<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/NCT02242916</url>
  </required_header>
  <id_info>
    <org_study_id>ROCOCO re-irradiation HN</org_study_id>
    <nct_id>NCT02242916</nct_id>
  </id_info>
  <brief_title>State of the Art Photon Therapy Versus Particle Therapy for Recurrent Head &amp; Neck Tumors; a Planning Study</brief_title>
  <acronym>ROCOCO</acronym>
  <official_title>In Silico Clinical Trial, Comparing State of the Art Photon Modalities With Proton and C-ion Therapy for Recurrent Head &amp; Neck Tumors: A Multicentric Planning Study From the ROCOCO (Radiation Oncology COllaborative COmparison) Group</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Maastricht Radiation Oncology</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>University of Pennsylvania</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Philipps University Marburg Medical Center</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>University Medical Center Nijmegen</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Maastricht Radiation Oncology</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      Given that the cost of proton therapy is considerably higher than that of conventional&#xD;
      radiotherapy with photons, it is necessary to establish whether these higher costs are&#xD;
      worthwhile in light of the expected advantages2,3,4. Thus, clear evidence of the situations&#xD;
      in which proton therapy outperforms conventional photon treatment is needed. The&#xD;
      investigators therefore aim to demonstrate through an in silico trial that proton therapy&#xD;
      decrease the amount of irradiated normal tissue and, consequently, the risk of side effects&#xD;
      in the surrounding normal tissue as well as the risk of secondary tumors. The same overall&#xD;
      treatment time and an equal number of fractions will be used for both treatment modalities&#xD;
      wherever possible. The most optimal technique for each individual patient, based on objective&#xD;
      criteria related to limiting dose to normal tissue, will be prescribed by the institution&#xD;
      concerned for each treatment option.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The CTV to PTV margin will be determined by the individual institutes according to the&#xD;
      treatment technique and treatment modality. For all treatment plans, modified ICRU 50 will be&#xD;
      applied. The ICRU 50 recommendation is that 100% of the target volume (PTV) receives at least&#xD;
      95% of the prescribed dose. In this work, participants agree that D98 &gt; = 95%, D2 &lt; = 107%,&#xD;
      cold (&lt; 95%) and hot (&gt; 107%) spots should be avoided in general, and that no hot spots will&#xD;
      be allowed outside the PTV. The same overall treatment time (OTT) and an equal number of&#xD;
      fractions will be used for all treatment modalities.&#xD;
&#xD;
      Treatment plans will be carried out using either photons, protons and C-ions for dose&#xD;
      calculation for the indication H&amp;N re-irradiation. A multicentric patient dataset, which can&#xD;
      be found on a secured website5,6, will be used. The output databases with matrices including&#xD;
      3D delineation, the deliverable physical dose, RBE map, and BED/ EQD2 will be made available.&#xD;
      To guarantee a similar set-up between the three treatments, similar dose distributions will&#xD;
      be used. For C-ion treatment planning, a 20% uncertainty in the RBE values will be taken into&#xD;
      account.&#xD;
&#xD;
      All treatment plans will be performed in centers that are already operating and have&#xD;
      experience in treatment planning. Photon treatment plans will be carried out in Nijmegen en&#xD;
      Maastricht, proton treatment plans at the University of Pennsylvania (UPENN) and the C-ion&#xD;
      treatment plans at the University Hospital Marburg (UHM). For photons, all primary treatment&#xD;
      plans were performed according to the planning procedure of each individual participating&#xD;
      center by selecting the best available technique. The secondary photon treatment plan will be&#xD;
      performed according predefined fractionation schedule and tumor dose. The proton treatment&#xD;
      plans for H&amp;N tumors will be planned with active beam delivery using IMPT and/or passive 4D&#xD;
      beam delivery (PSPT). The C-ion treatment plans will be planned using a raster-scanning&#xD;
      technique (IMIT).&#xD;
&#xD;
      All relevant OAR are delineated in the primary and secondary study set. GTV/CTV will be used&#xD;
      accordingly to the actual treatment. New DVH's will be calculated for the added OAR. The&#xD;
      secondary plan (i.e. re-irradiation plan) will be calculated again for the best currently&#xD;
      available options for Photon, proton and C-ions. Between primary and secondary treatment&#xD;
      there is a period of 1 to 5 years for all patients. To be on the save site a 30 % recovery of&#xD;
      brainstem and spinal cord is assumed. There will not be a correction for fraction size. For&#xD;
      practical reasons the location of the Dmax in the brainstem or spinal cord will not be taken&#xD;
      into account. A maximal cumulative dose of 120 Gy will be accepted in the mandibular.&#xD;
&#xD;
      If the mandibular is part of the CTV in the first as well as in the second treatment, a&#xD;
      higher dose will be accepted. A cumulative dose of max 120 Gy will also be accepted for the&#xD;
      larynx , for the arytenoid is this 100Gy, unless the larynx is within the CTV for the first&#xD;
      and second treatment than a higher dose will be accepted.&#xD;
&#xD;
      This means that for a total study population of 25 patients per tumor site and group at least&#xD;
      100 treatment plans will be carried out. All dose maps will be saved on the secure website as&#xD;
      part of the database mentioned above.&#xD;
&#xD;
      Photon, proton and C-ion treatments will be compared based on dosimetric parameters on normal&#xD;
      tissues such as mean parotic dose, etc. In addition, the NTCP for a fixed tumor dose or the&#xD;
      same expected TCP will be determined. Cobalt Gy equivalent doses will be used when reporting&#xD;
      the proton and C-ion dose. In the case of protons, a constant RBE value of 1.1 will be used&#xD;
      for both the tumor and the normal tissues. The RBE of C-ions will be calculated based on the&#xD;
      models used by the participating centers. The GSI in-house treatment planning system uses RBE&#xD;
      values calculated on the basis of the local effect model (LEM). The LEM I (alpha/beta=2) is&#xD;
      based on the radial dose distribution of each charged particle crossing into a cell nucleus,&#xD;
      as well as on the radiosensitivity and repair capacity of the tissue. The TPSs used by UHM is&#xD;
      also based on the LEM model. The model used at NIRS utilizes fixed RBE values that are&#xD;
      dependent on the depth in the body, but independent of dose level or tumor type.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>May 2014</start_date>
  <completion_date type="Actual">October 2015</completion_date>
  <primary_completion_date type="Actual">October 2015</primary_completion_date>
  <study_type>Observational</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <observational_model>Cohort</observational_model>
    <time_perspective>Retrospective</time_perspective>
  </study_design_info>
  <primary_outcome>
    <measure>Radiation exposure for organs at risk in H&amp;N cancer patients</measure>
    <time_frame>7 weeks</time_frame>
    <description>Radiation exposure for organs at risk in H&amp;N patients treated with radiotherapy for recurrent tumors after primary radiotherapy. Results are based on in silico planning study which compares photon, proton and Carbon-ion treatments. The same biological radiation dose, fractionation schedule and tumor dose inhomogeneity is used. A wide range of OAR is included in this study, to be able to document doses to organs that are further away from the target volume, and also to quantify low doses to organs.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Normal tissue complication probability (NTCP) for a fixed tumor dose</measure>
    <time_frame>3 years</time_frame>
    <description>Based on the OAR radiation exposure, the Normal tissue complication probability (NTCP) for a fixed tumor dose or the same expected Tumor Control Probability (TCP) will be determined using dose response curves.</description>
  </secondary_outcome>
  <other_outcome>
    <measure>Risk of secondary cancer</measure>
    <time_frame>10 years</time_frame>
    <description>Risk of secondary cancer</description>
  </other_outcome>
  <number_of_groups>1</number_of_groups>
  <enrollment type="Actual">25</enrollment>
  <condition>Carcinoma, Squamous Cell of Head and Neck</condition>
  <arm_group>
    <arm_group_label>Patients with recurrent HN tumors</arm_group_label>
    <description>Patients with recurrent Head and Neck tumors</description>
  </arm_group>
  <intervention>
    <intervention_type>Radiation</intervention_type>
    <intervention_name>Photon therapy versus proton therapy</intervention_name>
    <arm_group_label>Patients with recurrent HN tumors</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Radiation</intervention_type>
    <intervention_name>Photon therapy versus C-ion therapy</intervention_name>
    <arm_group_label>Patients with recurrent HN tumors</arm_group_label>
  </intervention>
  <eligibility>
    <study_pop>
      <textblock>
        patients with recurrent head and neck tumors&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Non-Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Primary treatment:&#xD;
&#xD;
               1. ≥ 50 Gy with curative intent (with or without chemo)&#xD;
&#xD;
               2. CTV includes primary tumor and at least level II-IV&#xD;
&#xD;
               3. Severe dental scatter artifacts or metal implants of unknown density will be&#xD;
                  excluded&#xD;
&#xD;
               4. IMRT plan available&#xD;
&#xD;
          -  Secondary treatment after ≥ 1 year, dose 70 Gy&#xD;
&#xD;
             a. Severe dental scatter artifacts or metal implants of unknown density will be&#xD;
             excluded&#xD;
&#xD;
          -  Overlap of at least one OAR in primary and secondary treatment&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Patients referred for postoperative radiotherapy&#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>Danielle Eekers, Dr.</last_name>
    <role>Principal Investigator</role>
    <affiliation>Maastro Clinic, Dr Tanslaan 12, Maastricht, The Netherlands</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Philippe lambin, prof, Dr</last_name>
    <role>Study Director</role>
    <affiliation>Maastro Clinic, Dr Tanslaan 12, Maastricht, The Netherlands</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Maastro Clinic</name>
      <address>
        <city>Maastricht</city>
        <zip>6229 ET</zip>
        <country>Netherlands</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Netherlands</country>
  </location_countries>
  <verification_date>January 2016</verification_date>
  <study_first_submitted>September 15, 2014</study_first_submitted>
  <study_first_submitted_qc>September 16, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">September 17, 2014</study_first_posted>
  <last_update_submitted>January 21, 2016</last_update_submitted>
  <last_update_submitted_qc>January 21, 2016</last_update_submitted_qc>
  <last_update_posted type="Estimate">January 22, 2016</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>reccurent Head and Neck tumors</keyword>
  <keyword>re-irradiation</keyword>
  <keyword>photon</keyword>
  <keyword>proton</keyword>
  <keyword>carbon-ion</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <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/NCT02242916
org study id: ROCOCO re-irradiation HN
nct id: NCT02242916
lead sponsor: 
collaborator: 
collaborator: 
collaborator: 
has dmc: Yes
Given that the cost of proton therapy is considerably higher than that of conventional
      radiotherapy with photons, it is necessary to establish whether these higher costs are
      worthwhile in light of the expected advantages2,3,4. Thus, clear evidence of the situations
      in which proton therapy outperforms conventional photon treatment is needed. The
      investigators therefore aim to demonstrate through an in silico trial that proton therapy
      decrease the amount of irradiated normal tissue and, consequently, the risk of side effects
      in the surrounding normal tissue as well as the risk of secondary tumors. The same overall
      treatment time and an equal number of fractions will be used for both treatment modalities
      wherever possible. The most optimal technique for each individual patient, based on objective
      criteria related to limiting dose to normal tissue, will be prescribed by the institution
      concerned for each treatment option.
The CTV to PTV margin will be determined by the individual institutes according to the
      treatment technique and treatment modality. For all treatment plans, modified ICRU 50 will be
      applied. The ICRU 50 recommendation is that 100% of the target volume (PTV) receives at least
      95% of the prescribed dose. In this work, participants agree that D98 > = 95%, D2 < = 107%,
      cold (< 95%) and hot (> 107%) spots should be avoided in general, and that no hot spots will
      be allowed outside the PTV. The same overall treatment time (OTT) and an equal number of
      fractions will be used for all treatment modalities.

      Treatment plans will be carried out using either photons, protons and C-ions for dose
      calculation for the indication H&N re-irradiation. A multicentric patient dataset, which can
      be found on a secured website5,6, will be used. The output databases with matrices including
      3D delineation, the deliverable physical dose, RBE map, and BED/ EQD2 will be made available.
      To guarantee a similar set-up between the three treatments, similar dose distributions will
      be used. For C-ion treatment planning, a 20% uncertainty in the RBE values will be taken into
      account.

      All treatment plans will be performed in centers that are already operating and have
      experience in treatment planning. Photon treatment plans will be carried out in Nijmegen en
      Maastricht, proton treatment plans at the University of Pennsylvania (UPENN) and the C-ion
      treatment plans at the University Hospital Marburg (UHM). For photons, all primary treatment
      plans were performed according to the planning procedure of each individual participating
      center by selecting the best available technique. The secondary photon treatment plan will be
      performed according predefined fractionation schedule and tumor dose. The proton treatment
      plans for H&N tumors will be planned with active beam delivery using IMPT and/or passive 4D
      beam delivery (PSPT). The C-ion treatment plans will be planned using a raster-scanning
      technique (IMIT).

      All relevant OAR are delineated in the primary and secondary study set. GTV/CTV will be used
      accordingly to the actual treatment. New DVH's will be calculated for the added OAR. The
      secondary plan (i.e. re-irradiation plan) will be calculated again for the best currently
      available options for Photon, proton and C-ions. Between primary and secondary treatment
      there is a period of 1 to 5 years for all patients. To be on the save site a 30 % recovery of
      brainstem and spinal cord is assumed. There will not be a correction for fraction size. For
      practical reasons the location of the Dmax in the brainstem or spinal cord will not be taken
      into account. A maximal cumulative dose of 120 Gy will be accepted in the mandibular.

      If the mandibular is part of the CTV in the first as well as in the second treatment, a
      higher dose will be accepted. A cumulative dose of max 120 Gy will also be accepted for the
      larynx , for the arytenoid is this 100Gy, unless the larynx is within the CTV for the first
      and second treatment than a higher dose will be accepted.

      This means that for a total study population of 25 patients per tumor site and group at least
      100 treatment plans will be carried out. All dose maps will be saved on the secure website as
      part of the database mentioned above.

      Photon, proton and C-ion treatments will be compared based on dosimetric parameters on normal
      tissues such as mean parotic dose, etc. In addition, the NTCP for a fixed tumor dose or the
      same expected TCP will be determined. Cobalt Gy equivalent doses will be used when reporting
      the proton and C-ion dose. In the case of protons, a constant RBE value of 1.1 will be used
      for both the tumor and the normal tissues. The RBE of C-ions will be calculated based on the
      models used by the participating centers. The GSI in-house treatment planning system uses RBE
      values calculated on the basis of the local effect model (LEM). The LEM I (alpha/beta=2) is
      based on the radial dose distribution of each charged particle crossing into a cell nucleus,
      as well as on the radiosensitivity and repair capacity of the tissue. The TPSs used by UHM is
      also based on the LEM model. The model used at NIRS utilizes fixed RBE values that are
      dependent on the depth in the body, but independent of dose level or tumor type.
observational model: Cohort
time perspective: Retrospective
measure: Radiation exposure for organs at risk in H&N cancer patients
time frame: 7 weeks
description: Radiation exposure for organs at risk in H&N patients treated with radiotherapy for recurrent tumors after primary radiotherapy. Results are based on in silico planning study which compares photon, proton and Carbon-ion treatments. The same biological radiation dose, fractionation schedule and tumor dose inhomogeneity is used. A wide range of OAR is included in this study, to be able to document doses to organs that are further away from the target volume, and also to quantify low doses to organs.
measure: Normal tissue complication probability (NTCP) for a fixed tumor dose
time frame: 3 years
description: Based on the OAR radiation exposure, the Normal tissue complication probability (NTCP) for a fixed tumor dose or the same expected Tumor Control Probability (TCP) will be determined using dose response curves.
measure: Risk of secondary cancer
time frame: 10 years
description: Risk of secondary cancer
arm group label: Patients with recurrent HN tumors
description: Patients with recurrent Head and Neck tumors
intervention type: Radiation
intervention name: Photon therapy versus proton therapy
arm group label: Patients with recurrent HN tumors
intervention type: Radiation
intervention name: Photon therapy versus C-ion therapy
arm group label: Patients with recurrent HN tumors
study pop: 
sampling method: Non-Probability Sample
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Danielle Eekers, Dr.
role: Principal Investigator
affiliation: Maastro Clinic, Dr Tanslaan 12, Maastricht, The Netherlands
last name: Philippe lambin, prof, Dr
role: Study Director
affiliation: Maastro Clinic, Dr Tanslaan 12, Maastricht, The Netherlands
facility: 
country: Netherlands
responsible party type: Sponsor
mesh term: Carcinoma, Squamous Cell
mesh term: Squamous Cell Carcinoma of Head and Neck