cisplatin: 100 mg/m^2 administered intravenously on days 8 and 29&#xD;
Placebo: 1500 mg placebo daily by mouth or by feeding tube starting 7 days before IMRT for 7 weeks prior to and during IMRT and 3 months after completion of IMRT</description>
          </group>
          <group group_id="O2">
            <title>IMRT + Cisplatin + Lapatinib</title>
            <description>IMRT: IMRT, 35 fractions over 6 weeks, 6 fractions per week for 5 weeks and 5 fractions per week for 1 week, 2 Gy per fraction to total dose of 70 Gy&#xD;
Cisplatin: 100 mg/m^2 administered intravenously on days 8 and 29&#xD;
Lapatinib: 1500 mg lapatinib by mouth or by feeding tube daily starting 7 days before IMRT for 7 weeks prior to and during IMRT and 3 months after completion of IMRT</description>
          </group>
        </group_list>
        <measure>
          <title>Percentage of Participants With Distant Metastases</title>
          <description>Failure for distant metastasis endpoint was defined as distant progression; local-regional failure and death due to any cause were considered competing risks. Distant metastasis time is defined as time from randomization to the date of progression/death or last known follow-up (censored). Rates are estimated by the cumulative incidence method. The protocol specifies that the distributions of failure times be compared between the arms, which is reported in the statistical analysis results. Five-year rates are provided.</description>
          <population>All randomized participants</population>
          <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="64"/>
                <count group_id="O2" value="63"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="19.9" lower_limit="10.1" upper_limit="32.2"/>
                    <measurement group_id="O2" value="12.4" lower_limit="5.4" upper_limit="22.5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.1743</p_value>
            <method>Log Rank</method>
            <method_desc>One-sided significance level = 0.05</method_desc>
            <param_type>Hazard Ratio (HR)</param_type>
            <param_value>0.64</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>0.25</ci_lower_limit>
            <ci_upper_limit>1.65</ci_upper_limit>
            <estimate_desc>Reference level = IMRT + cisplatin + placebo</estimate_desc>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Percentage of Participants With Treatment-related Grade 3 or Higher Adverse Events</title>
        <description>Adverse events (AE) were graded using the Common Terminology Criteria for Adverse Events (CTCAE) v4.0. Grade refers to the severity of the AE. The CTCAE v4.0 assigns Grades 1 through 5 with unique clinical descriptions of severity for each AE based on this general guideline: Grade 1 Mild, Grade 2 Moderate, Grade 3 Severe, Grade 4 Life-threatening or disabling, Grade 5 Death related to adverse event. &quot;Treatment-related&quot; is defined definitely, probably, or possibly related to treatment.</description>
        <time_frame>From start of treatment to last follow-up. Maximum follow-up at time of analysis was 7.1 years.</time_frame>
        <population>Participants Who Started Protocol Treatment</population>
        <group_list>
          <group group_id="O1">
            <title>IMRT + Cisplatin + Placebo</title>
            <description>IMRT: IMRT, 35 fractions over 6 weeks, 6 fractions per week for 5 weeks and 5 fractions per week for 1 week, 2 Gy per fraction to total dose of 70 Gy&#xD;
Cisplatin: 100 mg/m^2 administered intravenously on days 8 and 29&#xD;
Placebo: 1500 mg placebo daily by mouth or by feeding tube starting 7 days before IMRT for 7 weeks prior to and during IMRT and 3 months after completion of IMRT</description>
          </group>
          <group group_id="O2">
            <title>IMRT + Cisplatin + Lapatinib</title>
            <description>IMRT: IMRT, 35 fractions over 6 weeks, 6 fractions per week for 5 weeks and 5 fractions per week for 1 week, 2 Gy per fraction to total dose of 70 Gy&#xD;
Cisplatin: 100 mg/m^2 administered intravenously on days 8 and 29&#xD;
Lapatinib: 1500 mg lapatinib by mouth or by feeding tube daily starting 7 days before IMRT for 7 weeks prior to and during IMRT and 3 months after completion of IMRT</description>
          </group>
        </group_list>
        <measure>
          <title>Percentage of Participants With Treatment-related Grade 3 or Higher Adverse Events</title>
          <description>Adverse events (AE) were graded using the Common Terminology Criteria for Adverse Events (CTCAE) v4.0. Grade refers to the severity of the AE. The CTCAE v4.0 assigns Grades 1 through 5 with unique clinical descriptions of severity for each AE based on this general guideline: Grade 1 Mild, Grade 2 Moderate, Grade 3 Severe, Grade 4 Life-threatening or disabling, Grade 5 Death related to adverse event. &quot;Treatment-related&quot; is defined definitely, probably, or possibly related to treatment.</description>
          <population>Participants Who Started Protocol Treatment</population>
          <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="59"/>
                <count group_id="O2" value="60"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="84.7" lower_limit="73.0" upper_limit="92.8"/>
                    <measurement group_id="O2" value="86.7" lower_limit="75.4" upper_limit="94.1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.7989</p_value>
            <method>Fisher Exact</method>
            <method_desc>Two-sided significance level = 0.05</method_desc>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Percentage of Participants Who Complied With Protocol Treatment</title>
        <description>Compliance with protocol treatment is defined as &quot;per protocol&quot; or &quot;acceptable variation&quot; per study chair review for IMRT, cisplatin, pre-IMRT lapatinib/placebo, concurrent lapatinib/placebo, and maintenance lapatinib/placebo. Rates of treatment compliance were compared between groups by a 2-sided Fisher's exact test.</description>
        <time_frame>From start of treatment to end of treatment (approximately 5 months from randomization).</time_frame>
        <population>All randomized participants</population>
        <group_list>
          <group group_id="O1">
            <title>IMRT + Cisplatin + Placebo</title>
            <description>IMRT: IMRT, 35 fractions over 6 weeks, 6 fractions per week for 5 weeks and 5 fractions per week for 1 week, 2 Gy per fraction to total dose of 70 Gy&#xD;
Cisplatin: 100 mg/m^2 administered intravenously on days 8 and 29&#xD;
Placebo: 1500 mg placebo daily by mouth or by feeding tube starting 7 days before IMRT for 7 weeks prior to and during IMRT and 3 months after completion of IMRT</description>
          </group>
          <group group_id="O2">
            <title>IMRT + Cisplatin + Lapatinib</title>
            <description>IMRT: IMRT, 35 fractions over 6 weeks, 6 fractions per week for 5 weeks and 5 fractions per week for 1 week, 2 Gy per fraction to total dose of 70 Gy&#xD;
Cisplatin: 100 mg/m^2 administered intravenously on days 8 and 29&#xD;
Lapatinib: 1500 mg lapatinib by mouth or by feeding tube daily starting 7 days before IMRT for 7 weeks prior to and during IMRT and 3 months after completion of IMRT</description>
          </group>
        </group_list>
        <measure>
          <title>Percentage of Participants Who Complied With Protocol Treatment</title>
          <description>Compliance with protocol treatment is defined as &quot;per protocol&quot; or &quot;acceptable variation&quot; per study chair review for IMRT, cisplatin, pre-IMRT lapatinib/placebo, concurrent lapatinib/placebo, and maintenance lapatinib/placebo. Rates of treatment compliance were compared between groups by a 2-sided Fisher's exact test.</description>
          <population>All randomized participants</population>
          <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="64"/>
                <count group_id="O2" value="63"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>IMRT</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="76.6" lower_limit="66.2" upper_limit="86.9"/>
                    <measurement group_id="O2" value="84.1" lower_limit="75.1" upper_limit="93.2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Cisplatin</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="90.6" lower_limit="83.5" upper_limit="97.8"/>
                    <measurement group_id="O2" value="88.9" lower_limit="81.1" upper_limit="96.6"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Pre-IMRT lapatinib/placebo</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="84.4" lower_limit="75.5" upper_limit="93.3"/>
                    <measurement group_id="O2" value="87.3" lower_limit="79.1" upper_limit="95.5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Concurrent lapatinib/placebo</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="79.7" lower_limit="69.8" upper_limit="89.5"/>
                    <measurement group_id="O2" value="84.1" lower_limit="75.1" upper_limit="93.2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Maintenance lapatinib/placebo</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="56.3" lower_limit="44.1" upper_limit="68.4"/>
                    <measurement group_id="O2" value="49.2" lower_limit="36.9" upper_limit="61.6"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.3728</p_value>
            <p_value_desc>IMRT</p_value_desc>
            <method>Fisher Exact</method>
            <method_desc>Two-sided significance level = 0.05</method_desc>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <non_inferiority_type>Other</non_inferiority_type>
            <p_value>0.7781</p_value>
            <p_value_desc>Cisplatin</p_value_desc>
            <method>Fisher Exact</method>
            <method_desc>Two-sided significance level = 0.05</method_desc>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <non_inferiority_type>Other</non_inferiority_type>
            <p_value>0.8000</p_value>
            <p_value_desc>Pre-IMRT lapatinib/placebo</p_value_desc>
            <method>Fisher Exact</method>
            <method_desc>Two-sided significance level = 0.05</method_desc>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <non_inferiority_type>Other</non_inferiority_type>
            <p_value>0.6459</p_value>
            <p_value_desc>Concurrent lapatinib/placebo</p_value_desc>
            <method>Fisher Exact</method>
            <method_desc>Two-sided significance level = 0.05</method_desc>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <non_inferiority_type>Other</non_inferiority_type>
            <p_value>0.4792</p_value>
            <p_value_desc>Maintenance lapatinib/placebo</p_value_desc>
            <method>Fisher Exact</method>
            <method_desc>Two-sided significance level = 0.05</method_desc>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Percentage of Participants With Local-regional Progression</title>
        <description>Failure for local-regional control endpoint was defined as local or regional progression, salvage surgery of the primary tumor with tumor present/unknown, salvage neck dissection with tumor present/unknown &gt; 20 weeks after the end of radiation therapy, death due to study cancer without documented progression, or death due to unknown causes without documented progression; distant metastasis and death due to other causes were considered competing risks. Local-regional failure time is defined as time from randomization to the date of progression/death or last known follow-up (censored). Failure rates are estimated by the cumulative incidence method. The protocol specifies that the distributions of failure times be compared between the arms, which is reported in the statistical analysis results. Five-year rates are provided.</description>
        <time_frame>From randomization to last follow-up. Maximum follow-up at time of analysis was 7.1 years.</time_frame>
        <population>All randomized participants</population>
        <group_list>
          <group group_id="O1">
            <title>IMRT + Cisplatin + Placebo</title>
            <description>IMRT: IMRT, 35 fractions over 6 weeks, 6 fractions per week for 5 weeks and 5 fractions per week for 1 week, 2 Gy per fraction to total dose of 70 Gy&#xD;
Cisplatin: 100 mg/m^2 administered intravenously on days 8 and 29&#xD;
Placebo: 1500 mg placebo daily by mouth or by feeding tube starting 7 days before IMRT for 7 weeks prior to and during IMRT and 3 months after completion of IMRT</description>
          </group>
          <group group_id="O2">
            <title>IMRT + Cisplatin + Lapatinib</title>
            <description>IMRT: IMRT, 35 fractions over 6 weeks, 6 fractions per week for 5 weeks and 5 fractions per week for 1 week, 2 Gy per fraction to total dose of 70 Gy&#xD;
Cisplatin: 100 mg/m^2 administered intravenously on days 8 and 29&#xD;
Lapatinib: 1500 mg lapatinib by mouth or by feeding tube daily starting 7 days before IMRT for 7 weeks prior to and during IMRT and 3 months after completion of IMRT</description>
          </group>
        </group_list>
        <measure>
          <title>Percentage of Participants With Local-regional Progression</title>
          <description>Failure for local-regional control endpoint was defined as local or regional progression, salvage surgery of the primary tumor with tumor present/unknown, salvage neck dissection with tumor present/unknown &gt; 20 weeks after the end of radiation therapy, death due to study cancer without documented progression, or death due to unknown causes without documented progression; distant metastasis and death due to other causes were considered competing risks. Local-regional failure time is defined as time from randomization to the date of progression/death or last known follow-up (censored). Failure rates are estimated by the cumulative incidence method. The protocol specifies that the distributions of failure times be compared between the arms, which is reported in the statistical analysis results. Five-year rates are provided.</description>
          <population>All randomized participants</population>
          <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="64"/>
                <count group_id="O2" value="63"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="33.7" lower_limit="21.2" upper_limit="46.7"/>
                    <measurement group_id="O2" value="37.7" lower_limit="25.0" upper_limit="50.4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.6735</p_value>
            <method>Log Rank</method>
            <method_desc>One-sided significance level = 0.05</method_desc>
            <param_type>Hazard Ratio (HR)</param_type>
            <param_value>1.15</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>0.62</ci_lower_limit>
            <ci_upper_limit>2.17</ci_upper_limit>
            <estimate_desc>Reference level = IMRT + cisplatin + placebo</estimate_desc>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Performance Status Scale for Head &amp; Neck Cancer.</title>
        <time_frame>3 months, 1 year, and 2 years</time_frame>
        <posting_date>09/2023</posting_date>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Functional Assessment of Cancer Therapy - Head &amp; Neck.</title>
        <time_frame>3 months, 1 year, and 2 years.</time_frame>
        <posting_date>09/2023</posting_date>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>University of Michigan Xerostomia-Related Quality of Life Scale.</title>
        <time_frame>3 months, 1 year, and 2 years.</time_frame>
        <posting_date>09/2023</posting_date>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>HER2, EGFR, EMT as Biomarkers of Response.</title>
        <time_frame>End of Study</time_frame>
        <posting_date>09/2023</posting_date>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>Weekly during radiation therapy, then every 3 months for years 1 and 2, every 6 months for years 3-5, then annually</time_frame>
      <desc>All-cause mortality was assessed in all randomized participants. Adverse events were assessed in participants who started protocol treatment</desc>
      <group_list>
        <group group_id="E1">
          <title>IMRT + Cisplatin + Placebo</title>
          <description>IMRT: IMRT, 35 fractions over 6 weeks, 6 fractions per week for 5 weeks and 5 fractions per week for 1 week, 2 Gy per fraction to total dose of 70 Gy&#xD;
Cisplatin: 100 mg/m^2 administered intravenously on days 8 and 29&#xD;
Placebo: 1500 mg placebo daily by mouth or by feeding tube starting 7 days before IMRT for 7 weeks prior to and during IMRT and 3 months after completion of IMRT</description>
        </group>
        <group group_id="E2">
          <title>IMRT + Cisplatin + Lapatinib</title>
          <description>IMRT: IMRT, 35 fractions over 6 weeks, 6 fractions per week for 5 weeks and 5 fractions per week for 1 week, 2 Gy per fraction to total dose of 70 Gy&#xD;
Cisplatin: 100 mg/m^2 administered intravenously on days 8 and 29&#xD;
Lapatinib: 1500 mg lapatinib by mouth or by feeding tube daily starting 7 days before IMRT for 7 weeks prior to and during IMRT and 3 months after completion of IMRT</description>
        </group>
      </group_list>
      <serious_events>
        <default_vocab>CTCAE (4.0)</default_vocab>
        <default_assessment>Non-systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, all-cause mortality</sub_title>
                <counts group_id="E1" subjects_affected="23" subjects_at_risk="64"/>
                <counts group_id="E2" subjects_affected="26" subjects_at_risk="63"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="26" subjects_at_risk="59"/>
                <counts group_id="E2" subjects_affected="31" subjects_at_risk="60"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Blood and lymphatic system disorders</title>
            <event_list>
              <event>
                <sub_title>Anemia</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="59"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="60"/>
              </event>
              <event>
                <sub_title>Febrile neutropenia</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="59"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="60"/>
              </event>
              <event>
                <sub_title>Leukocytosis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="59"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="60"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Cardiac disorders</title>
            <event_list>
              <event>
                <sub_title>Atrial fibrillation</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="59"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="60"/>
              </event>
              <event>
                <sub_title>Cardiac arrest</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="59"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="60"/>
              </event>
              <event>
                <sub_title>Sinus tachycardia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="59"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="60"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Abdominal pain</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="59"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="60"/>
              </event>
              <event>
                <sub_title>Colitis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="59"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="60"/>
              </event>
              <event>
                <sub_title>Diarrhea</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="59"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="60"/>
              </event>
              <event>
                <sub_title>Dysphagia</sub_title>
                <assessment>Systematic Assessment</assessment>
                <counts group_id="E1" subjects_affected="6" subjects_at_risk="59"/>
                <counts group_id="E2" subjects_affected="4" subjects_at_risk="60"/>
              </event>
              <event>
                <sub_title>Esophagitis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="59"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="60"/>
              </event>
              <event>
                <sub_title>Gastrointestinal disorders - Other</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="59"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="60"/>
              </event>
              <event>
                <sub_title>Ileus</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="59"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="60"/>
              </event>
              <event>
                <sub_title>Mucositis oral</sub_title>
                <assessment>Systematic Assessment</assessment>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="59"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="60"/>
              </event>
              <event>
                <sub_title>Nausea</sub_title>
                <counts group_id="E1" subjects_affected="5" subjects_at_risk="59"/>
                <counts group_id="E2" subjects_affected="7" subjects_at_risk="60"/>
              </event>
              <event>
                <sub_title>Oral hemorrhage</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="59"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="60"/>
              </event>
              <event>
                <sub_title>Oral pain</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="59"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="60"/>
              </event>
              <event>
                <sub_title>Vomiting</sub_title>
                <counts group_id="E1" subjects_affected="5" subjects_at_risk="59"/>
                <counts group_id="E2" subjects_affected="6" subjects_at_risk="60"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Death NOS</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="59"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="60"/>
              </event>
              <event>
                <sub_title>Edema limbs</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="59"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="60"/>
              </event>
              <event>
                <sub_title>Fatigue</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="59"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="60"/>
              </event>
              <event>
                <sub_title>Fever</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="59"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="60"/>
              </event>
              <event>
                <sub_title>Pain</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="59"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="60"/>
              </event>
              <event>
                <sub_title>Sudden death NOS</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="59"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="60"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Bronchial infection</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="59"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="60"/>
              </event>
              <event>
                <sub_title>Infections and infestations - Other</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="59"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="60"/>
              </event>
              <event>
                <sub_title>Lung infection</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="59"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="60"/>
              </event>
              <event>
                <sub_title>Sepsis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="59"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="60"/>
              </event>
              <event>
                <sub_title>Soft tissue infection</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="59"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="60"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Injury, poisoning and procedural complications</title>
            <event_list>
              <event>
                <sub_title>Dermatitis radiation</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="59"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="60"/>
              </event>
              <event>
                <sub_title>Fall</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="59"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="60"/>
              </event>
              <event>
                <sub_title>Injury to carotid artery</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="59"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="60"/>
              </event>
              <event>
                <sub_title>Tracheal hemorrhage</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="59"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="60"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Investigations</title>
            <event_list>
              <event>
                <sub_title>Creatinine increased</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="59"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="60"/>
              </event>
              <event>
                <sub_title>Ejection fraction decreased</sub_title>
                <assessment>Systematic Assessment</assessment>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="59"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="60"/>
              </event>
              <event>
                <sub_title>Lymphocyte count decreased</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="59"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="60"/>
              </event>
              <event>
                <sub_title>Neutrophil count decreased</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="59"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="60"/>
              </event>
              <event>
                <sub_title>Weight loss</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="59"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="60"/>
              </event>
              <event>
                <sub_title>White blood cell decreased</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="59"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="60"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Metabolism and nutrition disorders</title>
            <event_list>
              <event>
                <sub_title>Anorexia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="59"/>
                <counts group_id="E2" subjects_affected="5" subjects_at_risk="60"/>
              </event>
              <event>
                <sub_title>Dehydration</sub_title>
                <counts group_id="E1" subjects_affected="8" subjects_at_risk="59"/>
                <counts group_id="E2" subjects_affected="7" subjects_at_risk="60"/>
              </event>
              <event>
                <sub_title>Hyperglycemia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="59"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="60"/>
              </event>
              <event>
                <sub_title>Hyperuricemia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="59"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="60"/>
              </event>
              <event>
                <sub_title>Hypocalcemia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="59"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="60"/>
              </event>
              <event>
                <sub_title>Hypokalemia</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="59"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="60"/>
              </event>
              <event>
                <sub_title>Hyponatremia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="59"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="60"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Musculoskeletal and connective tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Chest wall pain</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="59"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="60"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Cognitive disturbance</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="59"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="60"/>
              </event>
              <event>
                <sub_title>Depressed level of consciousness</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="59"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="60"/>
              </event>
              <event>
                <sub_title>Dizziness</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="59"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="60"/>
              </event>
              <event>
                <sub_title>Stroke</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="59"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="60"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Psychiatric disorders</title>
            <event_list>
              <event>
                <sub_title>Depression</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="59"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="60"/>
              </event>
              <event>
                <sub_title>Suicidal ideation</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="59"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="60"/>
              </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" subjects_affected="5" subjects_at_risk="59"/>
                <counts group_id="E2" subjects_affected="8" subjects_at_risk="60"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Aspiration</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="59"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="60"/>
              </event>
              <event>
                <sub_title>Dyspnea</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="59"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="60"/>
              </event>
              <event>
                <sub_title>Laryngeal edema</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="59"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="60"/>
              </event>
              <event>
                <sub_title>Laryngeal mucositis</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="59"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="60"/>
              </event>
              <event>
                <sub_title>Laryngeal stenosis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="59"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="60"/>
              </event>
              <event>
                <sub_title>Pleural effusion</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="59"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="60"/>
              </event>
              <event>
                <sub_title>Pneumonitis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="59"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="60"/>
              </event>
              <event>
                <sub_title>Respiratory failure</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="59"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="60"/>
              </event>
              <event>
                <sub_title>Respiratory, thoracic and mediastinal disorders - Other</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="59"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="60"/>
              </event>
              <event>
                <sub_title>Sore throat</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="59"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="60"/>
              </event>
              <event>
                <sub_title>Stridor</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="59"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="60"/>
              </event>
              <event>
                <sub_title>Tracheal mucositis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="59"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="60"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Skin and subcutaneous tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Rash acneiform</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="59"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="60"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Surgical and medical procedures</title>
            <event_list>
              <event>
                <sub_title>Surgical and medical procedures - Other</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="59"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="60"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Vascular disorders</title>
            <event_list>
              <event>
                <sub_title>Hypertension</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="59"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="60"/>
              </event>
              <event>
                <sub_title>Hypotension</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="59"/>
                <counts group_id="E2" subjects_affected="4" subjects_at_risk="60"/>
              </event>
              <event>
                <sub_title>Thromboembolic event</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="59"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="60"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>5</frequency_threshold>
        <default_vocab>CTCAE (4.0)</default_vocab>
        <default_assessment>Non-systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, other adverse events</sub_title>
                <counts group_id="E1" subjects_affected="59" subjects_at_risk="59"/>
                <counts group_id="E2" subjects_affected="60" subjects_at_risk="60"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Blood and lymphatic system disorders</title>
            <event_list>
              <event>
                <sub_title>Anemia</sub_title>
                <counts group_id="E1" subjects_affected="38" subjects_at_risk="59"/>
                <counts group_id="E2" subjects_affected="36" subjects_at_risk="60"/>
              </event>
              <event>
                <sub_title>Blood and lymphatic system disorders - Other</sub_title>
                <counts group_id="E1" subjects_affected="7" subjects_at_risk="59"/>
                <counts group_id="E2" subjects_affected="5" subjects_at_risk="60"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Cardiac disorders</title>
            <event_list>
              <event>
                <sub_title>Sinus tachycardia</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="59"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="60"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Ear and labyrinth disorders</title>
            <event_list>
              <event>
                <sub_title>Ear pain</sub_title>
                <counts group_id="E1" subjects_affected="14" subjects_at_risk="59"/>
                <counts group_id="E2" subjects_affected="12" subjects_at_risk="60"/>
              </event>
              <event>
                <sub_title>Hearing impaired</sub_title>
                <assessment>Systematic Assessment</assessment>
                <counts group_id="E1" subjects_affected="18" subjects_at_risk="59"/>
                <counts group_id="E2" subjects_affected="15" subjects_at_risk="60"/>
              </event>
              <event>
                <sub_title>Tinnitus</sub_title>
                <assessment>Systematic Assessment</assessment>
                <counts group_id="E1" subjects_affected="23" subjects_at_risk="59"/>
                <counts group_id="E2" subjects_affected="14" subjects_at_risk="60"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Endocrine disorders</title>
            <event_list>
              <event>
                <sub_title>Hyperthyroidism</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="59"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="60"/>
              </event>
              <event>
                <sub_title>Hypothyroidism</sub_title>
                <counts group_id="E1" subjects_affected="17" subjects_at_risk="59"/>
                <counts group_id="E2" subjects_affected="16" subjects_at_risk="60"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Abdominal pain</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="59"/>
                <counts group_id="E2" subjects_affected="4" subjects_at_risk="60"/>
              </event>
              <event>
                <sub_title>Constipation</sub_title>
                <counts group_id="E1" subjects_affected="32" subjects_at_risk="59"/>
                <counts group_id="E2" subjects_affected="17" subjects_at_risk="60"/>
              </event>
              <event>
                <sub_title>Dental caries</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="59"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="60"/>
              </event>
              <event>
                <sub_title>Diarrhea</sub_title>
                <counts group_id="E1" subjects_affected="8" subjects_at_risk="59"/>
                <counts group_id="E2" subjects_affected="24" subjects_at_risk="60"/>
              </event>
              <event>
                <sub_title>Dry mouth</sub_title>
                <counts group_id="E1" subjects_affected="47" subjects_at_risk="59"/>
                <counts group_id="E2" subjects_affected="46" subjects_at_risk="60"/>
              </event>
              <event>
                <sub_title>Dyspepsia</sub_title>
                <counts group_id="E1" subjects_affected="8" subjects_at_risk="59"/>
                <counts group_id="E2" subjects_affected="8" subjects_at_risk="60"/>
              </event>
              <event>
                <sub_title>Dysphagia</sub_title>
                <assessment>Systematic Assessment</assessment>
                <counts group_id="E1" subjects_affected="53" subjects_at_risk="59"/>
                <counts group_id="E2" subjects_affected="55" subjects_at_risk="60"/>
              </event>
              <event>
                <sub_title>Esophageal pain</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="59"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="60"/>
              </event>
              <event>
                <sub_title>Esophageal stenosis</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="59"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="60"/>
              </event>
              <event>
                <sub_title>Esophagitis</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="59"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="60"/>
              </event>
              <event>
                <sub_title>Gastroesophageal reflux disease</sub_title>
                <counts group_id="E1" subjects_affected="8" subjects_at_risk="59"/>
                <counts group_id="E2" subjects_affected="5" subjects_at_risk="60"/>
              </event>
              <event>
                <sub_title>Gastrointestinal disorders - Other</sub_title>
                <counts group_id="E1" subjects_affected="12" subjects_at_risk="59"/>
                <counts group_id="E2" subjects_affected="18" subjects_at_risk="60"/>
              </event>
              <event>
                <sub_title>Mucositis oral</sub_title>
                <assessment>Systematic Assessment</assessment>
                <counts group_id="E1" subjects_affected="45" subjects_at_risk="59"/>
                <counts group_id="E2" subjects_affected="48" subjects_at_risk="60"/>
              </event>
              <event>
                <sub_title>Nausea</sub_title>
                <counts group_id="E1" subjects_affected="32" subjects_at_risk="59"/>
                <counts group_id="E2" subjects_affected="35" subjects_at_risk="60"/>
              </event>
              <event>
                <sub_title>Oral pain</sub_title>
                <counts group_id="E1" subjects_affected="10" subjects_at_risk="59"/>
                <counts group_id="E2" subjects_affected="13" subjects_at_risk="60"/>
              </event>
              <event>
                <sub_title>Salivary duct inflammation</sub_title>
                <counts group_id="E1" subjects_affected="5" subjects_at_risk="59"/>
                <counts group_id="E2" subjects_affected="6" subjects_at_risk="60"/>
              </event>
              <event>
                <sub_title>Vomiting</sub_title>
                <counts group_id="E1" subjects_affected="20" subjects_at_risk="59"/>
                <counts group_id="E2" subjects_affected="25" subjects_at_risk="60"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Chills</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="59"/>
                <counts group_id="E2" subjects_affected="4" subjects_at_risk="60"/>
              </event>
              <event>
                <sub_title>Edema face</sub_title>
                <counts group_id="E1" subjects_affected="6" subjects_at_risk="59"/>
                <counts group_id="E2" subjects_affected="6" subjects_at_risk="60"/>
              </event>
              <event>
                <sub_title>Edema limbs</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="59"/>
                <counts group_id="E2" subjects_affected="5" subjects_at_risk="60"/>
              </event>
              <event>
                <sub_title>Fatigue</sub_title>
                <counts group_id="E1" subjects_affected="49" subjects_at_risk="59"/>
                <counts group_id="E2" subjects_affected="49" subjects_at_risk="60"/>
              </event>
              <event>
                <sub_title>Fever</sub_title>
                <counts group_id="E1" subjects_affected="8" subjects_at_risk="59"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="60"/>
              </event>
              <event>
                <sub_title>General disorders and administration site conditions - Other</sub_title>
                <counts group_id="E1" subjects_affected="7" subjects_at_risk="59"/>
                <counts group_id="E2" subjects_affected="5" subjects_at_risk="60"/>
              </event>
              <event>
                <sub_title>Localized edema</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="59"/>
                <counts group_id="E2" subjects_affected="8" subjects_at_risk="60"/>
              </event>
              <event>
                <sub_title>Neck edema</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="59"/>
                <counts group_id="E2" subjects_affected="7" subjects_at_risk="60"/>
              </event>
              <event>
                <sub_title>Non-cardiac chest pain</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="59"/>
                <counts group_id="E2" subjects_affected="6" subjects_at_risk="60"/>
              </event>
              <event>
                <sub_title>Pain</sub_title>
                <counts group_id="E1" subjects_affected="22" subjects_at_risk="59"/>
                <counts group_id="E2" subjects_affected="14" subjects_at_risk="60"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Infections and infestations - Other</sub_title>
                <counts group_id="E1" subjects_affected="5" subjects_at_risk="59"/>
                <counts group_id="E2" subjects_affected="4" subjects_at_risk="60"/>
              </event>
              <event>
                <sub_title>Laryngitis</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="59"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="60"/>
              </event>
              <event>
                <sub_title>Lung infection</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="59"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="60"/>
              </event>
              <event>
                <sub_title>Mucosal infection</sub_title>
                <counts group_id="E1" subjects_affected="9" subjects_at_risk="59"/>
                <counts group_id="E2" subjects_affected="5" subjects_at_risk="60"/>
              </event>
              <event>
                <sub_title>Skin infection</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="59"/>
                <counts group_id="E2" subjects_affected="4" subjects_at_risk="60"/>
              </event>
              <event>
                <sub_title>Upper respiratory infection</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="59"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="60"/>
              </event>
              <event>
                <sub_title>Urinary tract infection</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="59"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="60"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Injury, poisoning and procedural complications</title>
            <event_list>
              <event>
                <sub_title>Dermatitis radiation</sub_title>
                <counts group_id="E1" subjects_affected="39" subjects_at_risk="59"/>
                <counts group_id="E2" subjects_affected="35" subjects_at_risk="60"/>
              </event>
              <event>
                <sub_title>Fall</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="59"/>
                <counts group_id="E2" subjects_affected="4" subjects_at_risk="60"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Investigations</title>
            <event_list>
              <event>
                <sub_title>Alanine aminotransferase increased</sub_title>
                <assessment>Systematic Assessment</assessment>
                <counts group_id="E1" subjects_affected="12" subjects_at_risk="59"/>
                <counts group_id="E2" subjects_affected="14" subjects_at_risk="60"/>
              </event>
              <event>
                <sub_title>Alkaline phosphatase increased</sub_title>
                <counts group_id="E1" subjects_affected="9" subjects_at_risk="59"/>
                <counts group_id="E2" subjects_affected="4" subjects_at_risk="60"/>
              </event>
              <event>
                <sub_title>Aspartate aminotransferase increased</sub_title>
                <counts group_id="E1" subjects_affected="6" subjects_at_risk="59"/>
                <counts group_id="E2" subjects_affected="7" subjects_at_risk="60"/>
              </event>
              <event>
                <sub_title>Blood bilirubin increased</sub_title>
                <assessment>Systematic Assessment</assessment>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="59"/>
                <counts group_id="E2" subjects_affected="10" subjects_at_risk="60"/>
              </event>
              <event>
                <sub_title>CD4 lymphocytes decreased</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="59"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="60"/>
              </event>
              <event>
                <sub_title>Creatinine increased</sub_title>
                <counts group_id="E1" subjects_affected="18" subjects_at_risk="59"/>
                <counts group_id="E2" subjects_affected="19" subjects_at_risk="60"/>
              </event>
              <event>
                <sub_title>Investigations - Other</sub_title>
                <counts group_id="E1" subjects_affected="5" subjects_at_risk="59"/>
                <counts group_id="E2" subjects_affected="4" subjects_at_risk="60"/>
              </event>
              <event>
                <sub_title>Lymphocyte count decreased</sub_title>
                <counts group_id="E1" subjects_affected="22" subjects_at_risk="59"/>
                <counts group_id="E2" subjects_affected="26" subjects_at_risk="60"/>
              </event>
              <event>
                <sub_title>Neutrophil count decreased</sub_title>
                <counts group_id="E1" subjects_affected="22" subjects_at_risk="59"/>
                <counts group_id="E2" subjects_affected="13" subjects_at_risk="60"/>
              </event>
              <event>
                <sub_title>Platelet count decreased</sub_title>
                <counts group_id="E1" subjects_affected="16" subjects_at_risk="59"/>
                <counts group_id="E2" subjects_affected="14" subjects_at_risk="60"/>
              </event>
              <event>
                <sub_title>Weight loss</sub_title>
                <counts group_id="E1" subjects_affected="31" subjects_at_risk="59"/>
                <counts group_id="E2" subjects_affected="41" subjects_at_risk="60"/>
              </event>
              <event>
                <sub_title>White blood cell decreased</sub_title>
                <counts group_id="E1" subjects_affected="25" subjects_at_risk="59"/>
                <counts group_id="E2" subjects_affected="24" subjects_at_risk="60"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Metabolism and nutrition disorders</title>
            <event_list>
              <event>
                <sub_title>Anorexia</sub_title>
                <counts group_id="E1" subjects_affected="32" subjects_at_risk="59"/>
                <counts group_id="E2" subjects_affected="34" subjects_at_risk="60"/>
              </event>
              <event>
                <sub_title>Dehydration</sub_title>
                <counts group_id="E1" subjects_affected="15" subjects_at_risk="59"/>
                <counts group_id="E2" subjects_affected="14" subjects_at_risk="60"/>
              </event>
              <event>
                <sub_title>Hypercalcemia</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="59"/>
                <counts group_id="E2" subjects_affected="5" subjects_at_risk="60"/>
              </event>
              <event>
                <sub_title>Hyperglycemia</sub_title>
                <counts group_id="E1" subjects_affected="16" subjects_at_risk="59"/>
                <counts group_id="E2" subjects_affected="18" subjects_at_risk="60"/>
              </event>
              <event>
                <sub_title>Hyperkalemia</sub_title>
                <counts group_id="E1" subjects_affected="5" subjects_at_risk="59"/>
                <counts group_id="E2" subjects_affected="4" subjects_at_risk="60"/>
              </event>
              <event>
                <sub_title>Hypermagnesemia</sub_title>
                <counts group_id="E1" subjects_affected="5" subjects_at_risk="59"/>
                <counts group_id="E2" subjects_affected="4" subjects_at_risk="60"/>
              </event>
              <event>
                <sub_title>Hypernatremia</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="59"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="60"/>
              </event>
              <event>
                <sub_title>Hyperuricemia</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="59"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="60"/>
              </event>
              <event>
                <sub_title>Hypoalbuminemia</sub_title>
                <counts group_id="E1" subjects_affected="18" subjects_at_risk="59"/>
                <counts group_id="E2" subjects_affected="20" subjects_at_risk="60"/>
              </event>
              <event>
                <sub_title>Hypocalcemia</sub_title>
                <counts group_id="E1" subjects_affected="15" subjects_at_risk="59"/>
                <counts group_id="E2" subjects_affected="16" subjects_at_risk="60"/>
              </event>
              <event>
                <sub_title>Hypoglycemia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="59"/>
                <counts group_id="E2" subjects_affected="4" subjects_at_risk="60"/>
              </event>
              <event>
                <sub_title>Hypokalemia</sub_title>
                <counts group_id="E1" subjects_affected="17" subjects_at_risk="59"/>
                <counts group_id="E2" subjects_affected="23" subjects_at_risk="60"/>
              </event>
              <event>
                <sub_title>Hypomagnesemia</sub_title>
                <counts group_id="E1" subjects_affected="16" subjects_at_risk="59"/>
                <counts group_id="E2" subjects_affected="23" subjects_at_risk="60"/>
              </event>
              <event>
                <sub_title>Hyponatremia</sub_title>
                <counts group_id="E1" subjects_affected="26" subjects_at_risk="59"/>
                <counts group_id="E2" subjects_affected="29" subjects_at_risk="60"/>
              </event>
              <event>
                <sub_title>Hypophosphatemia</sub_title>
                <counts group_id="E1" subjects_affected="5" subjects_at_risk="59"/>
                <counts group_id="E2" subjects_affected="4" subjects_at_risk="60"/>
              </event>
              <event>
                <sub_title>Metabolism and nutrition disorders - Other</sub_title>
                <counts group_id="E1" subjects_affected="7" subjects_at_risk="59"/>
                <counts group_id="E2" subjects_affected="11" subjects_at_risk="60"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Musculoskeletal and connective tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Arthralgia</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="59"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="60"/>
              </event>
              <event>
                <sub_title>Back pain</sub_title>
                <counts group_id="E1" subjects_affected="7" subjects_at_risk="59"/>
                <counts group_id="E2" subjects_affected="5" subjects_at_risk="60"/>
              </event>
              <event>
                <sub_title>Bone pain</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="59"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="60"/>
              </event>
              <event>
                <sub_title>Fibrosis deep connective tissue</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="59"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="60"/>
              </event>
              <event>
                <sub_title>Generalized muscle weakness</sub_title>
                <counts group_id="E1" subjects_affected="5" subjects_at_risk="59"/>
                <counts group_id="E2" subjects_affected="6" subjects_at_risk="60"/>
              </event>
              <event>
                <sub_title>Musculoskeletal and connective tissue disorder - Other</sub_title>
                <counts group_id="E1" subjects_affected="8" subjects_at_risk="59"/>
                <counts group_id="E2" subjects_affected="11" subjects_at_risk="60"/>
              </event>
              <event>
                <sub_title>Neck pain</sub_title>
                <counts group_id="E1" subjects_affected="12" subjects_at_risk="59"/>
                <counts group_id="E2" subjects_affected="17" subjects_at_risk="60"/>
              </event>
              <event>
                <sub_title>Neck soft tissue necrosis</sub_title>
                <assessment>Systematic Assessment</assessment>
                <counts group_id="E1" subjects_affected="5" subjects_at_risk="59"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="60"/>
              </event>
              <event>
                <sub_title>Superficial soft tissue fibrosis</sub_title>
                <counts group_id="E1" subjects_affected="9" subjects_at_risk="59"/>
                <counts group_id="E2" subjects_affected="6" subjects_at_risk="60"/>
              </event>
              <event>
                <sub_title>Trismus</sub_title>
                <counts group_id="E1" subjects_affected="5" subjects_at_risk="59"/>
                <counts group_id="E2" subjects_affected="4" subjects_at_risk="60"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Dizziness</sub_title>
                <counts group_id="E1" subjects_affected="5" subjects_at_risk="59"/>
                <counts group_id="E2" subjects_affected="8" subjects_at_risk="60"/>
              </event>
              <event>
                <sub_title>Dysgeusia</sub_title>
                <counts group_id="E1" subjects_affected="36" subjects_at_risk="59"/>
                <counts group_id="E2" subjects_affected="38" subjects_at_risk="60"/>
              </event>
              <event>
                <sub_title>Headache</sub_title>
                <counts group_id="E1" subjects_affected="13" subjects_at_risk="59"/>
                <counts group_id="E2" subjects_affected="12" subjects_at_risk="60"/>
              </event>
              <event>
                <sub_title>Nervous system disorders - Other</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="59"/>
                <counts group_id="E2" subjects_affected="5" subjects_at_risk="60"/>
              </event>
              <event>
                <sub_title>Neuralgia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="59"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="60"/>
              </event>
              <event>
                <sub_title>Peripheral sensory neuropathy</sub_title>
                <assessment>Systematic Assessment</assessment>
                <counts group_id="E1" subjects_affected="11" subjects_at_risk="59"/>
                <counts group_id="E2" subjects_affected="11" subjects_at_risk="60"/>
              </event>
              <event>
                <sub_title>Tremor</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="59"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="60"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Psychiatric disorders</title>
            <event_list>
              <event>
                <sub_title>Anxiety</sub_title>
                <counts group_id="E1" subjects_affected="16" subjects_at_risk="59"/>
                <counts group_id="E2" subjects_affected="14" subjects_at_risk="60"/>
              </event>
              <event>
                <sub_title>Confusion</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="59"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="60"/>
              </event>
              <event>
                <sub_title>Depression</sub_title>
                <counts group_id="E1" subjects_affected="10" subjects_at_risk="59"/>
                <counts group_id="E2" subjects_affected="11" subjects_at_risk="60"/>
              </event>
              <event>
                <sub_title>Insomnia</sub_title>
                <counts group_id="E1" subjects_affected="13" subjects_at_risk="59"/>
                <counts group_id="E2" subjects_affected="20" subjects_at_risk="60"/>
              </event>
              <event>
                <sub_title>Psychiatric disorders - Other</sub_title>
                <counts group_id="E1" subjects_affected="5" subjects_at_risk="59"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="60"/>
              </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" subjects_affected="5" subjects_at_risk="59"/>
                <counts group_id="E2" subjects_affected="6" subjects_at_risk="60"/>
              </event>
              <event>
                <sub_title>Hematuria</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="59"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="60"/>
              </event>
              <event>
                <sub_title>Proteinuria</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="59"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="60"/>
              </event>
              <event>
                <sub_title>Urinary retention</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="59"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="60"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Aspiration</sub_title>
                <counts group_id="E1" subjects_affected="8" subjects_at_risk="59"/>
                <counts group_id="E2" subjects_affected="4" subjects_at_risk="60"/>
              </event>
              <event>
                <sub_title>Cough</sub_title>
                <counts group_id="E1" subjects_affected="22" subjects_at_risk="59"/>
                <counts group_id="E2" subjects_affected="20" subjects_at_risk="60"/>
              </event>
              <event>
                <sub_title>Dyspnea</sub_title>
                <counts group_id="E1" subjects_affected="21" subjects_at_risk="59"/>
                <counts group_id="E2" subjects_affected="16" subjects_at_risk="60"/>
              </event>
              <event>
                <sub_title>Hoarseness</sub_title>
                <counts group_id="E1" subjects_affected="29" subjects_at_risk="59"/>
                <counts group_id="E2" subjects_affected="29" subjects_at_risk="60"/>
              </event>
              <event>
                <sub_title>Laryngeal edema</sub_title>
                <counts group_id="E1" subjects_affected="12" subjects_at_risk="59"/>
                <counts group_id="E2" subjects_affected="12" subjects_at_risk="60"/>
              </event>
              <event>
                <sub_title>Laryngeal inflammation</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="59"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="60"/>
              </event>
              <event>
                <sub_title>Pharyngeal fistula</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="59"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="60"/>
              </event>
              <event>
                <sub_title>Pharyngeal mucositis</sub_title>
                <assessment>Systematic Assessment</assessment>
                <counts group_id="E1" subjects_affected="14" subjects_at_risk="59"/>
                <counts group_id="E2" subjects_affected="11" subjects_at_risk="60"/>
              </event>
              <event>
                <sub_title>Pharyngolaryngeal pain</sub_title>
                <counts group_id="E1" subjects_affected="5" subjects_at_risk="59"/>
                <counts group_id="E2" subjects_affected="4" subjects_at_risk="60"/>
              </event>
              <event>
                <sub_title>Pneumonitis</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="59"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="60"/>
              </event>
              <event>
                <sub_title>Productive cough</sub_title>
                <counts group_id="E1" subjects_affected="8" subjects_at_risk="59"/>
                <counts group_id="E2" subjects_affected="5" subjects_at_risk="60"/>
              </event>
              <event>
                <sub_title>Respiratory, thoracic and mediastinal disorders - Other</sub_title>
                <counts group_id="E1" subjects_affected="10" subjects_at_risk="59"/>
                <counts group_id="E2" subjects_affected="10" subjects_at_risk="60"/>
              </event>
              <event>
                <sub_title>Sore throat</sub_title>
                <counts group_id="E1" subjects_affected="21" subjects_at_risk="59"/>
                <counts group_id="E2" subjects_affected="25" subjects_at_risk="60"/>
              </event>
              <event>
                <sub_title>Voice alteration</sub_title>
                <counts group_id="E1" subjects_affected="12" subjects_at_risk="59"/>
                <counts group_id="E2" subjects_affected="10" subjects_at_risk="60"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Skin and subcutaneous tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Alopecia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="59"/>
                <counts group_id="E2" subjects_affected="7" subjects_at_risk="60"/>
              </event>
              <event>
                <sub_title>Dry skin</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="59"/>
                <counts group_id="E2" subjects_affected="4" subjects_at_risk="60"/>
              </event>
              <event>
                <sub_title>Pruritus</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="59"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="60"/>
              </event>
              <event>
                <sub_title>Rash acneiform</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="59"/>
                <counts group_id="E2" subjects_affected="7" subjects_at_risk="60"/>
              </event>
              <event>
                <sub_title>Rash maculo-papular</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="59"/>
                <counts group_id="E2" subjects_affected="5" subjects_at_risk="60"/>
              </event>
              <event>
                <sub_title>Skin and subcutaneous tissue disorders - Other</sub_title>
                <counts group_id="E1" subjects_affected="7" subjects_at_risk="59"/>
                <counts group_id="E2" subjects_affected="9" subjects_at_risk="60"/>
              </event>
              <event>
                <sub_title>Skin hyperpigmentation</sub_title>
                <counts group_id="E1" subjects_affected="5" subjects_at_risk="59"/>
                <counts group_id="E2" subjects_affected="7" subjects_at_risk="60"/>
              </event>
              <event>
                <sub_title>Telangiectasia</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="59"/>
                <counts group_id="E2" subjects_affected="4" subjects_at_risk="60"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Vascular disorders</title>
            <event_list>
              <event>
                <sub_title>Hot flashes</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="59"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="60"/>
              </event>
              <event>
                <sub_title>Hypertension</sub_title>
                <counts group_id="E1" subjects_affected="8" subjects_at_risk="59"/>
                <counts group_id="E2" subjects_affected="11" subjects_at_risk="60"/>
              </event>
              <event>
                <sub_title>Hypotension</sub_title>
                <counts group_id="E1" subjects_affected="11" subjects_at_risk="59"/>
                <counts group_id="E2" subjects_affected="4" subjects_at_risk="60"/>
              </event>
              <event>
                <sub_title>Lymphedema</sub_title>
                <counts group_id="E1" subjects_affected="6" subjects_at_risk="59"/>
                <counts group_id="E2" subjects_affected="6" subjects_at_risk="60"/>
              </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>PI's are required to abide by the sponsor's publication guidelines which require review by coauthors and subsequent review and approval by the sponsor.</restrictive_agreement>
    </certain_agreements>
    <limitations_and_caveats>A total of 69 progression-free survival (PFS) were required. As of September 13, 2020, the number of observed PFS events was 66. At the Radiation Therapy Oncology Group Foundation Data Monitoring Committee meeting on October 22, 2020, a decision was made to report the final results using data through November 30, 2020. This decision has a minor impact (&lt;1%) on the power given that 67 PFS events are included in the final analysis of this trial.</limitations_and_caveats>
    <point_of_contact>
      <name_or_title>Wendy Seiferheld</name_or_title>
      <organization>NRG Oncology</organization>
      <phone>215-574-3208</phone>
      <email>seiferheldw@nrgoncology.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/NCT01711658
org study id: RF-3501
secondary id: LAP116153
nct id: NCT01711658
lead sponsor: 
collaborator: 
collaborator: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
PURPOSE: This trial is studying if and how well lapatinib adds to the effectiveness of
      radiation therapy plus cisplatin in patients who have head and neck cancer that is not
      related to the human papillomavirus (HPV).
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
measure: Percentage of Participants Alive Without Progression (Progression-free Survival)
time frame: From randomization to last follow-up. Maximum follow-up at time of analysis was 7.1 years.
description: An event for progression-free survival is local, regional, or distant disease progression or death due to any cause. Progression-free survival time is defined as time from randomization to the date of progression/death or last known follow-up (censored). Rates are estimated by the Kaplan-Meier method. The protocol specifies that the distributions of survival times be compared between the arms, which is reported in the statistical analysis results. Five-year rates are provided. Analysis occurred after 67 progressions or deaths were reported.
measure: Percentage of Participants Alive (Overall Survival)
time frame: From randomization to last follow-up. Maximum follow-up at time of analysis was 7.1 years.
description: An event for overall survival is death due to any cause. Overall survival time is defined as time from randomization to the date of death or last known follow-up (censored). Rates are estimated by the Kaplan-Meier method. The protocol specifies that the distributions of survival times be compared between the arms, which is reported in the statistical analysis results. Five-year rates are provided.
measure: Percentage of Participants With Distant Metastases
time frame: From randomization to last follow-up. Maximum follow-up at time of analysis was 7.1 years.
description: Failure for distant metastasis endpoint was defined as distant progression; local-regional failure and death due to any cause were considered competing risks. Distant metastasis time is defined as time from randomization to the date of progression/death or last known follow-up (censored). Rates are estimated by the cumulative incidence method. The protocol specifies that the distributions of failure times be compared between the arms, which is reported in the statistical analysis results. Five-year rates are provided.
measure: Percentage of Participants With Treatment-related Grade 3 or Higher Adverse Events
time frame: From start of treatment to last follow-up. Maximum follow-up at time of analysis was 7.1 years.
description: Adverse events (AE) were graded using the Common Terminology Criteria for Adverse Events (CTCAE) v4.0. Grade refers to the severity of the AE. The CTCAE v4.0 assigns Grades 1 through 5 with unique clinical descriptions of severity for each AE based on this general guideline: Grade 1 Mild, Grade 2 Moderate, Grade 3 Severe, Grade 4 Life-threatening or disabling, Grade 5 Death related to adverse event. "Treatment-related" is defined definitely, probably, or possibly related to treatment.
measure: Percentage of Participants Who Complied With Protocol Treatment
time frame: From start of treatment to end of treatment (approximately 5 months from randomization).
description: Compliance with protocol treatment is defined as "per protocol" or "acceptable variation" per study chair review for IMRT, cisplatin, pre-IMRT lapatinib/placebo, concurrent lapatinib/placebo, and maintenance lapatinib/placebo. Rates of treatment compliance were compared between groups by a 2-sided Fisher's exact test.
measure: Percentage of Participants With Local-regional Progression
time frame: From randomization to last follow-up. Maximum follow-up at time of analysis was 7.1 years.
description: Failure for local-regional control endpoint was defined as local or regional progression, salvage surgery of the primary tumor with tumor present/unknown, salvage neck dissection with tumor present/unknown > 20 weeks after the end of radiation therapy, death due to study cancer without documented progression, or death due to unknown causes without documented progression; distant metastasis and death due to other causes were considered competing risks. Local-regional failure time is defined as time from randomization to the date of progression/death or last known follow-up (censored). Failure rates are estimated by the cumulative incidence method. The protocol specifies that the distributions of failure times be compared between the arms, which is reported in the statistical analysis results. Five-year rates are provided.
measure: Performance Status Scale for Head & Neck Cancer.
time frame: 3 months, 1 year, and 2 years
measure: Functional Assessment of Cancer Therapy - Head & Neck.
time frame: 3 months, 1 year, and 2 years.
measure: University of Michigan Xerostomia-Related Quality of Life Scale.
time frame: 3 months, 1 year, and 2 years.
measure: HER2, EGFR, EMT as Biomarkers of Response.
time frame: End of Study
arm group label: IMRT + cisplatin + placebo
arm group type: Placebo Comparator
description: Intensity Modulated Radiation Therapy (IMRT) with cisplatin and placebo
arm group label: IMRT + cisplatin + lapatinib
arm group type: Active Comparator
description: IMRT with cisplatin and lapatinib
intervention type: Radiation
intervention name: IMRT
description: Intensity modulated radiation therapy (IMRT), 35 fractions over 6 weeks, 6 fractions per week for 5 weeks and 5 fractions per week for 1 week, 2 Gy per fraction to total dose of 70 Gy
arm group label: IMRT + cisplatin + lapatinib
arm group label: IMRT + cisplatin + placebo
intervention type: Drug
intervention name: Cisplatin
description: 100 mg/m^2 administered intravenously on days 8 and 29
arm group label: IMRT + cisplatin + lapatinib
arm group label: IMRT + cisplatin + placebo
intervention type: Drug
intervention name: placebo
description: 1500 mg placebo daily by mouth or by feeding tube starting 7 days before IMRT for 7 weeks prior to and during IMRT and 3 months after completion of IMRT
arm group label: IMRT + cisplatin + placebo
intervention type: Drug
intervention name: Lapatinib
description: 1500 mg lapatinib by mouth or by feeding tube daily starting 7 days before IMRT for 7 weeks prior to and during IMRT and 3 months after completion of IMRT
arm group label: IMRT + cisplatin + lapatinib
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Stuart Wong, MD
role: Principal Investigator
affiliation: Medical College of Wisconsin
facility: 
facility: 
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country: Canada
country: United States
citation: Ang KK, Harris J, Wheeler R, Weber R, Rosenthal DI, Nguyen-Tan PF, Westra WH, Chung CH, Jordan RC, Lu C, Kim H, Axelrod R, Silverman CC, Redmond KP, Gillison ML. Human papillomavirus and survival of patients with oropharyngeal cancer. N Engl J Med. 2010 Jul 1;363(1):24-35. doi: 10.1056/NEJMoa0912217. Epub 2010 Jun 7.
PMID: 20530316
citation: Harrington K. et al. Phase II study of oral Lapatinib, a dual-tyrosine kinase inhibitor, combined with chemoradiotherapy (CRT) in patients with advanced squamous cell carcinoma of the head and neck (SCCHN). J Clin Oncol. 28:15s, 2010 suppl. Abstract 5505. GSK study 884
responsible party type: Sponsor
mesh term: Head and Neck Neoplasms
mesh term: Lapatinib
provided document: 
provided document: 
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
limitations and caveats: A total of 69 progression-free survival (PFS) were required. As of September 13, 2020, the number of observed PFS events was 66. At the Radiation Therapy Oncology Group Foundation Data Monitoring Committee meeting on October 22, 2020, a decision was made to report the final results using data through November 30, 2020. This decision has a minor impact (<1%) on the power given that 67 PFS events are included in the final analysis of this trial.
point of contact: 