<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/NCT02978677</url>
  </required_header>
  <id_info>
    <org_study_id>STR-PANAMA-2015</org_study_id>
    <nct_id>NCT02978677</nct_id>
  </id_info>
  <brief_title>Proton Dose Escalation for Patients With Atypical or Anaplastic Meningiomas</brief_title>
  <acronym>PANAMA</acronym>
  <official_title>Proton Dose Escalation for Patients With Atypical or Anaplastic Meningiomas</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Technische Universität Dresden</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>German Cancer Research Center</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Radiation Oncology Working Group of the German Cancer Society</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Technische Universität Dresden</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>
      The trial evaluates the effect of a moderately increased radiation dose in patients with&#xD;
      atypical (grade II) and anaplastic (grade III) meningioma after incomplete or no surgery.&#xD;
      Endpoint is recurrence-free survival after 5 years.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The trial intends to optimize treatment for grade II and grade III (atypical or anaplastic)&#xD;
      meningioma. Standard treatment for atypical or anaplastic meningioma is surgery. For grade&#xD;
      III (anaplastic) meningiomas, post-operative radiotherapy would be performed in all cases&#xD;
      using standard fractionation schedules to a total dose of ~60 Gy. For grade II (atypical)&#xD;
      meningiomas, although some small patient datasets support early onset of radiotherapy, the&#xD;
      standard treatment is still to irradiate if tumours are recurrent or if resection was&#xD;
      macroscopically incomplete. Total doses of 54 to ~60 Gy are applied using standard&#xD;
      fractionation schedules.&#xD;
&#xD;
      A major problem of the treatment of atypical or anaplastic meningioma is that beyond surgery&#xD;
      and radiotherapy, there are only experimental treatment options and the probability of local&#xD;
      recurrences is 50-100% within the first 5 years for grade II and grade III meningioma.&#xD;
&#xD;
      The present trial has been developed to evaluate efficacy of a dose-intensified radiotherapy&#xD;
      treatment schedule for incompletely or not resected meningioma to a total dose of 68 (grade&#xD;
      II) or 72 Gy (grade III). To minimize normal tissue toxicity, the boost dose or the complete&#xD;
      radiotherapy is applied using protons. The expectation is a higher recurrence-free survival&#xD;
      compared to previous reports on outcome of standard dose (60 Gy) radiotherapy.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Not yet recruiting</overall_status>
  <start_date type="Anticipated">October 2022</start_date>
  <completion_date type="Anticipated">December 2029</completion_date>
  <primary_completion_date type="Anticipated">December 2028</primary_completion_date>
  <phase>N/A</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Non-Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>progression-free survival</measure>
    <time_frame>5 years after start of radiotherapy</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>late toxicity</measure>
    <time_frame>5 years after start of radiotherapy</time_frame>
    <description>CTC-AE 4.0</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>acute toxicity</measure>
    <time_frame>5 years after start of radiotherapy</time_frame>
    <description>CTC-AE 4.0</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>overall survival</measure>
    <time_frame>5 years after start of radiotherapy</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>patterns of recurrence using MRI</measure>
    <time_frame>5 years after start of radiotherapy</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>quality of life by validated quality of life questionnaires</measure>
    <time_frame>5 years after start of radiotherapy</time_frame>
    <description>EORTC-QLQ-C30, EORTC-QLQ-BN20</description>
  </secondary_outcome>
  <number_of_arms>3</number_of_arms>
  <enrollment type="Anticipated">90</enrollment>
  <condition>Meningioma</condition>
  <arm_group>
    <arm_group_label>Grade II tumors (macroscopic)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Radiotherapy 68 Gy(RBE)</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Grade III tumors (macroscopic)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Radiotherapy 72 Gy(RBE)</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Grade II/III tumors (completely resected)</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Radiotherapy 60 Gy(RBE)</description>
  </arm_group>
  <intervention>
    <intervention_type>Radiation</intervention_type>
    <intervention_name>Radiotherapy 68 Gy(RBE)</intervention_name>
    <description>Radiotherapy 2.0 to 50 Gy(RBE) photon or proton and boost 2 to 18 Gy(RBE) proton</description>
    <arm_group_label>Grade II tumors (macroscopic)</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Radiation</intervention_type>
    <intervention_name>Radiotherapy 72 Gy(RBE)</intervention_name>
    <description>Radiotherapy 2.0 to 50 Gy(RBE) photon or proton and boost 2 to 18 Gy(RBE) proton and boost 2 to 4 Gy(RBE) proton</description>
    <arm_group_label>Grade III tumors (macroscopic)</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Radiation</intervention_type>
    <intervention_name>Radiotherapy 60 Gy(RBE)</intervention_name>
    <description>Radiotherapy 2.0 to 50 Gy(RBE) photon or proton and boost 2 to 10 Gy(RBE) proton</description>
    <arm_group_label>Grade II/III tumors (completely resected)</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  histologically confirmed atypical (WHO grade II) or anaplastic (WHO grade III)&#xD;
             meningioma with the indication for radiotherapy&#xD;
&#xD;
          -  MRI (within 24h post-operative, if not available than with a time interval of ~ 6&#xD;
             weeks) including contrast-enhanced T1 weighted 3D dataset and PET for evaluation of&#xD;
             macroscopic tumour (residuum)&#xD;
&#xD;
          -  Karnofsky Performance Score ≥ 60, ECOG ≤2&#xD;
&#xD;
          -  For women with childbearing potential, (and men) adequate contraception.&#xD;
&#xD;
          -  Ability of subject to understand character and individual consequences of the clinical&#xD;
             trial&#xD;
&#xD;
          -  Written informed consent (must be available before enrolment in the trial)&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  refusal of the patients to take part in the study&#xD;
&#xD;
          -  previous radiotherapy of the brain&#xD;
&#xD;
          -  several manifestations of the meningioma in different regions of the brain or&#xD;
             additional spinal manifestations&#xD;
&#xD;
          -  distant metastases&#xD;
&#xD;
          -  patients who are not suitable for radiotherapy&#xD;
&#xD;
          -  known other malignant disease within 5 years before radiotherapy (except tumours that&#xD;
             likely do not impact prognosis and likely not require treatment interfering with study&#xD;
             therapy, e.g. in-situ carcinoma of the breast or cervix uteri)&#xD;
&#xD;
          -  pregnant or lactating women&#xD;
&#xD;
          -  patients with non-MRI compatible metal implants, pacemaker or non-MRI compatible&#xD;
             external automatic defibrillators&#xD;
&#xD;
          -  patients not able to understand character and individual consequences of the clinical&#xD;
             trial&#xD;
&#xD;
          -  claustrophobic patients&#xD;
&#xD;
          -  current participation in another clinical intervention study&#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>Mechthild Krause, Prof.</last_name>
    <role>Study Chair</role>
    <affiliation>Technische Universität Dresden, German Cancer Consortium, Helmholtz-Zentrum Dresden - Rossendorf</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Mechthild Krause, Prof.</last_name>
    <phone>+49 351 458 5441</phone>
    <email>mechthild.krause@uniklinikum-dresden.de</email>
  </overall_contact>
  <verification_date>August 2022</verification_date>
  <study_first_submitted>October 19, 2016</study_first_submitted>
  <study_first_submitted_qc>November 28, 2016</study_first_submitted_qc>
  <study_first_posted type="Estimate">December 1, 2016</study_first_posted>
  <last_update_submitted>August 2, 2022</last_update_submitted>
  <last_update_submitted_qc>August 2, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">August 3, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Technische Universität Dresden</investigator_affiliation>
    <investigator_full_name>Mechthild Krause</investigator_full_name>
    <investigator_title>Principal Investigator</investigator_title>
  </responsible_party>
  <keyword>brain tumors</keyword>
  <keyword>proton radiotherapy</keyword>
  <keyword>photon radiotherapy</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Meningioma</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <!-- 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/NCT02978677
org study id: STR-PANAMA-2015
nct id: NCT02978677
lead sponsor: 
collaborator: 
collaborator: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
The trial evaluates the effect of a moderately increased radiation dose in patients with
      atypical (grade II) and anaplastic (grade III) meningioma after incomplete or no surgery.
      Endpoint is recurrence-free survival after 5 years.
The trial intends to optimize treatment for grade II and grade III (atypical or anaplastic)
      meningioma. Standard treatment for atypical or anaplastic meningioma is surgery. For grade
      III (anaplastic) meningiomas, post-operative radiotherapy would be performed in all cases
      using standard fractionation schedules to a total dose of ~60 Gy. For grade II (atypical)
      meningiomas, although some small patient datasets support early onset of radiotherapy, the
      standard treatment is still to irradiate if tumours are recurrent or if resection was
      macroscopically incomplete. Total doses of 54 to ~60 Gy are applied using standard
      fractionation schedules.

      A major problem of the treatment of atypical or anaplastic meningioma is that beyond surgery
      and radiotherapy, there are only experimental treatment options and the probability of local
      recurrences is 50-100% within the first 5 years for grade II and grade III meningioma.

      The present trial has been developed to evaluate efficacy of a dose-intensified radiotherapy
      treatment schedule for incompletely or not resected meningioma to a total dose of 68 (grade
      II) or 72 Gy (grade III). To minimize normal tissue toxicity, the boost dose or the complete
      radiotherapy is applied using protons. The expectation is a higher recurrence-free survival
      compared to previous reports on outcome of standard dose (60 Gy) radiotherapy.
allocation: Non-Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: progression-free survival
time frame: 5 years after start of radiotherapy
measure: late toxicity
time frame: 5 years after start of radiotherapy
description: CTC-AE 4.0
measure: acute toxicity
time frame: 5 years after start of radiotherapy
description: CTC-AE 4.0
measure: overall survival
time frame: 5 years after start of radiotherapy
measure: patterns of recurrence using MRI
time frame: 5 years after start of radiotherapy
measure: quality of life by validated quality of life questionnaires
time frame: 5 years after start of radiotherapy
description: EORTC-QLQ-C30, EORTC-QLQ-BN20
arm group label: Grade II tumors (macroscopic)
arm group type: Experimental
description: Radiotherapy 68 Gy(RBE)
arm group label: Grade III tumors (macroscopic)
arm group type: Experimental
description: Radiotherapy 72 Gy(RBE)
arm group label: Grade II/III tumors (completely resected)
arm group type: Active Comparator
description: Radiotherapy 60 Gy(RBE)
intervention type: Radiation
intervention name: Radiotherapy 68 Gy(RBE)
description: Radiotherapy 2.0 to 50 Gy(RBE) photon or proton and boost 2 to 18 Gy(RBE) proton
arm group label: Grade II tumors (macroscopic)
intervention type: Radiation
intervention name: Radiotherapy 72 Gy(RBE)
description: Radiotherapy 2.0 to 50 Gy(RBE) photon or proton and boost 2 to 18 Gy(RBE) proton and boost 2 to 4 Gy(RBE) proton
arm group label: Grade III tumors (macroscopic)
intervention type: Radiation
intervention name: Radiotherapy 60 Gy(RBE)
description: Radiotherapy 2.0 to 50 Gy(RBE) photon or proton and boost 2 to 10 Gy(RBE) proton
arm group label: Grade II/III tumors (completely resected)
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Mechthild Krause, Prof.
role: Study Chair
affiliation: Technische Universität Dresden, German Cancer Consortium, Helmholtz-Zentrum Dresden - Rossendorf
last name: Mechthild Krause, Prof.
phone: +49 351 458 5441
email: mechthild.krause@uniklinikum-dresden.de
responsible party type: Principal Investigator
investigator affiliation: Technische Universität Dresden
investigator full name: Mechthild Krause
investigator title: Principal Investigator
mesh term: Meningioma
sharing ipd: No