<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/NCT02220127</url>
  </required_header>
  <id_info>
    <org_study_id>14/0050</org_study_id>
    <secondary_id>14/LO/0791</secondary_id>
    <secondary_id>145268</secondary_id>
    <nct_id>NCT02220127</nct_id>
  </id_info>
  <brief_title>RCT of the 4mm vs. the 8mm Collimator for GKR of Brain Micrometastases</brief_title>
  <official_title>Optimal Radiation Method for Gamma Knife Radiosurgery of Brain Micrometastases: A Multi-centre Randomised Clinical Trial (RCT) of the 4mm vs. the 8mm Collimator.</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University College, London</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>University College London Hospitals</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>University College, London</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      Gamma Knife Radiosurgery (GKR) is a well-established treatment modality for brain metastasis&#xD;
      (Chiou 2013; Salvetti, Nagaraja et al. 2013). Large multicentre series have been published on&#xD;
      patients with single and multiple cerebral metastases, treated with GKR over a period of 30&#xD;
      years (Karlsson, Hanssens et al. 2009). Multiple institutions have reported a consistently&#xD;
      high local tumour control rate of 80%-90% following GKR (Chang, Lee et al. 2000; Da Silva,&#xD;
      Nagayama et al. 2009; Salvetti, Nagaraja et al. 2013).&#xD;
&#xD;
      There is controversy over the use of GKR and/or Whole Brain Radiotherapy (WBRT) in patients&#xD;
      with multiple metastases. WBRT provides a lower rate of distant recurrences, whereas GKR&#xD;
      achieves good local control of treated lesions without the deleterious side effects of&#xD;
      radiotherapy (Lippitz, Lindquist et al. 2014). This discussion is mainly focused on the risk&#xD;
      of distant recurrences, which is lower if WBRT is given. There is evidence showing that&#xD;
      Radiosurgery (RS) based on high contrast/resolution stereotactic MRI decreases the incidence&#xD;
      and lengthens the time to distant recurrences (Hanssens, Karlsson et al. 2011). As a result,&#xD;
      the current tendency is to treat all the lesions visible in high contrast/resolution images&#xD;
      the day of Gamma Knife; which is followed by regular MRI follow ups and subsequent GKR for&#xD;
      distant recurrences in order to avoid/delay WBRT.&#xD;
&#xD;
      It has been estimated that more than a half of distant recurrences will grow from tumour&#xD;
      cells that were already in the brain (as micrometastases) when radiosurgery is delivered, but&#xD;
      not much has been studied on the optimal prescription and radiation delivery method for these&#xD;
      lesions. There is controversy over which collimator should be used when treating&#xD;
      micro-metastases (BmM). These lesions can either be treated with the 4mm collimator at an&#xD;
      isodose between the 40% and 90%, or the 8mm collimator at an isodose above 90%. The 8 mm&#xD;
      collimator is thought to offer better Local Control Rate (LCR) with the advantage of faster&#xD;
      delivered treatments, while the 4 mm collimator is considered to be safer, given its steep&#xD;
      dose fall-off. It is the aim of this study to find out which of the 4 mm or 8 mm collimators&#xD;
      can achieve the higher LCR with less complications. A large number of lesions will be&#xD;
      randomised to either the 4 or the 8 mm collimator and the patients followed up to evaluate&#xD;
      clinical efficacy.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Recruiting</last_known_status>
  <start_date>September 2014</start_date>
  <completion_date type="Anticipated">April 2021</completion_date>
  <primary_completion_date type="Anticipated">April 2020</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>Single (Participant)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Local control rate (LCR)</measure>
    <time_frame>up to 24 months after treatment</time_frame>
    <description>LCR will be evaluated through volumetric assessment of the lesion the day of Gamma Knife and in subsequent follow up MRI scans</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Adverse radiation effects (ARE)</measure>
    <time_frame>up to two years</time_frame>
    <description>The following radiological and clinical outcomes will be used to assess ARE:&#xD;
Bleeding from randomised lesions, Perilesional radiation induced necrosis, Severe peri-lesional oedema, New onset or worsened neurological deficit attributable to a randomised lesion</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">298</enrollment>
  <condition>Brain Micrometastases</condition>
  <arm_group>
    <arm_group_label>8 mm collimator</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>GKR with a single shot of the 8 mm collimator</description>
  </arm_group>
  <arm_group>
    <arm_group_label>4 mm collimator</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>GKR with a single shot of the 4 mm collimator</description>
  </arm_group>
  <intervention>
    <intervention_type>Radiation</intervention_type>
    <intervention_name>GKR with a single shot of the 8 mm collimator</intervention_name>
    <description>Gamma Knife Radiosurgery (GKR) with a single shot of the 8 mm collimator at an isodose above 90%.</description>
    <arm_group_label>8 mm collimator</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Radiation</intervention_type>
    <intervention_name>GKR with a single shot of the 4 mm collimator</intervention_name>
    <description>Gamma Knife Radiosurgery (GKR) with a single shot of the 4 mm collimator at an isodose between the 40% and 90%.</description>
    <arm_group_label>4 mm collimator</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Adult patients with brain metastasis from any primary tumour receiving GKR.&#xD;
&#xD;
          -  All intracranial micro-metastases including lesions located in the cerebral&#xD;
             hemispheres, thalamus, basal ganglia and cerebellum and excluding lesions located in&#xD;
             the brain stem below the level of the superior colliculi.&#xD;
&#xD;
          -  Target volume &lt; 0.14 cc3 and maximum diameter &lt; 7 mm.&#xD;
&#xD;
          -  The subject consents to participate in the study.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Inability to consent&#xD;
&#xD;
          -  Younger than 18 years of age.&#xD;
&#xD;
          -  Lesions in the brainstem (below the level of the superior colliculi) are better&#xD;
             treated with the 4 mm collimator and they will be excluded from the study.&#xD;
&#xD;
          -  Patients with more than 25 brain lesions suitable for randomisation will be excluded&#xD;
             from the study.&#xD;
&#xD;
          -  Co-morbidity or previous treatment such as surgery, chemotherapy or WBRT is not to be&#xD;
             considered as exclusion criteria.&#xD;
&#xD;
          -  Pregnancy in the context of brain metastases is not a contraindication for GKR, and&#xD;
             therefore it will not be considered as exclusion criteria for this trial.&#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>Neil Kitchen, Mr</last_name>
    <role>Study Chair</role>
    <affiliation>The National Hospital for Neurology and Neurosurgery</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Alvaro Villabona, Dr</last_name>
    <phone>+44 020 3448 4076</phone>
    <email>a.villabona.11@ucl.ac.uk</email>
  </overall_contact>
  <location>
    <facility>
      <name>Gamma Knife Centre at BUPA Cromwell Hospital</name>
      <address>
        <city>London</city>
        <zip>SW5 0TU</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
    <status>Not yet recruiting</status>
    <contact>
      <last_name>Bodo Lippitz, MD</last_name>
      <phone>020 7460 5938</phone>
      <email>bodo.lippitz@cromwellhospital.com</email>
    </contact>
    <investigator>
      <last_name>Bodo Lippitz, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
    <investigator>
      <last_name>Christer Lindquist, MD, PhD</last_name>
      <role>Sub-Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>The Gamma Knife Centre at Queen Square</name>
      <address>
        <city>London</city>
        <zip>WC1N 3BG</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Alvaro Villabona, Dr</last_name>
      <phone>+44 020 3448 4076</phone>
      <email>a.villabona.11@ucl.ac.uk</email>
    </contact>
    <investigator>
      <last_name>Ian Paddick, MSc,MIPM</last_name>
      <role>Sub-Investigator</role>
    </investigator>
    <investigator>
      <last_name>Naomi Fersht, PhD, FRCR</last_name>
      <role>Sub-Investigator</role>
    </investigator>
    <investigator>
      <last_name>Rolf Jäger, MD, FRCR</last_name>
      <role>Sub-Investigator</role>
    </investigator>
    <investigator>
      <last_name>Katherine Miszkiel, MRCP, FRCR</last_name>
      <role>Sub-Investigator</role>
    </investigator>
    <investigator>
      <last_name>Alvaro Villabona, MBBS, MSc</last_name>
      <role>Sub-Investigator</role>
    </investigator>
    <investigator>
      <last_name>Neil Kitchen, MD, FRCS(SN)</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>BMI Thornbury Hospital</name>
      <address>
        <city>Sheffield</city>
        <zip>S10 3BR</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
    <status>Not yet recruiting</status>
    <contact>
      <last_name>Andras Kemeny, FRCS, MD</last_name>
      <phone>01142674651</phone>
      <email>aakemeny@gmail.com</email>
    </contact>
    <investigator>
      <last_name>Andras Kemeny, FRCS, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
    <investigator>
      <last_name>Matthias Radatz, FRCS</last_name>
      <role>Sub-Investigator</role>
    </investigator>
    <investigator>
      <last_name>Jeremy Rowe, FRCS</last_name>
      <role>Sub-Investigator</role>
    </investigator>
  </location>
  <location_countries>
    <country>United Kingdom</country>
  </location_countries>
  <link>
    <url>http://www.queensquaregammaknife.co.uk/clinical-trials/</url>
    <description>Related Info</description>
  </link>
  <verification_date>March 2015</verification_date>
  <study_first_submitted>August 18, 2014</study_first_submitted>
  <study_first_submitted_qc>August 18, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">August 19, 2014</study_first_posted>
  <last_update_submitted>March 19, 2015</last_update_submitted>
  <last_update_submitted_qc>March 19, 2015</last_update_submitted_qc>
  <last_update_posted type="Estimate">March 20, 2015</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Brain</keyword>
  <keyword>Neoplasm Micrometastasis</keyword>
  <keyword>Gamma Knife Radiosurgery</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Neoplasm Micrometastasis</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/NCT02220127
org study id: 14/0050
secondary id: 14/LO/0791
secondary id: 145268
nct id: NCT02220127
lead sponsor: 
collaborator: 
has dmc: Yes
Gamma Knife Radiosurgery (GKR) is a well-established treatment modality for brain metastasis
      (Chiou 2013; Salvetti, Nagaraja et al. 2013). Large multicentre series have been published on
      patients with single and multiple cerebral metastases, treated with GKR over a period of 30
      years (Karlsson, Hanssens et al. 2009). Multiple institutions have reported a consistently
      high local tumour control rate of 80%-90% following GKR (Chang, Lee et al. 2000; Da Silva,
      Nagayama et al. 2009; Salvetti, Nagaraja et al. 2013).

      There is controversy over the use of GKR and/or Whole Brain Radiotherapy (WBRT) in patients
      with multiple metastases. WBRT provides a lower rate of distant recurrences, whereas GKR
      achieves good local control of treated lesions without the deleterious side effects of
      radiotherapy (Lippitz, Lindquist et al. 2014). This discussion is mainly focused on the risk
      of distant recurrences, which is lower if WBRT is given. There is evidence showing that
      Radiosurgery (RS) based on high contrast/resolution stereotactic MRI decreases the incidence
      and lengthens the time to distant recurrences (Hanssens, Karlsson et al. 2011). As a result,
      the current tendency is to treat all the lesions visible in high contrast/resolution images
      the day of Gamma Knife; which is followed by regular MRI follow ups and subsequent GKR for
      distant recurrences in order to avoid/delay WBRT.

      It has been estimated that more than a half of distant recurrences will grow from tumour
      cells that were already in the brain (as micrometastases) when radiosurgery is delivered, but
      not much has been studied on the optimal prescription and radiation delivery method for these
      lesions. There is controversy over which collimator should be used when treating
      micro-metastases (BmM). These lesions can either be treated with the 4mm collimator at an
      isodose between the 40% and 90%, or the 8mm collimator at an isodose above 90%. The 8 mm
      collimator is thought to offer better Local Control Rate (LCR) with the advantage of faster
      delivered treatments, while the 4 mm collimator is considered to be safer, given its steep
      dose fall-off. It is the aim of this study to find out which of the 4 mm or 8 mm collimators
      can achieve the higher LCR with less complications. A large number of lesions will be
      randomised to either the 4 or the 8 mm collimator and the patients followed up to evaluate
      clinical efficacy.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Single (Participant)
measure: Local control rate (LCR)
time frame: up to 24 months after treatment
description: LCR will be evaluated through volumetric assessment of the lesion the day of Gamma Knife and in subsequent follow up MRI scans
measure: Adverse radiation effects (ARE)
time frame: up to two years
description: The following radiological and clinical outcomes will be used to assess ARE:
Bleeding from randomised lesions, Perilesional radiation induced necrosis, Severe peri-lesional oedema, New onset or worsened neurological deficit attributable to a randomised lesion
arm group label: 8 mm collimator
arm group type: Experimental
description: GKR with a single shot of the 8 mm collimator
arm group label: 4 mm collimator
arm group type: Experimental
description: GKR with a single shot of the 4 mm collimator
intervention type: Radiation
intervention name: GKR with a single shot of the 8 mm collimator
description: Gamma Knife Radiosurgery (GKR) with a single shot of the 8 mm collimator at an isodose above 90%.
arm group label: 8 mm collimator
intervention type: Radiation
intervention name: GKR with a single shot of the 4 mm collimator
description: Gamma Knife Radiosurgery (GKR) with a single shot of the 4 mm collimator at an isodose between the 40% and 90%.
arm group label: 4 mm collimator
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Neil Kitchen, Mr
role: Study Chair
affiliation: The National Hospital for Neurology and Neurosurgery
last name: Alvaro Villabona, Dr
phone: +44 020 3448 4076
email: a.villabona.11@ucl.ac.uk
facility: 
status: Not yet recruiting
contact: 
investigator: 
investigator: 
facility: 
status: Recruiting
contact: 
investigator: 
investigator: 
investigator: 
investigator: 
investigator: 
investigator: 
facility: 
status: Not yet recruiting
contact: 
investigator: 
investigator: 
investigator: 
country: United Kingdom
url: http://www.queensquaregammaknife.co.uk/clinical-trials/
description: Related Info
responsible party type: Sponsor
mesh term: Neoplasm Micrometastasis