<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/NCT02994069</url>
  </required_header>
  <id_info>
    <org_study_id>MCC-16-HN-29</org_study_id>
    <nct_id>NCT02994069</nct_id>
  </id_info>
  <brief_title>Cisplatin + Radiation in SCCHN and Correlation With Oxidative Stress Markers</brief_title>
  <official_title>Comparison of Every 3 Week Versus Weekly Cisplatin Concurrent With Radiation in Squamous Cell Carcinoma of the Head and Neck (SCCHN) and Correlation With Oxidative Stress Markers</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Susanne Arnold</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>University of Kentucky</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>
  </oversight_info>
  <brief_summary>
    <textblock>
      Patients will receive standard of care radiation therapy to the primary tumor of the head and&#xD;
      neck and involved nodal metastasis and draining nodal basin and either weekly cisplatin or&#xD;
      every 3-week cisplatin in locally advanced SCCHN. The relationship between cisplatin toxicity&#xD;
      and the level of reactive oxygen species generated by the drug in subjects with squamous cell&#xD;
      carcinoma of the head and neck treated on this trial.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Patients will first be designated as either: a) Cohort 1 (locally advanced non-nasopharyngeal&#xD;
      SCCHN that is unresectable) OR b) Cohort 2 (resected and at high risk of recurrence with at&#xD;
      least one of the following criteria: extracapsular nodal extension, or invasive cancer at the&#xD;
      primary tumor resection margin (positive margin), lymphovascular invasion or perineural&#xD;
      invasion, pT3 or pT4 primary, or the presence of multilevel nodal disease. Subjects will then&#xD;
      be randomized to receive either Arm 1 or Arm 2 cisplatin.&#xD;
&#xD;
      Radiation and Cisplatin will be given concurrently and should start on the same day, ±1 day.&#xD;
      Radiation will continue without interruption whenever possible.&#xD;
&#xD;
      Treatment will consist of standard of care radiation therapy to the primary tumor of the head&#xD;
      and neck and involved nodal metastasis and draining nodal basin, as determined by treating&#xD;
      radiation oncologist. Patients will be randomized to receive cisplatin at 100 mg/m2 every 3&#xD;
      weeks (3 doses) during radiation versus cisplatin at 40 mg/m2 once weekly (7 doses) during&#xD;
      radiation. This will provide similar cumulative doses of cisplatin in all arms of the&#xD;
      study.IMRT will be delivered in 30-35 fractions over 6-7 weeks, 5 fractions weekly.&#xD;
&#xD;
      In the absence of treatment delays due to adverse event(s), treatment will continue for 7&#xD;
      weeks or until one of the following criteria applies:&#xD;
&#xD;
      Disease progression,Intercurrent illness that prevents further administration of treatment,&#xD;
      Unacceptable adverse event(s), Patient decides to withdraw from the study, or General or&#xD;
      specific changes in the patient's condition render the patient unacceptable for further&#xD;
      treatment in the judgment of the investigator.&#xD;
&#xD;
      Patients will be followed for 2 years after completion of chemoradiation or until death,&#xD;
      whichever occurs first, for toxicity and PFS.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">April 11, 2017</start_date>
  <completion_date type="Anticipated">October 31, 2029</completion_date>
  <primary_completion_date type="Anticipated">October 31, 2023</primary_completion_date>
  <phase>Phase 2</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
    <masking_description>Unblinded trial</masking_description>
  </study_design_info>
  <primary_outcome>
    <measure>Adverse event rate</measure>
    <time_frame>90 days</time_frame>
    <description>Rate of grade 3-5 cisplatin-related adverse events occurring within 90 days of initiation of concurrent radiation and chemotherapy</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Local control rates</measure>
    <time_frame>2 years</time_frame>
    <description>2 year local control rate</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Survival</measure>
    <time_frame>2 years</time_frame>
    <description>Overall survival</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">80</enrollment>
  <condition>Carcinoma, Squamous Cell</condition>
  <condition>Head and Neck Cancer</condition>
  <arm_group>
    <arm_group_label>Every 3 Weeks Cisplatin + XRT</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Every 3 Weeks Cisplatin + XRT</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Weekly Cisplatin + XRT</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Weekly Cisplatin + XRT</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Cisplatin</intervention_name>
    <description>Cisplatin</description>
    <arm_group_label>Every 3 Weeks Cisplatin + XRT</arm_group_label>
    <arm_group_label>Weekly Cisplatin + XRT</arm_group_label>
    <other_name>chemotherapy</other_name>
  </intervention>
  <intervention>
    <intervention_type>Radiation</intervention_type>
    <intervention_name>XRT</intervention_name>
    <description>Radiation Therapy</description>
    <arm_group_label>Every 3 Weeks Cisplatin + XRT</arm_group_label>
    <arm_group_label>Weekly Cisplatin + XRT</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Patients must have pathologically (histologically or cytologically) proven diagnosis&#xD;
             of head and neck squamous cell carcinoma (HNSCC) involving the oral cavity,&#xD;
             oropharynx, larynx, hypopharynx, paranasal sinuses or unknown primary squamous&#xD;
             carcinoma limited to the head and neck region. Cohort 1: Unresectable locally advanced&#xD;
             non-nasopharyngeal SCCHN without evidence of distant metastases. Cohort 2: Patients&#xD;
             with non-nasopharyngeal SCCHN who have undergone gross total surgical resection within&#xD;
             63 days prior to registration. Patients must have at least 1 of the following&#xD;
             high-risk pathologic features: extracapsular nodal extension, invasive cancer at the&#xD;
             primary tumor resection margin (positive margin), lymphovascular invasion or&#xD;
             perineural invasion, or the presence of multilevel nodal disease. Patients must be&#xD;
             without evidence of distant metastases.&#xD;
&#xD;
          -  Women of childbearing potential and male participants who are sexually active must&#xD;
             agree to use a medically effective means of birth control.&#xD;
&#xD;
          -  Cohort 1: Patients in Cohort 1 must have measurable disease, defined as at least one&#xD;
             lesion that can be accurately measured in at least one dimension (longest diameter to&#xD;
             be recorded for non-nodal lesions and short axis for nodal lesions) as ≥ 20 mm (≥ 2&#xD;
             cm) with conventional techniques or as ≥ 10 mm (≥ 1 cm) with spiral CT scan, MRI, or&#xD;
             calipers by clinical exam. See Section 11 for the evaluation of measurable disease.&#xD;
             Cohort 2: Subjects in the post-operative setting (Cohort 2) are not required to have&#xD;
             measurable disease and response rate will not be assessed in cohort 2.&#xD;
&#xD;
          -  Patients may have a history of prior head and neck malignancy, but must be able to&#xD;
             tolerate full dose radiation and chemotherapy for the current head and neck cancer, as&#xD;
             determined by the treating oncologist.&#xD;
&#xD;
          -  Age ≥18 years.&#xD;
&#xD;
          -  ECOG performance status 0, 1 or 2&#xD;
&#xD;
          -  Life expectancy of greater than 12 weeks.&#xD;
&#xD;
          -  Patients must have normal organ and marrow function assessed within 14 days prior to&#xD;
             registration as defined below: absolute neutrophil count ≥1,000/mcL, platelets&#xD;
             ≥100,000/mcL, creatinine within normal institutional limits OR creatinine clearance&#xD;
             ≥60 mL/min/1.73 m2 (for patients with creatinine levels above institutional normal).&#xD;
&#xD;
          -  No prior chemotherapy for the current locally advanced SCCHN is allowed. Prior&#xD;
             radiation or chemotherapy for a previous head and neck cancer is allowed provided full&#xD;
             dose cisplatin and radiation can be delivered to the patient in this clinical trial&#xD;
             and provided the patient is in remission from the prior head and neck cancer, and can&#xD;
             undergo full dose radiation and chemotherapy for the current primary head and neck&#xD;
             cancer.&#xD;
&#xD;
          -  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,&#xD;
             throughout the duration of active treatment and for 4 months after completion of&#xD;
             chemotherapy and radiation.&#xD;
&#xD;
          -  Cisplatin and radiation are known teratogens. For this reason, women of child-bearing&#xD;
             potential and men must agree to use adequate contraception (hormonal or barrier method&#xD;
             of birth control; abstinence) prior to study entry, throughout the duration of active&#xD;
             treatment and for 4 months after completion of chemotherapy and radiation. Should a&#xD;
             woman become pregnant or suspect she is pregnant while she or her partner is&#xD;
             participating in this study, she should inform her treating physician immediately. Men&#xD;
             treated or enrolled on this protocol must also agree to use adequate contraception&#xD;
             prior to the study, for the duration of active study treatment, and for 4 months after&#xD;
             completion of chemotherapy and radiation (both induction and definitive)&#xD;
             administration.&#xD;
&#xD;
          -  Ability to understand and the willingness to sign a written informed consent document.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Patients who have had chemotherapy or radiotherapy within 4 weeks (6 weeks for&#xD;
             nitrosoureas or mitomycin C) prior to entering the study or those who have not&#xD;
             recovered from adverse events due to agents administered more than 4 weeks earlier.&#xD;
&#xD;
          -  Patients who are receiving any other investigational agents.&#xD;
&#xD;
          -  History of allergic reactions attributed to compounds of similar chemical or biologic&#xD;
             composition to cisplatin.&#xD;
&#xD;
          -  Patients with greater than grade 2 hearing loss.&#xD;
&#xD;
          -  No other prior malignancy is allowed except for the following: head and neck cancer in&#xD;
             remission, adequately treated basal cell or squamous cell skin cancer, in situ&#xD;
             cervical cancer, adequately treated previous Stage I or II cancer from which the&#xD;
             patient is currently in complete remission or other cancer from which the patient has&#xD;
             been disease-free for 2 years.&#xD;
&#xD;
          -  Patients with nasopharynx or salivary gland primary site.&#xD;
&#xD;
          -  Patients with distant metastatic disease (M1c) from the current head and neck cancer&#xD;
             including brain metastasis.&#xD;
&#xD;
          -  Uncontrolled intercurrent illness including, but not limited to, ongoing or active&#xD;
             infection (grade 3 or greater), symptomatic congestive heart failure, unstable angina&#xD;
             pectoris, symptomatic cardiac arrhythmia, or psychiatric illness/social situations&#xD;
             that would limit compliance with study requirements. Subjects with significant&#xD;
             symptoms of congestive heart failure who would not be expected to tolerate the IV&#xD;
             hydration for cisplatin are excluded.&#xD;
&#xD;
          -  Pregnant women are excluded from this study because cisplatin and radiation are agents&#xD;
             with the potential for teratogenic or abortifacient effects. Because there is an&#xD;
             unknown but potential risk for adverse events in nursing infants secondary to&#xD;
             treatment of the mother with cisplatin and radiation, breastfeeding should be&#xD;
             discontinued if the mother is treated with cisplatin or radiation on this trial.&#xD;
&#xD;
          -  HIV-positive patients with uncontrolled HIV despite combination antiretroviral therapy&#xD;
             are ineligible because of the potential for increased risk of lethal infections when&#xD;
             treated with marrow-suppressive therapy. Appropriate studies will be undertaken in&#xD;
             patients receiving combination antiretroviral therapy when indicated&#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>Susanne Arnold, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>University of Kentucky</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Susanne Arnold, MD</last_name>
    <phone>(859) 323-8043</phone>
    <email>susanne.arnold@uky.edu</email>
  </overall_contact>
  <location>
    <facility>
      <name>University of Kentucky</name>
      <address>
        <city>Lexington</city>
        <state>Kentucky</state>
        <zip>40536</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Susanne Arnold, MD</last_name>
      <phone>859-323-8043</phone>
      <email>susanne.arnold@uky.edu</email>
    </contact>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>December 2022</verification_date>
  <study_first_submitted>December 12, 2016</study_first_submitted>
  <study_first_submitted_qc>December 12, 2016</study_first_submitted_qc>
  <study_first_posted type="Estimate">December 15, 2016</study_first_posted>
  <last_update_submitted>December 6, 2022</last_update_submitted>
  <last_update_submitted_qc>December 6, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">December 8, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor-Investigator</responsible_party_type>
    <investigator_affiliation>University of Kentucky</investigator_affiliation>
    <investigator_full_name>Susanne Arnold</investigator_full_name>
    <investigator_title>Principal Investigator</investigator_title>
  </responsible_party>
  <keyword>Cisplatin</keyword>
  <keyword>Squamous Cell</keyword>
  <keyword>Carcinoma</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>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Cisplatin</mesh_term>
  </intervention_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/NCT02994069
org study id: MCC-16-HN-29
nct id: NCT02994069
lead sponsor: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
Patients will receive standard of care radiation therapy to the primary tumor of the head and
      neck and involved nodal metastasis and draining nodal basin and either weekly cisplatin or
      every 3-week cisplatin in locally advanced SCCHN. The relationship between cisplatin toxicity
      and the level of reactive oxygen species generated by the drug in subjects with squamous cell
      carcinoma of the head and neck treated on this trial.
Patients will first be designated as either: a) Cohort 1 (locally advanced non-nasopharyngeal
      SCCHN that is unresectable) OR b) Cohort 2 (resected and at high risk of recurrence with at
      least one of the following criteria: extracapsular nodal extension, or invasive cancer at the
      primary tumor resection margin (positive margin), lymphovascular invasion or perineural
      invasion, pT3 or pT4 primary, or the presence of multilevel nodal disease. Subjects will then
      be randomized to receive either Arm 1 or Arm 2 cisplatin.

      Radiation and Cisplatin will be given concurrently and should start on the same day, ±1 day.
      Radiation will continue without interruption whenever possible.

      Treatment will consist of standard of care radiation therapy to the primary tumor of the head
      and neck and involved nodal metastasis and draining nodal basin, as determined by treating
      radiation oncologist. Patients will be randomized to receive cisplatin at 100 mg/m2 every 3
      weeks (3 doses) during radiation versus cisplatin at 40 mg/m2 once weekly (7 doses) during
      radiation. This will provide similar cumulative doses of cisplatin in all arms of the
      study.IMRT will be delivered in 30-35 fractions over 6-7 weeks, 5 fractions weekly.

      In the absence of treatment delays due to adverse event(s), treatment will continue for 7
      weeks or until one of the following criteria applies:

      Disease progression,Intercurrent illness that prevents further administration of treatment,
      Unacceptable adverse event(s), Patient decides to withdraw from the study, or General or
      specific changes in the patient's condition render the patient unacceptable for further
      treatment in the judgment of the investigator.

      Patients will be followed for 2 years after completion of chemoradiation or until death,
      whichever occurs first, for toxicity and PFS.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
masking description: Unblinded trial
measure: Adverse event rate
time frame: 90 days
description: Rate of grade 3-5 cisplatin-related adverse events occurring within 90 days of initiation of concurrent radiation and chemotherapy
measure: Local control rates
time frame: 2 years
description: 2 year local control rate
measure: Survival
time frame: 2 years
description: Overall survival
arm group label: Every 3 Weeks Cisplatin + XRT
arm group type: Experimental
description: Every 3 Weeks Cisplatin + XRT
arm group label: Weekly Cisplatin + XRT
arm group type: Experimental
description: Weekly Cisplatin + XRT
intervention type: Drug
intervention name: Cisplatin
description: Cisplatin
arm group label: Every 3 Weeks Cisplatin + XRT
arm group label: Weekly Cisplatin + XRT
other name: chemotherapy
intervention type: Radiation
intervention name: XRT
description: Radiation Therapy
arm group label: Every 3 Weeks Cisplatin + XRT
arm group label: Weekly Cisplatin + XRT
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Susanne Arnold, MD
role: Principal Investigator
affiliation: University of Kentucky
last name: Susanne Arnold, MD
phone: (859) 323-8043
email: susanne.arnold@uky.edu
facility: 
status: Recruiting
contact: 
country: United States
responsible party type: Sponsor-Investigator
investigator affiliation: University of Kentucky
investigator full name: Susanne Arnold
investigator title: Principal Investigator
mesh term: Carcinoma
mesh term: Carcinoma, Squamous Cell
mesh term: Cisplatin