<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/NCT04474925</url>
  </required_header>
  <id_info>
    <org_study_id>IIT-0010</org_study_id>
    <nct_id>NCT04474925</nct_id>
  </id_info>
  <brief_title>Pre- Versus Post-operative SRS for Resectable Brain Metastases</brief_title>
  <official_title>A Randomized Controlled Trial of Pre-operative Versus Post-operative Stereotactic Radiosurgery for Patients With Surgically Resectable Brain Metastases</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>AHS Cancer Control Alberta</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>AHS Cancer Control Alberta</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 purpose of this study is to determine if performing radiotherapy (SRS) prior to surgery&#xD;
      results in better treatment outcomes than performing surgery before radiotherapy for patients&#xD;
      with brain metastases.&#xD;
&#xD;
      Brain metastases occur when cancer cells from a primary cancer (e.g. lung, breast, colon)&#xD;
      travel through the bloodstream and spread (metastasize) to the brain. As these new tumors&#xD;
      grow they apply pressure and change how healthy brain tissue works. This can lead to a loss&#xD;
      of brain function and worsening quality of life. Treatments for patients whose cancer has&#xD;
      spread to the brain is often surgery, radiation therapy (radiotherapy) or a combination of&#xD;
      both.&#xD;
&#xD;
      Surgery is one the main treatments for brain tumors. To remove the tumor, a neurosurgeon&#xD;
      makes an opening in the skull and attempts to the remove the entire tumor. If the tumor is&#xD;
      too close to important brain tissue, the surgeon may attempt to remove part of the tumor.&#xD;
      Removal of the tumor from the brain tissue is called resection. The complete or partial&#xD;
      removal of tumor helps to relieve symptoms by reducing pressure on healthy tissues and&#xD;
      reduces the amount of tumor that needs to be treated by radiotherapy.&#xD;
&#xD;
      One type of radiotherapy used to treat brain metastases is stereotactic radiosurgery (SRS).&#xD;
      SRS uses many focused radiation beams to treat tumors within the brain. Unlike surgery, there&#xD;
      is no incision or cut being made. Instead, SRS uses an accurate map of your brain to deliver&#xD;
      a precise beam of radiation to the tumors. The radiation damages the tumor cells forcing them&#xD;
      to shrink and die off. The focused radiation beams also limit damage to healthy brain tissue&#xD;
      minimizing side effects.&#xD;
&#xD;
      Surgery followed by radiotherapy is a standard treatment for brain metastases. However, there&#xD;
      are still risks associated with the combination of treatments. This study plans to&#xD;
      investigate whether performing surgery prior to SRS results in improved quality of life and&#xD;
      decreased side effects.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">September 27, 2021</start_date>
  <completion_date type="Anticipated">August 1, 2026</completion_date>
  <primary_completion_date type="Anticipated">September 1, 2025</primary_completion_date>
  <phase>Phase 3</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 Control</measure>
    <time_frame>This will be assessed at 12 months</time_frame>
    <description>To compare local control (in months) of pre-operative versus post-operative SRS</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Local Control</measure>
    <time_frame>This will be assessed at 6 and 24 months.</time_frame>
    <description>To compare local control (in months) of pre-operative versus post-operative SRS</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Distant Brain Recurrence Rate</measure>
    <time_frame>This will be assessed at 6,12 and 24 months.</time_frame>
    <description>To compare Distant Brain Recurrence Rate (%) of pre-operative versus post-operative SRS</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Leptomeningeal Recurrence Rate</measure>
    <time_frame>This will be assessed at 6,12 and 24 months.</time_frame>
    <description>To compare the Leptomeningeal Recurrence Rate (%) of pre-operative versus post-operative SRS</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Overall Survival</measure>
    <time_frame>This will be assessed at 6,12 and 24 months.</time_frame>
    <description>Overall survival will be compared between both treatment arms</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Hopkins Verbal Learning Test</measure>
    <time_frame>This will be assessed at 3,6,9,12,16 and 24 months.</time_frame>
    <description>Participants are scored using a points based system on Total Recall, Delayed Recall, Retention (% retained), and a Recognition Discrimination Index.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Controlled Oral Word Association</measure>
    <time_frame>This will be assessed at 3,6,9,12,16 and 24 months.</time_frame>
    <description>Participants are scored on their ability to generate words starting with a specific letter in a one minute timeframe.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Trial Making Tests</measure>
    <time_frame>This will be assessed at 3,6,9,12,16 and 24 months.</time_frame>
    <description>Participants are scored on their ability to complete the test within a certain timeframe.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">88</enrollment>
  <condition>Brain Metastases</condition>
  <arm_group>
    <arm_group_label>Surgical Resection followed by SRS (Non-Experimental)</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Surgical Resection followed by SRS within 3 weeks of surgery date.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>SRS followed by Surgical Resection (Experimental)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>SRS followed by surgery within 1 week of radiotherapy end date.</description>
  </arm_group>
  <intervention>
    <intervention_type>Procedure</intervention_type>
    <intervention_name>Brain Surgery</intervention_name>
    <description>Surgery to remove brain metastases</description>
    <arm_group_label>SRS followed by Surgical Resection (Experimental)</arm_group_label>
    <arm_group_label>Surgical Resection followed by SRS (Non-Experimental)</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Radiation</intervention_type>
    <intervention_name>Stereotactic Radiosurgery</intervention_name>
    <description>SRS uses many focused radiation beams to treat tumors within the brain</description>
    <arm_group_label>SRS followed by Surgical Resection (Experimental)</arm_group_label>
    <arm_group_label>Surgical Resection followed by SRS (Non-Experimental)</arm_group_label>
    <other_name>SRS</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Age ≥ 18 years&#xD;
&#xD;
          -  Pathologically-proven primary malignancy&#xD;
&#xD;
          -  ECOG 0-2&#xD;
&#xD;
          -  Ability to complete neurocognitive testing without assistance from family or friends.&#xD;
&#xD;
          -  Previous SRS to lesions other than the one being resected is allowed&#xD;
&#xD;
          -  Patients of childbearing / reproductive potential must have a negative urine or serum&#xD;
             pregnancy test ≤7 days before enrollment&#xD;
&#xD;
          -  Participants capable of giving informed consent, or if appropriate participants having&#xD;
             an acceptable individual capable of giving consent&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Patients who have received prior WBRT, or SRS to the lesion being resected at time of&#xD;
             study accrual&#xD;
&#xD;
          -  Patients unable to undergo MRI scan (e.g. pacemaker)&#xD;
&#xD;
          -  Leptomeningeal disease&#xD;
&#xD;
          -  Germ cell tumor, small cell lung cancer or hematological primary malignancy&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>100 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <location>
    <facility>
      <name>Tom Baker Cancer Centre</name>
      <address>
        <city>Calgary</city>
        <state>Alberta</state>
        <country>Canada</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Muhammad Faruqi, MD</last_name>
      <phone>403-521-3620</phone>
      <email>Muhammad.Faruqi@albertahealthservices.ca</email>
    </contact>
    <investigator>
      <last_name>Huhammad Faruqi, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Cross Cancer Institute</name>
      <address>
        <city>Edmonton</city>
        <state>Alberta</state>
        <zip>T6G 1Z2</zip>
        <country>Canada</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Samir Patel, MD</last_name>
      <phone>780-432-8518</phone>
      <email>samir.patel2@albertahealthservices.ca</email>
    </contact>
    <investigator>
      <last_name>Samir Patel, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location_countries>
    <country>Canada</country>
  </location_countries>
  <verification_date>January 2023</verification_date>
  <study_first_submitted>July 14, 2020</study_first_submitted>
  <study_first_submitted_qc>July 14, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">July 17, 2020</study_first_posted>
  <last_update_submitted>January 17, 2023</last_update_submitted>
  <last_update_submitted_qc>January 17, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">January 18, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Neurosurgery</keyword>
  <keyword>Stereotactic Radiosurgery</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>
  </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/NCT04474925
org study id: IIT-0010
nct id: NCT04474925
lead sponsor: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
The purpose of this study is to determine if performing radiotherapy (SRS) prior to surgery
      results in better treatment outcomes than performing surgery before radiotherapy for patients
      with brain metastases.

      Brain metastases occur when cancer cells from a primary cancer (e.g. lung, breast, colon)
      travel through the bloodstream and spread (metastasize) to the brain. As these new tumors
      grow they apply pressure and change how healthy brain tissue works. This can lead to a loss
      of brain function and worsening quality of life. Treatments for patients whose cancer has
      spread to the brain is often surgery, radiation therapy (radiotherapy) or a combination of
      both.

      Surgery is one the main treatments for brain tumors. To remove the tumor, a neurosurgeon
      makes an opening in the skull and attempts to the remove the entire tumor. If the tumor is
      too close to important brain tissue, the surgeon may attempt to remove part of the tumor.
      Removal of the tumor from the brain tissue is called resection. The complete or partial
      removal of tumor helps to relieve symptoms by reducing pressure on healthy tissues and
      reduces the amount of tumor that needs to be treated by radiotherapy.

      One type of radiotherapy used to treat brain metastases is stereotactic radiosurgery (SRS).
      SRS uses many focused radiation beams to treat tumors within the brain. Unlike surgery, there
      is no incision or cut being made. Instead, SRS uses an accurate map of your brain to deliver
      a precise beam of radiation to the tumors. The radiation damages the tumor cells forcing them
      to shrink and die off. The focused radiation beams also limit damage to healthy brain tissue
      minimizing side effects.

      Surgery followed by radiotherapy is a standard treatment for brain metastases. However, there
      are still risks associated with the combination of treatments. This study plans to
      investigate whether performing surgery prior to SRS results in improved quality of life and
      decreased side effects.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Local Control
time frame: This will be assessed at 12 months
description: To compare local control (in months) of pre-operative versus post-operative SRS
measure: Local Control
time frame: This will be assessed at 6 and 24 months.
description: To compare local control (in months) of pre-operative versus post-operative SRS
measure: Distant Brain Recurrence Rate
time frame: This will be assessed at 6,12 and 24 months.
description: To compare Distant Brain Recurrence Rate (%) of pre-operative versus post-operative SRS
measure: Leptomeningeal Recurrence Rate
time frame: This will be assessed at 6,12 and 24 months.
description: To compare the Leptomeningeal Recurrence Rate (%) of pre-operative versus post-operative SRS
measure: Overall Survival
time frame: This will be assessed at 6,12 and 24 months.
description: Overall survival will be compared between both treatment arms
measure: Hopkins Verbal Learning Test
time frame: This will be assessed at 3,6,9,12,16 and 24 months.
description: Participants are scored using a points based system on Total Recall, Delayed Recall, Retention (% retained), and a Recognition Discrimination Index.
measure: Controlled Oral Word Association
time frame: This will be assessed at 3,6,9,12,16 and 24 months.
description: Participants are scored on their ability to generate words starting with a specific letter in a one minute timeframe.
measure: Trial Making Tests
time frame: This will be assessed at 3,6,9,12,16 and 24 months.
description: Participants are scored on their ability to complete the test within a certain timeframe.
arm group label: Surgical Resection followed by SRS (Non-Experimental)
arm group type: Active Comparator
description: Surgical Resection followed by SRS within 3 weeks of surgery date.
arm group label: SRS followed by Surgical Resection (Experimental)
arm group type: Experimental
description: SRS followed by surgery within 1 week of radiotherapy end date.
intervention type: Procedure
intervention name: Brain Surgery
description: Surgery to remove brain metastases
arm group label: SRS followed by Surgical Resection (Experimental)
arm group label: Surgical Resection followed by SRS (Non-Experimental)
intervention type: Radiation
intervention name: Stereotactic Radiosurgery
description: SRS uses many focused radiation beams to treat tumors within the brain
arm group label: SRS followed by Surgical Resection (Experimental)
arm group label: Surgical Resection followed by SRS (Non-Experimental)
other name: SRS
criteria: 
gender: All
minimum age: 18 Years
maximum age: 100 Years
healthy volunteers: No
facility: 
status: Recruiting
contact: 
investigator: 
facility: 
status: Recruiting
contact: 
investigator: 
country: Canada
responsible party type: Sponsor
mesh term: Neoplasm Metastasis
mesh term: Brain Neoplasms
sharing ipd: No