<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/NCT01705548</url>
  </required_header>
  <id_info>
    <org_study_id>IRB00055063</org_study_id>
    <secondary_id>NCI-2012-01933</secondary_id>
    <secondary_id>RAD2156-11</secondary_id>
    <secondary_id>P30CA138292</secondary_id>
    <nct_id>NCT01705548</nct_id>
  </id_info>
  <brief_title>Hypofractionated Stereotactic Radiosurgery in Treating Patients With Large Brain Metastasis</brief_title>
  <official_title>Phase I Dose Escalation Trial of Hypofractionated Radiosurgery for Large Brain Metastasis</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Emory University</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>National Institutes of Health (NIH)</agency>
      <agency_class>NIH</agency_class>
    </collaborator>
    <collaborator>
      <agency>National Cancer Institute (NCI)</agency>
      <agency_class>NIH</agency_class>
    </collaborator>
  </sponsors>
  <source>Emory University</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      This phase I trial studies the side effects and best dose of hypofractionated radiosurgery in&#xD;
      treating patients with large brain metastasis. Stereotactic radiosurgery can send x-rays&#xD;
      directly to the tumor and cause less damage to normal tissue. Giving fractionated&#xD;
      stereotactic radiosurgery may kill more tumor cells.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      PRIMARY OBJECTIVE:&#xD;
&#xD;
      To demonstrate the safety and feasibility of treating brain metastases or resection cavities&#xD;
      greater than 3 cm with hypofractionated radiosurgery and to determine the maximum-tolerated&#xD;
      radiation dose for hypofractionated radiosurgery (HR) delivered in 5 fractions, 2-3 fractions&#xD;
      per week.&#xD;
&#xD;
      OUTLINE: This is a dose-escalation study.&#xD;
&#xD;
      Patients undergo hypofractionated stereotactic radiosurgery 2-3 times weekly (5 fractions&#xD;
      total) for 2-3 weeks.&#xD;
&#xD;
      After completion of study treatment, patients are followed up at 1 month and then every 3&#xD;
      months thereafter.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Active, not recruiting</overall_status>
  <start_date type="Actual">September 24, 2012</start_date>
  <completion_date type="Anticipated">December 31, 2024</completion_date>
  <primary_completion_date type="Anticipated">December 31, 2023</primary_completion_date>
  <phase>N/A</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>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Maximum tolerated dose (MTD) of hypofractionated radiosurgery defined as the highest dose level where a grade 3 or greater with an attribution score of ≥ 3 develops in ≤ 2 of 6 patients in a dose group</measure>
    <time_frame>4 months</time_frame>
    <description>Graded according to the Common Terminology Criteria for Adverse Events (CTCAE) version 4.03. The rate of toxicities will be calculated with 95% confidence interval (CI).</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Neurologic toxicity due to treatment, graded according to the CTCAE version 4.03</measure>
    <time_frame>Up to 2 years</time_frame>
    <description>Calculated with 95% CI.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Local control; lack of progression of disease in resection cavity as defined by Response Evaluation Criteria In Solid Tumors (RECIST) criteria</measure>
    <time_frame>4 months</time_frame>
    <description>The median time to local brain progression will be calculated by Kaplan-Meier method with 95% CI.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Distant control: lack of progression of disease in surrounding brain as defined by RECIST criteria</measure>
    <time_frame>4 months</time_frame>
    <description>The median time to distant brain progression will be calculated by Kaplan-Meier method with 95% CI.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Freedom from failure/progression free survival</measure>
    <time_frame>Up to 2 years</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Overall survival (OS): death from any cause</measure>
    <time_frame>Up to 2 years</time_frame>
    <description>The median of OS time with 95% CI will be calculated by Kaplan-Meier method.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Long-term neurocognitive outcomes: using the Hopkins Verbal Learning Test-Revised (HVLT-R), Mini Mental Status Exam (MMSE) and Cognitive Functioning Subscale of the Medical Outcomes Scale (MOS)</measure>
    <time_frame>Up to 2 years</time_frame>
    <description>Neurocognitive effect will be regressed over time using generalized estimating equation (GEE) model. The population change over time (slope) will be estimated with 95% CI.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Quality of life (QOL) outcomes: using the quality of life questionnaire for the Functional Assessment of Cancer Therapy-Brain (FACT-Br).</measure>
    <time_frame>Up to 2 years</time_frame>
    <description>QOL outcomes will be regressed over time using GEE model. The population change over time (slope) will be estimated with 95% CI.</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Anticipated">25</enrollment>
  <condition>Metastatic Malignant Neoplasm to Brain</condition>
  <condition>Unspecified Adult Solid Tumor, Protocol Specific</condition>
  <arm_group>
    <arm_group_label>Hypofractionated Radiosurgery</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>HR (Hypofractionated Radiosurgery) delivered in 5 fractions, with a minimum of 2 and a maximum of 3 fractions being delivered per week, to patients with brain metastases or resection cavity greater than 3 cm and less than 6 cm.&#xD;
Dose escalation will proceed according to the Escalation with Overdose Control (EWOC) method with a planned total enrollment of 24 patients, in 8 patient cohorts with 3 patients per cohort. A 4 month observation period will occur for each completed cohort prior to dose escalation, with a goal timeline for trial completion of 4 years from first patient enrollment.</description>
  </arm_group>
  <intervention>
    <intervention_type>Radiation</intervention_type>
    <intervention_name>Hypofractionated Radiosurgery</intervention_name>
    <description>Radiation Therapy will consist of partial brain irradiation delivered to the metastatic brain tumor or resection cavity, delivered in 5 treatments with 2-3 treatments delivered per week.</description>
    <arm_group_label>Hypofractionated Radiosurgery</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Pathologic proven diagnosis of solid tumor malignancy&#xD;
&#xD;
          -  One brain metastasis or brain metastasis resection cavity with maximal diameter ≥ 3 cm&#xD;
             (or ≥ 14 cc.) and ≤ 6 cm (or ≤ 113 cc.)&#xD;
&#xD;
          -  Recursive partitioning analysis (RPA) class I-II/ Karnofsky Performance status (KPS) ≥&#xD;
             70%&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Prior stereotactic radiosurgery (SRS) to adjacent lesion such that planning target&#xD;
             volume would have received more than 12 Gy&#xD;
&#xD;
          -  RPA class III (KPS &lt; 70%)&#xD;
&#xD;
          -  Brain metastasis or resection cavity volume &lt; 3 cm or &gt; 6 cm&#xD;
&#xD;
          -  Radiosensitive or non-solid (eg. small cell lung carcinomas, germ cell tumors,&#xD;
             leukemias, or lymphomas) or unknown tumor histologies&#xD;
&#xD;
          -  Concurrent chemotherapy (no chemotherapy starting 14 days before start of radiation)&#xD;
&#xD;
          -  Evidence of leptomeningeal disease by magnetic resonance imaging (MRI) and/or&#xD;
             cerebrospinal fluid (CSF) cytology&#xD;
&#xD;
          -  Current pregnancy&#xD;
&#xD;
          -  More than 8 weeks between resection and radiosurgical procedure&#xD;
&#xD;
          -  Metastases to brain stem, midbrain, pons, or medulla or within 5 mm of the optic&#xD;
             apparatus (optic nerves and chiasm)&#xD;
&#xD;
          -  Inability to undergo MRI evaluation for treatment planning and follow-up&#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>Bree Eaton, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Emory University</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Emory University Hospital/Winship Cancer Institute</name>
      <address>
        <city>Atlanta</city>
        <state>Georgia</state>
        <zip>30322</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Emory Saint Joseph's Hospital</name>
      <address>
        <city>Atlanta</city>
        <state>Georgia</state>
        <zip>30342</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>May 2023</verification_date>
  <study_first_submitted>October 10, 2012</study_first_submitted>
  <study_first_submitted_qc>October 10, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">October 12, 2012</study_first_posted>
  <last_update_submitted>May 8, 2023</last_update_submitted>
  <last_update_submitted_qc>May 8, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">May 10, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Emory University</investigator_affiliation>
    <investigator_full_name>Bree Eaton</investigator_full_name>
    <investigator_title>Principal Investigator</investigator_title>
  </responsible_party>
  <keyword>Brain metastasis</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>
  <provided_document_section>
    <provided_document>
      <document_type>Informed Consent Form</document_type>
      <document_has_protocol>No</document_has_protocol>
      <document_has_icf>Yes</document_has_icf>
      <document_has_sap>No</document_has_sap>
      <document_date>May 1, 2020</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/48/NCT01705548/ICF_000.pdf</document_url>
    </provided_document>
  </provided_document_section>
  <!-- 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/NCT01705548
org study id: IRB00055063
secondary id: NCI-2012-01933
secondary id: RAD2156-11
secondary id: P30CA138292
nct id: NCT01705548
lead sponsor: 
collaborator: 
collaborator: 
has dmc: Yes
This phase I trial studies the side effects and best dose of hypofractionated radiosurgery in
      treating patients with large brain metastasis. Stereotactic radiosurgery can send x-rays
      directly to the tumor and cause less damage to normal tissue. Giving fractionated
      stereotactic radiosurgery may kill more tumor cells.
PRIMARY OBJECTIVE:

      To demonstrate the safety and feasibility of treating brain metastases or resection cavities
      greater than 3 cm with hypofractionated radiosurgery and to determine the maximum-tolerated
      radiation dose for hypofractionated radiosurgery (HR) delivered in 5 fractions, 2-3 fractions
      per week.

      OUTLINE: This is a dose-escalation study.

      Patients undergo hypofractionated stereotactic radiosurgery 2-3 times weekly (5 fractions
      total) for 2-3 weeks.

      After completion of study treatment, patients are followed up at 1 month and then every 3
      months thereafter.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Maximum tolerated dose (MTD) of hypofractionated radiosurgery defined as the highest dose level where a grade 3 or greater with an attribution score of ≥ 3 develops in ≤ 2 of 6 patients in a dose group
time frame: 4 months
description: Graded according to the Common Terminology Criteria for Adverse Events (CTCAE) version 4.03. The rate of toxicities will be calculated with 95% confidence interval (CI).
measure: Neurologic toxicity due to treatment, graded according to the CTCAE version 4.03
time frame: Up to 2 years
description: Calculated with 95% CI.
measure: Local control; lack of progression of disease in resection cavity as defined by Response Evaluation Criteria In Solid Tumors (RECIST) criteria
time frame: 4 months
description: The median time to local brain progression will be calculated by Kaplan-Meier method with 95% CI.
measure: Distant control: lack of progression of disease in surrounding brain as defined by RECIST criteria
time frame: 4 months
description: The median time to distant brain progression will be calculated by Kaplan-Meier method with 95% CI.
measure: Freedom from failure/progression free survival
time frame: Up to 2 years
measure: Overall survival (OS): death from any cause
time frame: Up to 2 years
description: The median of OS time with 95% CI will be calculated by Kaplan-Meier method.
measure: Long-term neurocognitive outcomes: using the Hopkins Verbal Learning Test-Revised (HVLT-R), Mini Mental Status Exam (MMSE) and Cognitive Functioning Subscale of the Medical Outcomes Scale (MOS)
time frame: Up to 2 years
description: Neurocognitive effect will be regressed over time using generalized estimating equation (GEE) model. The population change over time (slope) will be estimated with 95% CI.
measure: Quality of life (QOL) outcomes: using the quality of life questionnaire for the Functional Assessment of Cancer Therapy-Brain (FACT-Br).
time frame: Up to 2 years
description: QOL outcomes will be regressed over time using GEE model. The population change over time (slope) will be estimated with 95% CI.
arm group label: Hypofractionated Radiosurgery
arm group type: Experimental
description: HR (Hypofractionated Radiosurgery) delivered in 5 fractions, with a minimum of 2 and a maximum of 3 fractions being delivered per week, to patients with brain metastases or resection cavity greater than 3 cm and less than 6 cm.
Dose escalation will proceed according to the Escalation with Overdose Control (EWOC) method with a planned total enrollment of 24 patients, in 8 patient cohorts with 3 patients per cohort. A 4 month observation period will occur for each completed cohort prior to dose escalation, with a goal timeline for trial completion of 4 years from first patient enrollment.
intervention type: Radiation
intervention name: Hypofractionated Radiosurgery
description: Radiation Therapy will consist of partial brain irradiation delivered to the metastatic brain tumor or resection cavity, delivered in 5 treatments with 2-3 treatments delivered per week.
arm group label: Hypofractionated Radiosurgery
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Bree Eaton, MD
role: Principal Investigator
affiliation: Emory University
facility: 
facility: 
country: United States
responsible party type: Principal Investigator
investigator affiliation: Emory University
investigator full name: Bree Eaton
investigator title: Principal Investigator
mesh term: Neoplasm Metastasis
mesh term: Brain Neoplasms
mesh term: Neoplasms
provided document: 