<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/NCT03281889</url>
  </required_header>
  <id_info>
    <org_study_id>17-283</org_study_id>
    <secondary_id>U19CA021239-37</secondary_id>
    <nct_id>NCT03281889</nct_id>
  </id_info>
  <brief_title>Proton Craniospinal Irradiation With Bone Sparing to Decrease Growth Decrement From Radiation</brief_title>
  <official_title>Craniospinal Irradiation Using Proton Beam Scanning With Selective Vertebral Body/Bone Sparing to Improve Marrow Reserve and Decrease Growth Decrement for Children</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Massachusetts General Hospital</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>National Cancer Institute (NCI)</agency>
      <agency_class>NIH</agency_class>
    </collaborator>
  </sponsors>
  <source>Massachusetts General Hospital</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>Yes</is_fda_regulated_device>
    <is_us_export>No</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      This research study is studying proton radiation as a possible treatment for brain tumor that&#xD;
      requires radiation.&#xD;
&#xD;
      The radiation involved in this study is:&#xD;
&#xD;
      -Proton Radiation&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This research study is a Pilot Study to determine whether using proton therapy in&#xD;
      participants that require craniospinal radiation (whole brain and spinal cord radiation&#xD;
      therapy) with sparing of the bony spine will work. This is the first time investigators are&#xD;
      examining bone sparing proton therapy in pediatric craniospinal radiation.&#xD;
&#xD;
      The FDA (the U.S. Food and Drug Administration) has not approved proton radiation for this&#xD;
      specific disease but it has been approved for other uses.&#xD;
&#xD;
      In this research study, the investigators are studying proton radiation in participants that&#xD;
      require craniospinal radiation. The standard of care for this procedure is photon radiation,&#xD;
      which is very similar to proton radiation. The investigators believe that the precision of&#xD;
      proton radiation may help to reduce the negative effects radiation has on the surrounding&#xD;
      non-cancerous growing and developing tissue&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">January 4, 2018</start_date>
  <completion_date type="Anticipated">March 31, 2025</completion_date>
  <primary_completion_date type="Anticipated">March 31, 2022</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>Feasibility of cranio-spinal irradiation (CSI) utilizing intensity-modulated proton therapy (IMPT) with pencil beam scanning (PBS) for vertebral body sparing (VBS) in pediatric patients.</measure>
    <time_frame>3 months</time_frame>
    <description>IMPT using PBS delivery will be considered to be feasible as a VBS technique for CSI in pediatric patients if the rate of grade 3/4 hematologic toxicity were no more than 5% within 3 months after the completion of radiation treatment, within the range associated with conventional techniques of CSI. Toxicity will be assess using Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Early marrow changes in the vertebral bodies</measure>
    <time_frame>2 years</time_frame>
    <description>Summary of early marrow changes in the vertebral bodies by Magnetic resonance imaging (MRI) of the spine during radiation therapy (RT) by comparing one study MRI to the baseline pre-RT MRI.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Vertebral column growth (measured by MRI) over 5 years</measure>
    <time_frame>Annually for 5 years</time_frame>
    <description>Summary of vertebral column growth (measured by MRI) over 5 years following vertebral body sparing cranio-spinal irradiation in pediatric patients.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in sitting height and standing height</measure>
    <time_frame>Annually for 5 years</time_frame>
    <description>Summary of the changes in the participants sitting and standing heights.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time to abnormality in spinal curvature</measure>
    <time_frame>5 years</time_frame>
    <description>Participants are monitored both clinically and by MRI for any abnormality in spinal curvature. The time to abnormality in spine curvature will be measured from the start of radiation to the date of documented abnormality or censored at the date of last follow-up for patients still alive with normal spine.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Disease Free Survival</measure>
    <time_frame>5 years</time_frame>
    <description>Disease-free survival is measured from the start of radiation to the date of progressive disease based on imaging studies obtained as standard care or to the date of death due to any cause, whichever is earlier. Disease-free survival will be estimated using the Kaplan-Meier method. Patients without progressive disease and still alive will be censored at their date of last contact.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Pattern of Disease Relapse</measure>
    <time_frame>2 years</time_frame>
    <description>Summary of the sites where the cancer relapses. Relapse is the regrowth of cancer cells.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Complete blood counts (CBC) over time</measure>
    <time_frame>Annually for 5 years</time_frame>
    <description>Summary of the change in complete blood counts (CBC) over time as determined by yearly blood samples.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in levels of vitamin D, calcium, and growth hormones over time</measure>
    <time_frame>Annually for 5 years</time_frame>
    <description>Summary of the changes in blood levels of vitamin D, calcium, and growth hormones.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Weight</measure>
    <time_frame>Annually for 5 years</time_frame>
    <description>Summary of the changes in weight of the participants as assessed by yearly evaluations.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>BMI</measure>
    <time_frame>Annually for 5 years</time_frame>
    <description>Summary of the body mass index (BMI) of the participants as assessed by yearly physical evaluations.</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Anticipated">20</enrollment>
  <condition>Brain Tumor</condition>
  <arm_group>
    <arm_group_label>Proton Radiotherapy</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Patients will be treated with Proton Beam once daily 5 days per week.&#xD;
Doses will be prescribed such that maximum possible coverage is achieved</description>
  </arm_group>
  <intervention>
    <intervention_type>Radiation</intervention_type>
    <intervention_name>Proton Beam</intervention_name>
    <description>precision radiation that reduce the negative effects radiation has on the surrounding non-cancerous growing and developing tissue</description>
    <arm_group_label>Proton Radiotherapy</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Age ≥ 3 years and ≤ 18 years at the time of registration&#xD;
&#xD;
          -  Histologically proven malignancy necessitating cranio-spinal irradiation. This will&#xD;
             include patients with a diagnosis of medulloblastoma, Supratentorial primitive&#xD;
             neuroectodermal tumor (SPNET), germ cell tumor (GCT), disseminated ependymoma,&#xD;
             embryonal tumor with abundant neuropil and true rosettes (ETANTR), Atypical&#xD;
             Teratoid/Rhabdoid Tumor (ATRT), and disseminated low-grade glioma (LGG).&#xD;
&#xD;
          -  Life expectancy ≥ 12 months.&#xD;
&#xD;
          -  Signed informed consent document and assent when appropriate.&#xD;
&#xD;
          -  HGB of &gt; 10 g/L and PLT count &gt; 80 K/uL&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Any prior therapeutic radiation therapy &gt; 500 cGy has been delivered.&#xD;
&#xD;
          -  Individuals with a history of a different malignancy are ineligible except for the&#xD;
             following circumstances: if they have been disease-free for at least 5 years and are&#xD;
             deemed by the investigator to be a low-risk for recurrence of that malignancy; or,&#xD;
             have had only cervical cancer in situ, or basal cell or squamous cell carcinoma of the&#xD;
             skin.&#xD;
&#xD;
          -  Any major uncontrolled or poorly controlled intercurrent illness that would limit&#xD;
             compliance with study requirements.&#xD;
&#xD;
          -  Pregnant females are excluded. Females of childbearing age/menstruating must confirm&#xD;
             that either they are not sexually active or have a negative pregnancy test prior to&#xD;
             initiation of radiation therapy.&#xD;
&#xD;
          -  Patients that receive concurrent chemotherapy with the exception of concurrent&#xD;
             Vincristine.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>3 Years</minimum_age>
    <maximum_age>18 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Shannon MacDonald, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Massachusetts General Hospital</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Shannon MacDonald, MD</last_name>
    <phone>617-643-7250</phone>
    <email>smacdonald@mgh.harvard.edu</email>
  </overall_contact>
  <location>
    <facility>
      <name>Massachusetts General Hospital</name>
      <address>
        <city>Boston</city>
        <state>Massachusetts</state>
        <zip>02214</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Shannon MacDonald, MD</last_name>
      <phone>617-643-7250</phone>
      <email>smacdonald@mgh.harvard.edu</email>
    </contact>
    <investigator>
      <last_name>Shannon MacDonald, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>MD Anderson Cancer Center</name>
      <address>
        <city>Houston</city>
        <state>Texas</state>
        <zip>77030</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Susan McGovern, MD</last_name>
      <email>slmcgove@mdanderson.org</email>
    </contact>
    <investigator>
      <last_name>Susan McGovern, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>January 2021</verification_date>
  <study_first_submitted>September 8, 2017</study_first_submitted>
  <study_first_submitted_qc>September 11, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">September 13, 2017</study_first_posted>
  <last_update_submitted>January 3, 2021</last_update_submitted>
  <last_update_submitted_qc>January 3, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">January 5, 2021</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Massachusetts General Hospital</investigator_affiliation>
    <investigator_full_name>Shannon MacDonald, MD</investigator_full_name>
    <investigator_title>Principal Investigator</investigator_title>
  </responsible_party>
  <keyword>Brain Tumor</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <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/NCT03281889
org study id: 17-283
secondary id: U19CA021239-37
nct id: NCT03281889
lead sponsor: 
collaborator: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: Yes
is us export: No
This research study is studying proton radiation as a possible treatment for brain tumor that
      requires radiation.

      The radiation involved in this study is:

      -Proton Radiation
This research study is a Pilot Study to determine whether using proton therapy in
      participants that require craniospinal radiation (whole brain and spinal cord radiation
      therapy) with sparing of the bony spine will work. This is the first time investigators are
      examining bone sparing proton therapy in pediatric craniospinal radiation.

      The FDA (the U.S. Food and Drug Administration) has not approved proton radiation for this
      specific disease but it has been approved for other uses.

      In this research study, the investigators are studying proton radiation in participants that
      require craniospinal radiation. The standard of care for this procedure is photon radiation,
      which is very similar to proton radiation. The investigators believe that the precision of
      proton radiation may help to reduce the negative effects radiation has on the surrounding
      non-cancerous growing and developing tissue
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Feasibility of cranio-spinal irradiation (CSI) utilizing intensity-modulated proton therapy (IMPT) with pencil beam scanning (PBS) for vertebral body sparing (VBS) in pediatric patients.
time frame: 3 months
description: IMPT using PBS delivery will be considered to be feasible as a VBS technique for CSI in pediatric patients if the rate of grade 3/4 hematologic toxicity were no more than 5% within 3 months after the completion of radiation treatment, within the range associated with conventional techniques of CSI. Toxicity will be assess using Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0.
measure: Early marrow changes in the vertebral bodies
time frame: 2 years
description: Summary of early marrow changes in the vertebral bodies by Magnetic resonance imaging (MRI) of the spine during radiation therapy (RT) by comparing one study MRI to the baseline pre-RT MRI.
measure: Vertebral column growth (measured by MRI) over 5 years
time frame: Annually for 5 years
description: Summary of vertebral column growth (measured by MRI) over 5 years following vertebral body sparing cranio-spinal irradiation in pediatric patients.
measure: Change in sitting height and standing height
time frame: Annually for 5 years
description: Summary of the changes in the participants sitting and standing heights.
measure: Time to abnormality in spinal curvature
time frame: 5 years
description: Participants are monitored both clinically and by MRI for any abnormality in spinal curvature. The time to abnormality in spine curvature will be measured from the start of radiation to the date of documented abnormality or censored at the date of last follow-up for patients still alive with normal spine.
measure: Disease Free Survival
time frame: 5 years
description: Disease-free survival is measured from the start of radiation to the date of progressive disease based on imaging studies obtained as standard care or to the date of death due to any cause, whichever is earlier. Disease-free survival will be estimated using the Kaplan-Meier method. Patients without progressive disease and still alive will be censored at their date of last contact.
measure: Pattern of Disease Relapse
time frame: 2 years
description: Summary of the sites where the cancer relapses. Relapse is the regrowth of cancer cells.
measure: Complete blood counts (CBC) over time
time frame: Annually for 5 years
description: Summary of the change in complete blood counts (CBC) over time as determined by yearly blood samples.
measure: Change in levels of vitamin D, calcium, and growth hormones over time
time frame: Annually for 5 years
description: Summary of the changes in blood levels of vitamin D, calcium, and growth hormones.
measure: Weight
time frame: Annually for 5 years
description: Summary of the changes in weight of the participants as assessed by yearly evaluations.
measure: BMI
time frame: Annually for 5 years
description: Summary of the body mass index (BMI) of the participants as assessed by yearly physical evaluations.
arm group label: Proton Radiotherapy
arm group type: Experimental
description: Patients will be treated with Proton Beam once daily 5 days per week.
Doses will be prescribed such that maximum possible coverage is achieved
intervention type: Radiation
intervention name: Proton Beam
description: precision radiation that reduce the negative effects radiation has on the surrounding non-cancerous growing and developing tissue
arm group label: Proton Radiotherapy
criteria: 
gender: All
minimum age: 3 Years
maximum age: 18 Years
healthy volunteers: No
last name: Shannon MacDonald, MD
role: Principal Investigator
affiliation: Massachusetts General Hospital
last name: Shannon MacDonald, MD
phone: 617-643-7250
email: smacdonald@mgh.harvard.edu
facility: 
status: Recruiting
contact: 
investigator: 
facility: 
status: Recruiting
contact: 
investigator: 
country: United States
responsible party type: Principal Investigator
investigator affiliation: Massachusetts General Hospital
investigator full name: Shannon MacDonald, MD
investigator title: Principal Investigator
mesh term: Brain Neoplasms
sharing ipd: No