<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/NCT04403620</url>
  </required_header>
  <id_info>
    <org_study_id>STU 2020-0522</org_study_id>
    <nct_id>NCT04403620</nct_id>
  </id_info>
  <brief_title>HYPORT: A Phase I/II Study of Hypofractionated Post-operative Radiation Therapy for Head and Neck Cancer</brief_title>
  <official_title>HYPORT: A Phase I/II Study of Hypofractionated Post-operative Radiation Therapy for Head and Neck Squamous Cell Carcinoma</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of Texas Southwestern Medical Center</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>University of Texas Southwestern Medical Center</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>
      There is a strong radiobiological and economic rationale for hypofractionated radiation&#xD;
      therapy in head and neck cancer. Phase 1 of the trial aims to assess the acute toxicity and&#xD;
      tolerability of hypofractionated radiation therapy in the post-operative setting, and to&#xD;
      determine the dose/fractionation for Phase 2. Phase 2 aims to establish non-inferiority of&#xD;
      swallowing-related quality of life and to assess the toxicity and efficacy of&#xD;
      hypofractionated radiation therapy compared to conventionally fractionated radiation therapy&#xD;
      in the post-operative setting.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The trial will assess the effects of aggressive hypofractionated radiation therapy in&#xD;
      patients with oral cavity, oropharynx, hypopharynx, or larynx cancer after surgical resection&#xD;
      with pathology showing intermediate risk factors requiring post-operative radiation therapy&#xD;
      without concurrent chemotherapy. During Phase 1, the maximum tolerated dose/fractionation and&#xD;
      tolerability will be determined. During Phase 2, patients will be randomized between&#xD;
      conventionally fractionated radiation therapy (6 weeks) vs. hypofractionated radiation&#xD;
      therapy (3 weeks) to establish non-inferiority of hypofractionated radiation therapy.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">July 28, 2020</start_date>
  <completion_date type="Anticipated">August 2027</completion_date>
  <primary_completion_date type="Anticipated">August 2027</primary_completion_date>
  <phase>Phase 1/Phase 2</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Sequential Assignment</intervention_model>
    <intervention_model_description>Dose/fractionation finding Phase 1 study, followed by a randomized Phase 2 study</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Phase 1: Maximally tolerated dose of hypofractionated radiation therapy</measure>
    <time_frame>3 months</time_frame>
    <description>Dose and fractionation to be used for Phase 2</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Phase 2: Swallowing-related patient-reported quality of life</measure>
    <time_frame>12 months</time_frame>
    <description>MD Anderson Dysphagia Inventory (MDADI) composite score: 20-100, higher scores mean better quality of life</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Clinician-reported acute toxicities</measure>
    <time_frame>1-3 months</time_frame>
    <description>CTCAE v5.0</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Clinician-reported late toxicities</measure>
    <time_frame>6-24 months</time_frame>
    <description>CTCAE v5.0</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Locoregional control</measure>
    <time_frame>12-24 months</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Progression free survival</measure>
    <time_frame>12-24 months</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Swallowing-related patient-reported quality of life</measure>
    <time_frame>1-24 months</time_frame>
    <description>MD Anderson Dysphagia Inventory (MDADI): 20-100, higher scores mean better quality of life</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Head and neck patient-reported quality of life</measure>
    <time_frame>1-24 months</time_frame>
    <description>University of Washington QOL questionnaire (UW-QOL): 0-100, higher scores mean better quality of life</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Xerostomia-related patient-reported quality of life</measure>
    <time_frame>1-24 months</time_frame>
    <description>University of Michigan Xerostomia questionnaire (XQ): 0-100, higher scores mean worse quality of life</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>General patient-reported quality of life</measure>
    <time_frame>1-24 months</time_frame>
    <description>EuroQol-5 dimensions (EQ-5D-5L): 1-5, higher scores mean worse quality of life</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Feeding tube dependence</measure>
    <time_frame>1-24 months</time_frame>
    <description>Feeding tube dependence defined as daily use of the feeding tube with ≥2 nutritional supplements (e.g. Ensure, Boost, etc.) per day at the time of enrollment on trial</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">98</enrollment>
  <condition>Squamous Cell Carcinoma of Head and Neck</condition>
  <arm_group>
    <arm_group_label>Conventionally fractionated radiotherapy</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>60 Gy in 30 fractions, 5 fractions/week</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Hypofractionated radiotherapy</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Dose and fractionation determined by Phase I:&#xD;
Level 1: 44.4 Gy in 12 fractions, 4 fractions/week&#xD;
Level 0: 46.5 Gy in 15 fractions, 5 fractions/week&#xD;
Level -1: 52 Gy in 20 fractions, 5 fractions/week&#xD;
Level -2: 50 Gy in 20 fractions, 5 fractions/week</description>
  </arm_group>
  <intervention>
    <intervention_type>Radiation</intervention_type>
    <intervention_name>Intensity-modulated Radiation Therapy (IMRT)</intervention_name>
    <description>Patients will receive adjuvant radiation therapy using intensity-modulated radiation therapy (IMRT) within 8 weeks of surgical resection</description>
    <arm_group_label>Conventionally fractionated radiotherapy</arm_group_label>
    <arm_group_label>Hypofractionated radiotherapy</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
        Inclusion criteria will be the same for Phase I and Phase II.&#xD;
&#xD;
          1. Pathologically proven diagnosis of stage I-IVB squamous cell carcinoma of the oral&#xD;
             cavity, oropharynx, hypopharynx, or larynx status post gross total resection with&#xD;
             pathology showing one or more of the following intermediate risk factors:&#xD;
&#xD;
               -  T3/4 disease (AJCC 8th edition), positive lymph node(s), close margin(s),&#xD;
                  perineural invasion, and/or lymphovascular invasion&#xD;
&#xD;
               -  Close margin(s) defined as either:&#xD;
&#xD;
                    -  Final patient margin of &lt;5 mm without disease on ink OR&#xD;
&#xD;
                    -  Initial positive margin in the specimen regardless of the final patient&#xD;
                       margin (e.g. if resection margin on the initial specimen is positive, final&#xD;
                       patient margin after subsequent resections can be ≥5 mm and still be&#xD;
                       considered close margin)&#xD;
&#xD;
          2. Age ≥18 years&#xD;
&#xD;
          3. ECOG performance status 0-2&#xD;
&#xD;
          4. Women of child-bearing potential and men must agree to use adequate contraception&#xD;
             (hormonal or barrier method of birth control; abstinence) prior to study entry, for&#xD;
             the duration of study participation, and for 90 days following completion of therapy.&#xD;
&#xD;
             Medically acceptable birth control (contraceptives) includes:&#xD;
&#xD;
               -  approved hormonal contraceptives (such as birth control pills, patch or ring;&#xD;
                  Depo-Provera, Implanon), or&#xD;
&#xD;
               -  barrier methods (such as condom or diaphragm) used with a spermicide&#xD;
&#xD;
             Should a woman become pregnant or suspect she is pregnant while participating in this&#xD;
             study, she should inform her treating physician immediately.&#xD;
&#xD;
             A female of child-bearing potential is any woman (regardless of sexual orientation,&#xD;
             having undergone a tubal ligation, or remaining celibate by choice) who meets the&#xD;
             following criteria:&#xD;
&#xD;
               -  Has not undergone a hysterectomy or bilateral oophorectomy; or&#xD;
&#xD;
               -  Has not been naturally postmenopausal for at least 12 consecutive months (i.e.,&#xD;
                  has had menses at any time in the preceding 12 consecutive months).&#xD;
&#xD;
          5. Negative serum or urine pregnancy test within 2 weeks before registration for women of&#xD;
             childbearing potential.&#xD;
&#xD;
          6. Ability to understand and the willingness to sign a written informed consent&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
        Phase I:&#xD;
&#xD;
          1. Distant metastasis&#xD;
&#xD;
          2. Stage I and II glottic squamous cell carcinoma&#xD;
&#xD;
          3. High risk factors following surgical resection requiring concurrent chemotherapy:&#xD;
             final positive margin(s) and/or extranodal extension&#xD;
&#xD;
          4. Feeding tube dependence at baseline assessment.&#xD;
&#xD;
          5. Synchronous non-skin cancer primaries outside of the oropharynx, oral cavity, larynx,&#xD;
             and hypopharynx except for low- and intermediate-risk prostate cancer and synchronous&#xD;
             well-differentiated thyroid cancer. For prostate cancer, patient should not be&#xD;
             receiving active treatment. For thyroid cancer, thyroid surgery may occur before or&#xD;
             after treatment, provided all other eligibility criteria are met.&#xD;
&#xD;
          6. Prior invasive malignancy with an expected disease-free interval of less than 3 years&#xD;
&#xD;
          7. Prior radiotherapy to the region of the study cancer that would result in overlap of&#xD;
             radiation fields&#xD;
&#xD;
          8. Subjects may not be receiving any other investigational agents for the treatment of&#xD;
             the cancer under study.&#xD;
&#xD;
          9. Uncontrolled intercurrent illness including, but not limited to, ongoing or active&#xD;
             infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac&#xD;
             arrhythmia, or psychiatric illness/social situations that, in the opinion of the&#xD;
             investigator, would limit compliance with study requirements&#xD;
&#xD;
         10. Subjects must not be pregnant or nursing due to the potential for congenital&#xD;
             abnormalities and the potential of this regimen to harm nursing infants.&#xD;
&#xD;
         11. History of severe immunosuppression, including HIV, and organ or autologous or&#xD;
             allogeneic stem cell transplant&#xD;
&#xD;
        Phase II:&#xD;
&#xD;
        The exclusion criteria will be the same as Phase I except for feeding tube dependence.&#xD;
        Patients who are feeding tube dependent are excluded from Phase I to accurately assess&#xD;
        treatment associated toxicity affecting swallowing and oral intake. During Phase II,&#xD;
        patients who are feeding tube dependent will be eligible to enroll and stratified at&#xD;
        randomization.&#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>Dominic Moon, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>UT Southwestern Medical Center</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Sarah Neufeld, MS</last_name>
    <phone>214-645-8525</phone>
    <email>sarah.hardee@utsouthwestern.edu</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Kajal Desai, MS</last_name>
    <email>kajal.desai@utsouthwestern.edu</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>University of Texas Southwestern Medical Center</name>
      <address>
        <city>Dallas</city>
        <state>Texas</state>
        <zip>75390</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>March 2023</verification_date>
  <study_first_submitted>May 14, 2020</study_first_submitted>
  <study_first_submitted_qc>May 21, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">May 27, 2020</study_first_posted>
  <last_update_submitted>March 1, 2023</last_update_submitted>
  <last_update_submitted_qc>March 1, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">March 2, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>University of Texas Southwestern Medical Center</investigator_affiliation>
    <investigator_full_name>Dominic Moon</investigator_full_name>
    <investigator_title>Assistant Professor</investigator_title>
  </responsible_party>
  <keyword>Radiation Dose Hypofractionation</keyword>
  <keyword>Adjuvant Radiotherapy</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>
    <mesh_term>Squamous Cell Carcinoma of Head and Neck</mesh_term>
  </condition_browse>
  <!-- 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/NCT04403620
org study id: STU 2020-0522
nct id: NCT04403620
lead sponsor: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
There is a strong radiobiological and economic rationale for hypofractionated radiation
      therapy in head and neck cancer. Phase 1 of the trial aims to assess the acute toxicity and
      tolerability of hypofractionated radiation therapy in the post-operative setting, and to
      determine the dose/fractionation for Phase 2. Phase 2 aims to establish non-inferiority of
      swallowing-related quality of life and to assess the toxicity and efficacy of
      hypofractionated radiation therapy compared to conventionally fractionated radiation therapy
      in the post-operative setting.
The trial will assess the effects of aggressive hypofractionated radiation therapy in
      patients with oral cavity, oropharynx, hypopharynx, or larynx cancer after surgical resection
      with pathology showing intermediate risk factors requiring post-operative radiation therapy
      without concurrent chemotherapy. During Phase 1, the maximum tolerated dose/fractionation and
      tolerability will be determined. During Phase 2, patients will be randomized between
      conventionally fractionated radiation therapy (6 weeks) vs. hypofractionated radiation
      therapy (3 weeks) to establish non-inferiority of hypofractionated radiation therapy.
allocation: Randomized
intervention model: Sequential Assignment
intervention model description: Dose/fractionation finding Phase 1 study, followed by a randomized Phase 2 study
primary purpose: Treatment
masking: None (Open Label)
measure: Phase 1: Maximally tolerated dose of hypofractionated radiation therapy
time frame: 3 months
description: Dose and fractionation to be used for Phase 2
measure: Phase 2: Swallowing-related patient-reported quality of life
time frame: 12 months
description: MD Anderson Dysphagia Inventory (MDADI) composite score: 20-100, higher scores mean better quality of life
measure: Clinician-reported acute toxicities
time frame: 1-3 months
description: CTCAE v5.0
measure: Clinician-reported late toxicities
time frame: 6-24 months
description: CTCAE v5.0
measure: Locoregional control
time frame: 12-24 months
measure: Progression free survival
time frame: 12-24 months
measure: Swallowing-related patient-reported quality of life
time frame: 1-24 months
description: MD Anderson Dysphagia Inventory (MDADI): 20-100, higher scores mean better quality of life
measure: Head and neck patient-reported quality of life
time frame: 1-24 months
description: University of Washington QOL questionnaire (UW-QOL): 0-100, higher scores mean better quality of life
measure: Xerostomia-related patient-reported quality of life
time frame: 1-24 months
description: University of Michigan Xerostomia questionnaire (XQ): 0-100, higher scores mean worse quality of life
measure: General patient-reported quality of life
time frame: 1-24 months
description: EuroQol-5 dimensions (EQ-5D-5L): 1-5, higher scores mean worse quality of life
measure: Feeding tube dependence
time frame: 1-24 months
description: Feeding tube dependence defined as daily use of the feeding tube with ≥2 nutritional supplements (e.g. Ensure, Boost, etc.) per day at the time of enrollment on trial
arm group label: Conventionally fractionated radiotherapy
arm group type: Active Comparator
description: 60 Gy in 30 fractions, 5 fractions/week
arm group label: Hypofractionated radiotherapy
arm group type: Experimental
description: Dose and fractionation determined by Phase I:
Level 1: 44.4 Gy in 12 fractions, 4 fractions/week
Level 0: 46.5 Gy in 15 fractions, 5 fractions/week
Level -1: 52 Gy in 20 fractions, 5 fractions/week
Level -2: 50 Gy in 20 fractions, 5 fractions/week
intervention type: Radiation
intervention name: Intensity-modulated Radiation Therapy (IMRT)
description: Patients will receive adjuvant radiation therapy using intensity-modulated radiation therapy (IMRT) within 8 weeks of surgical resection
arm group label: Conventionally fractionated radiotherapy
arm group label: Hypofractionated radiotherapy
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Dominic Moon, MD
role: Principal Investigator
affiliation: UT Southwestern Medical Center
last name: Sarah Neufeld, MS
phone: 214-645-8525
email: sarah.hardee@utsouthwestern.edu
last name: Kajal Desai, MS
email: kajal.desai@utsouthwestern.edu
facility: 
status: Recruiting
country: United States
responsible party type: Principal Investigator
investigator affiliation: University of Texas Southwestern Medical Center
investigator full name: Dominic Moon
investigator title: Assistant Professor
mesh term: Carcinoma
mesh term: Carcinoma, Squamous Cell
mesh term: Squamous Cell Carcinoma of Head and Neck