<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/NCT02201355</url>
  </required_header>
  <id_info>
    <org_study_id>STU 112013-007</org_study_id>
    <nct_id>NCT02201355</nct_id>
  </id_info>
  <brief_title>Hypofractionated Reduced-Volume Chemoradiation for T1/2N0-2 SCC Head and Neck</brief_title>
  <official_title>A Phase I Study of Reduced-Volume Hypofractionated, PET-directed Intensity Modulated Radiotherapy Concurrent With Weekly Cisplatin Chemotherapy for T1/2N0-2 Squamous Cell Carcinoma of the Head and Neck</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>
  </oversight_info>
  <brief_summary>
    <textblock>
      Primary Objectives:&#xD;
&#xD;
      To determine whether patients with T1/2N0-2 Squamous Cell Carcinoma of the oropharynx,&#xD;
      hypopharynx or larynx can tolerate treatment with cisplatin chemoradiation in three weeks&#xD;
      using reduced volume IMRT&#xD;
&#xD;
      Secondary Objectives:&#xD;
&#xD;
      To describe the adverse events associated with hypofractionated, reduced volume cisplatin&#xD;
      chemoradiation.&#xD;
&#xD;
      To estimate response rates and progression-free survival rates of hypofractionated, reduced&#xD;
      volume cisplatin chemoradiation.&#xD;
&#xD;
      To determine HRQOL following hypofractionated, reduced volume cisplatin chemoradiation.&#xD;
&#xD;
      If patients can safely be treated in three weeks rather than six weeks, such a schedule would&#xD;
      provide a much more convenient alternative for patients and result in a significant reduction&#xD;
      in the health care resources currently expended on cure of these patients.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Head and neck squamous cell carcinomas (HNSCC) are frequently occurring tumors with more than&#xD;
      500,000 new cases worldwide and 45,000 in the USA yearly . Most patients present with&#xD;
      local-regionally advanced diseases. Chemotherapy given concurrently with radiation is an&#xD;
      integrated treatment component in the management of these patients. Concurrent chemoradiation&#xD;
      can be given in unresectable diseases, in organ preservation to avoid surgery and preserve&#xD;
      functions, and in high risk patients after surgery . Randomized clinical trials and&#xD;
      meta-analyses have shown that concurrent chemoradiation are superior to radiation alone in&#xD;
      these settings.&#xD;
&#xD;
      One way of reducing overall treatment time and toxicity is to reduce the number of fractions&#xD;
      by increasing the daily radiotherapy dose. The consequence of increased daily dose is both an&#xD;
      increase in acute side effects as well as an increase in late toxicity. A widely accepted&#xD;
      model of these radiobiologic effects over the range of typical 2-4 Gy daily fractions is the&#xD;
      alpha-beta model that distinguishes acute responses and late responses based on a&#xD;
      linear-quadratic fitting of extrapolated clonogenic survival curves. A time factor can be&#xD;
      incorporated to account for the effect of repopulation. Equivalent biologically effective&#xD;
      dose schedules using a reduced number of fractions may be calculated for any conventionally&#xD;
      fractionated course. Because 70Gy/35/6 weeks with chemoradiation has been demonstrated to be&#xD;
      tolerable, and because 66Gy/30/6 weeks has been shown with IMRT to produce 90% control for&#xD;
      T1/2 oropharyngeal primary tumors, we will take the biological equivalent of 66Gy/33&#xD;
      fractions over six weeks as the biologic equivalent standard we wish to maintain in&#xD;
      hypofractionated courses of radiation. Because 54Gy/30 over six weeks is a well-known&#xD;
      elective radiation dose schedule producing 95% control of occult nodal disease, we will take&#xD;
      this as the biologically equivalent standard we wish to maintain in our hypofractionated&#xD;
      schedules.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Terminated</overall_status>
  <why_stopped>
    PI LEFT THE DEPARTMENT&#xD;
  </why_stopped>
  <start_date type="Actual">September 18, 2014</start_date>
  <completion_date type="Actual">May 15, 2020</completion_date>
  <primary_completion_date type="Actual">January 23, 2018</primary_completion_date>
  <phase>Phase 1</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>Treatment completion</measure>
    <time_frame>3 weeks</time_frame>
    <description>To determine whether patients with locally advanced SCC of the oropharynx, hypopharynx or larynx can tolerate treatment with cisplatin chemoradiation in three weeks using reduced volume IMRT.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>adverse events</measure>
    <time_frame>90 days</time_frame>
    <description>To describe the adverse events associated with hypofractionated, reduced volume cisplatin chemoradiation.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>progression-free survival rates</measure>
    <time_frame>5 years</time_frame>
    <description>To estimate response rates and progression-free survival rates of hypofractionated, reduced volume cisplatin chemoradiation.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Health-related quality of life</measure>
    <time_frame>2 years</time_frame>
    <description>To determine HRQOL following hypofractionated, reduced volume cisplatin chemoradiation.</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">8</enrollment>
  <condition>Squamous Cell Carcinoma of the Head and Neck T1/2N0-2</condition>
  <arm_group>
    <arm_group_label>chemoradiation</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Hypofractionated, PET-directed, Intensity Modulated Radiotherapy Concurrent with Weekly Cisplatin Chemotherapy</description>
  </arm_group>
  <intervention>
    <intervention_type>Radiation</intervention_type>
    <intervention_name>Intensity Modulated Radiotherapy</intervention_name>
    <description>Patients treated five fractions per week with radiotherapy dose per fraction and cisplatin dose increased according to the treatment table</description>
    <arm_group_label>chemoradiation</arm_group_label>
    <other_name>Hypofractionated,</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. T1/2N0-2M0 SCC of the oropharynx, hypopharynx or larynx&#xD;
&#xD;
          2. Age ≥ 18 years.&#xD;
&#xD;
          3. Performance status ECOG 0-1&#xD;
&#xD;
          4. Adequate organ and marrow function as determined by medical oncology evaluation.&#xD;
&#xD;
          5. 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;
             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;
        6. 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 following&#xD;
        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., has&#xD;
             had menses at any time in the preceding 12 consecutive months).&#xD;
&#xD;
             7 Ability to understand and the willingness to sign a written informed consent.&#xD;
&#xD;
             8. Creatinine clearance (CC) ≥ 50 ml/min within 4 weeks prior to registration&#xD;
             determined by 24-hour collection or estimated by Cockcroft-Gault formula: CCr male =&#xD;
             [(140 - age) x (wt in kg)]/[(Serum Cr mg/dl) x (72)] (CCr female = 0.85 x (CrCl&#xD;
             male)).&#xD;
&#xD;
             9. History/physical examination within 4 weeks prior to registration, including&#xD;
             assessment of weight and weight loss in past 6 months.&#xD;
&#xD;
             10. Medical oncology examination to evaluate medical contraindications prior to start&#xD;
             chemotherapy 11 Dental evaluation with management prior to start of radiation 12&#xD;
             Nutrition evaluation with consideration of percutaneous endoscopic gastrostomy (PEG)&#xD;
             tube placement 13 No distant metastasis by PET/CT&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. T3/4 or N3&#xD;
&#xD;
          2. T1N0 disease&#xD;
&#xD;
          3. Metastatic disease&#xD;
&#xD;
          4. Prior invasive malignancy (except non-melanomatous skin cancer) unless disease free&#xD;
             for a minimum of 3 years&#xD;
&#xD;
          5. Prior radiotherapy to the region of the study cancer that would result in overlap of&#xD;
             radiation therapy fields&#xD;
&#xD;
          6. Primary site of tumor of oral cavity, nasopharynx, sinuses, or salivary glands&#xD;
&#xD;
          7. Neck adenopathy that involves the overlying skin.&#xD;
&#xD;
          8. Initial surgical treatment including tonsillectomy or neck dissection, but excluding&#xD;
             diagnostic biopsy of the primary site or nodal sampling of neck disease&#xD;
&#xD;
          9. Pre-existing grade &gt; 2 peripheral sensory neuropathy&#xD;
&#xD;
         10. Subjects may not be receiving any other investigational agents.&#xD;
&#xD;
         11. 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 would limit compliance with&#xD;
             study requirements.&#xD;
&#xD;
         12. 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;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>99 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Lucien Nedzi, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>UTSW</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>University of Texas at Southwestern Medical Center</name>
      <address>
        <city>Dallas</city>
        <state>Texas</state>
        <zip>75390</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>January 2021</verification_date>
  <study_first_submitted>July 23, 2014</study_first_submitted>
  <study_first_submitted_qc>July 23, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">July 28, 2014</study_first_posted>
  <last_update_submitted>January 28, 2021</last_update_submitted>
  <last_update_submitted_qc>January 28, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">February 2, 2021</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Head and Neck cancer</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/NCT02201355
org study id: STU 112013-007
nct id: NCT02201355
lead sponsor: 
has dmc: Yes
Primary Objectives:

      To determine whether patients with T1/2N0-2 Squamous Cell Carcinoma of the oropharynx,
      hypopharynx or larynx can tolerate treatment with cisplatin chemoradiation in three weeks
      using reduced volume IMRT

      Secondary Objectives:

      To describe the adverse events associated with hypofractionated, reduced volume cisplatin
      chemoradiation.

      To estimate response rates and progression-free survival rates of hypofractionated, reduced
      volume cisplatin chemoradiation.

      To determine HRQOL following hypofractionated, reduced volume cisplatin chemoradiation.

      If patients can safely be treated in three weeks rather than six weeks, such a schedule would
      provide a much more convenient alternative for patients and result in a significant reduction
      in the health care resources currently expended on cure of these patients.
Head and neck squamous cell carcinomas (HNSCC) are frequently occurring tumors with more than
      500,000 new cases worldwide and 45,000 in the USA yearly . Most patients present with
      local-regionally advanced diseases. Chemotherapy given concurrently with radiation is an
      integrated treatment component in the management of these patients. Concurrent chemoradiation
      can be given in unresectable diseases, in organ preservation to avoid surgery and preserve
      functions, and in high risk patients after surgery . Randomized clinical trials and
      meta-analyses have shown that concurrent chemoradiation are superior to radiation alone in
      these settings.

      One way of reducing overall treatment time and toxicity is to reduce the number of fractions
      by increasing the daily radiotherapy dose. The consequence of increased daily dose is both an
      increase in acute side effects as well as an increase in late toxicity. A widely accepted
      model of these radiobiologic effects over the range of typical 2-4 Gy daily fractions is the
      alpha-beta model that distinguishes acute responses and late responses based on a
      linear-quadratic fitting of extrapolated clonogenic survival curves. A time factor can be
      incorporated to account for the effect of repopulation. Equivalent biologically effective
      dose schedules using a reduced number of fractions may be calculated for any conventionally
      fractionated course. Because 70Gy/35/6 weeks with chemoradiation has been demonstrated to be
      tolerable, and because 66Gy/30/6 weeks has been shown with IMRT to produce 90% control for
      T1/2 oropharyngeal primary tumors, we will take the biological equivalent of 66Gy/33
      fractions over six weeks as the biologic equivalent standard we wish to maintain in
      hypofractionated courses of radiation. Because 54Gy/30 over six weeks is a well-known
      elective radiation dose schedule producing 95% control of occult nodal disease, we will take
      this as the biologically equivalent standard we wish to maintain in our hypofractionated
      schedules.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Treatment completion
time frame: 3 weeks
description: To determine whether patients with locally advanced SCC of the oropharynx, hypopharynx or larynx can tolerate treatment with cisplatin chemoradiation in three weeks using reduced volume IMRT.
measure: adverse events
time frame: 90 days
description: To describe the adverse events associated with hypofractionated, reduced volume cisplatin chemoradiation.
measure: progression-free survival rates
time frame: 5 years
description: To estimate response rates and progression-free survival rates of hypofractionated, reduced volume cisplatin chemoradiation.
measure: Health-related quality of life
time frame: 2 years
description: To determine HRQOL following hypofractionated, reduced volume cisplatin chemoradiation.
arm group label: chemoradiation
arm group type: Experimental
description: Hypofractionated, PET-directed, Intensity Modulated Radiotherapy Concurrent with Weekly Cisplatin Chemotherapy
intervention type: Radiation
intervention name: Intensity Modulated Radiotherapy
description: Patients treated five fractions per week with radiotherapy dose per fraction and cisplatin dose increased according to the treatment table
arm group label: chemoradiation
other name: Hypofractionated,
criteria: 
gender: All
minimum age: 18 Years
maximum age: 99 Years
healthy volunteers: No
last name: Lucien Nedzi, MD
role: Principal Investigator
affiliation: UTSW
facility: 
country: United States
responsible party type: Sponsor
mesh term: Carcinoma
mesh term: Carcinoma, Squamous Cell
mesh term: Squamous Cell Carcinoma of Head and Neck