<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/NCT03789149</url>
  </required_header>
  <id_info>
    <org_study_id>2315/17</org_study_id>
    <nct_id>NCT03789149</nct_id>
  </id_info>
  <brief_title>Focal Intraoperative Radiotherapy of Brain Metastases</brief_title>
  <official_title>Focal Intraoperative Radiotherapy After Resection of Brain Metastases</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>AC Camargo Cancer Center</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Carl Zeiss Meditec AG</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>AC Camargo Cancer Center</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>
      Brain metastases (BM) are the most prevalent tumors of the central nervous system (CNS), with&#xD;
      a ratio of 10: 1 in relation to primary tumors. In prospective studies, whole-brain&#xD;
      radiotherapy (WBRT) reduced the risk of local recurrence after resection of brain metastases&#xD;
      from 46-59% to 10-28%. Furthermore, WBRT reduces the incidence of new metastases and death&#xD;
      from disease, but no apparent improvement in overall survival (OS). Due to the potential&#xD;
      neurocognitive effects associated with WBRT compared to isolated focal approach, several&#xD;
      authors have suggested delaying WBRT and perform focal adjuvant RT after resection of&#xD;
      isolated BM. In this context, intraoperative radiotherapy (IORT) in the cavity after&#xD;
      resection of BM may be an appealing option.&#xD;
&#xD;
      The primary objectives of this study are to evaluate local control (LC) and the control of&#xD;
      brain disease (LC associated with the absence of new distant BM) after IORT for one&#xD;
      completely resected supratentorial BM in the presence of up to 10 lesions suggestive of BM.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Brain metastases (BM) are the most prevalent tumors of the central nervous system (CNS), with&#xD;
      a ratio of 10: 1 in relation to primary tumors. This type of metastasis occurs in 20-40% of&#xD;
      cancer patients and are related to significant morbidity and mortality.&#xD;
&#xD;
      In prospective studies, whole-brain radiotherapy (WBRT) reduced the risk of local recurrence&#xD;
      after resection of brain metastases from 46-59% to 10-28%. Furthermore, WBRT reduces the&#xD;
      incidence of new metastases and death from disease, but no apparent improvement in overall&#xD;
      survival (OS). Due to the potential neurocognitive effects associated with WBRT compared to&#xD;
      isolated focal approach, several authors have suggested delaying WBRT and perform focal&#xD;
      adjuvant RT after resection of isolated BM.&#xD;
&#xD;
      The utilization of intraoperative radiotherapy (IORT) in the cavity after resection of&#xD;
      primary or BM has been described in the literature, the majority of reports describes&#xD;
      performing brachytherapy with iodine seeds or interstitial radiosurgery. However, there is a&#xD;
      paucity of information regarding the use of IORT with low energy X-ray for focal treatment&#xD;
      after resection of brain BM.&#xD;
&#xD;
      The objectives of this study are evaluate local control (LC), the control of brain disease in&#xD;
      patients with metastatic brain disease (up to 10 lesions) submitted to focal IORT to an&#xD;
      isolated surgical cavity, evaluate overall survival (OS), evaluate the frequency of radiation&#xD;
      necrosis and correlate the prognostic factors related to the patient with OS and the&#xD;
      parameters of the treatment (dose, volume, lesion location) with the LC and radiation&#xD;
      necrosis.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Terminated</overall_status>
  <why_stopped>
    Planning to join a prospective multicentric trial after evaluation of 10 first participants&#xD;
  </why_stopped>
  <start_date type="Actual">May 2, 2019</start_date>
  <completion_date type="Actual">June 30, 2022</completion_date>
  <primary_completion_date type="Actual">June 30, 2022</primary_completion_date>
  <phase>Phase 2</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>N/A</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <intervention_model_description>Single group assignment</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Local control (LC)</measure>
    <time_frame>1 year</time_frame>
    <description>Rate of local failure in the surgical cavity</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Control of Brain Disease (CBD)</measure>
    <time_frame>1 year</time_frame>
    <description>Rate of control in the brain outside</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Overall Survival (OS)</measure>
    <time_frame>1 year</time_frame>
    <description>Rate of death related to any cause</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Frequency of radiation necrosis</measure>
    <time_frame>1 year</time_frame>
    <description>Imaging evaluation</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">10</enrollment>
  <condition>Brain Metastases, Adult</condition>
  <condition>Central Nervous System Metastases</condition>
  <arm_group>
    <arm_group_label>Intraoperative Radiotherapy</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Intraoperative Radiotherapy with a mobile device (Intrabeam, Carl Zeiss AG)</description>
  </arm_group>
  <intervention>
    <intervention_type>Radiation</intervention_type>
    <intervention_name>Intraoperative Radiotherapy</intervention_name>
    <description>Intraoperative Radiotherapy with a mobile device (Intrabeam, Carl Zeiss AG) consisting of a small source of low energy x-rays (30-50 kV) mounted on a mechanical arm with six degrees of freedom. The resulting dose distribution is isotropic around the tip of the X-ray source. A set of spherical applicators with diameters ranging from 1.5 to 5 cm is available to connect to the source. The treatment time may vary from 20-30 minutes with the suggested dose of 18 Gy to the resection cavity to a depth of 1 mm.</description>
    <arm_group_label>Intraoperative Radiotherapy</arm_group_label>
    <other_name>Intrabeam</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Age &gt;18 years&#xD;
&#xD;
          -  Histologically confirmed diagnosis of invasive cancer in the presence of up to 10&#xD;
             lesions suggestive of BM&#xD;
&#xD;
          -  Indication of resection of single lesion suggestive of BM and evidence of macroscopic&#xD;
             complete resection&#xD;
&#xD;
          -  Patient consent to participate in the study&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Previous cranial radiotherapy&#xD;
&#xD;
          -  Any kind of antineoplasic systemic treatment for less than 7 days of the procedure&#xD;
&#xD;
          -  Cavities with proximity &lt; 10 mm from the brainstem or optical pathway.&#xD;
&#xD;
          -  Pregnant patients&#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>Douglas G Castro, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>AC Camargo Cancer Center</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>AC Camargo Cancer Center</name>
      <address>
        <city>São Paulo</city>
        <state>SP</state>
        <zip>01509-900</zip>
        <country>Brazil</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Brazil</country>
  </location_countries>
  <verification_date>July 2022</verification_date>
  <study_first_submitted>December 26, 2018</study_first_submitted>
  <study_first_submitted_qc>December 26, 2018</study_first_submitted_qc>
  <study_first_posted type="Actual">December 28, 2018</study_first_posted>
  <last_update_submitted>July 24, 2023</last_update_submitted>
  <last_update_submitted_qc>July 24, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">July 27, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Intraoperative Radiotherapy</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Neoplasm Metastasis</mesh_term>
    <mesh_term>Neoplasms, Second Primary</mesh_term>
    <mesh_term>Brain Neoplasms</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>Yes</sharing_ipd>
    <ipd_info_type>Study Protocol</ipd_info_type>
    <ipd_info_type>Clinical Study Report (CSR)</ipd_info_type>
    <ipd_time_frame>6 months after publication</ipd_time_frame>
    <ipd_access_criteria>Correlated Area Investigators with publishing background and a defined objective</ipd_access_criteria>
  </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/NCT03789149
org study id: 2315/17
nct id: NCT03789149
lead sponsor: 
collaborator: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
Brain metastases (BM) are the most prevalent tumors of the central nervous system (CNS), with
      a ratio of 10: 1 in relation to primary tumors. In prospective studies, whole-brain
      radiotherapy (WBRT) reduced the risk of local recurrence after resection of brain metastases
      from 46-59% to 10-28%. Furthermore, WBRT reduces the incidence of new metastases and death
      from disease, but no apparent improvement in overall survival (OS). Due to the potential
      neurocognitive effects associated with WBRT compared to isolated focal approach, several
      authors have suggested delaying WBRT and perform focal adjuvant RT after resection of
      isolated BM. In this context, intraoperative radiotherapy (IORT) in the cavity after
      resection of BM may be an appealing option.

      The primary objectives of this study are to evaluate local control (LC) and the control of
      brain disease (LC associated with the absence of new distant BM) after IORT for one
      completely resected supratentorial BM in the presence of up to 10 lesions suggestive of BM.
Brain metastases (BM) are the most prevalent tumors of the central nervous system (CNS), with
      a ratio of 10: 1 in relation to primary tumors. This type of metastasis occurs in 20-40% of
      cancer patients and are related to significant morbidity and mortality.

      In prospective studies, whole-brain radiotherapy (WBRT) reduced the risk of local recurrence
      after resection of brain metastases from 46-59% to 10-28%. Furthermore, WBRT reduces the
      incidence of new metastases and death from disease, but no apparent improvement in overall
      survival (OS). Due to the potential neurocognitive effects associated with WBRT compared to
      isolated focal approach, several authors have suggested delaying WBRT and perform focal
      adjuvant RT after resection of isolated BM.

      The utilization of intraoperative radiotherapy (IORT) in the cavity after resection of
      primary or BM has been described in the literature, the majority of reports describes
      performing brachytherapy with iodine seeds or interstitial radiosurgery. However, there is a
      paucity of information regarding the use of IORT with low energy X-ray for focal treatment
      after resection of brain BM.

      The objectives of this study are evaluate local control (LC), the control of brain disease in
      patients with metastatic brain disease (up to 10 lesions) submitted to focal IORT to an
      isolated surgical cavity, evaluate overall survival (OS), evaluate the frequency of radiation
      necrosis and correlate the prognostic factors related to the patient with OS and the
      parameters of the treatment (dose, volume, lesion location) with the LC and radiation
      necrosis.
allocation: N/A
intervention model: Single Group Assignment
intervention model description: Single group assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Local control (LC)
time frame: 1 year
description: Rate of local failure in the surgical cavity
measure: Control of Brain Disease (CBD)
time frame: 1 year
description: Rate of control in the brain outside
measure: Overall Survival (OS)
time frame: 1 year
description: Rate of death related to any cause
measure: Frequency of radiation necrosis
time frame: 1 year
description: Imaging evaluation
arm group label: Intraoperative Radiotherapy
arm group type: Experimental
description: Intraoperative Radiotherapy with a mobile device (Intrabeam, Carl Zeiss AG)
intervention type: Radiation
intervention name: Intraoperative Radiotherapy
description: Intraoperative Radiotherapy with a mobile device (Intrabeam, Carl Zeiss AG) consisting of a small source of low energy x-rays (30-50 kV) mounted on a mechanical arm with six degrees of freedom. The resulting dose distribution is isotropic around the tip of the X-ray source. A set of spherical applicators with diameters ranging from 1.5 to 5 cm is available to connect to the source. The treatment time may vary from 20-30 minutes with the suggested dose of 18 Gy to the resection cavity to a depth of 1 mm.
arm group label: Intraoperative Radiotherapy
other name: Intrabeam
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Douglas G Castro, MD
role: Principal Investigator
affiliation: AC Camargo Cancer Center
facility: 
country: Brazil
responsible party type: Sponsor
mesh term: Neoplasm Metastasis
mesh term: Neoplasms, Second Primary
mesh term: Brain Neoplasms
sharing ipd: Yes
ipd info type: Study Protocol
ipd info type: Clinical Study Report (CSR)
ipd time frame: 6 months after publication
ipd access criteria: Correlated Area Investigators with publishing background and a defined objective