<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/NCT03286335</url>
  </required_header>
  <id_info>
    <org_study_id>17-250</org_study_id>
    <nct_id>NCT03286335</nct_id>
  </id_info>
  <brief_title>Local Control, Quality of Life and Toxicities in Adults With Benign or Indolent Brain Tumors Undergoing Proton Radiation Therapy</brief_title>
  <official_title>Local Control, Quality of Life and Toxicities in Adults With Benign or Indolent Brain Tumors Undergoing Proton Radiation Therapy</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Massachusetts General Hospital</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </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.&#xD;
&#xD;
      The radiation involved in this study is:&#xD;
&#xD;
      -Proton Radiation&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The main purpose of this study is to see how well the tumor is responding to the Proton&#xD;
      Radiation up to 5 years after the participant receive it. The investigators are also looking&#xD;
      for how this type of radiation affects the quality of life as well as any type of side effect&#xD;
      the participant may have after the radiation is administered.&#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;
    </textblock>
  </detailed_description>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">September 26, 2018</start_date>
  <completion_date type="Anticipated">September 30, 2027</completion_date>
  <primary_completion_date type="Anticipated">September 30, 2025</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>Duration of Local Control</measure>
    <time_frame>2 years</time_frame>
    <description>The duration of local control will be measured from the start date of protocol radiation until the date of progressive disease. Local control is defined as the lack of tumor growth as determined by a brain MRI (magnetic resonance imaging). This will include tumors that appear unchanged in size as compared to the baseline pre-radiation scan and also tumors that appear slightly reduced in size as may occur in response to radiation therapy. Inflammation secondary to radiation therapy can radiographically mimic subtle disease progression and may need to be confirmed with serial imaging.&#xD;
Progression is defined as an increase in the size of the tumor, a significant increase in T2/FLAIR non-enhancing lesion on sable or increasing doses of corticosteroids compared to baseline, the appearance of any new lesion, clear clinical deterioration not attributable to any other cause apart from the tumor, or failure to return for evaluation due to death or deteriorating condition.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Quality of Life Assessment EORTC-QLQ-C30</measure>
    <time_frame>2 years</time_frame>
    <description>Quality of life in relation to overall physical functioning will be assessed using the European Organization for the Research and Treatment of Cancer (EORTC) Quality of Life Questionnaires (QLQ). Overall functioning will be assessed at baseline and follow-up evaluations using EORTC-QLQ-C30.&#xD;
Mixed effects models will be used to analyze the repeated measures of EORTC-QLQ with participant-specific intercepts and slopes assumed as random effects. Tumor type will be modeled as fixed effects in order to estimate quality of life changes over time among participants with each benign and malignant diagnosis.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Quality of Life Assessment EORTC-QLQ-BN20</measure>
    <time_frame>2 Years</time_frame>
    <description>Quality of life in relation to symptoms specific to brain cancer will be assessed using the European Organization for the Research and Treatment of Cancer (EORTC) Quality of Life Questionnaires (QLQ). Brain cancer-specific symptoms will be assessed at baseline and follow-up evaluations using EORTC-QLQ-BN20.&#xD;
Mixed effects models will be used to analyze the repeated measures of EORTC-QLQ with participant-specific intercepts and slopes assumed as random effects. Tumor type will be modeled as fixed effects in order to estimate quality of life changes over time among participants with each benign and malignant diagnosis.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Quality of Life Assessment HADS</measure>
    <time_frame>2 Years</time_frame>
    <description>State anxiety and depression will be measured with the Hospital Anxiety and Depression Scale (HADS). HADS screens for mood disorders in medically ill participants; it focuses on subjective rather than physical symptoms, which may be confounded with illness.&#xD;
Mixed effects models will be used to analyze the repeated measures of HADS with participant-specific intercepts and slopes assumed as random effects. Tumor type will be modeled as fixed effects in order to estimate mood changes over time among participants with each benign and malignant diagnosis.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Vision Loss</measure>
    <time_frame>2 years</time_frame>
    <description>Those participants determined to have had proton radiation exposure to any part of the optic pathway that could potentially affect vision will undergo standard afferent neuro-ophthalmological evaluation, which includes tests of visual acuity, color perception, pupillary function, visual field testing, and optic disc appearance. Participants with any tumor type will be evaluable for visual outcome if the battery of neuro-ophthalmology evaluation were performed at baseline. Testing will be discontinued if the participant becomes blind.&#xD;
The cumulative incidence of developing vision loss among evaluable participants will be analyzed with failure defined as decline in one or more of the vision function tests and with competing risks of progressive disease and death.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Ototoxicity</measure>
    <time_frame>2 years</time_frame>
    <description>For participants with proton radiation exposure to the skull base audiologic system, standard audiologic testing will be performed, unless poor hearing inadequate for useful function is present at baseline. Testing will be discontinued if the participant becomes deaf. Participants with any tumor type will be evaluable for hearing outcome if audiology evaluation were performed at baseline.&#xD;
The cumulative incidence of developing ototoxicity among evaluable participants will be analyzed with failure defined as significant decrease in Pure Tone Average or/and Word Recognition Score and with competing risks of progressive disease and death</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Neuroendocrine dysfunction</measure>
    <time_frame>2 years</time_frame>
    <description>Participants will be candidates for neuroendocrine testing if they were determined to have any radiation exposure to the hypothalamus or pituitary gland or to have a target lesion within 2 cm of either of these normal structures, unless panhypopituitarism is present at baseline. Participants with any tumor type will be evaluable for endocrine outcome if neuroendocrine evaluation were performed at baseline.&#xD;
The cumulative incidence of developing neuroendocrine dysfunction among evaluable participants will be analyzed with failure defined as any hormonal deficiency confirmed by test criteria and with competing risks of progressive disease and death.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Neurocognitive effects</measure>
    <time_frame>2 years</time_frame>
    <description>Participants with any tumor type will be evaluable for neurocognitive analysis if the optional neuropsychological evaluation were performed at baseline and/or at least one follow-up. Mixed effects models will be used to analyze the repeated measures of intelligence, language, visuospatial/motor functioning, learning/memory and attention/executive functioning, with participant-specific intercepts and slopes assumed as random effects. Tumor and treatment characteristics may be modeled as fixed effects in order to estimate their effects on neurocognitive changes over time.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Alopecia</measure>
    <time_frame>2 years</time_frame>
    <description>Participants with any tumor type will be evaluable for alopecia unless they are virtually bald at baseline and graded using Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. Maximal hair loss will be documented between the last week of radiation and 4 weeks later, while permanent hair loss will be defined at 2 years post-treatment.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>CD4 count</measure>
    <time_frame>2 years</time_frame>
    <description>Participants with any tumor type will be evaluable for CD4 analysis if they were to consent to the optional assessment of CD4 count. The worst grade of CD4 count will be defined using Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 during the short term (on-treatment and 1 to 3 months post-radiation) and long term (6 months to 2 years post-radiation).</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Anticipated">100</enrollment>
  <condition>Brain Tumor</condition>
  <arm_group>
    <arm_group_label>Proton Radiation</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Radiation therapy will be delivered typically five (5) days per week on weekdays&#xD;
Proton Radiation dose be determine by histology</description>
  </arm_group>
  <intervention>
    <intervention_type>Radiation</intervention_type>
    <intervention_name>Proton Radiation</intervention_name>
    <description>Radiation treatment</description>
    <arm_group_label>Proton Radiation</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Biopsy-proven benign or malignant brain tumor requiring tumor bed or tumor&#xD;
             irradiation. This may include, but is not limited to, low-grade or favorable&#xD;
             high-grade glioma, pituitary adenoma, vestibular schwannoma (acoustic neuroma), and&#xD;
             meningioma as the most common diagnoses. Other tumor types that require irradiation&#xD;
             and are deemed appropriate for proton radiation therapy are also eligible. Patients&#xD;
             with a presumed diagnosis based on imaging and clinical characteristics will be&#xD;
             permitted on this trial without pathological diagnostic confirmation if it is within&#xD;
             standard of care to offer radiation therapy without a biopsy.&#xD;
&#xD;
          -  Participants must otherwise be indicated for proton radiation therapy&#xD;
&#xD;
          -  Age 18 years or older&#xD;
&#xD;
          -  Karnofsky performance status ≥ 60 (see Appendix A)&#xD;
&#xD;
          -  Participants may have had any extent of prior surgery and/or chemotherapy.&#xD;
&#xD;
          -  Must be able to speak and comprehend English&#xD;
&#xD;
          -  Ability to understand and willingness to sign a written informed consent document&#xD;
&#xD;
          -  The effects of proton radiation therapy on the developing human fetus are known to be&#xD;
             teratogenic. For this reason, women of child-bearing potential and men must agree to&#xD;
             use adequate contraception (hormonal or barrier method of birth control; abstinence)&#xD;
             prior to study entry, for the duration of study treatment, and 4 months after&#xD;
             completion of proton therapy. Should a woman become pregnant or suspect she is&#xD;
             pregnant while she or her partner is participating in this study, she should inform&#xD;
             her treating physician immediately. Men treated or enrolled on this protocol must also&#xD;
             agree to use adequate contraception prior to the study, for the duration of study&#xD;
             treatment, and 4 months after completion of proton therapy.&#xD;
&#xD;
          -  Life expectancy greater than or equal to 6 months.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Uncontrolled intercurrent illness including, but not limited to ongoing or active&#xD;
             infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac&#xD;
             arrhythmia, or psychiatric illness/social situations that would limit compliance with&#xD;
             study requirements.&#xD;
&#xD;
          -  Pregnant or lactating women are excluded from this study because radiation is known to&#xD;
             have teratogenic or abortifacient effects. Because there is an unknown but potential&#xD;
             risk of adverse events in nursing infants secondary to treatment of the mother with&#xD;
             radiation therapy, breastfeeding should be discontinued if the mother is treated with&#xD;
             radiation therapy.&#xD;
&#xD;
          -  Individuals with a history of a different malignancy are ineligible except for the&#xD;
             following circumstances. Individuals with a history of other malignancies are eligible&#xD;
             if they have been disease-free for at least 3 years and are deemed by the investigator&#xD;
             to be at low risk for recurrence of that malignancy. Individuals with the following&#xD;
             cancers are eligible if diagnosed and treated within the past 3 years: cervical cancer&#xD;
             in situ, and basal cell or squamous cell carcinoma of the skin&#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>Helen A Shih, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Massachusetts General Hospital</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Tarin Grillo</last_name>
    <phone>617-724-3661</phone>
    <email>TGRILLO@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>Tarin Grillo</last_name>
      <phone>617-724-3661</phone>
      <email>TGRILLO@mgh.harvard.edu</email>
    </contact>
    <investigator>
      <last_name>Helen A Shih, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>August 2020</verification_date>
  <study_first_submitted>September 12, 2017</study_first_submitted>
  <study_first_submitted_qc>September 13, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">September 18, 2017</study_first_posted>
  <last_update_submitted>August 17, 2020</last_update_submitted>
  <last_update_submitted_qc>August 17, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">August 18, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Massachusetts General Hospital</investigator_affiliation>
    <investigator_full_name>Helen A. Shih, MD</investigator_full_name>
    <investigator_title>Shih, Helen A, MD</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/NCT03286335
org study id: 17-250
nct id: NCT03286335
lead sponsor: 
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.

      The radiation involved in this study is:

      -Proton Radiation
The main purpose of this study is to see how well the tumor is responding to the Proton
      Radiation up to 5 years after the participant receive it. The investigators are also looking
      for how this type of radiation affects the quality of life as well as any type of side effect
      the participant may have after the radiation is administered.

      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.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Duration of Local Control
time frame: 2 years
description: The duration of local control will be measured from the start date of protocol radiation until the date of progressive disease. Local control is defined as the lack of tumor growth as determined by a brain MRI (magnetic resonance imaging). This will include tumors that appear unchanged in size as compared to the baseline pre-radiation scan and also tumors that appear slightly reduced in size as may occur in response to radiation therapy. Inflammation secondary to radiation therapy can radiographically mimic subtle disease progression and may need to be confirmed with serial imaging.
Progression is defined as an increase in the size of the tumor, a significant increase in T2/FLAIR non-enhancing lesion on sable or increasing doses of corticosteroids compared to baseline, the appearance of any new lesion, clear clinical deterioration not attributable to any other cause apart from the tumor, or failure to return for evaluation due to death or deteriorating condition.
measure: Quality of Life Assessment EORTC-QLQ-C30
time frame: 2 years
description: Quality of life in relation to overall physical functioning will be assessed using the European Organization for the Research and Treatment of Cancer (EORTC) Quality of Life Questionnaires (QLQ). Overall functioning will be assessed at baseline and follow-up evaluations using EORTC-QLQ-C30.
Mixed effects models will be used to analyze the repeated measures of EORTC-QLQ with participant-specific intercepts and slopes assumed as random effects. Tumor type will be modeled as fixed effects in order to estimate quality of life changes over time among participants with each benign and malignant diagnosis.
measure: Quality of Life Assessment EORTC-QLQ-BN20
time frame: 2 Years
description: Quality of life in relation to symptoms specific to brain cancer will be assessed using the European Organization for the Research and Treatment of Cancer (EORTC) Quality of Life Questionnaires (QLQ). Brain cancer-specific symptoms will be assessed at baseline and follow-up evaluations using EORTC-QLQ-BN20.
Mixed effects models will be used to analyze the repeated measures of EORTC-QLQ with participant-specific intercepts and slopes assumed as random effects. Tumor type will be modeled as fixed effects in order to estimate quality of life changes over time among participants with each benign and malignant diagnosis.
measure: Quality of Life Assessment HADS
time frame: 2 Years
description: State anxiety and depression will be measured with the Hospital Anxiety and Depression Scale (HADS). HADS screens for mood disorders in medically ill participants; it focuses on subjective rather than physical symptoms, which may be confounded with illness.
Mixed effects models will be used to analyze the repeated measures of HADS with participant-specific intercepts and slopes assumed as random effects. Tumor type will be modeled as fixed effects in order to estimate mood changes over time among participants with each benign and malignant diagnosis.
measure: Vision Loss
time frame: 2 years
description: Those participants determined to have had proton radiation exposure to any part of the optic pathway that could potentially affect vision will undergo standard afferent neuro-ophthalmological evaluation, which includes tests of visual acuity, color perception, pupillary function, visual field testing, and optic disc appearance. Participants with any tumor type will be evaluable for visual outcome if the battery of neuro-ophthalmology evaluation were performed at baseline. Testing will be discontinued if the participant becomes blind.
The cumulative incidence of developing vision loss among evaluable participants will be analyzed with failure defined as decline in one or more of the vision function tests and with competing risks of progressive disease and death.
measure: Ototoxicity
time frame: 2 years
description: For participants with proton radiation exposure to the skull base audiologic system, standard audiologic testing will be performed, unless poor hearing inadequate for useful function is present at baseline. Testing will be discontinued if the participant becomes deaf. Participants with any tumor type will be evaluable for hearing outcome if audiology evaluation were performed at baseline.
The cumulative incidence of developing ototoxicity among evaluable participants will be analyzed with failure defined as significant decrease in Pure Tone Average or/and Word Recognition Score and with competing risks of progressive disease and death
measure: Neuroendocrine dysfunction
time frame: 2 years
description: Participants will be candidates for neuroendocrine testing if they were determined to have any radiation exposure to the hypothalamus or pituitary gland or to have a target lesion within 2 cm of either of these normal structures, unless panhypopituitarism is present at baseline. Participants with any tumor type will be evaluable for endocrine outcome if neuroendocrine evaluation were performed at baseline.
The cumulative incidence of developing neuroendocrine dysfunction among evaluable participants will be analyzed with failure defined as any hormonal deficiency confirmed by test criteria and with competing risks of progressive disease and death.
measure: Neurocognitive effects
time frame: 2 years
description: Participants with any tumor type will be evaluable for neurocognitive analysis if the optional neuropsychological evaluation were performed at baseline and/or at least one follow-up. Mixed effects models will be used to analyze the repeated measures of intelligence, language, visuospatial/motor functioning, learning/memory and attention/executive functioning, with participant-specific intercepts and slopes assumed as random effects. Tumor and treatment characteristics may be modeled as fixed effects in order to estimate their effects on neurocognitive changes over time.
measure: Alopecia
time frame: 2 years
description: Participants with any tumor type will be evaluable for alopecia unless they are virtually bald at baseline and graded using Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. Maximal hair loss will be documented between the last week of radiation and 4 weeks later, while permanent hair loss will be defined at 2 years post-treatment.
measure: CD4 count
time frame: 2 years
description: Participants with any tumor type will be evaluable for CD4 analysis if they were to consent to the optional assessment of CD4 count. The worst grade of CD4 count will be defined using Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 during the short term (on-treatment and 1 to 3 months post-radiation) and long term (6 months to 2 years post-radiation).
arm group label: Proton Radiation
arm group type: Experimental
description: Radiation therapy will be delivered typically five (5) days per week on weekdays
Proton Radiation dose be determine by histology
intervention type: Radiation
intervention name: Proton Radiation
description: Radiation treatment
arm group label: Proton Radiation
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Helen A Shih, MD
role: Principal Investigator
affiliation: Massachusetts General Hospital
last name: Tarin Grillo
phone: 617-724-3661
email: TGRILLO@mgh.harvard.edu
facility: 
status: Recruiting
contact: 
investigator: 
country: United States
responsible party type: Principal Investigator
investigator affiliation: Massachusetts General Hospital
investigator full name: Helen A. Shih, MD
investigator title: Shih, Helen A, MD
mesh term: Brain Neoplasms
sharing ipd: No