<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/NCT04444869</url>
  </required_header>
  <id_info>
    <org_study_id>2017520</org_study_id>
    <nct_id>NCT04444869</nct_id>
  </id_info>
  <brief_title>Testing Less Intensive Radiation With Chemotherapy to Treat Low-risk Patients With HPV-positive Oropharyngeal Cancer</brief_title>
  <acronym>ENID</acronym>
  <official_title>Phase II Trial of Definitive Chemoradiation With Elective Nodal Irradiation Dose De-escalation for p16 Positive Squamous Cell Carcinoma of the Oropharynx &quot;ENID&quot;</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of Missouri-Columbia</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>University of Missouri-Columbia</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>
    <is_us_export>No</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      This trial will explore giving standard dose chemotherapy and radiation therapy to sites of&#xD;
      disease including all lymph nodes involved with HPV-positive oropharyngeal cancer, but&#xD;
      administer lower doses of radiation therapy to the lymph nodes that are not known to be&#xD;
      involved with cancer. By doing so, it is hypothesized that there will be equally good long&#xD;
      term loco-regional and distant disease control but will reduced long term treatment side&#xD;
      effects and improved quality of life in persons living well beyond their cancer treatment.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This is a trial of definitive chemotherapy and radiation therapy in human papilloma virus&#xD;
      positive oropharyngeal cancers, in a population whose cancer is thought to be highly&#xD;
      radio-sensitive. This is a population whose outcomes are already known to be very good with&#xD;
      high rates of local and distant control of the disease. With the long term disease control&#xD;
      and survival of patients with this disease, long term treatment toxicity and resulting&#xD;
      reduction in quality of life poses new problems. This has lead to several studies to examine&#xD;
      the role of radiation dose de-escalation through various strategies in attempt to reduce long&#xD;
      term toxicity from treatment and yet achieve equivalent long term disease control.&#xD;
&#xD;
      This trial specifically hypothesizes that a lower dose of radiation therapy to the clinically&#xD;
      and radiographically uninvolved lymph nodes will no detrimental effect on loco-regional&#xD;
      control or overall survival and will improve the long-term side effect profile, particularly&#xD;
      with regards to xerostomia and dysphagia. The goal of this study is therefore to determine&#xD;
      whether a lower dose to the clinically and radiographically uninvolved lymph nodes can be&#xD;
      done safely and with better long-term toxicity profile and better overall quality of life&#xD;
      without compromising the expected outcomes of progression free survival.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">September 28, 2020</start_date>
  <completion_date type="Anticipated">June 2025</completion_date>
  <primary_completion_date type="Anticipated">June 2024</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>
    <intervention_model_description>All patients are treated with the same approach.</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Rate of PEG tube placement</measure>
    <time_frame>During the procedure</time_frame>
    <description>To determine rate of PEG tube placement</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Progression-free survival</measure>
    <time_frame>Two years post treatment</time_frame>
    <description>Progression-free survival of 85% or more at measured a 2 years post treatment</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Dysphagia index</measure>
    <time_frame>Baseline, 1 month and 6 months after treatment</time_frame>
    <description>To report the change in dysphagia using the M. D. Anderson Dysphagia Inventory (MDADI) scores. Scores are 0 (lowest functioning) to 100 (highest functioning).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Patient Reported Outcomes</measure>
    <time_frame>Baseline and 1, 6, and 12 months after end of treatment</time_frame>
    <description>European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Survival</measure>
    <time_frame>At 6 months and at 2 years</time_frame>
    <description>To determine overall survival and progression-free survival</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Toxicity profiles</measure>
    <time_frame>1 year and 2 years post treatment</time_frame>
    <description>Incidence of Common Terminology Criteria for Adverse Events (CTCAE) grade 2 or higher for mucositis, dysphagia, xerostomia and altered taste</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Hypothyroidism incidence</measure>
    <time_frame>At 1 and 2 years post treatment</time_frame>
    <description>To monitor rate of hypothyroidism</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Anticipated">28</enrollment>
  <condition>Cancer of the Head and Neck</condition>
  <condition>Oropharynx Cancer</condition>
  <condition>HPV Positive Oropharyngeal Squamous Cell Carcinoma</condition>
  <condition>Throat Carcinoma</condition>
  <arm_group>
    <arm_group_label>Open label single-arm study</arm_group_label>
    <arm_group_type>Other</arm_group_type>
    <description>All patients will receive concurrent cisplatin and radiation therapy with radiation dose de-escalation to clinically and radiologically uninvolved lymph nodes.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Cisplatin injection</intervention_name>
    <description>Standard dose cisplatin given concurrently with radiation therapy</description>
    <arm_group_label>Open label single-arm study</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Patients generally must have the psychological ability and general health that permits&#xD;
             completion of the study requirements and required follow up.&#xD;
&#xD;
          -  Women of childbearing potential and men who are sexually active should be willing and&#xD;
             able to use medically acceptable forms of contraception throughout the treatment phase&#xD;
             of the trial and until at least 60 days following the last study treatment.&#xD;
&#xD;
          -  Pathologically (histologically or cytologically) proven diagnosis of squamous cell&#xD;
             carcinoma (including the histological variants papillary squamous cell carcinoma and&#xD;
             basaloid squamous cell carcinoma) of the oropharynx (tonsil, base of tongue, soft&#xD;
             palate, or oropharyngeal walls); cytologic diagnosis from a cervical lymph node is&#xD;
             sufficient in the presence of clinical evidence of a primary tumor in the oropharynx.&#xD;
             Clinical evidence should be documented, may consist of palpation, imaging, or&#xD;
             endoscopic evaluation, and should be sufficient to estimate the size of the primary&#xD;
             (for T stage).&#xD;
&#xD;
          -  Patients must have clinically or radiographically evident measurable disease at the&#xD;
             primary site or at nodal stations. Tonsillectomy or local excision of the primary&#xD;
             without removal of nodal disease is permitted, as is excision removing gross nodal&#xD;
             disease but with intact primary site. Limited neck dissections retrieving ≤ 4 nodes&#xD;
             are permitted and considered as non-therapeutic nodal excisions.&#xD;
&#xD;
          -  Immunohistochemical staining for p16 must be performed on tissue and documented in the&#xD;
             pathology report(s) with reported result positive for p16.&#xD;
&#xD;
          -  Clinical stage T1-T3, N0-N2c (AJCC, 7th ed.), which is equal to T1-T3, N0-2 (AJCC, 8th&#xD;
             ed.) including no distant metastases based on the following diagnostic workup:&#xD;
&#xD;
               -  General history and physical examination within 30 days prior to registration;&#xD;
&#xD;
               -  Fiberoptic exam with laryngopharyngoscopy (mirror and/or fiberoptic and/or direct&#xD;
                  procedure) within 60 days prior to registration;&#xD;
&#xD;
               -  One of the following combinations of imaging is required within 45 days prior to&#xD;
                  registration:&#xD;
&#xD;
                    1. A CT scan of the neck (with contrast) and a chest CT scan (with or without&#xD;
                       contrast);&#xD;
&#xD;
                    2. or an MRI of the neck (with contrast) and a chest CT scan (with or without&#xD;
                       contrast);&#xD;
&#xD;
                    3. or a CT scan of neck (with contrast) and a PET/CT of neck and chest (with or&#xD;
                       without contrast);&#xD;
&#xD;
                    4. or an MRI of the neck (with contrast) and a PET/CT of neck and chest (with&#xD;
                       or without contrast).&#xD;
&#xD;
        Note: A CT scan of neck and/or a PET/CT performed for the purposes of radiation planning&#xD;
        may serve as both staging and planning tools.&#xD;
&#xD;
          -  Patients will be asked about their personal smoking history prior to enrollment. Only&#xD;
             active smokers with greater than 10 pack years will be excluded from the trial. The&#xD;
             total number of pack years will be collected at baseline. Current smokers who wish to&#xD;
             discontinue will be offered smoking cessation information, and if they are able to&#xD;
             discontinue smoking prior to initiation of radiation therapy, they can remain eligible&#xD;
             for the trial.&#xD;
&#xD;
        Number of pack-years = [Frequency of smoking (number of cigarettes per day) × duration of&#xD;
        cigarette smoking (years)] / 20 Note: Twenty cigarettes is considered equivalent to one&#xD;
        pack. The effect of non-cigarette tobacco products on the survival of patients with&#xD;
        p16-positive oropharyngeal cancers is undefined.&#xD;
&#xD;
          -  Zubrod Performance Status of 0-1 within 30 days prior to registration;&#xD;
&#xD;
          -  Adequate hematologic function within 14 days prior to registration, defined as&#xD;
             follows:&#xD;
&#xD;
               -  Absolute neutrophil count (ANC) ≥ 1,500 cells/mm3;&#xD;
&#xD;
               -  Platelets ≥ 100,000 cells/mm3;&#xD;
&#xD;
               -  Hemoglobin ≥ 8.0 g/dl; Note: The use of transfusion or other intervention to&#xD;
                  achieve Hgb ≥ 8.0 g/dl is acceptable.&#xD;
&#xD;
          -  Adequate renal function within 14 days prior to registration, defined as follows:&#xD;
&#xD;
               -  Serum creatinine &lt; 1.5 mg/dl or creatinine clearance (CC) ≥ 50 ml/min&#xD;
&#xD;
          -  Adequate hepatic function within 14 days prior to registration defined as follows:&#xD;
&#xD;
               -  Bilirubin &lt; 2 mg/dl;&#xD;
&#xD;
               -  AST or ALT &lt; 3 x the upper limit of normal.&#xD;
&#xD;
          -  Negative serum pregnancy test within 14 days prior to registration for women of&#xD;
             childbearing potential&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Cancers considered to be from an oral cavity site (oral tongue, floor mouth, alveolar&#xD;
             ridge, buccal or lip), or the nasopharynx, hypopharynx, or larynx, even if p16&#xD;
             positive;&#xD;
&#xD;
          -  Carcinoma of the neck of unknown primary site origin (even if p16 positive);&#xD;
&#xD;
          -  T1-T2 N0-1 lateralized squamous cell carcinoma of the tonsil.&#xD;
&#xD;
          -  Radiographically matted nodes, that span 6 cm or more; N3 disease&#xD;
&#xD;
          -  Supraclavicular nodes, defined as nodes visualized on the same axial imaging slice as&#xD;
             the clavicle;&#xD;
&#xD;
          -  Definitive clinical or radiologic evidence of metastatic disease or adenopathy below&#xD;
             the clavicles;&#xD;
&#xD;
          -  Gross total excision of both primary and nodal disease; this includes tonsillectomy,&#xD;
             local excision of primary site, and nodal excision that removes all clinically and&#xD;
             radiographically evident disease.&#xD;
&#xD;
          -  Simultaneous primary cancers or separate bilateral primary tumor sites;&#xD;
&#xD;
          -  Prior invasive malignancy (except non-melanomatous skin cancer) unless disease free&#xD;
             for a minimum of 5 years (for example, carcinoma in situ of the breast, oral cavity,&#xD;
             or cervix are all permissible);&#xD;
&#xD;
          -  Prior systemic chemotherapy for the study cancer; note that prior chemotherapy for a&#xD;
             different cancer is allowable;&#xD;
&#xD;
          -  Prior radiotherapy to the region of the study cancer that would result in overlap of&#xD;
             radiation therapy fields;&#xD;
&#xD;
          -  Severe, active co-morbidity defined as follows:&#xD;
&#xD;
               -  Unstable angina and/or congestive heart failure requiring hospitalization within&#xD;
                  the last 6 months;&#xD;
&#xD;
               -  Transmural myocardial infarction within the last 6 months;&#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 days of&#xD;
                  registration;&#xD;
&#xD;
               -  Hepatic insufficiency resulting in clinical jaundice and/or coagulation defects;&#xD;
                  note, however, that laboratory tests for liver function and coagulation&#xD;
                  parameters are not required for entry into this protocol other than those&#xD;
                  requested in Section 3.2.11 of the 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>Gregory Biedermann, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>University of Missouri - Ellis Fischel Cancer Center</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Joanne Cassani, RN</last_name>
    <phone>573-882-3677</phone>
    <email>cassanij@health.missouri.edu</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Min Cao, RN, MD</last_name>
    <phone>573-882-9165</phone>
    <email>caom@health.missouri.edu</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>University of Missouri</name>
      <address>
        <city>Columbia</city>
        <state>Missouri</state>
        <zip>65203</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Joanne Cassani, RN, CCRC</last_name>
      <phone>573-882-3677</phone>
      <email>cassanij@health.missouri.edu</email>
    </contact>
    <contact_backup>
      <last_name>Ken Baker, RN</last_name>
      <phone>(573) 884-6479</phone>
      <email>bakerrk@health.missouri.edu</email>
    </contact_backup>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>October 2022</verification_date>
  <study_first_submitted>May 28, 2020</study_first_submitted>
  <study_first_submitted_qc>June 22, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">June 24, 2020</study_first_posted>
  <last_update_submitted>October 31, 2022</last_update_submitted>
  <last_update_submitted_qc>October 31, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">November 2, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>University of Missouri-Columbia</investigator_affiliation>
    <investigator_full_name>Gregory Biedermann</investigator_full_name>
    <investigator_title>Assistant Professor of Clinical Radiology / Radiation Oncologist</investigator_title>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Carcinoma</mesh_term>
    <mesh_term>Carcinoma, Squamous Cell</mesh_term>
    <mesh_term>Squamous Cell Carcinoma of Head and Neck</mesh_term>
    <mesh_term>Head and Neck Neoplasms</mesh_term>
    <mesh_term>Oropharyngeal Neoplasms</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Cisplatin</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <!-- Results have not yet been posted for this study                                          -->
</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/NCT04444869
org study id: 2017520
nct id: NCT04444869
lead sponsor: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
is us export: No
This trial will explore giving standard dose chemotherapy and radiation therapy to sites of
      disease including all lymph nodes involved with HPV-positive oropharyngeal cancer, but
      administer lower doses of radiation therapy to the lymph nodes that are not known to be
      involved with cancer. By doing so, it is hypothesized that there will be equally good long
      term loco-regional and distant disease control but will reduced long term treatment side
      effects and improved quality of life in persons living well beyond their cancer treatment.
This is a trial of definitive chemotherapy and radiation therapy in human papilloma virus
      positive oropharyngeal cancers, in a population whose cancer is thought to be highly
      radio-sensitive. This is a population whose outcomes are already known to be very good with
      high rates of local and distant control of the disease. With the long term disease control
      and survival of patients with this disease, long term treatment toxicity and resulting
      reduction in quality of life poses new problems. This has lead to several studies to examine
      the role of radiation dose de-escalation through various strategies in attempt to reduce long
      term toxicity from treatment and yet achieve equivalent long term disease control.

      This trial specifically hypothesizes that a lower dose of radiation therapy to the clinically
      and radiographically uninvolved lymph nodes will no detrimental effect on loco-regional
      control or overall survival and will improve the long-term side effect profile, particularly
      with regards to xerostomia and dysphagia. The goal of this study is therefore to determine
      whether a lower dose to the clinically and radiographically uninvolved lymph nodes can be
      done safely and with better long-term toxicity profile and better overall quality of life
      without compromising the expected outcomes of progression free survival.
allocation: N/A
intervention model: Single Group Assignment
intervention model description: All patients are treated with the same approach.
primary purpose: Treatment
masking: None (Open Label)
measure: Rate of PEG tube placement
time frame: During the procedure
description: To determine rate of PEG tube placement
measure: Progression-free survival
time frame: Two years post treatment
description: Progression-free survival of 85% or more at measured a 2 years post treatment
measure: Dysphagia index
time frame: Baseline, 1 month and 6 months after treatment
description: To report the change in dysphagia using the M. D. Anderson Dysphagia Inventory (MDADI) scores. Scores are 0 (lowest functioning) to 100 (highest functioning).
measure: Patient Reported Outcomes
time frame: Baseline and 1, 6, and 12 months after end of treatment
description: European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire
measure: Survival
time frame: At 6 months and at 2 years
description: To determine overall survival and progression-free survival
measure: Toxicity profiles
time frame: 1 year and 2 years post treatment
description: Incidence of Common Terminology Criteria for Adverse Events (CTCAE) grade 2 or higher for mucositis, dysphagia, xerostomia and altered taste
measure: Hypothyroidism incidence
time frame: At 1 and 2 years post treatment
description: To monitor rate of hypothyroidism
arm group label: Open label single-arm study
arm group type: Other
description: All patients will receive concurrent cisplatin and radiation therapy with radiation dose de-escalation to clinically and radiologically uninvolved lymph nodes.
intervention type: Drug
intervention name: Cisplatin injection
description: Standard dose cisplatin given concurrently with radiation therapy
arm group label: Open label single-arm study
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Gregory Biedermann, MD
role: Principal Investigator
affiliation: University of Missouri - Ellis Fischel Cancer Center
last name: Joanne Cassani, RN
phone: 573-882-3677
email: cassanij@health.missouri.edu
last name: Min Cao, RN, MD
phone: 573-882-9165
email: caom@health.missouri.edu
facility: 
status: Recruiting
contact: 
contact backup: 
country: United States
responsible party type: Principal Investigator
investigator affiliation: University of Missouri-Columbia
investigator full name: Gregory Biedermann
investigator title: Assistant Professor of Clinical Radiology / Radiation Oncologist
mesh term: Carcinoma
mesh term: Carcinoma, Squamous Cell
mesh term: Squamous Cell Carcinoma of Head and Neck
mesh term: Head and Neck Neoplasms
mesh term: Oropharyngeal Neoplasms
mesh term: Cisplatin
sharing ipd: No