<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/NCT04427228</url>
  </required_header>
  <id_info>
    <org_study_id>IRB19-2022</org_study_id>
    <nct_id>NCT04427228</nct_id>
  </id_info>
  <brief_title>Single vs Multi-fraction SRS Patients on Immunotherapy</brief_title>
  <acronym>MIGRAINE</acronym>
  <official_title>MIGRAINE: Randomized trIal of Single Versus Multifraction Radiosurgery on Immunotherapy</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of Chicago</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>University of Chicago</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>Yes</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      This study is meant to compare different surgical approaches to brain cancer.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Withdrawn</overall_status>
  <why_stopped>
    unable to enroll&#xD;
  </why_stopped>
  <start_date type="Actual">June 29, 2020</start_date>
  <completion_date type="Actual">December 12, 2022</completion_date>
  <primary_completion_date type="Actual">December 12, 2022</primary_completion_date>
  <phase>Phase 2</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 (Care Provider)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Multi-Fraction SRS superiority compared to single fraction SRS</measure>
    <time_frame>4 years</time_frame>
    <description>To determine if Multi-Fraction SRS will decrease the rate of radionecrosis when compared to single-fraction SRS for patients with small metastases and are on immunotherapy.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Target metastasis progression</measure>
    <time_frame>4 years</time_frame>
    <description>Target metastasis progression will be assessed using adapted Response Assessment in Neuro-Oncology Brain Metastases (RANO-BM) consensus imaging criteria. In brief, progressive disease is defined as a ≥20% relative increase in the longest diameter (LD) of the target metastasis compared to its smallest LD recorded on study, with a minimum absolute increase of 5 mm</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Overall Survival Rate</measure>
    <time_frame>4 years</time_frame>
    <description>Time from randomization to death</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Acute CTCAE v5.0 CNS Grade 2+ and Grade 3+ toxicities</measure>
    <time_frame>4 years</time_frame>
    <description>Any acute CTCAE v5.0 CNS Grade 2+ and Grade 3+ toxicities, within 90 days of SRS completion (toxicity must be specified).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Late CTCAE v5.0 CNS Grade 2+ and Grade 3+ toxicities</measure>
    <time_frame>4 years</time_frame>
    <description>Any late CTCAE v5.0 CNS Grade 2+ and Grade 3+ toxicities, greater than 90 days from SRS completion (toxicity must be specified).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>rate of individual metastases radionecrosis</measure>
    <time_frame>4 years</time_frame>
    <description>To compare the rates over time of individual metastases radionecrosis using a parametric survival analysis</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>rate of individual metastases rates of edema</measure>
    <time_frame>4 years</time_frame>
    <description>To compare rates over time of individual metastases rates of edema using a parametric survival analysis.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Rates of Symptomatic Edema</measure>
    <time_frame>1 year</time_frame>
    <description>To compare rates of symptomatic edema at 3 months, 6 months, and 1 year.1</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time to any distant intracranial failure</measure>
    <time_frame>4 years</time_frame>
    <description>Time to any distant intracranial failure (ie, appearance of brain metastasis at untreated site).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time to initiation of any combination</measure>
    <time_frame>4 years</time_frame>
    <description>Time to initiation of any combination of death, salvage SRS, WBRT, or neurosurgical resection for intracranial failure.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">0</enrollment>
  <condition>Brain Cancer</condition>
  <condition>Brain Metastases</condition>
  <arm_group>
    <arm_group_label>Arm A</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
  </arm_group>
  <arm_group>
    <arm_group_label>ARM B</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
  </arm_group>
  <intervention>
    <intervention_type>Radiation</intervention_type>
    <intervention_name>Radiosurgery Single Treatment</intervention_name>
    <description>Frameless single-fraction SRS. One large treatment done on each brain tumor. 20 Gy for GTVs (or resection cavity CTVs) &lt; 2 cm, and 18 Gy for GTVs (or resection cavity CTVs) between 2-3 cm in the single-fraction.</description>
    <arm_group_label>ARM B</arm_group_label>
    <other_name>SRS</other_name>
  </intervention>
  <intervention>
    <intervention_type>Radiation</intervention_type>
    <intervention_name>Radiosurgery Three Treatments</intervention_name>
    <description>Multi-fraction SRS. Three small doses done on each brain tumor. 27 Gy in 3 fractions in the multi-fraction group</description>
    <arm_group_label>Arm A</arm_group_label>
    <other_name>SRS</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
        i. Adult patients (≥ 18 years old) with an ECOG Performance Status 0-2 and a life&#xD;
        expectancy of 3 months or more.&#xD;
&#xD;
        ii. Histologically confirmed systemic malignancy with gadolinium contrast-enhanced MRI scan&#xD;
        demonstrating 1-10 newly diagnosed intraparenchymal brain metastases.&#xD;
&#xD;
        iii. Well-circumscribed, measureable intraparenchymal brain metastasis(s) with maximum&#xD;
        tumor diameter ≤3.0 cm. If multiple metastases are present, the other(s) must not exceed&#xD;
        3.0 cm in maximum diameter. At least one metastasis must be ≥ 0.5 cm in maximum diameter to&#xD;
        be considered measurable disease.&#xD;
&#xD;
        iv. Negative urine or serum pregnancy test done ≤ 21 days prior to CT simulation, for women&#xD;
        of child bearing potential only.&#xD;
&#xD;
        v. Ability to understand and willingness to sign a written informed consent document.&#xD;
&#xD;
        vi. Must have received immunotherapy (PD-1/PD-L1 and/or CTLA-4 inhibitor(s)) within the&#xD;
        past 6 months or plan on receiving immunotherapy within the next 1 month.&#xD;
&#xD;
        vii. Must have a Gustave Roussy Immune Score (GRIm-Score) of 0 or 1&#xD;
        (neutrophil-to-lymphocyte ratio &gt; 6 = 1 point, LDH &gt; Upper Limit of Normal = 1 point, and&#xD;
        Albumin &lt; 3.5 g/dL = 1 point).&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
        i. Diagnosis of germ cell tumor or hematologic malignancy. ii. Metastases in the brain&#xD;
        stem, midbrain, pons, medulla, or within 7 mm of the optic apparatus (optic nerves, chiasm&#xD;
        and optic tracts).&#xD;
&#xD;
        iii. Diagnosis of leptomeningeal disease. iv. Prior SRS to an immediately adjacent&#xD;
        lesion(s) of interest or to the current lesion(s) of interest.&#xD;
&#xD;
        v. Prior history of pseudoprogression or radionecrosis from cranial radiotherapy.&#xD;
&#xD;
        vi. A neurosurgical resection cavity deemed too large by the radiation oncologist to be&#xD;
        treated with a single fraction of stereotactic radiosurgery.&#xD;
&#xD;
        vii. Contraindications to gadolinium contrast-enhanced MRI (eg, non-compatible pacemaker,&#xD;
        eGFR &lt;30, gadolinium allergy).&#xD;
&#xD;
        viii. A Gustave Roussy Immune Score (GRIm-Score) &gt; 1 (neutrophil-to-lymphocyte ratio &gt; 6 =&#xD;
        1 point, LDH &gt; Upper Limit of Normal = 1 point, and Albumin &lt; 3.5 g/dL = 1 point).&#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>Steven Chmura, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>University of Chicago</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>University Of Chicago</name>
      <address>
        <city>Chicago</city>
        <state>Illinois</state>
        <zip>60637</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>August 2023</verification_date>
  <study_first_submitted>June 8, 2020</study_first_submitted>
  <study_first_submitted_qc>June 8, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">June 11, 2020</study_first_posted>
  <last_update_submitted>August 24, 2023</last_update_submitted>
  <last_update_submitted_qc>August 24, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">August 28, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Brain 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/NCT04427228
org study id: IRB19-2022
nct id: NCT04427228
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: Yes
This study is meant to compare different surgical approaches to brain cancer.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Single (Care Provider)
measure: Multi-Fraction SRS superiority compared to single fraction SRS
time frame: 4 years
description: To determine if Multi-Fraction SRS will decrease the rate of radionecrosis when compared to single-fraction SRS for patients with small metastases and are on immunotherapy.
measure: Target metastasis progression
time frame: 4 years
description: Target metastasis progression will be assessed using adapted Response Assessment in Neuro-Oncology Brain Metastases (RANO-BM) consensus imaging criteria. In brief, progressive disease is defined as a ≥20% relative increase in the longest diameter (LD) of the target metastasis compared to its smallest LD recorded on study, with a minimum absolute increase of 5 mm
measure: Overall Survival Rate
time frame: 4 years
description: Time from randomization to death
measure: Acute CTCAE v5.0 CNS Grade 2+ and Grade 3+ toxicities
time frame: 4 years
description: Any acute CTCAE v5.0 CNS Grade 2+ and Grade 3+ toxicities, within 90 days of SRS completion (toxicity must be specified).
measure: Late CTCAE v5.0 CNS Grade 2+ and Grade 3+ toxicities
time frame: 4 years
description: Any late CTCAE v5.0 CNS Grade 2+ and Grade 3+ toxicities, greater than 90 days from SRS completion (toxicity must be specified).
measure: rate of individual metastases radionecrosis
time frame: 4 years
description: To compare the rates over time of individual metastases radionecrosis using a parametric survival analysis
measure: rate of individual metastases rates of edema
time frame: 4 years
description: To compare rates over time of individual metastases rates of edema using a parametric survival analysis.
measure: Rates of Symptomatic Edema
time frame: 1 year
description: To compare rates of symptomatic edema at 3 months, 6 months, and 1 year.1
measure: Time to any distant intracranial failure
time frame: 4 years
description: Time to any distant intracranial failure (ie, appearance of brain metastasis at untreated site).
measure: Time to initiation of any combination
time frame: 4 years
description: Time to initiation of any combination of death, salvage SRS, WBRT, or neurosurgical resection for intracranial failure.
arm group label: Arm A
arm group type: Experimental
arm group label: ARM B
arm group type: Active Comparator
intervention type: Radiation
intervention name: Radiosurgery Single Treatment
description: Frameless single-fraction SRS. One large treatment done on each brain tumor. 20 Gy for GTVs (or resection cavity CTVs) < 2 cm, and 18 Gy for GTVs (or resection cavity CTVs) between 2-3 cm in the single-fraction.
arm group label: ARM B
other name: SRS
intervention type: Radiation
intervention name: Radiosurgery Three Treatments
description: Multi-fraction SRS. Three small doses done on each brain tumor. 27 Gy in 3 fractions in the multi-fraction group
arm group label: Arm A
other name: SRS
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Steven Chmura, MD
role: Principal Investigator
affiliation: University of Chicago
facility: 
country: United States
responsible party type: Sponsor
mesh term: Brain Neoplasms