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/NCT06030440</url>
    </required_header>
    <id_info>
      <org_study_id>DIREKHT2</org_study_id>
      <nct_id>NCT06030440</nct_id>
    </id_info>
    <brief_title>De-Intensification of Postoperative Radiotherapy in Patients With Squamous Cell Carcinoma of the Head and Neck</brief_title>
    <acronym>DIREKHT2</acronym>
    <official_title>De-Intensification of Postoperative Radiotherapy in Patients With Squamous Cell Carcinoma of the Head and Neck</official_title>
    <sponsors>
      <lead_sponsor>
        <agency>University of Erlangen-Nürnberg Medical School</agency>
        <agency_class>Other</agency_class>
      </lead_sponsor>
    </sponsors>
    <source>University of Erlangen-Nürnberg Medical School</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>
        This randomized, prospective, multicenter phase II/III trial will study the reduction of&#xD;
        radiation volume by eliminating radiotherapy (RT) to the elective neck using strictly defined&#xD;
        surgical and radio-oncological standards to reduce radiotherapy-related long-term side&#xD;
        effects without affecting locoregional control.&#xD;
      </textblock>
    </brief_summary>
    <detailed_description>
      <textblock>
        This study aims to determine whether it is possible to achieve an individual target volume&#xD;
        concept that eliminates elective irradiation of uninvolved lymph drainage areas while&#xD;
        maintaining clearly defined surgical standards and using modern imaging and radiation&#xD;
        techniques. The aim of this study is to achieve reduced late toxicity without compromising&#xD;
        locoregional control.&#xD;
  &#xD;
        Patients will be randomized to: either RT to primary tumor region, regions with lymph node&#xD;
        metastases and elective nodal irradiation (control arm) or RT to primary tumor region and&#xD;
        regions with lymph node metastases without elective nodal irradiation (investigational arm)&#xD;
  &#xD;
        A two-stage design was chosen for this purpose.&#xD;
  &#xD;
        Phase II:&#xD;
  &#xD;
        A randomized phase II study whose primary endpoint is the 1-year percutaneous endoscopic&#xD;
        gastrostomy (PEG) tube dependence rate will be performed first.&#xD;
  &#xD;
        Phase III:&#xD;
  &#xD;
        If the primary endpoint of the phase II study is met and the interim analysis shows no&#xD;
        increase in the locoregional recurrence rate in the study/investigational arm, the study will&#xD;
        be continued as a phase III study whose primary endpoint is the locoregional control rate.&#xD;
      </textblock>
    </detailed_description>
    <overall_status>Not yet recruiting</overall_status>
    <start_date type="Anticipated">October 2023</start_date>
    <completion_date type="Anticipated">September 2033</completion_date>
    <primary_completion_date type="Anticipated">September 2031</primary_completion_date>
    <phase>Phase 2/Phase 3</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>
    </study_design_info>
    <primary_outcome>
      <measure>Phase II: 1-year PEG feeding tube dependence rate</measure>
      <time_frame>PEG-dependent 1 year after radiotherapy</time_frame>
      <description>observe change of PEG-dependence due to different target volumes</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Phase III: Time to local relapse</measure>
      <time_frame>From the date of randomization until the date of observation of local relapse or the date of last observation if no LR occurred, whichever came first (assessed up to 26 months)</time_frame>
      <description>difference between the date of randomization and the date of observation of local relapse (LR), or the date of last observation if no LR occurred (censored observation)</description>
    </primary_outcome>
    <secondary_outcome>
      <measure>Disease-free survival</measure>
      <time_frame>up to 26 months</time_frame>
      <description>Disease-free survival</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Distant-metastasis-free survival</measure>
      <time_frame>through study completion, an average of 26 months</time_frame>
      <description>Distant-metastasis-free survival</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Overall survival (OS)</measure>
      <time_frame>up to 26 months</time_frame>
      <description>Overall survival (OS)</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Cause of death (tumor-related, not tumor-related)</measure>
      <time_frame>through study completion, an average of 26 months</time_frame>
      <description>Cause of death (tumor-related, not tumor-related)</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Acute toxicity according to Common Terminology Criteria (CTC) version 5.0</measure>
      <time_frame>up to 2 months</time_frame>
      <description>Acute toxicity according to CTC version 5.0</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Late toxicity according to CTC version 5.0</measure>
      <time_frame>up to 24 months</time_frame>
      <description>Late toxicity according to CTC version 5.0</description>
    </secondary_outcome>
    <number_of_arms>2</number_of_arms>
    <enrollment type="Anticipated">508</enrollment>
    <condition>Squamous Cell Carcinoma of the Oral Cavity</condition>
    <condition>Squamous Cell Carcinoma of the Larynx</condition>
    <condition>Squamous Cell Carcinoma of the Hypopharynx</condition>
    <condition>Squamous Cell Carcinoma of the Oropharynx</condition>
    <arm_group>
      <arm_group_label>Control Arm</arm_group_label>
      <arm_group_type>Active Comparator</arm_group_type>
      <description>postoperative radiotherapy of the head and neck region according to current standard including elective nodal irradiation</description>
    </arm_group>
    <arm_group>
      <arm_group_label>Investigational Arm</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>postoperative radiotherapy of the head and neck region without elective nodal irradiation</description>
    </arm_group>
    <intervention>
      <intervention_type>Radiation</intervention_type>
      <intervention_name>Eliminating RT to the elective neck</intervention_name>
      <description>Reduction of radiation volume by eliminating radiotherapy to the elective neck</description>
      <arm_group_label>Investigational Arm</arm_group_label>
    </intervention>
    <intervention>
      <intervention_type>Radiation</intervention_type>
      <intervention_name>RT standard of care</intervention_name>
      <description>postoperative radiotherapy of the head and neck region according to current standard including elective nodal irradiation</description>
      <arm_group_label>Control Arm</arm_group_label>
    </intervention>
    <eligibility>
      <criteria>
        <textblock>
          Inclusion Criteria:&#xD;
  &#xD;
            1. Histologically proven squamous cell carcinoma of the oral cavity/larynx/oro-or&#xD;
               hypopharynx (except glottis cancer (pT1/2pN0))&#xD;
  &#xD;
            2. Surgery of primary tumor and neck dissection performed according to predefined&#xD;
               surgical standard&#xD;
  &#xD;
            3. Indication for postoperative radio(chemo)therapy&#xD;
  &#xD;
            4. No lymph node metastases &gt; 6cm&#xD;
  &#xD;
            5. Lymph node metastases in not more than 3 lymph node level&#xD;
  &#xD;
            6. No distant metastases (cM0)&#xD;
  &#xD;
            7. Age ≥ 18 years, no upper age limit&#xD;
  &#xD;
            8. Eastern Cooperative Oncology Group (ECOG) ≤ 2&#xD;
  &#xD;
            9. Patients who understood protocol contents and are able to behave according to protocol&#xD;
  &#xD;
           10. Signed study-specific consent form prior to therapy&#xD;
  &#xD;
           11. Start of radiotherapy at least 6 weeks after last tumor-specific surgery (e.g.&#xD;
               resection primary tumor, neck dissection, excluded are surgeries according to wound&#xD;
               healing complications)&#xD;
  &#xD;
          Exclusion Criteria:&#xD;
  &#xD;
            1. macroscopic incomplete resection R2&#xD;
  &#xD;
            2. Distant metastases (cM1)&#xD;
  &#xD;
            3. Radiologically or histologically proven early recurrence after surgery (time frame&#xD;
               from surgery to start of radio(chemo)therapy)&#xD;
  &#xD;
            4. Lymph node metastases in &gt; 3 lymph node level&#xD;
  &#xD;
            5. pregnant or lactating/nursing women&#xD;
  &#xD;
            6. fertile patients that are not willing to use highly effective methods of contraception&#xD;
               (per institutional standards) during treatment&#xD;
  &#xD;
            7. Any condition potentially hampering compliance with the study protocol and follow-up&#xD;
               schedule&#xD;
  &#xD;
            8. On-treatment participation on other clinical therapeutic trials&#xD;
  &#xD;
            9. Prior tumor-specific therapy any other than surgery (like prior radiotherapy in the&#xD;
               head and neck region, prior chemo- or immunotherapy (neoadjuvant/induction))&#xD;
  &#xD;
           10. Patients who have contraindication for MRI and CT with contrast agent (both)&#xD;
  &#xD;
           11. Prior (&gt; 2 months before beginning of radio(chemo)therapy) neck dissection or surgery&#xD;
               in the head and neck area affecting lymph drainage&#xD;
  &#xD;
           12. History of another primary malignancy except for malignancy treated with curative&#xD;
               intent and with no known active disease ≥5 years before diagnosis of head and neck&#xD;
               cancer, adequately treated non-melanoma skin cancer or lentigo maligna without&#xD;
               evidence of disease, adequately treated carcinoma in situ without evidence of disease&#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>Sarina Müller, PD</last_name>
      <role>Study Director</role>
      <affiliation>Universitätsklinikum Erlangen, HNO</affiliation>
    </overall_official>
    <overall_official>
      <last_name>Rainer Fietkau, Prof</last_name>
      <role>Principal Investigator</role>
      <affiliation>Universitätsklinikum Erlangen, Radiation Oncology</affiliation>
    </overall_official>
    <overall_contact>
      <last_name>Marlen Haderlein, PD</last_name>
      <phone>+49913185</phone>
      <phone_ext>33968</phone_ext>
      <email>marlen.haderlein@uk-erlangen.de</email>
    </overall_contact>
    <overall_contact_backup>
      <last_name>Studiensekretariat</last_name>
      <phone>+49913185</phone>
      <phone_ext>33968</phone_ext>
      <email>studiensekretariat.ST@uk-erlangen.de</email>
    </overall_contact_backup>
    <location>
      <facility>
        <name>Universitätsklinikum Erlangen, Strahlenklinik</name>
        <address>
          <city>Erlangen</city>
          <state>Bavaria</state>
          <zip>91054</zip>
          <country>Germany</country>
        </address>
      </facility>
      <contact>
        <last_name>Marlen Haderlein, PD</last_name>
        <phone>+49913185</phone>
        <phone_ext>33968</phone_ext>
        <email>marlen.haderlein@uk-erlangen.de</email>
      </contact>
      <contact_backup>
        <last_name>Rainer Fietkau, Prof</last_name>
        <phone>+49913185</phone>
        <phone_ext>33968</phone_ext>
        <email>rainer.fietkau@uk-erlangen.de</email>
      </contact_backup>
    </location>
    <location_countries>
      <country>Germany</country>
    </location_countries>
    <verification_date>August 2023</verification_date>
    <study_first_submitted>August 11, 2023</study_first_submitted>
    <study_first_submitted_qc>September 8, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">September 11, 2023</study_first_posted>
    <last_update_submitted>September 8, 2023</last_update_submitted>
    <last_update_submitted_qc>September 8, 2023</last_update_submitted_qc>
    <last_update_posted type="Actual">September 11, 2023</last_update_posted>
    <responsible_party>
      <responsible_party_type>Sponsor</responsible_party_type>
    </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>
    </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/NCT06030440
  org study id: DIREKHT2
  nct id: NCT06030440
  lead sponsor: 
  has dmc: Yes
  is fda regulated drug: No
  is fda regulated device: No
  This randomized, prospective, multicenter phase II/III trial will study the reduction of
        radiation volume by eliminating radiotherapy (RT) to the elective neck using strictly defined
        surgical and radio-oncological standards to reduce radiotherapy-related long-term side
        effects without affecting locoregional control.
  This study aims to determine whether it is possible to achieve an individual target volume
        concept that eliminates elective irradiation of uninvolved lymph drainage areas while
        maintaining clearly defined surgical standards and using modern imaging and radiation
        techniques. The aim of this study is to achieve reduced late toxicity without compromising
        locoregional control.
  
        Patients will be randomized to: either RT to primary tumor region, regions with lymph node
        metastases and elective nodal irradiation (control arm) or RT to primary tumor region and
        regions with lymph node metastases without elective nodal irradiation (investigational arm)
  
        A two-stage design was chosen for this purpose.
  
        Phase II:
  
        A randomized phase II study whose primary endpoint is the 1-year percutaneous endoscopic
        gastrostomy (PEG) tube dependence rate will be performed first.
  
        Phase III:
  
        If the primary endpoint of the phase II study is met and the interim analysis shows no
        increase in the locoregional recurrence rate in the study/investigational arm, the study will
        be continued as a phase III study whose primary endpoint is the locoregional control rate.
  allocation: Randomized
  intervention model: Parallel Assignment
  primary purpose: Treatment
  masking: None (Open Label)
  measure: Phase II: 1-year PEG feeding tube dependence rate
  time frame: PEG-dependent 1 year after radiotherapy
  description: observe change of PEG-dependence due to different target volumes
  measure: Phase III: Time to local relapse
  time frame: From the date of randomization until the date of observation of local relapse or the date of last observation if no LR occurred, whichever came first (assessed up to 26 months)
  description: difference between the date of randomization and the date of observation of local relapse (LR), or the date of last observation if no LR occurred (censored observation)
  measure: Disease-free survival
  time frame: up to 26 months
  description: Disease-free survival
  measure: Distant-metastasis-free survival
  time frame: through study completion, an average of 26 months
  description: Distant-metastasis-free survival
  measure: Overall survival (OS)
  time frame: up to 26 months
  description: Overall survival (OS)
  measure: Cause of death (tumor-related, not tumor-related)
  time frame: through study completion, an average of 26 months
  description: Cause of death (tumor-related, not tumor-related)
  measure: Acute toxicity according to Common Terminology Criteria (CTC) version 5.0
  time frame: up to 2 months
  description: Acute toxicity according to CTC version 5.0
  measure: Late toxicity according to CTC version 5.0
  time frame: up to 24 months
  description: Late toxicity according to CTC version 5.0
  arm group label: Control Arm
  arm group type: Active Comparator
  description: postoperative radiotherapy of the head and neck region according to current standard including elective nodal irradiation
  arm group label: Investigational Arm
  arm group type: Experimental
  description: postoperative radiotherapy of the head and neck region without elective nodal irradiation
  intervention type: Radiation
  intervention name: Eliminating RT to the elective neck
  description: Reduction of radiation volume by eliminating radiotherapy to the elective neck
  arm group label: Investigational Arm
  intervention type: Radiation
  intervention name: RT standard of care
  description: postoperative radiotherapy of the head and neck region according to current standard including elective nodal irradiation
  arm group label: Control Arm
  criteria: 
  gender: All
  minimum age: 18 Years
  maximum age: N/A
  healthy volunteers: No
  last name: Sarina Müller, PD
  role: Study Director
  affiliation: Universitätsklinikum Erlangen, HNO
  last name: Rainer Fietkau, Prof
  role: Principal Investigator
  affiliation: Universitätsklinikum Erlangen, Radiation Oncology
  last name: Marlen Haderlein, PD
  phone: +49913185
  phone ext: 33968
  email: marlen.haderlein@uk-erlangen.de
  last name: Studiensekretariat
  phone: +49913185
  phone ext: 33968
  email: studiensekretariat.ST@uk-erlangen.de
  facility: 
  contact: 
  contact backup: 
  country: Germany
  responsible party type: Sponsor
  mesh term: Carcinoma
  mesh term: Carcinoma, Squamous Cell
  mesh term: Squamous Cell Carcinoma of Head and Neck
  sharing ipd: No