<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/NCT03750513</url>
  </required_header>
  <id_info>
    <org_study_id>2018-0344</org_study_id>
    <secondary_id>NCI-2018-02519</secondary_id>
    <secondary_id>2018-0344</secondary_id>
    <secondary_id>P30CA016672</secondary_id>
    <secondary_id>U19CA021239</secondary_id>
    <nct_id>NCT03750513</nct_id>
  </id_info>
  <brief_title>LET Optimized IMPT in Treating Pediatric Patients With Ependymoma</brief_title>
  <official_title>Pilot Trial of LET Optimized IMPT for Pediatric Patients With Ependymoma</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>M.D. Anderson Cancer Center</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>National Cancer Institute (NCI)</agency>
      <agency_class>NIH</agency_class>
    </collaborator>
  </sponsors>
  <source>M.D. Anderson Cancer Center</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      This phase I trial studies the side effects of linear energy transfer (LET) optimized image&#xD;
      modulated proton therapy (IMPT) in treating pediatric patients with ependymoma. Radiation&#xD;
      therapy such as LET optimized IMPT, uses proton beams to kill tumor cells and shrink tumors&#xD;
      without damaging surrounding normal tissues.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      PRIMARY OBJECTIVES:&#xD;
&#xD;
      I. To evaluate the safety of linear energy transfer (LET) optimized image modulated proton&#xD;
      therapy (IMPT) (bio-IMPT) for pediatric patients with ependymoma.&#xD;
&#xD;
      SECONDARY OBJECTIVES:&#xD;
&#xD;
      I. To utilize advanced multiparametric magnetic resonance (MR) imaging to identify imaging&#xD;
      biomarkers of structural and biological changes after proton therapy in pediatric ependymoma&#xD;
      patients.&#xD;
&#xD;
      II. To compare quantitative image biomarkers in patients treated with bio-IMPT and standard&#xD;
      proton therapy using a voxel level analysis.&#xD;
&#xD;
      III. To test and evaluate the validity of relative biological effectiveness (RBE) models and&#xD;
      enhance their precision based on prospectively collected clinical image biomarkers.&#xD;
&#xD;
      IV. To evaluate acute and late toxicities, including pseudoprogression and symptom burden, in&#xD;
      patients treated with bio-IMPT.&#xD;
&#xD;
      V. To estimate progression-free survival (PFS) and overall survival (OS). VI. To evaluate&#xD;
      disease outcomes following the use of a simultaneous integrated boost (SIB) for pediatric&#xD;
      ependymoma patients with gross residual disease following surgery.&#xD;
&#xD;
      OUTLINE:&#xD;
&#xD;
      Patients receive LET optimized IMPT for up to 6 weeks.&#xD;
&#xD;
      After completion of study treatment, patients are followed up at 1 month, then every 3 months&#xD;
      for up to 24 months.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">April 1, 2019</start_date>
  <completion_date type="Anticipated">December 31, 2027</completion_date>
  <primary_completion_date type="Anticipated">December 31, 2027</primary_completion_date>
  <phase>Phase 1</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>Incidence of adverse events</measure>
    <time_frame>Up to 6 months post treatment</time_frame>
    <description>The safety of linear energy transfer-optimized intensity modulated proton therapy will be defined by treatment failures which include imaging changes consistent with necrosis in the presence of Common Terminology Criteria for Adverse Events version 4.03 symptoms of grade 3 brain necrosis and/or local recurrence within the first 6 months from the end of proton therapy.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Identify imaging biomarkers of structural and biological changes after proton therapy</measure>
    <time_frame>Up to 24 months post-treatment</time_frame>
    <description>Descriptive statistics will be used to summarize the study data.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Quantitative image biomarkers</measure>
    <time_frame>Up to 24 months post-treatment</time_frame>
    <description>Descriptive statistics will be used to summarize the study data.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Validity of relative biological effectiveness models</measure>
    <time_frame>Up to 24 months post-treatment</time_frame>
    <description>Descriptive statistics will be used to summarize the study data.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Incidence of late and acute toxicities</measure>
    <time_frame>Up to 24 months post treatment</time_frame>
    <description>Descriptive statistics will be used to summarize the study data. For each study cohort, we will tabulate treatment- failures and other relevant clinically-related features. Interval estimates for proportions will be provided using exact 95% confidence intervals.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Progression-free survival</measure>
    <time_frame>Up to 24 months post treatment</time_frame>
    <description>The method of Kaplan and Meier will be used to provide estimates.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Overall survival</measure>
    <time_frame>Up to 24 months post treatment</time_frame>
    <description>The method of Kaplan and Meier will be used to provide estimates.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Disease outcomes following the use of a simultaneous integrated boost</measure>
    <time_frame>Up to 24 months post-treatment</time_frame>
    <description>Descriptive statistics will be used to summarize the study data.</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Anticipated">48</enrollment>
  <condition>Anaplastic Ependymoma</condition>
  <condition>Ependymoma</condition>
  <arm_group>
    <arm_group_label>Treatment (LET optimized IMPT)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Patients receive LET optimized IMPT for up to 6 weeks.</description>
  </arm_group>
  <intervention>
    <intervention_type>Radiation</intervention_type>
    <intervention_name>Linear Energy Transfer-Optimized Intensity Modulated Proton Therapy</intervention_name>
    <description>Given LET optimized IMPT</description>
    <arm_group_label>Treatment (LET optimized IMPT)</arm_group_label>
    <other_name>LET-Optimized IMPT</other_name>
    <other_name>LET-Optimized Intensity Modulated Proton Therapy</other_name>
    <other_name>Linear Energy Transfer (LET)-Optimized Intensity Modulated Proton Therapy (IMPT)</other_name>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Quality-of-Life Assessment</intervention_name>
    <description>Ancillary studies</description>
    <arm_group_label>Treatment (LET optimized IMPT)</arm_group_label>
    <other_name>Quality of Life Assessment</other_name>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Questionnaire Administration</intervention_name>
    <description>Ancillary studies</description>
    <arm_group_label>Treatment (LET optimized IMPT)</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Previous pathologic confirmation of ependymoma, World Health Organization (WHO) grade&#xD;
             II or III&#xD;
&#xD;
          -  Disease must be confined to the brain (no evidence of spread on MR imaging of the&#xD;
             spine or on staging lumbar puncture)&#xD;
&#xD;
          -  Patient may not receive chemotherapy concurrent with radiation&#xD;
&#xD;
          -  Signed informed consent by patient and/or parents or legal guardian&#xD;
&#xD;
          -  Lansky performance status score of 50 -100&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Patients with previous radiation therapy to the brain&#xD;
&#xD;
          -  Ependymoma of the spine&#xD;
&#xD;
          -  Disseminated ependymoma requiring craniospinal radiation therapy&#xD;
&#xD;
          -  Pregnancy&#xD;
&#xD;
          -  Inability to undergo MR imaging&#xD;
&#xD;
          -  Inability to receive gadolinium-based contrast agent&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>N/A</minimum_age>
    <maximum_age>22 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>David R Grosshans</last_name>
    <role>Principal Investigator</role>
    <affiliation>M.D. Anderson Cancer Center</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>David Grosshans</last_name>
    <phone>713-563-2300</phone>
    <email>dgrossha@mdanderson.org</email>
  </overall_contact>
  <location>
    <facility>
      <name>Massachusetts General Hospital Cancer Center</name>
      <address>
        <city>Boston</city>
        <state>Massachusetts</state>
        <zip>02114</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Not yet recruiting</status>
    <contact>
      <last_name>Tristin Flood</last_name>
      <email>TEFLOOD@mgh.harvard.edu</email>
    </contact>
    <investigator>
      <last_name>Shannon M. MacDonald</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>M D 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>David R. Grosshans</last_name>
      <phone>713-563-2300</phone>
    </contact>
    <investigator>
      <last_name>David R. Grosshans</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <link>
    <url>http://www.mdanderson.org</url>
    <description>MD Anderson Cancer Center Website</description>
  </link>
  <verification_date>September 2023</verification_date>
  <study_first_submitted>November 15, 2018</study_first_submitted>
  <study_first_submitted_qc>November 20, 2018</study_first_submitted_qc>
  <study_first_posted type="Actual">November 23, 2018</study_first_posted>
  <last_update_submitted>September 13, 2023</last_update_submitted>
  <last_update_submitted_qc>September 13, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">September 14, 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>Ependymoma</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/NCT03750513
org study id: 2018-0344
secondary id: NCI-2018-02519
secondary id: 2018-0344
secondary id: P30CA016672
secondary id: U19CA021239
nct id: NCT03750513
lead sponsor: 
collaborator: 
has dmc: No
is fda regulated drug: Yes
is fda regulated device: No
This phase I trial studies the side effects of linear energy transfer (LET) optimized image
      modulated proton therapy (IMPT) in treating pediatric patients with ependymoma. Radiation
      therapy such as LET optimized IMPT, uses proton beams to kill tumor cells and shrink tumors
      without damaging surrounding normal tissues.
PRIMARY OBJECTIVES:

      I. To evaluate the safety of linear energy transfer (LET) optimized image modulated proton
      therapy (IMPT) (bio-IMPT) for pediatric patients with ependymoma.

      SECONDARY OBJECTIVES:

      I. To utilize advanced multiparametric magnetic resonance (MR) imaging to identify imaging
      biomarkers of structural and biological changes after proton therapy in pediatric ependymoma
      patients.

      II. To compare quantitative image biomarkers in patients treated with bio-IMPT and standard
      proton therapy using a voxel level analysis.

      III. To test and evaluate the validity of relative biological effectiveness (RBE) models and
      enhance their precision based on prospectively collected clinical image biomarkers.

      IV. To evaluate acute and late toxicities, including pseudoprogression and symptom burden, in
      patients treated with bio-IMPT.

      V. To estimate progression-free survival (PFS) and overall survival (OS). VI. To evaluate
      disease outcomes following the use of a simultaneous integrated boost (SIB) for pediatric
      ependymoma patients with gross residual disease following surgery.

      OUTLINE:

      Patients receive LET optimized IMPT for up to 6 weeks.

      After completion of study treatment, patients are followed up at 1 month, then every 3 months
      for up to 24 months.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Incidence of adverse events
time frame: Up to 6 months post treatment
description: The safety of linear energy transfer-optimized intensity modulated proton therapy will be defined by treatment failures which include imaging changes consistent with necrosis in the presence of Common Terminology Criteria for Adverse Events version 4.03 symptoms of grade 3 brain necrosis and/or local recurrence within the first 6 months from the end of proton therapy.
measure: Identify imaging biomarkers of structural and biological changes after proton therapy
time frame: Up to 24 months post-treatment
description: Descriptive statistics will be used to summarize the study data.
measure: Quantitative image biomarkers
time frame: Up to 24 months post-treatment
description: Descriptive statistics will be used to summarize the study data.
measure: Validity of relative biological effectiveness models
time frame: Up to 24 months post-treatment
description: Descriptive statistics will be used to summarize the study data.
measure: Incidence of late and acute toxicities
time frame: Up to 24 months post treatment
description: Descriptive statistics will be used to summarize the study data. For each study cohort, we will tabulate treatment- failures and other relevant clinically-related features. Interval estimates for proportions will be provided using exact 95% confidence intervals.
measure: Progression-free survival
time frame: Up to 24 months post treatment
description: The method of Kaplan and Meier will be used to provide estimates.
measure: Overall survival
time frame: Up to 24 months post treatment
description: The method of Kaplan and Meier will be used to provide estimates.
measure: Disease outcomes following the use of a simultaneous integrated boost
time frame: Up to 24 months post-treatment
description: Descriptive statistics will be used to summarize the study data.
arm group label: Treatment (LET optimized IMPT)
arm group type: Experimental
description: Patients receive LET optimized IMPT for up to 6 weeks.
intervention type: Radiation
intervention name: Linear Energy Transfer-Optimized Intensity Modulated Proton Therapy
description: Given LET optimized IMPT
arm group label: Treatment (LET optimized IMPT)
other name: LET-Optimized IMPT
other name: LET-Optimized Intensity Modulated Proton Therapy
other name: Linear Energy Transfer (LET)-Optimized Intensity Modulated Proton Therapy (IMPT)
intervention type: Other
intervention name: Quality-of-Life Assessment
description: Ancillary studies
arm group label: Treatment (LET optimized IMPT)
other name: Quality of Life Assessment
intervention type: Other
intervention name: Questionnaire Administration
description: Ancillary studies
arm group label: Treatment (LET optimized IMPT)
criteria: 
gender: All
minimum age: N/A
maximum age: 22 Years
healthy volunteers: No
last name: David R Grosshans
role: Principal Investigator
affiliation: M.D. Anderson Cancer Center
last name: David Grosshans
phone: 713-563-2300
email: dgrossha@mdanderson.org
facility: 
status: Not yet recruiting
contact: 
investigator: 
facility: 
status: Recruiting
contact: 
investigator: 
country: United States
url: http://www.mdanderson.org
description: MD Anderson Cancer Center Website
responsible party type: Sponsor
mesh term: Ependymoma