<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/NCT01716195</url>
  </required_header>
  <id_info>
    <org_study_id>359512</org_study_id>
    <secondary_id>CCRO022</secondary_id>
    <nct_id>NCT01716195</nct_id>
  </id_info>
  <brief_title>Induction Chemotherapy Followed by Chemoradiotherapy for Head and Neck Cancer</brief_title>
  <official_title>Phase II Trial Of Induction Chemotherapy Followed By Attenuated Chemoradiotherapy For Locally Advanced Head And Neck Squamous Cell Carcinoma Associated With Human Papillomavirus (HPV)</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of California, Davis</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>University of California, Davis</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The purpose of this study is to determine whether human papillomavirus (HPV)-positive head&#xD;
      and neck cancer can be treated with a less aggressive regimen of radiation therapy and&#xD;
      chemotherapy (paclitaxel) after initially receiving two cycles of chemotherapy&#xD;
      (carboplatin/paclitaxel).&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Given the toxicity of high dose cisplatin, attention has focused on identifying patients at&#xD;
      lower risk for failure who may potentially benefit from less aggressive chemoradiotherapy&#xD;
      approaches. HPV-positive Head and Neck Cancer responds favorably to radiation therapy. This&#xD;
      has prompted investigators to suggest that patients with these cancers might be&#xD;
      &quot;over-treated&quot; and unnecessarily subjected to the toxicity of intensive chemoradiotherapy&#xD;
      with excessively high radiation doses.&#xD;
&#xD;
      This study will select patients with HPV-positive Head and Neck cancer for attenuated therapy&#xD;
      and may have important implications for individualization of care in the future. The regimen&#xD;
      of carboplatin and paclitaxel was selected for the induction chemotherapy phase because of&#xD;
      its ease of administration, improved toxicity profile, high rates of dose delivery, and&#xD;
      excellent published results showing high response rates and overall survival. This study will&#xD;
      use induction chemotherapy primarily as a means to select HPV-positive Head and Neck Cancer&#xD;
      patients, who may benefit from significant radiation dose de-intensification in the&#xD;
      concurrent chemoradiotherapy phase of treatment. The rationale for this risk-adapted approach&#xD;
      to local therapy based on HPV status is to administer effective comprehensive treatment&#xD;
      individualized at diagnosis and after assessment of response to induction chemotherapy (for&#xD;
      patients with HPV-positive tumors), thus avoiding unnecessary and potentially toxic&#xD;
      treatment, and hence optimizing the therapeutic ratio.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>October 2012</start_date>
  <completion_date type="Actual">October 1, 2020</completion_date>
  <primary_completion_date type="Actual">March 8, 2017</primary_completion_date>
  <phase>Phase 2</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>N/A</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Number of Participants With Progression-free Survival</measure>
    <time_frame>Up to 2 years</time_frame>
    <description>Defined from date of registration to date of first documentation of progression and/or distant metastasis, or death due to any cause. The true 2-year progression-free survival rate will be estimated by the proportion of efficacy-evaluable patients on study without documentation of disease progression or death 2 years from registration. A 95% confidence interval (CI) for the true progression-free survival rate will be constructed using the Duffy-Santner approach. However, Kaplan-Meier methodology will be used to estimate the final 2-year progression-free survival rate and its 95% CI in case there are censored patients.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Number of Participants With Overall Survival</measure>
    <time_frame>Up to 5 years</time_frame>
    <description>Defined as the time from registration to death using the Kaplan-Meier method..</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of Patients With Toxicity of Concurrent Chemoradiotherapy</measure>
    <time_frame>Up to 5 years</time_frame>
    <description>Assessed by NCI Common Toxicity Criteria for Adverse Effects, Version 4.0. Reported participants who experienced an AE during concurrent chemoradiotherapy.</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">18</enrollment>
  <condition>Head and Neck Cancer</condition>
  <arm_group>
    <arm_group_label>Response Adapted Chemoradiation</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Paclitaxel 175 mg/m2 + Carboplatin area under curve (AUC) 6 followed by response adapted Radiation Therapy (5 - 6 weeks) + Paclitaxel</description>
  </arm_group>
  <intervention>
    <intervention_type>Radiation</intervention_type>
    <intervention_name>Induction Chemotherapy followed by Response Adapted Chemoradiation</intervention_name>
    <description>All patients receive induction chemotherapy with 2 cycles of paclitaxel and carboplatin followed by response adapted, de-escalated chemoradiation. Patients with a complete or partial response will receive 54 Gy with concurrent paclitaxel and patients with stable disease will receive 60 Gy with concurrent paclitaxel.</description>
    <arm_group_label>Response Adapted Chemoradiation</arm_group_label>
    <other_name>Paclitaxel</other_name>
    <other_name>Carboplatin</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Pathologically proven diagnosis of HPV-positive squamous cell carcinoma of the&#xD;
             oropharynx, hypopharynx, or larynx. HPV-positivity will be defined as tumors that are&#xD;
             p16-positive by immunohistochemistry.&#xD;
&#xD;
          -  Clinical stage III or IV disease; Note: Patients with M1 tumors are not eligible.&#xD;
&#xD;
          -  Appropriate stage for protocol entry, including no distant metastases, based upon&#xD;
             minimum diagnostic workup&#xD;
&#xD;
          -  Zubrod Performance Status 0-1&#xD;
&#xD;
          -  Age &gt; 18&#xD;
&#xD;
          -  Adequate bone marrow function&#xD;
&#xD;
          -  Adequate hepatic function&#xD;
&#xD;
          -  Adequate renal function&#xD;
&#xD;
          -  Pregnancy test within 4 weeks prior to registration for women of childbearing&#xD;
             potential&#xD;
&#xD;
          -  Women of childbearing potential and male participants must agree to use a medically&#xD;
             effective means of birth control throughout their participation in the treatment phase&#xD;
             of the study (until at least 60 days following the last study treatment)&#xD;
&#xD;
          -  Patient must sign study specific informed consent prior to study entry.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Prior invasive malignancy (except non-melanomatous skin cancer) unless disease free&#xD;
             for a minimum of 3 years;&#xD;
&#xD;
          -  Patients with simultaneous primaries or bilateral tumors are excluded.&#xD;
&#xD;
          -  Patients who present with a cervical lymph node metastasis of unknown primary origin;&#xD;
&#xD;
          -  Prior systemic chemotherapy for the study cancer; note that prior chemotherapy for a&#xD;
             different cancer is allowable;&#xD;
&#xD;
          -  Prior radiotherapy that would result in overlap of radiation therapy fields;&#xD;
&#xD;
          -  Primary site of tumor of oral cavity, nasopharynx, nasal cavity, paranasal sinuses, or&#xD;
             salivary glands;&#xD;
&#xD;
          -  Recurrent head and neck cancer;&#xD;
&#xD;
          -  Severe, active co-morbidity&#xD;
&#xD;
          -  Pregnant or lactating women or women of childbearing potential and men who are&#xD;
             sexually active and not willing/able to use medically acceptable forms of&#xD;
             contraception; this exclusion is necessary because the treatment involved in this&#xD;
             study may be significantly teratogenic.&#xD;
&#xD;
          -  Prior allergic reaction to the study drug(s) involved in this protocol.&#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>Megan Daly, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>University of California, Davis</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>University of California Comprehensive Cancer Center</name>
      <address>
        <city>Sacramento</city>
        <state>California</state>
        <zip>95817</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>February 2021</verification_date>
  <study_first_submitted>October 25, 2012</study_first_submitted>
  <study_first_submitted_qc>October 25, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">October 29, 2012</study_first_posted>
  <results_first_submitted>December 21, 2020</results_first_submitted>
  <results_first_submitted_qc>February 24, 2021</results_first_submitted_qc>
  <results_first_posted type="Actual">February 26, 2021</results_first_posted>
  <last_update_submitted>February 24, 2021</last_update_submitted>
  <last_update_submitted_qc>February 24, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">February 26, 2021</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Human Papillomavirus</keyword>
  <keyword>HPV</keyword>
  <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>Paclitaxel</mesh_term>
    <mesh_term>Carboplatin</mesh_term>
  </intervention_browse>
  <provided_document_section>
    <provided_document>
      <document_type>Study Protocol, Statistical Analysis Plan, and Informed Consent Form</document_type>
      <document_has_protocol>Yes</document_has_protocol>
      <document_has_icf>Yes</document_has_icf>
      <document_has_sap>Yes</document_has_sap>
      <document_date>February 25, 2014</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/95/NCT01716195/Prot_SAP_ICF_000.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <group_list>
        <group group_id="P1">
          <title>Response Adapted Chemoradiation</title>
          <description>Paclitaxel 175 mg/m2 + Carboplatin area under curve (AUC) 6 followed by response adapted Radiation Therapy (5 - 6 weeks) + Paclitaxel&#xD;
Induction Chemotherapy followed by Response Adapted Chemoradiation: All patients receive induction chemotherapy with 2 cycles of paclitaxel and carboplatin followed by response adapted, de-escalated chemoradiation. Patients with a complete or partial response will receive 54 Gy with concurrent paclitaxel and patients with stable disease will receive 60 Gy with concurrent paclitaxel.</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="18"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="17"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
              </participants_list>
            </milestone>
          </milestone_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>Response Adapted Chemoradiation</title>
          <description>Paclitaxel 175 mg/m2 + Carboplatin area under curve (AUC) 6 followed by response adapted Radiation Therapy (5 - 6 weeks) + Paclitaxel&#xD;
Induction Chemotherapy followed by Response Adapted Chemoradiation: All patients receive induction chemotherapy with 2 cycles of paclitaxel and carboplatin followed by response adapted, de-escalated chemoradiation. Patients with a complete or partial response will receive 54 Gy with concurrent paclitaxel and patients with stable disease will receive 60 Gy with concurrent paclitaxel.</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="18"/>
          </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="18"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="63.1" lower_limit="40.5" upper_limit="73.1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Sex: Female, Male</title>
          <population>One subject withdrew consent during treatment phase</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="17"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <title>Female</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="17"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Ethnicity (NIH/OMB)</title>
          <population>One subject withdrew consent during treatment phase</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="17"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <title>Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Not Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="16"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Race (NIH/OMB)</title>
          <population>One subject withdrew consent during treatment</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="17"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <title>American Indian or Alaska Native</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Asian</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Native Hawaiian or Other Pacific Islander</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Black or African American</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>White</title>
                  <measurement_list>
                    <measurement group_id="B1" value="17"/>
                  </measurement_list>
                </category>
                <category>
                  <title>More than one race</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Number of Participants With Progression-free Survival</title>
        <description>Defined from date of registration to date of first documentation of progression and/or distant metastasis, or death due to any cause. The true 2-year progression-free survival rate will be estimated by the proportion of efficacy-evaluable patients on study without documentation of disease progression or death 2 years from registration. A 95% confidence interval (CI) for the true progression-free survival rate will be constructed using the Duffy-Santner approach. However, Kaplan-Meier methodology will be used to estimate the final 2-year progression-free survival rate and its 95% CI in case there are censored patients.</description>
        <time_frame>Up to 2 years</time_frame>
        <population>One subject withdrew consent prior to completing study</population>
        <group_list>
          <group group_id="O1">
            <title>Response Adapted Chemoradiation</title>
            <description>Paclitaxel 175 mg/m2 + Carboplatin area under curve (AUC) 6 followed by response adapted Radiation Therapy (5 - 6 weeks) + Paclitaxel&#xD;
Induction Chemotherapy followed by Response Adapted Chemoradiation: All patients receive induction chemotherapy with 2 cycles of paclitaxel and carboplatin followed by response adapted, de-escalated chemoradiation. Patients with a complete or partial response will receive 54 Gy with concurrent paclitaxel and patients with stable disease will receive 60 Gy with concurrent paclitaxel.</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Participants With Progression-free Survival</title>
          <description>Defined from date of registration to date of first documentation of progression and/or distant metastasis, or death due to any cause. The true 2-year progression-free survival rate will be estimated by the proportion of efficacy-evaluable patients on study without documentation of disease progression or death 2 years from registration. A 95% confidence interval (CI) for the true progression-free survival rate will be constructed using the Duffy-Santner approach. However, Kaplan-Meier methodology will be used to estimate the final 2-year progression-free survival rate and its 95% CI in case there are censored patients.</description>
          <population>One subject withdrew consent prior to completing study</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="17"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="17"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Number of Participants With Overall Survival</title>
        <description>Defined as the time from registration to death using the Kaplan-Meier method..</description>
        <time_frame>Up to 5 years</time_frame>
        <population>One subject withdrew consent prior to completing study.</population>
        <group_list>
          <group group_id="O1">
            <title>Response Adapted Chemoradiation</title>
            <description>Paclitaxel 175 mg/m2 + Carboplatin area under curve (AUC) 6 followed by response adapted Radiation Therapy (5 - 6 weeks) + Paclitaxel&#xD;
Induction Chemotherapy followed by Response Adapted Chemoradiation: All patients receive induction chemotherapy with 2 cycles of paclitaxel and carboplatin followed by response adapted, de-escalated chemoradiation. Patients with a complete or partial response will receive 54 Gy with concurrent paclitaxel and patients with stable disease will receive 60 Gy with concurrent paclitaxel.</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Participants With Overall Survival</title>
          <description>Defined as the time from registration to death using the Kaplan-Meier method..</description>
          <population>One subject withdrew consent prior to completing study.</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="17"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="16"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Number of Patients With Toxicity of Concurrent Chemoradiotherapy</title>
        <description>Assessed by NCI Common Toxicity Criteria for Adverse Effects, Version 4.0. Reported participants who experienced an AE during concurrent chemoradiotherapy.</description>
        <time_frame>Up to 5 years</time_frame>
        <population>One subject withdrew consent prior to completing study.</population>
        <group_list>
          <group group_id="O1">
            <title>Response Adapted Chemoradiation</title>
            <description>Paclitaxel 175 mg/m2 + Carboplatin area under curve (AUC) 6 followed by response adapted Radiation Therapy (5 - 6 weeks) + Paclitaxel&#xD;
Induction Chemotherapy followed by Response Adapted Chemoradiation: All patients receive induction chemotherapy with 2 cycles of paclitaxel and carboplatin followed by response adapted, de-escalated chemoradiation. Patients with a complete or partial response will receive 54 Gy with concurrent paclitaxel and patients with stable disease will receive 60 Gy with concurrent paclitaxel.</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Patients With Toxicity of Concurrent Chemoradiotherapy</title>
          <description>Assessed by NCI Common Toxicity Criteria for Adverse Effects, Version 4.0. Reported participants who experienced an AE during concurrent chemoradiotherapy.</description>
          <population>One subject withdrew consent prior to completing study.</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="17"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="17"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>5 years</time_frame>
      <group_list>
        <group group_id="E1">
          <title>Response Adapted Chemoradiation</title>
          <description>Paclitaxel 175 mg/m2 + Carboplatin area under curve (AUC) 6 followed by response adapted Radiation Therapy (5 - 6 weeks) + Paclitaxel&#xD;
Induction Chemotherapy followed by Response Adapted Chemoradiation: All patients receive induction chemotherapy with 2 cycles of paclitaxel and carboplatin followed by response adapted, de-escalated chemoradiation. Patients with a complete or partial response will receive 54 Gy with concurrent paclitaxel and patients with stable disease will receive 60 Gy with concurrent paclitaxel.</description>
        </group>
      </group_list>
      <serious_events>
        <default_assessment>Systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, all-cause mortality</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="18"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="18"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Nausea</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="18"/>
              </event>
              <event>
                <sub_title>Dysphagia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="18"/>
              </event>
              <event>
                <sub_title>Sore throat</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="18"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Skin Infection</sub_title>
                <description>MRSA cellulitis</description>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="18"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Metabolism and nutrition disorders</title>
            <event_list>
              <event>
                <sub_title>Anorexia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="18"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>5</frequency_threshold>
        <default_assessment>Non-systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, other adverse events</sub_title>
                <counts group_id="E1" subjects_affected="13" subjects_at_risk="18"/>
              </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="13" subjects_at_risk="18"/>
              </event>
              <event>
                <sub_title>Lymphocyte count decreased</sub_title>
                <counts group_id="E1" subjects_affected="6" subjects_at_risk="18"/>
              </event>
              <event>
                <sub_title>White blood cell decreased</sub_title>
                <counts group_id="E1" subjects_affected="9" subjects_at_risk="18"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Cardiac disorders</title>
            <event_list>
              <event>
                <sub_title>Sinus bradycardia</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="18"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Ear and labyrinth disorders</title>
            <event_list>
              <event>
                <sub_title>Tinnitus</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="18"/>
              </event>
              <event>
                <sub_title>Ear Pain</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="18"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Mucositis oral</sub_title>
                <counts group_id="E1" subjects_affected="8" subjects_at_risk="18"/>
              </event>
              <event>
                <sub_title>Dysphagia</sub_title>
                <counts group_id="E1" subjects_affected="8" subjects_at_risk="18"/>
              </event>
              <event>
                <sub_title>Dysgeusia</sub_title>
                <counts group_id="E1" subjects_affected="5" subjects_at_risk="18"/>
              </event>
              <event>
                <sub_title>Sore throat</sub_title>
                <counts group_id="E1" subjects_affected="5" subjects_at_risk="18"/>
              </event>
              <event>
                <sub_title>Diarrhea</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="18"/>
              </event>
              <event>
                <sub_title>Constipation</sub_title>
                <counts group_id="E1" subjects_affected="5" subjects_at_risk="18"/>
              </event>
              <event>
                <sub_title>Vomiting</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="18"/>
              </event>
              <event>
                <sub_title>Oral Pain</sub_title>
                <counts group_id="E1" subjects_affected="5" subjects_at_risk="18"/>
              </event>
              <event>
                <sub_title>Dry Mouth</sub_title>
                <counts group_id="E1" subjects_affected="6" subjects_at_risk="18"/>
              </event>
              <event>
                <sub_title>Nausea</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="18"/>
              </event>
              <event>
                <sub_title>Gastroesophageal reflux disorder</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="18"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Fatigue</sub_title>
                <counts group_id="E1" subjects_affected="10" subjects_at_risk="18"/>
              </event>
              <event>
                <sub_title>Myalgia</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="18"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Hepatobiliary disorders</title>
            <event_list>
              <event>
                <sub_title>Alanine aminotransferase increased</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="18"/>
              </event>
              <event>
                <sub_title>Aspartate aminotransferase increased</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="18"/>
              </event>
              <event>
                <sub_title>Alkaline phosphatese increased</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="18"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Immune system disorders</title>
            <event_list>
              <event>
                <sub_title>Neutrophil count decreased</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="18"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Metabolism and nutrition disorders</title>
            <event_list>
              <event>
                <sub_title>Hypercalcemia</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="18"/>
              </event>
              <event>
                <sub_title>Hyponatremia</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="18"/>
              </event>
              <event>
                <sub_title>Anorexia</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="18"/>
              </event>
              <event>
                <sub_title>Weight loss</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="18"/>
              </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="18"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Peripheral Sensory Neuropathy</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="18"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Psychiatric disorders</title>
            <event_list>
              <event>
                <sub_title>Anxiety</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="18"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Cough</sub_title>
                <counts group_id="E1" subjects_affected="6" subjects_at_risk="18"/>
              </event>
              <event>
                <sub_title>Hoarseness</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="18"/>
              </event>
              <event>
                <sub_title>Hiccups</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="18"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Skin and subcutaneous tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Erythema Multiforme</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="18"/>
              </event>
              <event>
                <sub_title>Dermatitis radiation</sub_title>
                <counts group_id="E1" subjects_affected="7" subjects_at_risk="18"/>
              </event>
              <event>
                <sub_title>Rash acneiform</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="18"/>
              </event>
              <event>
                <sub_title>Alopecia</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="18"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </other_events>
    </reported_events>

    <certain_agreements>
      <pi_employee>All Principal Investigators ARE employed by the organization sponsoring the study.</pi_employee>
      <restrictive_agreement>There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed. </restrictive_agreement>
    </certain_agreements>
    <point_of_contact>
      <name_or_title>Dr. Megan Daly</name_or_title>
      <organization>University of California Davis</organization>
      <phone>916-734-5428</phone>
      <email>medaly@ucdavis.edu</email>
    </point_of_contact>
  </clinical_results>
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT01716195
org study id: 359512
secondary id: CCRO022
nct id: NCT01716195
lead sponsor: 
has dmc: Yes
The purpose of this study is to determine whether human papillomavirus (HPV)-positive head
      and neck cancer can be treated with a less aggressive regimen of radiation therapy and
      chemotherapy (paclitaxel) after initially receiving two cycles of chemotherapy
      (carboplatin/paclitaxel).
Given the toxicity of high dose cisplatin, attention has focused on identifying patients at
      lower risk for failure who may potentially benefit from less aggressive chemoradiotherapy
      approaches. HPV-positive Head and Neck Cancer responds favorably to radiation therapy. This
      has prompted investigators to suggest that patients with these cancers might be
      "over-treated" and unnecessarily subjected to the toxicity of intensive chemoradiotherapy
      with excessively high radiation doses.

      This study will select patients with HPV-positive Head and Neck cancer for attenuated therapy
      and may have important implications for individualization of care in the future. The regimen
      of carboplatin and paclitaxel was selected for the induction chemotherapy phase because of
      its ease of administration, improved toxicity profile, high rates of dose delivery, and
      excellent published results showing high response rates and overall survival. This study will
      use induction chemotherapy primarily as a means to select HPV-positive Head and Neck Cancer
      patients, who may benefit from significant radiation dose de-intensification in the
      concurrent chemoradiotherapy phase of treatment. The rationale for this risk-adapted approach
      to local therapy based on HPV status is to administer effective comprehensive treatment
      individualized at diagnosis and after assessment of response to induction chemotherapy (for
      patients with HPV-positive tumors), thus avoiding unnecessary and potentially toxic
      treatment, and hence optimizing the therapeutic ratio.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Number of Participants With Progression-free Survival
time frame: Up to 2 years
description: Defined from date of registration to date of first documentation of progression and/or distant metastasis, or death due to any cause. The true 2-year progression-free survival rate will be estimated by the proportion of efficacy-evaluable patients on study without documentation of disease progression or death 2 years from registration. A 95% confidence interval (CI) for the true progression-free survival rate will be constructed using the Duffy-Santner approach. However, Kaplan-Meier methodology will be used to estimate the final 2-year progression-free survival rate and its 95% CI in case there are censored patients.
measure: Number of Participants With Overall Survival
time frame: Up to 5 years
description: Defined as the time from registration to death using the Kaplan-Meier method..
measure: Number of Patients With Toxicity of Concurrent Chemoradiotherapy
time frame: Up to 5 years
description: Assessed by NCI Common Toxicity Criteria for Adverse Effects, Version 4.0. Reported participants who experienced an AE during concurrent chemoradiotherapy.
arm group label: Response Adapted Chemoradiation
arm group type: Experimental
description: Paclitaxel 175 mg/m2 + Carboplatin area under curve (AUC) 6 followed by response adapted Radiation Therapy (5 - 6 weeks) + Paclitaxel
intervention type: Radiation
intervention name: Induction Chemotherapy followed by Response Adapted Chemoradiation
description: All patients receive induction chemotherapy with 2 cycles of paclitaxel and carboplatin followed by response adapted, de-escalated chemoradiation. Patients with a complete or partial response will receive 54 Gy with concurrent paclitaxel and patients with stable disease will receive 60 Gy with concurrent paclitaxel.
arm group label: Response Adapted Chemoradiation
other name: Paclitaxel
other name: Carboplatin
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Megan Daly, MD
role: Principal Investigator
affiliation: University of California, Davis
facility: 
country: United States
responsible party type: Sponsor
mesh term: Head and Neck Neoplasms
mesh term: Paclitaxel
mesh term: Carboplatin
provided document: 
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 