xml: <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/NCT05962242</url>
    </required_header>
    <id_info>
      <org_study_id>HSR220263</org_study_id>
      <nct_id>NCT05962242</nct_id>
    </id_info>
    <brief_title>HPV DNA-Guided Radiotherapy De-intensification of Head and Neck Squamous Cell Carcinoma</brief_title>
    <acronym>HN001</acronym>
    <official_title>Circulating Tumor Modified HPV DNA-Guided Radiotherapy De-intensification of the Elective Neck (RaDEN) in Squamous Cell Carcinoma of the Head and Neck</official_title>
    <sponsors>
      <lead_sponsor>
        <agency>University of Virginia</agency>
        <agency_class>Other</agency_class>
      </lead_sponsor>
    </sponsors>
    <source>University of Virginia</source>
    <oversight_info>
      <has_dmc>Yes</has_dmc>
      <is_fda_regulated_drug>No</is_fda_regulated_drug>
      <is_fda_regulated_device>No</is_fda_regulated_device>
    </oversight_info>
    <brief_summary>
      <textblock>
        The study will evaluate the safety and effectiveness of a lower than standard dose of&#xD;
        radiation for definitive or adjuvant treatment of head and neck squamous cell carcinomas.&#xD;
      </textblock>
    </brief_summary>
    <detailed_description>
      <textblock>
        In squamous cell carcinomas of the head and neck, regional recurrence is rare within lymph&#xD;
        node stations treated with elective radiation. However, radiotherapy to the neck is toxic,&#xD;
        and leads to a variety of unpleasant side effects, especially coupled with concurrent&#xD;
        systemic therapy. There is growing evidence from previous studies showing that lower&#xD;
        radiation doses may be adequate in preventing locoregional recurrence of disease. The&#xD;
        hypothesis is that lower dose of radiation will have equal effectiveness but less toxicity&#xD;
        than standard approaches for the treatment of squamous cell carcinomas of the head and neck.&#xD;
  &#xD;
        The study evaluates the effectiveness and safety of reduced dose radiotherapy for definitive&#xD;
        and adjuvant treatment of Human papillomavirus (HPV) positive oropharyngeal squamous cell&#xD;
        carcinomas.&#xD;
  &#xD;
        Participants will be treated with a radiation therapy regimen that has a lower dose to less&#xD;
        tissue area (dose and volume de-escalation) than standard of care radiation therapy. The&#xD;
        dosing will be determined by whether concurrent chemotherapy will be given and results from&#xD;
        on treatment HPV blood test called NavDx. On treatment NavDx results indicating a slow&#xD;
        (non-rapid) response to the treatment will receive an additional boost of radiation. Routine&#xD;
        NavDx testing will be performed to assess treatment response and recurrence. Participants&#xD;
        will also be asked to complete surveys about overall health and wellbeing.&#xD;
      </textblock>
    </detailed_description>
    <overall_status>Not yet recruiting</overall_status>
    <start_date type="Anticipated">September 1, 2023</start_date>
    <completion_date type="Anticipated">September 1, 2029</completion_date>
    <primary_completion_date type="Anticipated">September 1, 2027</primary_completion_date>
    <phase>Phase 2</phase>
    <study_type>Interventional</study_type>
    <has_expanded_access>No</has_expanded_access>
    <study_design_info>
      <allocation>Non-Randomized</allocation>
      <intervention_model>Parallel Assignment</intervention_model>
      <intervention_model_description>Participants on this study will undergo a reduced dose regimen starting with a boost to gross disease of 24 Gy, then 30-36 Gy to entire volume based on the plan for concurrent chemotherapy. Non-responders will receive a boost to the entire volume for an additional 10 Gy.</intervention_model_description>
      <primary_purpose>Treatment</primary_purpose>
      <masking>None (Open Label)</masking>
    </study_design_info>
    <primary_outcome>
      <measure>To assess the disease control of participants who receive dose and volume-de-escalated radiotherapy to the neck, guided by treatment response through circulating tumor-modified HPV DNA testing</measure>
      <time_frame>up to 2 years after radiotherapy</time_frame>
      <description>Incidence of disease free survival as measured by circulating HPV on Nav Dx blood tests.</description>
    </primary_outcome>
    <secondary_outcome>
      <measure>To assess safety for treatment with reduced dose and volume-de-escalated radiotherapy to the neck</measure>
      <time_frame>Evaluated through 6 months and 1 year post- radiation.</time_frame>
      <description>Incidence of grade 3 (or greater) adverse events as defined by the CTCAE v5.0</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>To estimate quality of life of participants who receive reduced dose and volume-de-escalated radiotherapy to the neck</measure>
      <time_frame>up to 2 years after radiotherapy</time_frame>
      <description>Quality of life as determined by the EORTC H&amp;N35. Questions are scaled from 1-4 with 1 meaning the symptom/problem was not experienced and 4 meaning the symptom/problem was experienced at a high level.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>To estimate quality of life of participants who receive reduced dose and volume-de-escalated radiotherapy to the neck</measure>
      <time_frame>up to 2 years after radiotherapy</time_frame>
      <description>Quality of life as determined by the EORTC QLQ-C30. Majority of questions are scaled from 1-4 with 1 meaning the symptom/problem was not experienced and 4 meaning the symptom/problem was experienced at a high level. Two questions are scaled from 1-7 with 1 meaning very poor (worse outcome) and 7 meaning excellent (best outcome).</description>
    </secondary_outcome>
    <other_outcome>
      <measure>To estimate long-term survival for participants treated with dose and volume-de-escalated radiotherapy to the neck</measure>
      <time_frame>up to 5 years after radiotherapy</time_frame>
      <description>Overall survival</description>
    </other_outcome>
    <other_outcome>
      <measure>To estimate the relationship between baseline lymphocyte counts and disease progression outcomes.</measure>
      <time_frame>up to 2 years after radiotherapy</time_frame>
      <description>Baseline lymphocyte counts from CBC with Differential blood test</description>
    </other_outcome>
    <other_outcome>
      <measure>To estimate the relationship between baseline lymphocyte counts and disease progression</measure>
      <time_frame>up to 2 years after radiotherapy</time_frame>
      <description>Occurrence of disease progression</description>
    </other_outcome>
    <number_of_arms>4</number_of_arms>
    <enrollment type="Anticipated">90</enrollment>
    <condition>Squamous Cell Carcinoma of the Oropharynx</condition>
    <arm_group>
      <arm_group_label>Reduce Dose without Concurrent Chemotherapy Non- Rapid Responder</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>A reduced dose regimen of 24 Gy in 12 fractions to gross disease and intermediate nodes. Then 36 Gy in 18 fractions to entire volume. Non-responders will receive an additional boost of 10 Gy in 5 fractions to entire volume.</description>
    </arm_group>
    <arm_group>
      <arm_group_label>Reduce Dose with Concurrent Chemotherapy Non-Rapid Responder</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>A reduced dose regimen of 24 Gy in 12 fractions to gross disease and intermediate nodes. Then 30 Gy in 15 fractions to entire volume. Non-responders will receive an additional boost of 10 Gy in 5 fractions to entire volume.</description>
    </arm_group>
    <arm_group>
      <arm_group_label>Reduce Dose without Concurrent Chemotherapy Rapid Responder</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>A reduced dose regimen of 24 Gy in 12 fractions to gross disease and intermediate nodes. Then 36 Gy in 18 fractions to entire volume.</description>
    </arm_group>
    <arm_group>
      <arm_group_label>Reduce Dose with Concurrent Chemotherapy Rapid Responder</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>A reduced dose regimen of 24 Gy in 12 fractions to gross disease and intermediate nodes. Then 30 Gy in 15 fractions to entire volume.</description>
    </arm_group>
    <intervention>
      <intervention_type>Radiation</intervention_type>
      <intervention_name>Radiation Therapy</intervention_name>
      <description>External Beam Radiation to Head and Neck</description>
      <arm_group_label>Reduce Dose with Concurrent Chemotherapy Non-Rapid Responder</arm_group_label>
      <arm_group_label>Reduce Dose with Concurrent Chemotherapy Rapid Responder</arm_group_label>
      <arm_group_label>Reduce Dose without Concurrent Chemotherapy Non- Rapid Responder</arm_group_label>
      <arm_group_label>Reduce Dose without Concurrent Chemotherapy Rapid Responder</arm_group_label>
    </intervention>
    <eligibility>
      <criteria>
        <textblock>
          Inclusion Criteria:&#xD;
  &#xD;
            1. Provision of signed and dated informed consent form&#xD;
  &#xD;
            2. Stated willingness to comply with all study procedures and availability for the&#xD;
               duration of the study&#xD;
  &#xD;
            3. Male or female, ≥ 18 years of age&#xD;
  &#xD;
            4. Pathologically proven diagnosis of squamous cell carcinoma of the oropharynx of any&#xD;
               AJCC 8th edition stage.&#xD;
  &#xD;
            5. Eligible for and planning to receive definitive treatment or adjuvant treatment with&#xD;
               radiotherapy.&#xD;
  &#xD;
            6. Participants who are receiving concurrent systemic anticancer therapy (e.g.&#xD;
               chemotherapy or immunotherapy) for oropharyngeal cancer are eligible.&#xD;
  &#xD;
                 1. For participants with T1-2 and N0 disease, chemotherapy is not required for&#xD;
                    eligibility. Participants may or may not receive chemotherapy per physician&#xD;
                    discretion.&#xD;
  &#xD;
                 2. For participants with T3-4 and/or N+ disease, chemotherapy is required for&#xD;
                    eligibility.&#xD;
  &#xD;
            7. Participants may receive investigational agents with prior approval from the Principal&#xD;
               Investigator.&#xD;
  &#xD;
            8. ECOG Performance Status of 0-2.&#xD;
  &#xD;
            9. p16 positive HPV as determined by NavDx&#xD;
  &#xD;
           10. For females of reproductive potential: agreement to use adequate contraception during&#xD;
               radiation treatment and for 6 months (or more if applicable based on other&#xD;
               medications) after the end of radiation treatment.&#xD;
  &#xD;
          Exclusion Criteria:&#xD;
  &#xD;
            1. Evidence of distant metastatic disease&#xD;
  &#xD;
            2. Prior history of radiotherapy to the head and/or neck&#xD;
  &#xD;
            3. Had surgery for oropharyngeal cancer within 8 months of enrollment.&#xD;
  &#xD;
            4. Diagnosis of T3-4 and/or N+ disease with no plans to receive concurrent chemotherapy.&#xD;
  &#xD;
            5. Diagnosis of a current or prior invasive malignancy (except non-melanoma skin cancer)&#xD;
               unless the participant has been disease free for at least 3 years.&#xD;
  &#xD;
            6. Participant is a prisoner&#xD;
  &#xD;
            7. Known contraindications to head and neck radiation therapy such as ataxia&#xD;
               telangiectasia or scleroderma.&#xD;
  &#xD;
            8. Pregnancy or lactation&#xD;
  &#xD;
            9. Active or severe co-morbidities as defined by the following:&#xD;
  &#xD;
                 1. Unstable angina and/or congestive heart failure requiring hospitalization up to&#xD;
                    180 days before registration&#xD;
  &#xD;
                 2. Transmural myocardial infarction up to 180 days before registration&#xD;
  &#xD;
                 3. Acute bacterial or fungal infection requiring intravenous antibiotics at the time&#xD;
                    of registration&#xD;
  &#xD;
                 4. Chronic obstructive pulmonary disease exacerbation or other respiratory illness&#xD;
                    requiring hospitalization or precluding study therapy at the time of registration&#xD;
  &#xD;
                 5. Hepatic insufficiency as determined by the treating clinician resulting in&#xD;
                    clinical jaundice and/or coagulation effects or severe liver dysfunction.&#xD;
  &#xD;
                 6. Acquired immune deficiency syndrome (AIDS) based upon current CDC definition. The&#xD;
                    need to exclude patients with AIDS from this protocol is necessary because the&#xD;
                    treatments involved in this protocol may be slightly immunosuppressive.&#xD;
                    Protocol-specific requirements may also exclude immuno-compromised patients.&#xD;
  &#xD;
           10. Tobacco smoking history of 10 pack years or greater, or ≥ 20 pack years if smoking&#xD;
               cessation occurred at least 1 year prior to enrollment&#xD;
  &#xD;
           11. Current use of antineoplastic drugs for other malignancies.&#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>Chris McLaughlin, M.D.</last_name>
      <role>Principal Investigator</role>
      <affiliation>UVA</affiliation>
    </overall_official>
    <overall_contact>
      <last_name>Song W</last_name>
      <phone>434-243-0008</phone>
      <email>UVARADONCClinicalTrials@uvahealth.org</email>
    </overall_contact>
    <location>
      <facility>
        <name>Miami Cancer Institute</name>
        <address>
          <city>Miami</city>
          <state>Florida</state>
          <zip>33176</zip>
          <country>United States</country>
        </address>
      </facility>
      <contact>
        <last_name>Noah Kalman, M.D.</last_name>
      </contact>
    </location>
    <location>
      <facility>
        <name>University of Virginia</name>
        <address>
          <city>Charlottesville</city>
          <state>Virginia</state>
          <zip>22908</zip>
          <country>United States</country>
        </address>
      </facility>
      <contact>
        <last_name>Song W</last_name>
        <phone>434-243-0008</phone>
        <email>UVARADONCClinicalTrials@uvahealth.org</email>
      </contact>
      <investigator>
        <last_name>Chris McLaughlin, M.D.</last_name>
        <role>Principal Investigator</role>
      </investigator>
    </location>
    <location>
      <facility>
        <name>Eastern Virginia Medical School</name>
        <address>
          <city>Norfolk</city>
          <state>Virginia</state>
          <zip>23507</zip>
          <country>United States</country>
        </address>
      </facility>
      <contact>
        <last_name>Edwin Crandley, M.D.</last_name>
      </contact>
    </location>
    <location>
      <facility>
        <name>Virginia Commonwealth University</name>
        <address>
          <city>Richmond</city>
          <state>Virginia</state>
          <zip>23284</zip>
          <country>United States</country>
        </address>
      </facility>
      <contact>
        <last_name>Shiyu Song, M.D.</last_name>
      </contact>
    </location>
    <location_countries>
      <country>United States</country>
    </location_countries>
    <verification_date>July 2023</verification_date>
    <study_first_submitted>June 30, 2023</study_first_submitted>
    <study_first_submitted_qc>July 22, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">July 27, 2023</study_first_posted>
    <last_update_submitted>July 22, 2023</last_update_submitted>
    <last_update_submitted_qc>July 22, 2023</last_update_submitted_qc>
    <last_update_posted type="Actual">July 27, 2023</last_update_posted>
    <responsible_party>
      <responsible_party_type>Principal Investigator</responsible_party_type>
      <investigator_affiliation>University of Virginia</investigator_affiliation>
      <investigator_full_name>Christopher McLaughlin, MD</investigator_full_name>
      <investigator_title>Assistant Professor of Radiation Oncology</investigator_title>
    </responsible_party>
    <keyword>Radiation Therapy</keyword>
    <keyword>Radiotherapy</keyword>
    <keyword>Head Cancer</keyword>
    <keyword>Neck Cancer</keyword>
    <keyword>Low Dose Radiation</keyword>
    <condition_browse>
      <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
      <mesh_term>Carcinoma</mesh_term>
      <mesh_term>Carcinoma, Squamous Cell</mesh_term>
    </condition_browse>
    <patient_data>
      <sharing_ipd>No</sharing_ipd>
    </patient_data>
    <!-- Results have not yet been posted for this study                                          -->
  </clinical_study>
  
  
text: 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/NCT05962242
  org study id: HSR220263
  nct id: NCT05962242
  lead sponsor: 
  has dmc: Yes
  is fda regulated drug: No
  is fda regulated device: No
  The study will evaluate the safety and effectiveness of a lower than standard dose of
        radiation for definitive or adjuvant treatment of head and neck squamous cell carcinomas.
  In squamous cell carcinomas of the head and neck, regional recurrence is rare within lymph
        node stations treated with elective radiation. However, radiotherapy to the neck is toxic,
        and leads to a variety of unpleasant side effects, especially coupled with concurrent
        systemic therapy. There is growing evidence from previous studies showing that lower
        radiation doses may be adequate in preventing locoregional recurrence of disease. The
        hypothesis is that lower dose of radiation will have equal effectiveness but less toxicity
        than standard approaches for the treatment of squamous cell carcinomas of the head and neck.
  
        The study evaluates the effectiveness and safety of reduced dose radiotherapy for definitive
        and adjuvant treatment of Human papillomavirus (HPV) positive oropharyngeal squamous cell
        carcinomas.
  
        Participants will be treated with a radiation therapy regimen that has a lower dose to less
        tissue area (dose and volume de-escalation) than standard of care radiation therapy. The
        dosing will be determined by whether concurrent chemotherapy will be given and results from
        on treatment HPV blood test called NavDx. On treatment NavDx results indicating a slow
        (non-rapid) response to the treatment will receive an additional boost of radiation. Routine
        NavDx testing will be performed to assess treatment response and recurrence. Participants
        will also be asked to complete surveys about overall health and wellbeing.
  allocation: Non-Randomized
  intervention model: Parallel Assignment
  intervention model description: Participants on this study will undergo a reduced dose regimen starting with a boost to gross disease of 24 Gy, then 30-36 Gy to entire volume based on the plan for concurrent chemotherapy. Non-responders will receive a boost to the entire volume for an additional 10 Gy.
  primary purpose: Treatment
  masking: None (Open Label)
  measure: To assess the disease control of participants who receive dose and volume-de-escalated radiotherapy to the neck, guided by treatment response through circulating tumor-modified HPV DNA testing
  time frame: up to 2 years after radiotherapy
  description: Incidence of disease free survival as measured by circulating HPV on Nav Dx blood tests.
  measure: To assess safety for treatment with reduced dose and volume-de-escalated radiotherapy to the neck
  time frame: Evaluated through 6 months and 1 year post- radiation.
  description: Incidence of grade 3 (or greater) adverse events as defined by the CTCAE v5.0
  measure: To estimate quality of life of participants who receive reduced dose and volume-de-escalated radiotherapy to the neck
  time frame: up to 2 years after radiotherapy
  description: Quality of life as determined by the EORTC H&N35. Questions are scaled from 1-4 with 1 meaning the symptom/problem was not experienced and 4 meaning the symptom/problem was experienced at a high level.
  measure: To estimate quality of life of participants who receive reduced dose and volume-de-escalated radiotherapy to the neck
  time frame: up to 2 years after radiotherapy
  description: Quality of life as determined by the EORTC QLQ-C30. Majority of questions are scaled from 1-4 with 1 meaning the symptom/problem was not experienced and 4 meaning the symptom/problem was experienced at a high level. Two questions are scaled from 1-7 with 1 meaning very poor (worse outcome) and 7 meaning excellent (best outcome).
  measure: To estimate long-term survival for participants treated with dose and volume-de-escalated radiotherapy to the neck
  time frame: up to 5 years after radiotherapy
  description: Overall survival
  measure: To estimate the relationship between baseline lymphocyte counts and disease progression outcomes.
  time frame: up to 2 years after radiotherapy
  description: Baseline lymphocyte counts from CBC with Differential blood test
  measure: To estimate the relationship between baseline lymphocyte counts and disease progression
  time frame: up to 2 years after radiotherapy
  description: Occurrence of disease progression
  arm group label: Reduce Dose without Concurrent Chemotherapy Non- Rapid Responder
  arm group type: Experimental
  description: A reduced dose regimen of 24 Gy in 12 fractions to gross disease and intermediate nodes. Then 36 Gy in 18 fractions to entire volume. Non-responders will receive an additional boost of 10 Gy in 5 fractions to entire volume.
  arm group label: Reduce Dose with Concurrent Chemotherapy Non-Rapid Responder
  arm group type: Experimental
  description: A reduced dose regimen of 24 Gy in 12 fractions to gross disease and intermediate nodes. Then 30 Gy in 15 fractions to entire volume. Non-responders will receive an additional boost of 10 Gy in 5 fractions to entire volume.
  arm group label: Reduce Dose without Concurrent Chemotherapy Rapid Responder
  arm group type: Experimental
  description: A reduced dose regimen of 24 Gy in 12 fractions to gross disease and intermediate nodes. Then 36 Gy in 18 fractions to entire volume.
  arm group label: Reduce Dose with Concurrent Chemotherapy Rapid Responder
  arm group type: Experimental
  description: A reduced dose regimen of 24 Gy in 12 fractions to gross disease and intermediate nodes. Then 30 Gy in 15 fractions to entire volume.
  intervention type: Radiation
  intervention name: Radiation Therapy
  description: External Beam Radiation to Head and Neck
  arm group label: Reduce Dose with Concurrent Chemotherapy Non-Rapid Responder
  arm group label: Reduce Dose with Concurrent Chemotherapy Rapid Responder
  arm group label: Reduce Dose without Concurrent Chemotherapy Non- Rapid Responder
  arm group label: Reduce Dose without Concurrent Chemotherapy Rapid Responder
  criteria: 
  gender: All
  minimum age: 18 Years
  maximum age: N/A
  healthy volunteers: No
  last name: Chris McLaughlin, M.D.
  role: Principal Investigator
  affiliation: UVA
  last name: Song W
  phone: 434-243-0008
  email: UVARADONCClinicalTrials@uvahealth.org
  facility: 
  contact: 
  facility: 
  contact: 
  investigator: 
  facility: 
  contact: 
  facility: 
  contact: 
  country: United States
  responsible party type: Principal Investigator
  investigator affiliation: University of Virginia
  investigator full name: Christopher McLaughlin, MD
  investigator title: Assistant Professor of Radiation Oncology
  mesh term: Carcinoma
  mesh term: Carcinoma, Squamous Cell
  sharing ipd: No