<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/NCT01667640</url>
  </required_header>
  <id_info>
    <org_study_id>Sektorradv_4.0_04-2012</org_study_id>
    <nct_id>NCT01667640</nct_id>
  </id_info>
  <brief_title>Sector Irradiation Versus Whole Brain Irradiation for Brain Metastasis</brief_title>
  <official_title>Sector Irradiation Versus Whole Brain Irradiation After Resection of Singular or Solitary Brain Metastasis - a Prospective Randomized Monocentric Trial</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Medical University Innsbruck</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Marcel Seiz-Rosenhagen MD, PD</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Meinhard Nevinny-Stickel MD, Prof.</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Christian F Freyschlag MD</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Günther Stockhammer MD, Prof.</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Bernhard Holzner MD, Doz</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Johannes Giesinger Mag</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Margarete Delazer MD, Prof.</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Thomas Bodner MD, MSc</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Claudius Thomé MD, Prof.</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Medical University Innsbruck</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      Microneurosurgical resection of intracerebral metastases leads to prolonged survival and&#xD;
      relief of symptoms in selected patients.&#xD;
&#xD;
      To minimize the risk of intracranial recurrence whole brain irradiation has been established&#xD;
      as standard adjuvant treatment in those patients. Sector irradiation resembles a brain -&#xD;
      tissue - sparing method by focusing the irradiation in the area of the tumor bed and a&#xD;
      surrounding 1mm security margin.&#xD;
&#xD;
      The aim of this study is to investigate whether adjuvant &quot;sector&quot;&quot;-irradiation following&#xD;
      microsurgical resection is equal to adjuvant whole brain irradiation in terms of local&#xD;
      control and superior to in terms of quality of life and neurocognitive deficits in a&#xD;
      prospective randomized trial.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Microneurosurgical resection of intracerebral metastases leads to prolonged survival and&#xD;
      relief of symptoms in selected patients. Traditionally whole-brain irradiation is the&#xD;
      treatment of choice following surgical resection. Whole brain irradiation has been the&#xD;
      standard approach to minimize the risk of intracranial recurrence following resection of&#xD;
      brain metastases. Almost 2 decades ago, Patchell et al. established the superiority of&#xD;
      resection of solitary metastases followed by whole brain irradiation compared with whole&#xD;
      brain irradiation alone with regard to survival, local control, and length of functional&#xD;
      independence. A following study by the same group failed to show a survival advantage for the&#xD;
      addition of whole brain irradiation compared to surgical resection alone in patients with a&#xD;
      solitary intracranial metastasis, although the likelihood of local and distant recurrence and&#xD;
      death from neurological causes were significantly reduced by whole brain irradiation. Due to&#xD;
      potential delayed neurocognitive effects associated with whole brain irradiation,&#xD;
      investigators have evaluated the use of partial brain irradiation in the form of stereotactic&#xD;
      radiosurgery instead of whole brain irradiation after resection of brain metastases. They&#xD;
      showed that despite whole brain irradiation means superior control of brain recurrence in&#xD;
      sites other than the resection bed, stereotactic radiosurgery after resection resulted in&#xD;
      equivalent survival times and neurological preservation. In a retrospective series of 52&#xD;
      patients Karlovits et al. could show that stereotactic radiosurgery following surgical&#xD;
      resection leads to equal local control compared to standard whole brain irradiation.&#xD;
&#xD;
      Study objective&#xD;
&#xD;
      The aim of this study is to investigate whether adjuvant &quot;sector&quot; -irradiation following&#xD;
      microsurgical resection is equal to adjuvant whole brain irradiation in terms of local&#xD;
      control and superior to in terms of quality of life and neurocognitive deficits in a&#xD;
      prospective randomized trial.&#xD;
&#xD;
      Hypothesis&#xD;
&#xD;
        1. Sector irradiation is equal to whole-brain irradiation in local tumor control after 3,&#xD;
           6, 12 and 36 months and&#xD;
&#xD;
        2. Sector irradiation&quot; is superior to whole-brain irradiation in terms of quality of life&#xD;
           and neurocognitive function&#xD;
&#xD;
      Patients and Methods&#xD;
&#xD;
      Patients with a single brain metastasis amenable to surgical resection fulfilling the&#xD;
      inclusion criteria will be consecutively enrolled in this study. After microsurgical complete&#xD;
      resection documented by early postoperative MRI within 72 hours and histological proven brain&#xD;
      metastasis patients will be randomized in arm A or B. Radiotherapy will start after 14th&#xD;
      postoperative day within 3 weeks postoperatively. Study arm A means postoperative sector&#xD;
      irradiation (30Gy), study arm B includes standard whole brain radiotherapy (40Gy). Follow up&#xD;
      MRI will be every 3 months. Neurocognitive evaluation will be performed before radiotherapy&#xD;
      and 6 and 12 months postoperatively. In case of local recurrence or developing further&#xD;
      metastases a cross over to whole brain radiotherapy or focal irradiation is possible.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Recruiting</last_known_status>
  <start_date>April 2012</start_date>
  <completion_date type="Anticipated">April 2017</completion_date>
  <primary_completion_date type="Anticipated">April 2016</primary_completion_date>
  <phase>N/A</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>local tumor control</measure>
    <time_frame>time from date of randomization until the date of first documented progression, assessed up to 36 months</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>distant brain metastasis</measure>
    <time_frame>Time from date of randomization until the date of first documented progression elsewhere than the resection cavity, assessed at 3, 6, 12 and 36 months</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>time to clinical deterioration</measure>
    <time_frame>Time from randomization to clinical deterioration, assessed by neurosurgeon in regular follow up visits at 3, 6, 12 and 36 months</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>local progression free survival</measure>
    <time_frame>Time from randomization to the first documented tumor progressions in the resection cavity borders, assessed up to 36 months</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>quality of life</measure>
    <time_frame>3, 6, 12 and 36 months</time_frame>
    <description>standardized assessment via &quot;EORTC QLQ-C30/BN20&quot; and the &quot;FACT-Br&quot; - questionary at 3, 6, 12 and 36 months after date of randomization</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>neurocognitive functions</measure>
    <time_frame>3, 6, 12 and 36 months postoperative</time_frame>
    <description>Neurocognitive testing by independent neuropsychologist at 3, 6, 12 and 36 months after date of randomization</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>steroid dosage</measure>
    <time_frame>3, 6, 12 and 36 months postoperative</time_frame>
    <description>Need of adjuvant steroid, assessed at 3, 6, 12 and 36 months after date of randomization</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>overall survival</measure>
    <time_frame>From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 36 months</time_frame>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">50</enrollment>
  <condition>Metastatic Malignant Neoplasm to the Adult Brain</condition>
  <arm_group>
    <arm_group_label>whole brain irradiation</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>whole brain irradiation with 40 Gy, with fixation mask, radiation of the entire brain, skull base and meninges</description>
  </arm_group>
  <arm_group>
    <arm_group_label>sector irradiation</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>irradiation of the resection margin plus 5 mm safety margin with 30 Gy in 5 fractions</description>
  </arm_group>
  <intervention>
    <intervention_type>Radiation</intervention_type>
    <intervention_name>sector irradiation</intervention_name>
    <description>Gross Tumor Volume (GTV) is defined as the visible margin of the resection on post- operative MRI and planning- CT-scan. The Clinical Treatment Volume (CTV) is the same as the GTV plus a 5 mm margin The Planning Treatment Volume (PTV) includes the CTV plus a 1mm margin.&#xD;
A non-invasive immobilization is used for the planning CT and treatment delivery with an accuracy of ≤ 1mm.&#xD;
Treatment planning will conform to ICRU 50/62 rules for coverage of GTV, CTV and PTV. Additionally, organs at risk are delineated according to the ICRU 62 rules.&#xD;
Treatment with radiotherapy will start 2 to 3 weeks after surgery. The prescribed dose for the PTV is 30 Gy in 5 fractions.&#xD;
Isodose distributions will be calculated through the target in three planes. Dose volume histograms will be reported.</description>
    <arm_group_label>sector irradiation</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Radiation</intervention_type>
    <intervention_name>whole brain irradiation</intervention_name>
    <description>For whole brain radiation the entire brain, the base of the skull and the meninges are included.&#xD;
Radiation is performed fractionated with 40 Gy. The caudal boundary of the radiation-target volume is between the 2. and the 3. cervical vertebra. The radiation is performed via two lateral, opposing and isocentric contra fields. The face/ventral skull is shielded with individual blocs or MLC.&#xD;
The used energy for the radiation fields should be between 6 and 16 MV. The specification point of the dose or the standardization point has to be chosen in that way that the point is in the middle of the target volume. The target volume is radiated within the tolerance range of 95% - 107 %. The maximum/minimum doses in the target volume and possible doses peaks are documented.</description>
    <arm_group_label>whole brain irradiation</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Solitary/singular brain metastasis&#xD;
&#xD;
          -  Karnofsky Performance Index &gt; 60%&#xD;
&#xD;
          -  Stable extracranial disease /CUP&#xD;
&#xD;
          -  Informed consent&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Small cell lung cancer&#xD;
&#xD;
          -  Squamous cell lung cancer&#xD;
&#xD;
          -  HER2-negative breast cancer&#xD;
&#xD;
          -  Deep-seated location (e.g. basal ganglia)&#xD;
&#xD;
          -  Expected surgery related neurological deficit&#xD;
&#xD;
          -  Tumor diameter &lt; 3cm&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>80 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Marcel Seiz-Rosenhagen, MD, PD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Department of Neurosurgery, Medical University Innsbruck</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Johannes Kerschbaumer, MD</last_name>
    <phone>+43-512-504-82848</phone>
    <email>johannes.kerschbaumer@uki.at</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Christian F Freyschlag, MD</last_name>
    <phone>+43-512-504-82595</phone>
    <email>christian.freyschlag@uki.at</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>Department of neurosurgery - Innsbruck</name>
      <address>
        <city>Innsbruck</city>
        <state>Tyrol</state>
        <zip>6020</zip>
        <country>Austria</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Sabine Strauss, Mag</last_name>
      <phone>+43-512-504-27286</phone>
    </contact>
  </location>
  <location_countries>
    <country>Austria</country>
  </location_countries>
  <link>
    <url>http://neurochirurgie.uklibk.ac.at</url>
    <description>Study center hompage.</description>
  </link>
  <verification_date>April 2015</verification_date>
  <study_first_submitted>August 7, 2012</study_first_submitted>
  <study_first_submitted_qc>August 16, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">August 17, 2012</study_first_posted>
  <last_update_submitted>April 28, 2015</last_update_submitted>
  <last_update_submitted_qc>April 28, 2015</last_update_submitted_qc>
  <last_update_posted type="Estimate">April 29, 2015</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Medical University Innsbruck</investigator_affiliation>
    <investigator_full_name>Kerschbaumer Johannes</investigator_full_name>
    <investigator_title>MD</investigator_title>
  </responsible_party>
  <keyword>Brain metastases</keyword>
  <keyword>radiation</keyword>
  <keyword>sector</keyword>
  <keyword>singular</keyword>
  <keyword>solitary</keyword>
  <keyword>neurocognition</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Neoplasm Metastasis</mesh_term>
    <mesh_term>Brain Neoplasms</mesh_term>
    <mesh_term>Neoplasms</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/NCT01667640
org study id: Sektorradv_4.0_04-2012
nct id: NCT01667640
lead sponsor: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
has dmc: No
Microneurosurgical resection of intracerebral metastases leads to prolonged survival and
      relief of symptoms in selected patients.

      To minimize the risk of intracranial recurrence whole brain irradiation has been established
      as standard adjuvant treatment in those patients. Sector irradiation resembles a brain -
      tissue - sparing method by focusing the irradiation in the area of the tumor bed and a
      surrounding 1mm security margin.

      The aim of this study is to investigate whether adjuvant "sector""-irradiation following
      microsurgical resection is equal to adjuvant whole brain irradiation in terms of local
      control and superior to in terms of quality of life and neurocognitive deficits in a
      prospective randomized trial.
Microneurosurgical resection of intracerebral metastases leads to prolonged survival and
      relief of symptoms in selected patients. Traditionally whole-brain irradiation is the
      treatment of choice following surgical resection. Whole brain irradiation has been the
      standard approach to minimize the risk of intracranial recurrence following resection of
      brain metastases. Almost 2 decades ago, Patchell et al. established the superiority of
      resection of solitary metastases followed by whole brain irradiation compared with whole
      brain irradiation alone with regard to survival, local control, and length of functional
      independence. A following study by the same group failed to show a survival advantage for the
      addition of whole brain irradiation compared to surgical resection alone in patients with a
      solitary intracranial metastasis, although the likelihood of local and distant recurrence and
      death from neurological causes were significantly reduced by whole brain irradiation. Due to
      potential delayed neurocognitive effects associated with whole brain irradiation,
      investigators have evaluated the use of partial brain irradiation in the form of stereotactic
      radiosurgery instead of whole brain irradiation after resection of brain metastases. They
      showed that despite whole brain irradiation means superior control of brain recurrence in
      sites other than the resection bed, stereotactic radiosurgery after resection resulted in
      equivalent survival times and neurological preservation. In a retrospective series of 52
      patients Karlovits et al. could show that stereotactic radiosurgery following surgical
      resection leads to equal local control compared to standard whole brain irradiation.

      Study objective

      The aim of this study is to investigate whether adjuvant "sector" -irradiation following
      microsurgical resection is equal to adjuvant whole brain irradiation in terms of local
      control and superior to in terms of quality of life and neurocognitive deficits in a
      prospective randomized trial.

      Hypothesis

        1. Sector irradiation is equal to whole-brain irradiation in local tumor control after 3,
           6, 12 and 36 months and

        2. Sector irradiation" is superior to whole-brain irradiation in terms of quality of life
           and neurocognitive function

      Patients and Methods

      Patients with a single brain metastasis amenable to surgical resection fulfilling the
      inclusion criteria will be consecutively enrolled in this study. After microsurgical complete
      resection documented by early postoperative MRI within 72 hours and histological proven brain
      metastasis patients will be randomized in arm A or B. Radiotherapy will start after 14th
      postoperative day within 3 weeks postoperatively. Study arm A means postoperative sector
      irradiation (30Gy), study arm B includes standard whole brain radiotherapy (40Gy). Follow up
      MRI will be every 3 months. Neurocognitive evaluation will be performed before radiotherapy
      and 6 and 12 months postoperatively. In case of local recurrence or developing further
      metastases a cross over to whole brain radiotherapy or focal irradiation is possible.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: local tumor control
time frame: time from date of randomization until the date of first documented progression, assessed up to 36 months
measure: distant brain metastasis
time frame: Time from date of randomization until the date of first documented progression elsewhere than the resection cavity, assessed at 3, 6, 12 and 36 months
measure: time to clinical deterioration
time frame: Time from randomization to clinical deterioration, assessed by neurosurgeon in regular follow up visits at 3, 6, 12 and 36 months
measure: local progression free survival
time frame: Time from randomization to the first documented tumor progressions in the resection cavity borders, assessed up to 36 months
measure: quality of life
time frame: 3, 6, 12 and 36 months
description: standardized assessment via "EORTC QLQ-C30/BN20" and the "FACT-Br" - questionary at 3, 6, 12 and 36 months after date of randomization
measure: neurocognitive functions
time frame: 3, 6, 12 and 36 months postoperative
description: Neurocognitive testing by independent neuropsychologist at 3, 6, 12 and 36 months after date of randomization
measure: steroid dosage
time frame: 3, 6, 12 and 36 months postoperative
description: Need of adjuvant steroid, assessed at 3, 6, 12 and 36 months after date of randomization
measure: overall survival
time frame: From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 36 months
arm group label: whole brain irradiation
arm group type: Active Comparator
description: whole brain irradiation with 40 Gy, with fixation mask, radiation of the entire brain, skull base and meninges
arm group label: sector irradiation
arm group type: Experimental
description: irradiation of the resection margin plus 5 mm safety margin with 30 Gy in 5 fractions
intervention type: Radiation
intervention name: sector irradiation
description: Gross Tumor Volume (GTV) is defined as the visible margin of the resection on post- operative MRI and planning- CT-scan. The Clinical Treatment Volume (CTV) is the same as the GTV plus a 5 mm margin The Planning Treatment Volume (PTV) includes the CTV plus a 1mm margin.
A non-invasive immobilization is used for the planning CT and treatment delivery with an accuracy of ≤ 1mm.
Treatment planning will conform to ICRU 50/62 rules for coverage of GTV, CTV and PTV. Additionally, organs at risk are delineated according to the ICRU 62 rules.
Treatment with radiotherapy will start 2 to 3 weeks after surgery. The prescribed dose for the PTV is 30 Gy in 5 fractions.
Isodose distributions will be calculated through the target in three planes. Dose volume histograms will be reported.
arm group label: sector irradiation
intervention type: Radiation
intervention name: whole brain irradiation
description: For whole brain radiation the entire brain, the base of the skull and the meninges are included.
Radiation is performed fractionated with 40 Gy. The caudal boundary of the radiation-target volume is between the 2. and the 3. cervical vertebra. The radiation is performed via two lateral, opposing and isocentric contra fields. The face/ventral skull is shielded with individual blocs or MLC.
The used energy for the radiation fields should be between 6 and 16 MV. The specification point of the dose or the standardization point has to be chosen in that way that the point is in the middle of the target volume. The target volume is radiated within the tolerance range of 95% - 107 %. The maximum/minimum doses in the target volume and possible doses peaks are documented.
arm group label: whole brain irradiation
criteria: 
gender: All
minimum age: 18 Years
maximum age: 80 Years
healthy volunteers: No
last name: Marcel Seiz-Rosenhagen, MD, PD
role: Principal Investigator
affiliation: Department of Neurosurgery, Medical University Innsbruck
last name: Johannes Kerschbaumer, MD
phone: +43-512-504-82848
email: johannes.kerschbaumer@uki.at
last name: Christian F Freyschlag, MD
phone: +43-512-504-82595
email: christian.freyschlag@uki.at
facility: 
status: Recruiting
contact: 
country: Austria
url: http://neurochirurgie.uklibk.ac.at
description: Study center hompage.
responsible party type: Principal Investigator
investigator affiliation: Medical University Innsbruck
investigator full name: Kerschbaumer Johannes
investigator title: MD
mesh term: Neoplasm Metastasis
mesh term: Brain Neoplasms
mesh term: Neoplasms