<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/NCT03291990</url>
  </required_header>
  <id_info>
    <org_study_id>J1745</org_study_id>
    <secondary_id>IRB00129314</secondary_id>
    <nct_id>NCT03291990</nct_id>
  </id_info>
  <brief_title>5 Fraction Stereotactic Radiosurgery With Temozolomide for Glioblastoma Multiforme</brief_title>
  <official_title>A Pilot Study to Assess Feasibility of 5 Fraction Hypofractionated Stereotactic Radiosurgery Along With Standard Temozolomide as a Lymphocyte Sparing Therapy for Glioblastoma Multiforme</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
    <is_us_export>No</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      This investigation is not only to develop an improved radiation/temozolomide approach, but&#xD;
      also develop a regimen with potential to form the basis of better combined therapy with&#xD;
      immune based treatments.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Glioblastoma has a poor prognosis with median survival is 14-16 months for patients enrolling&#xD;
      in clinical trials, and across the United States one year survival is reported in the&#xD;
      Surveillance, Epidemiology, and End Results (SEER) registry to be only 35%. Radiation&#xD;
      treatment related lymphopenia has been associated with poor tumor outcome in Glioblastoma and&#xD;
      a variety of other tumor types. As this lymphopenias is prolonged, it may also reduce&#xD;
      efficacy of the checkpoint inhibitor lymphocyte mediated immune therapies now approved by the&#xD;
      FDA for an increasing number of indications. Modeling and clinical studies suggest that&#xD;
      administering radiation over 5 or fewer days (rather than standard 30 days of treatment) may&#xD;
      reduce the incidence of lymphopenia.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">October 18, 2017</start_date>
  <completion_date type="Actual">August 19, 2020</completion_date>
  <primary_completion_date type="Actual">August 19, 2020</primary_completion_date>
  <phase>Early 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>
    <intervention_model_description>5 fraction hypofractionated stereotacic radiosurgery along with standard temozolomide</intervention_model_description>
    <primary_purpose>Other</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Rate of change of lymphopenia</measure>
    <time_frame>10 weeks</time_frame>
    <description>To measure the incidence of &gt; grade 3ymphopenia resulting from combined stereotactic hypofractionated radiotherapy and standard temozolomide in malignant glioma at the the standard follow-up 10 weeks after the initiation of therapy.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Percentage change in Cluster of differentiation 4 (CD4) count (antigen found on helper T cells)</measure>
    <time_frame>10 weeks</time_frame>
    <description>To describe the percent of patients with CD4 count &lt; 200 mm/m3 at the standard week 10 follow-up</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Rate of change of lymphocytes</measure>
    <time_frame>10 weeks</time_frame>
    <description>Describe recovery of lymphocyte counts during routine clinical follow-up.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Rate of survival</measure>
    <time_frame>10 weeks</time_frame>
    <description>To describe clinical/survival outcome based upon routine standard of care.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Rate of change in serious adverse events</measure>
    <time_frame>10 weeks</time_frame>
    <description>To describe treatment related serious adverse effects</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">3</enrollment>
  <condition>Glioblastoma Multiforme</condition>
  <arm_group>
    <arm_group_label>5 fraction radiotherapy with standard temozolomide</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>5 fraction hypofractionated stereotactic radiosurgery along with standard temozolomide</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Temozolomide</intervention_name>
    <description>5 fraction hypofractionated stereotactic radiosurgery along with standard temozolomide</description>
    <arm_group_label>5 fraction radiotherapy with standard temozolomide</arm_group_label>
    <other_name>5 fraction radiosurgery with temozolomide</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Patients must be at least 18 years of age.&#xD;
&#xD;
          -  Patients must have confirmed glioblastoma multiforme (GBM)&#xD;
&#xD;
          -  Maximum postoperative dimension of cavity plus residual contrast enhancing tumor of &lt;&#xD;
             * If a patient is found on the radiation planning scan to have a tumor target larger&#xD;
             than this size, the patient will be removed from the study.&#xD;
&#xD;
          -  Patient must be selected for standard temozolomide chemotherapy to be administered&#xD;
             with radiotherapy.&#xD;
&#xD;
          -  Patient agrees to have 10 week follow-up visit at a participating Johns Hopkins&#xD;
             facility.&#xD;
&#xD;
          -  Patient agrees to allow access to or provide clinical, imaging, and laboratory&#xD;
             follow-up information for three years whether or not obtained from Johns Hopkins&#xD;
             providers.&#xD;
&#xD;
        3.1.7. Patients must not have received prior radiation therapy, chemotherapy, immunotherapy&#xD;
        or therapy with biologic agents (including immunotoxins, immunoconjugates, antisense,&#xD;
        peptide receptor antagonists, interferons, interleukins, Tumor-infiltrating lymphocytes&#xD;
        (TIL), Lymphokine-Activated Killer Cell (LAK) or gene therapy), or hormonal therapy for&#xD;
        their brain tumor. Glucocorticoid therapy is allowed.&#xD;
&#xD;
          -  Patients must have a Karnofsky performance status 60% or higher (i.e. the patient must&#xD;
             be able to care for himself/herself with occasional help from others).&#xD;
&#xD;
          -  Patients must be able to provide written informed consent.&#xD;
&#xD;
          -  Patients with the potential for pregnancy or impregnating their partner must agree to&#xD;
             follow acceptable birth control methods to avoid conception. Women of childbearing&#xD;
             potential must have a negative pregnancy test.&#xD;
&#xD;
          -  Patients must be able to undergo MRI scan with gadolinium contrast for treatment&#xD;
             planning.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Patients may not plan to receive any other approved or investigational agents to treat&#xD;
             their glioblastoma besides temozolomide prior to the evaluation visit 10 weeks after&#xD;
             the initiation of radiotherapy and temozolomide.&#xD;
&#xD;
          -  No prior malignancy is allowed except for adequately treated basal cell or squamous&#xD;
             cell skin cancer, cervical carcinoma in situ, or other cancer from which the patient&#xD;
             has been disease free for at least 2 years.&#xD;
&#xD;
          -  Patients with uncontrolled intercurrent illness including, but not limited to, ongoing&#xD;
             or active infection, symptomatic congestive heart failure, unstable angina pectoris,&#xD;
             cardiac arrhythmia, or psychiatric illness/social situations that would limit&#xD;
             compliance with study requirements will be excluded.&#xD;
&#xD;
          -  Pregnant and breastfeeding women are excluded. Women of child-bearing potential who&#xD;
             are unwilling or unable to use an acceptable method of birth control to avoid&#xD;
             pregnancy for the entire study period and up to 12 weeks after the study are excluded.&#xD;
             This applies to any woman who has not experienced menarche and who has not undergone&#xD;
             successful surgical sterilization or is not postmenopausal (defined as amenorrhea for&#xD;
             at least 12 consecutive months). Male subjects must also agree to use effective&#xD;
             contraception for the same period as above.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>100 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Lawrence Kleinberg, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>SKCCC at Johns Hopkins (East Baltimore)</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Sibley Hospital</name>
      <address>
        <city>Washington</city>
        <state>District of Columbia</state>
        <zip>20016</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Suburban Hospital</name>
      <address>
        <city>Washington</city>
        <state>District of Columbia</state>
        <zip>20818</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>SKCCC at Johns Hopkins (East Baltimore)</name>
      <address>
        <city>Baltimore</city>
        <state>Maryland</state>
        <zip>21287</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>February 2021</verification_date>
  <study_first_submitted>September 15, 2017</study_first_submitted>
  <study_first_submitted_qc>September 21, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">September 25, 2017</study_first_posted>
  <last_update_submitted>November 17, 2021</last_update_submitted>
  <last_update_submitted_qc>November 17, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">November 19, 2021</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>Glioblastoma</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Temozolomide</mesh_term>
  </intervention_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/NCT03291990
org study id: J1745
secondary id: IRB00129314
nct id: NCT03291990
lead sponsor: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
is us export: No
This investigation is not only to develop an improved radiation/temozolomide approach, but
      also develop a regimen with potential to form the basis of better combined therapy with
      immune based treatments.
Glioblastoma has a poor prognosis with median survival is 14-16 months for patients enrolling
      in clinical trials, and across the United States one year survival is reported in the
      Surveillance, Epidemiology, and End Results (SEER) registry to be only 35%. Radiation
      treatment related lymphopenia has been associated with poor tumor outcome in Glioblastoma and
      a variety of other tumor types. As this lymphopenias is prolonged, it may also reduce
      efficacy of the checkpoint inhibitor lymphocyte mediated immune therapies now approved by the
      FDA for an increasing number of indications. Modeling and clinical studies suggest that
      administering radiation over 5 or fewer days (rather than standard 30 days of treatment) may
      reduce the incidence of lymphopenia.
allocation: N/A
intervention model: Single Group Assignment
intervention model description: 5 fraction hypofractionated stereotacic radiosurgery along with standard temozolomide
primary purpose: Other
masking: None (Open Label)
measure: Rate of change of lymphopenia
time frame: 10 weeks
description: To measure the incidence of > grade 3ymphopenia resulting from combined stereotactic hypofractionated radiotherapy and standard temozolomide in malignant glioma at the the standard follow-up 10 weeks after the initiation of therapy.
measure: Percentage change in Cluster of differentiation 4 (CD4) count (antigen found on helper T cells)
time frame: 10 weeks
description: To describe the percent of patients with CD4 count < 200 mm/m3 at the standard week 10 follow-up
measure: Rate of change of lymphocytes
time frame: 10 weeks
description: Describe recovery of lymphocyte counts during routine clinical follow-up.
measure: Rate of survival
time frame: 10 weeks
description: To describe clinical/survival outcome based upon routine standard of care.
measure: Rate of change in serious adverse events
time frame: 10 weeks
description: To describe treatment related serious adverse effects
arm group label: 5 fraction radiotherapy with standard temozolomide
arm group type: Experimental
description: 5 fraction hypofractionated stereotactic radiosurgery along with standard temozolomide
intervention type: Drug
intervention name: Temozolomide
description: 5 fraction hypofractionated stereotactic radiosurgery along with standard temozolomide
arm group label: 5 fraction radiotherapy with standard temozolomide
other name: 5 fraction radiosurgery with temozolomide
criteria: 
gender: All
minimum age: 18 Years
maximum age: 100 Years
healthy volunteers: No
last name: Lawrence Kleinberg, MD
role: Principal Investigator
affiliation: SKCCC at Johns Hopkins (East Baltimore)
facility: 
facility: 
facility: 
country: United States
responsible party type: Sponsor
mesh term: Glioblastoma
mesh term: Temozolomide
sharing ipd: No