<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/NCT01734512</url>
  </required_header>
  <id_info>
    <org_study_id>120817</org_study_id>
    <secondary_id>NCI-2012-02774</secondary_id>
    <nct_id>NCT01734512</nct_id>
  </id_info>
  <brief_title>PNOC 001: Phase II Study of Everolimus for Recurrent or Progressive Low-grade Gliomas in Children</brief_title>
  <official_title>PNOC 001: Phase II Study of Everolimus for Recurrent or Progressive Low-grade Gliomas in Children</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of California, San Francisco</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Novartis Pharmaceuticals</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
    <collaborator>
      <agency>Pacific Pediatric Neuro-Oncology Consortium</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>The Pediatric Low Grade Astrocytoma (PLGA) Foundation</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>University of California, San Francisco</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 is an open label study of everolimus in children with recurrent or progressive low-grade&#xD;
      glioma.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This is an open label study of everolimus in children with recurrent or progressive low-grade&#xD;
      glioma. All patients will receive everolimus at a dose of 5 mg/m2/dose daily. An adaptive&#xD;
      Simon two-stage design for phase 2 studies of targeted therapies will be used to assess the&#xD;
      efficacy primary objective. The proposed treatment with everolimus will be deemed not worthy&#xD;
      of further investigation in this patient population if the true PFS at 6-months (PFS6) is&#xD;
      less than 50%. If in the first stage, with a combined sample size of 25, there is preliminary&#xD;
      evidence to suggest efficacy of everolimus is restricted to patients with PI3K/AKT/mTOR&#xD;
      activation as measured by p-S6 positivity, a total of 45 patients will be enrolled and the&#xD;
      design will have 81% statistical power to detect a true disease stabilization rate ≥70%. If&#xD;
      in the first stage there is preliminary evidence to suggest efficacy of everolimus is&#xD;
      independent of PI3K/AKT/mTOR activation, a total of 65 patients will be enrolled and the&#xD;
      design will have &gt;95% statistical power to detect a true disease stabilization rate ≥70%.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Active, not recruiting</overall_status>
  <start_date type="Actual">December 13, 2012</start_date>
  <completion_date type="Anticipated">July 31, 2024</completion_date>
  <primary_completion_date type="Actual">January 31, 2020</primary_completion_date>
  <phase>Phase 2</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>Percentage of Participants With Progression Free Survival at 6 Months</measure>
    <time_frame>Up to 6 months</time_frame>
    <description>Response was be determined by bi-dimensional diameters. RECIST criteria will be collected and used for secondary evaluation. Patients will have brain MRI scans with and without gadolinium performed prior to therapy, after every second course in the first year, after every third course in the second year, and at the End of Study visit (if not done within prior 3 months). Spine MRIs should be performed prior to therapy and at the same time points as standard brain MRIs if clinically indicated.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Proportion of Participants With Objective Response</measure>
    <time_frame>Up to 6 months</time_frame>
    <description>The proportion of participants who demonstrated a complete or partial response as defined by Response Evaluation Criteria in Solid Tumors (RECIST) v1 Criteria where complete Response (CR) is defined as the complete disappearance of all known disease for &gt;=8 weeks. Complete response is dated from time all lesions have disappeared on a stable or decreasing dose of corticosteroids. A Partial Response (PR) is a reduction of at least 50% in the size of all measurable tumor as quantitated by sum of the products of the largest diameters (SLD) of measurable lesions and maintained for &gt;=8 weeks on a stable or decreasing dose of corticosteroids. Partial response is dated from the time of first observation. Overall response also takes into account the response in both the target and non-target lesion, and the appearance of new lesions, where applicable and depend on the achievement of both measurement and confirmation criteria.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Median Progression Free Survival in Recurrent Pediatric Low-grade Glioma (LGGs)</measure>
    <time_frame>Up to 5 years</time_frame>
    <description>Progression free survival will be calculated from date of first treatment to the date of first observation of progressive disease, non-reversible neurological progression or increasing steroid requirements (applies to stable disease only), death due to any cause, or early discontinuation of treatment</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Median Overall Survival in Recurrent Pediatric LGGs</measure>
    <time_frame>Up to 5 years</time_frame>
    <description>Overall survival will be calculated from date of original diagnoses to death and also from the date of study registration to death. The latter will be an endpoint for assessment of benefit of this therapy.</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">65</enrollment>
  <condition>Pediatric Recurrent Progressive Low-grade Gliomas</condition>
  <condition>Pediatric Progressive Low-grade Gliomas</condition>
  <arm_group>
    <arm_group_label>Everolimus</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Everolimus tablet will be taken daily by mouth with water. Twenty-eight days will constitute one course and subsequent courses will immediately follow with no break in the administration of the drug. Dosing is based on the body surface area (BSA) calculated at the beginning of each course of therapy. Patients will also be provided with a drug diary for everolimus. The maximum time on study is 24-months, but if there is no disease progression or adverse events, the patient may speak with a doctor about continuing the treatment off-study.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Everolimus</intervention_name>
    <description>Everolimus tablet will be taken daily by mouth with water. All patients will be given a dose of 5 mg/m2/dose daily.</description>
    <arm_group_label>Everolimus</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
        --Patients must have radiographic progressive or recurrent confirmed world health&#xD;
        organization (WHO) grade I or II astrocytomas, that was confirmed histologically.&#xD;
        Progressive or recurrent disease should be based on MRI according to the definition below.&#xD;
&#xD;
        Eligible histologies:&#xD;
&#xD;
          -  Pilocytic Astrocytoma - 90600112&#xD;
&#xD;
          -  Astrocytoma, Low Grade (Fibrillary astrocytoma, WHO Grade 2) - 10065886&#xD;
&#xD;
          -  Astrocytoma, Low Grade (Low-grade Astrocytoma, not otherwise specified (NOS), WHO&#xD;
             Grade 2) - 10003571&#xD;
&#xD;
               -  Tissue from the initial diagnosis or recurrence must be made available for&#xD;
                  correlative testing.&#xD;
&#xD;
               -  Patients must have measurable disease, defined as at least one lesion that can be&#xD;
                  accurately measured in at least two dimensions on MRI.&#xD;
&#xD;
               -  Patients may have had treatment (chemotherapy and/or radiotherapy) for any number&#xD;
                  of relapses prior to this recurrence.&#xD;
&#xD;
               -  Patients must have received their last dose of myelosuppressive anticancer&#xD;
                  chemotherapy at least three (3) weeks prior to study registration or at least six&#xD;
                  (6)weeks of nitrosourea.&#xD;
&#xD;
               -  Patients must have received their last dose of other investigational or&#xD;
                  biological agent &gt; 7 days prior to study entry.&#xD;
&#xD;
        For agents that have known adverse events occurring beyond 7 days after administration,&#xD;
        this period should be extended beyond the time during which adverse events are known to&#xD;
        occur. This should be discussed with the study chair.&#xD;
&#xD;
          -  If patients received prior monoclonal antibody treatment, at least three half-lives&#xD;
             must be elapsed by the time of treatment initiation. These patients should also be&#xD;
             discussed with the study chair.&#xD;
&#xD;
          -  Patients must have received their last fraction of craniospinal or focal radiation to&#xD;
             primary tumor or other sites &gt;12 weeks (3 months) prior to registration.&#xD;
&#xD;
             --Age ≥3 and ≤21 years.&#xD;
&#xD;
          -  Because no dosing or adverse event data are currently available on the use of&#xD;
             everolimus in patients &lt;3 years of age, these young children are excluded from this&#xD;
             study.&#xD;
&#xD;
               -  Life expectancy of greater than 8 weeks.&#xD;
&#xD;
               -  Patients must be able to swallow pills.&#xD;
&#xD;
               -  Patient must have a Karnofsky (if ≥ 16 years of age) or Lansky Performance score&#xD;
                  (if ≤ 16 years of age) of ≥50 by the time of registration.&#xD;
&#xD;
               -  Patients must have adequate bone marrow function (ANC ≥ 1,000/mm3, platelet count&#xD;
                  of ≥ 100,000/mm3, and hemoglobin ≥ 9 gm/dL) before starting therapy. Eligibility&#xD;
                  level for hemoglobin may be reached by transfusion.&#xD;
&#xD;
               -  International Normalized Ratio (INR) ≤1.5. (Anticoagulation is allowed if target&#xD;
                  INR ≤ 1.5 on a stable dose of warfarin or on a stable dose of low molecular&#xD;
                  weight (LMW) heparin for &gt;2 weeks at time of randomization).&#xD;
&#xD;
               -  Patients must have adequate liver function (SGPT/alanine aminotransferase (ALT) ≤&#xD;
                  2.5 times ULN and bilirubin ≤ 1.5 times ULN) before starting therapy.&#xD;
&#xD;
               -  Patients must have adequate renal function (serum creatinine ≤ 1.5 times&#xD;
                  institutional ULN for age or Glomerular filtration rate (GFR) ≥ 70 ml/min/1.73&#xD;
                  m2) before starting therapy.&#xD;
&#xD;
               -  Patients must have cholesterol level &lt;350 mg/dL and triglycerides &lt; 400 mg/dL&#xD;
                  before starting therapy. In case one or both of these are exceeded, the patient&#xD;
                  can only be included after initiation of appropriate lipid lowering medication&#xD;
                  and documentation of cholesterol &lt; 350mg/dL and triglycerides &lt; 400mg/dl before&#xD;
                  start of therapy.&#xD;
&#xD;
               -  Patients must have normal pulmonary function testing for age based on pulse&#xD;
                  oximetry.&#xD;
&#xD;
               -  The effects of everolimus on the developing human fetus at the recommended&#xD;
                  therapeutic dose are unknown. For this reason and because everolimus are known to&#xD;
                  be teratogenic, women of child-bearing potential and men must agree to use&#xD;
                  adequate contraception (hormonal or barrier method of birth control; abstinence)&#xD;
                  prior to study entry and for the duration of study participation. Should a woman&#xD;
                  become pregnant or suspect she is pregnant while participating in this study, she&#xD;
                  should inform her treating physician immediately.&#xD;
&#xD;
               -  Female patients of child bearing potential must not be breastfeeding or pregnant&#xD;
                  as evidenced by a negative pregnancy test.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Patients with primary spinal cord tumors&#xD;
&#xD;
          -  Patients receiving concomitant medication that may interfere with study outcome. For&#xD;
             example, patients cannot be on enzyme inducing anticonvulsants like phenytoin.&#xD;
&#xD;
          -  Patients should not receive immunization with attenuated live vaccines within one week&#xD;
             of study entry or during study period. Close contact with those who have received&#xD;
             attenuated live vaccines should be avoided during treatment with everolimus. Examples&#xD;
             of live vaccines include intranasal influenza, measles, mumps, rubella, oral polio,&#xD;
             bacille Calmette-Guerin (BCG), yellow fever, varicella and TY21a typhoid vaccines&#xD;
&#xD;
          -  Hepatitis B/C blood test must be done at screening for all patients. Patients who test&#xD;
             positive for Hepatitis C antibodies and the Hepatitis B antigen are ineligible.&#xD;
&#xD;
          -  A known history of HIV seropositivity. HIV-positive patients on combination&#xD;
             antiretroviral therapy are ineligible because of the potential for pharmacokinetic&#xD;
             interactions with everolimus. In addition, these patients are at increased risk of&#xD;
             lethal infections when treated with marrow-suppressive therapy.&#xD;
&#xD;
          -  Patients receiving chronic, systemic treatment with corticosteroids or another&#xD;
             immunosuppressive agent. Topical or inhaled corticosteroids are allowed.&#xD;
&#xD;
          -  Patients may not have therapy for this recurrence (including radiation).&#xD;
&#xD;
          -  Patients who do not have measurable disease on MRI.&#xD;
&#xD;
          -  Patients who have been previously treated with an mTOR inhibitor.&#xD;
&#xD;
          -  Patients with a known hypersensitivity to everolimus or other rapamycins (e.g.&#xD;
             sirolimus, temsirolimus).&#xD;
&#xD;
          -  Patients receiving any other concurrent anticancer or investigational therapy.&#xD;
&#xD;
          -  Patients with any clinically significant unrelated systemic illness that would&#xD;
             compromise the patient's ability to tolerate protocol therapy.&#xD;
&#xD;
          -  Impairment of gastrointestinal function or gastrointestinal disease that may&#xD;
             significantly alter the absorption of everolimus (e.g., ulcerative disease,&#xD;
             uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome or small bowel&#xD;
             resection.&#xD;
&#xD;
          -  Patients with inability to return for follow-up visits to assess toxicity to therapy.&#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;
          -  Patients with a history of any other cancer (except non-melanoma skin cancer or&#xD;
             carcinoma in situ of the cervix), unless in complete remission and off of all therapy&#xD;
             for that disease for a minimum of 3 years.&#xD;
&#xD;
        Note: A detailed assessment of Hepatitis B/C medical history and risk factors must be done&#xD;
        at screening for all patients. Hepatitis B Virus (HBV) DNA and Hepatitis C Virus (HCV) RNA&#xD;
        Polymerase chain reaction (PCR) testing are required at screening for all patients with a&#xD;
        positive medical history based on risk factors and/or confirmation of prior HBV/HCV&#xD;
        infection.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>3 Years</minimum_age>
    <maximum_age>21 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Daphne Haas-Kogan, MD</last_name>
    <role>Study Chair</role>
    <affiliation>Dana-Farber Cancer Institute</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Sabine Mueller, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>University of California, San Francisco</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Children's Hospital Los Angeles</name>
      <address>
        <city>Los Angeles</city>
        <state>California</state>
        <zip>90027</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of California, Los Angeles</name>
      <address>
        <city>Los Angeles</city>
        <state>California</state>
        <zip>90027</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Children's Hospital Oakland</name>
      <address>
        <city>Oakland</city>
        <state>California</state>
        <zip>94609</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of California, San Diego Rady Children's Hospital</name>
      <address>
        <city>San Diego</city>
        <state>California</state>
        <zip>92123</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of California, San Francisco</name>
      <address>
        <city>San Francisco</city>
        <state>California</state>
        <zip>94158</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Children's National Medical Center</name>
      <address>
        <city>Washington</city>
        <state>District of Columbia</state>
        <zip>20010</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Florida</name>
      <address>
        <city>Gainesville</city>
        <state>Florida</state>
        <zip>32611</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Ann &amp; Robert H. Lurie Children's Hospital of Chicago</name>
      <address>
        <city>Chicago</city>
        <state>Illinois</state>
        <zip>60611</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Johns Hopkins University</name>
      <address>
        <city>Baltimore</city>
        <state>Maryland</state>
        <zip>21218</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Dana-Farber Cancer Institute</name>
      <address>
        <city>Boston</city>
        <state>Massachusetts</state>
        <zip>02215</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Children's Hospitals and Clinics of Minneapolis</name>
      <address>
        <city>Minneapolis</city>
        <state>Minnesota</state>
        <zip>55404</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>St. Louis Children's Hospital, Washington University</name>
      <address>
        <city>Saint Louis</city>
        <state>Missouri</state>
        <zip>63130</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Nationwide Children's Hospital</name>
      <address>
        <city>Columbus</city>
        <state>Ohio</state>
        <zip>43205</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Oregon Health &amp; Science University</name>
      <address>
        <city>Portland</city>
        <state>Oregon</state>
        <zip>97239</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>The Children's Hospital Of Philadelphia</name>
      <address>
        <city>Philadelphia</city>
        <state>Pennsylvania</state>
        <zip>19104</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>St. Jude Children's Research Hospital</name>
      <address>
        <city>Memphis</city>
        <state>Tennessee</state>
        <zip>38105</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Utah</name>
      <address>
        <city>Salt Lake City</city>
        <state>Utah</state>
        <zip>84112</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Washington, Seattle</name>
      <address>
        <city>Seattle</city>
        <state>Washington</state>
        <zip>98195</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>July 2023</verification_date>
  <study_first_submitted>November 21, 2012</study_first_submitted>
  <study_first_submitted_qc>November 21, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">November 27, 2012</study_first_posted>
  <results_first_submitted>January 14, 2021</results_first_submitted>
  <results_first_submitted_qc>January 29, 2021</results_first_submitted_qc>
  <results_first_posted type="Actual">February 18, 2021</results_first_posted>
  <last_update_submitted>July 19, 2023</last_update_submitted>
  <last_update_submitted_qc>July 19, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">July 27, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>pediatric recurrent progressive low-grade gliomas</keyword>
  <keyword>pediatric progressive low-grade gliomas</keyword>
  <keyword>everolimus</keyword>
  <keyword>mTOR inhibition</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Glioma</mesh_term>
    <mesh_term>Recurrence</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Everolimus</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <provided_document_section>
    <provided_document>
      <document_type>Study Protocol and Statistical Analysis Plan</document_type>
      <document_has_protocol>Yes</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>Yes</document_has_sap>
      <document_date>January 7, 2019</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/12/NCT01734512/Prot_SAP_000.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <group_list>
        <group group_id="P1">
          <title>Everolimus</title>
          <description>Everolimus tablet will be taken daily by mouth with water. Twenty-eight days will constitute one course and subsequent courses will immediately follow with no break in the administration of the drug. Dosing is based on the body surface area (BSA) calculated at the beginning of each course of therapy. Patients will also be provided with a drug diary for everolimus. The maximum time on study is 24-months, but if there is no disease progression or adverse events, the patient may speak with a doctor about continuing the treatment off-study.&#xD;
Everolimus: Everolimus tablet will be taken daily by mouth with water. All patients will be given a dose of 5 mg/m2/dose daily.</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="65"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="65"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
              </participants_list>
            </milestone>
          </milestone_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>Everolimus</title>
          <description>Everolimus tablet will be taken daily by mouth with water. Twenty-eight days will constitute one course and subsequent courses will immediately follow with no break in the administration of the drug. Dosing is based on the body surface area (BSA) calculated at the beginning of each course of therapy. Patients will also be provided with a drug diary for everolimus. The maximum time on study is 24-months, but if there is no disease progression or adverse events, the patient may speak with a doctor about continuing the treatment off-study.&#xD;
Everolimus: Everolimus tablet will be taken daily by mouth with water. All patients will be given a dose of 5 mg/m2/dose daily.</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="65"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age, Customized</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <title>3-9 years old</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="35"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>10-21 years old</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="30"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Sex: Female, Male</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Female</title>
                  <measurement_list>
                    <measurement group_id="B1" value="29"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="36"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Ethnicity (NIH/OMB)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="15"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Not Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="47"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Race (NIH/OMB)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>American Indian or Alaska Native</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Asian</title>
                  <measurement_list>
                    <measurement group_id="B1" value="2"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Native Hawaiian or Other Pacific Islander</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Black or African American</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                  </measurement_list>
                </category>
                <category>
                  <title>White</title>
                  <measurement_list>
                    <measurement group_id="B1" value="47"/>
                  </measurement_list>
                </category>
                <category>
                  <title>More than one race</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="14"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Region of Enrollment</title>
          <units>participants</units>
          <param>Number</param>
          <class_list>
            <class>
              <title>United States</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="65"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Percentage of Participants With Progression Free Survival at 6 Months</title>
        <description>Response was be determined by bi-dimensional diameters. RECIST criteria will be collected and used for secondary evaluation. Patients will have brain MRI scans with and without gadolinium performed prior to therapy, after every second course in the first year, after every third course in the second year, and at the End of Study visit (if not done within prior 3 months). Spine MRIs should be performed prior to therapy and at the same time points as standard brain MRIs if clinically indicated.</description>
        <time_frame>Up to 6 months</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Everolimus</title>
            <description>Everolimus tablet will be taken daily by mouth with water. Twenty-eight days will constitute one course and subsequent courses will immediately follow with no break in the administration of the drug. Dosing is based on the body surface area (BSA) calculated at the beginning of each course of therapy. Patients will also be provided with a drug diary for everolimus. The maximum time on study is 24-months, but if there is no disease progression or adverse events, the patient may speak with a doctor about continuing the treatment off-study.&#xD;
Everolimus: Everolimus tablet will be taken daily by mouth with water. All patients will be given a dose of 5 mg/m2/dose daily.</description>
          </group>
        </group_list>
        <measure>
          <title>Percentage of Participants With Progression Free Survival at 6 Months</title>
          <description>Response was be determined by bi-dimensional diameters. RECIST criteria will be collected and used for secondary evaluation. Patients will have brain MRI scans with and without gadolinium performed prior to therapy, after every second course in the first year, after every third course in the second year, and at the End of Study visit (if not done within prior 3 months). Spine MRIs should be performed prior to therapy and at the same time points as standard brain MRIs if clinically indicated.</description>
          <units>percentage</units>
          <param>Number</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="65"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="67" lower_limit="54" upper_limit="77"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Proportion of Participants With Objective Response</title>
        <description>The proportion of participants who demonstrated a complete or partial response as defined by Response Evaluation Criteria in Solid Tumors (RECIST) v1 Criteria where complete Response (CR) is defined as the complete disappearance of all known disease for &gt;=8 weeks. Complete response is dated from time all lesions have disappeared on a stable or decreasing dose of corticosteroids. A Partial Response (PR) is a reduction of at least 50% in the size of all measurable tumor as quantitated by sum of the products of the largest diameters (SLD) of measurable lesions and maintained for &gt;=8 weeks on a stable or decreasing dose of corticosteroids. Partial response is dated from the time of first observation. Overall response also takes into account the response in both the target and non-target lesion, and the appearance of new lesions, where applicable and depend on the achievement of both measurement and confirmation criteria.</description>
        <time_frame>Up to 6 months</time_frame>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Median Progression Free Survival in Recurrent Pediatric Low-grade Glioma (LGGs)</title>
        <description>Progression free survival will be calculated from date of first treatment to the date of first observation of progressive disease, non-reversible neurological progression or increasing steroid requirements (applies to stable disease only), death due to any cause, or early discontinuation of treatment</description>
        <time_frame>Up to 5 years</time_frame>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Median Overall Survival in Recurrent Pediatric LGGs</title>
        <description>Overall survival will be calculated from date of original diagnoses to death and also from the date of study registration to death. The latter will be an endpoint for assessment of benefit of this therapy.</description>
        <time_frame>Up to 5 years</time_frame>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>Up to 5 years</time_frame>
      <group_list>
        <group group_id="E1">
          <title>Everolimus</title>
          <description>Everolimus tablet will be taken daily by mouth with water. Twenty-eight days will constitute one course and subsequent courses will immediately follow with no break in the administration of the drug. Dosing is based on the body surface area (BSA) calculated at the beginning of each course of therapy. Patients will also be provided with a drug diary for everolimus. The maximum time on study is 24-months, but if there is no disease progression or adverse events, the patient may speak with a doctor about continuing the treatment off-study.&#xD;
Everolimus: Everolimus tablet will be taken daily by mouth with water. All patients will be given a dose of 5 mg/m2/dose daily.</description>
        </group>
      </group_list>
      <serious_events>
        <default_vocab>CTCAE (4.0)</default_vocab>
        <default_assessment>Systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, all-cause mortality</sub_title>
                <counts group_id="E1" subjects_affected="5" subjects_at_risk="65"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="20" subjects_at_risk="65"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Ear and labyrinth disorders</title>
            <event_list>
              <event>
                <sub_title>Hearing Impaired</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="65"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Vomiting</sub_title>
                <counts group_id="E1" events="2" subjects_affected="1" subjects_at_risk="65"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Edema face</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="65"/>
              </event>
              <event>
                <sub_title>Fever</sub_title>
                <counts group_id="E1" events="4" subjects_affected="2" subjects_at_risk="65"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Sepsis</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="65"/>
              </event>
              <event>
                <sub_title>Catheter related infection</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="65"/>
              </event>
              <event>
                <sub_title>Infections and infestations - Other</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="65"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Injury, poisoning and procedural complications</title>
            <event_list>
              <event>
                <sub_title>Injury, poisoning and procedural complications - Other</sub_title>
                <counts group_id="E1" events="5" subjects_affected="2" subjects_at_risk="65"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Metabolism and nutrition disorders</title>
            <event_list>
              <event>
                <sub_title>Dehydration</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="65"/>
              </event>
              <event>
                <sub_title>Hypernatremia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="65"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Neoplasms benign, malignant and unspecified (incl cysts and polyps)</title>
            <event_list>
              <event>
                <sub_title>Neoplasms benign, malignant and unspecified (incl cysts and polyps) - Other</sub_title>
                <counts group_id="E1" events="3" subjects_affected="3" subjects_at_risk="65"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Seizure</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="65"/>
              </event>
              <event>
                <sub_title>Cognitive disturbance</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="65"/>
              </event>
              <event>
                <sub_title>Hydrocephalus</sub_title>
                <counts group_id="E1" events="11" subjects_affected="6" subjects_at_risk="65"/>
              </event>
              <event>
                <sub_title>Encephalopathy</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="65"/>
              </event>
              <event>
                <sub_title>Headache</sub_title>
                <counts group_id="E1" events="4" subjects_affected="2" subjects_at_risk="65"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Respiratory failure</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="65"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Skin and subcutaneous tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Skin infection</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="65"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Surgical and medical procedures</title>
            <event_list>
              <event>
                <sub_title>Surgical and medical procedures - Other</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="65"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Vascular disorders</title>
            <event_list>
              <event>
                <sub_title>Hypertension</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="65"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>5</frequency_threshold>
        <default_vocab>CTCAE (4.0)</default_vocab>
        <default_assessment>Systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, other adverse events</sub_title>
                <counts group_id="E1" subjects_affected="62" subjects_at_risk="65"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Blood and lymphatic system disorders</title>
            <event_list>
              <event>
                <sub_title>Anemia</sub_title>
                <counts group_id="E1" events="47" subjects_affected="18" subjects_at_risk="65"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Cardiac disorders</title>
            <event_list>
              <event>
                <sub_title>Sinus tachycardia</sub_title>
                <counts group_id="E1" events="13" subjects_affected="8" subjects_at_risk="65"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Mucositis oral</sub_title>
                <counts group_id="E1" events="93" subjects_affected="35" subjects_at_risk="65"/>
              </event>
              <event>
                <sub_title>Diarrhea</sub_title>
                <counts group_id="E1" events="30" subjects_affected="15" subjects_at_risk="65"/>
              </event>
              <event>
                <sub_title>Nausea</sub_title>
                <counts group_id="E1" events="16" subjects_affected="14" subjects_at_risk="65"/>
              </event>
              <event>
                <sub_title>Vomiting</sub_title>
                <counts group_id="E1" events="13" subjects_affected="11" subjects_at_risk="65"/>
              </event>
              <event>
                <sub_title>Oral pain</sub_title>
                <counts group_id="E1" events="11" subjects_affected="8" subjects_at_risk="65"/>
              </event>
              <event>
                <sub_title>Abdominal pain</sub_title>
                <counts group_id="E1" events="8" subjects_affected="7" subjects_at_risk="65"/>
              </event>
              <event>
                <sub_title>Gastrointestinal disorders - Other</sub_title>
                <counts group_id="E1" events="6" subjects_affected="5" subjects_at_risk="65"/>
              </event>
              <event>
                <sub_title>Stomach pain</sub_title>
                <counts group_id="E1" events="7" subjects_affected="4" subjects_at_risk="65"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Fatigue</sub_title>
                <counts group_id="E1" events="36" subjects_affected="25" subjects_at_risk="65"/>
              </event>
              <event>
                <sub_title>Fever</sub_title>
                <counts group_id="E1" events="18" subjects_affected="9" subjects_at_risk="65"/>
              </event>
              <event>
                <sub_title>Pain</sub_title>
                <counts group_id="E1" events="4" subjects_affected="4" subjects_at_risk="65"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Upper respiratory infection</sub_title>
                <counts group_id="E1" events="9" subjects_affected="8" subjects_at_risk="65"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Investigations</title>
            <event_list>
              <event>
                <sub_title>Cholesterol high</sub_title>
                <counts group_id="E1" events="63" subjects_affected="34" subjects_at_risk="65"/>
              </event>
              <event>
                <sub_title>Aspartate aminotransferase increased</sub_title>
                <counts group_id="E1" events="62" subjects_affected="30" subjects_at_risk="65"/>
              </event>
              <event>
                <sub_title>Alanine aminotransferase increased</sub_title>
                <counts group_id="E1" events="58" subjects_affected="26" subjects_at_risk="65"/>
              </event>
              <event>
                <sub_title>Neutrophil count decreased</sub_title>
                <counts group_id="E1" events="38" subjects_affected="19" subjects_at_risk="65"/>
              </event>
              <event>
                <sub_title>Lymphocyte count decreased</sub_title>
                <counts group_id="E1" events="25" subjects_affected="15" subjects_at_risk="65"/>
              </event>
              <event>
                <sub_title>White blood cell decreased</sub_title>
                <counts group_id="E1" events="46" subjects_affected="15" subjects_at_risk="65"/>
              </event>
              <event>
                <sub_title>Platelet count decreased</sub_title>
                <counts group_id="E1" events="23" subjects_affected="14" subjects_at_risk="65"/>
              </event>
              <event>
                <sub_title>Investigations - Other</sub_title>
                <counts group_id="E1" events="27" subjects_affected="11" subjects_at_risk="65"/>
              </event>
              <event>
                <sub_title>Weight loss</sub_title>
                <counts group_id="E1" events="8" subjects_affected="6" subjects_at_risk="65"/>
              </event>
              <event>
                <sub_title>Alkaline phosphatase increased</sub_title>
                <counts group_id="E1" events="6" subjects_affected="5" subjects_at_risk="65"/>
              </event>
              <event>
                <sub_title>Creatinine increased</sub_title>
                <counts group_id="E1" events="8" subjects_affected="4" subjects_at_risk="65"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Metabolism and nutrition disorders</title>
            <event_list>
              <event>
                <sub_title>Hypertriglyceridemia</sub_title>
                <counts group_id="E1" events="98" subjects_affected="34" subjects_at_risk="65"/>
              </event>
              <event>
                <sub_title>Hyperglycemia</sub_title>
                <counts group_id="E1" events="27" subjects_affected="16" subjects_at_risk="65"/>
              </event>
              <event>
                <sub_title>Hypophosphatemia</sub_title>
                <counts group_id="E1" events="21" subjects_affected="14" subjects_at_risk="65"/>
              </event>
              <event>
                <sub_title>Hypokalemia</sub_title>
                <counts group_id="E1" events="30" subjects_affected="13" subjects_at_risk="65"/>
              </event>
              <event>
                <sub_title>Anorexia</sub_title>
                <counts group_id="E1" events="12" subjects_affected="9" subjects_at_risk="65"/>
              </event>
              <event>
                <sub_title>Hypernatremia</sub_title>
                <counts group_id="E1" events="19" subjects_affected="9" subjects_at_risk="65"/>
              </event>
              <event>
                <sub_title>Metabolism and nutrition disorders - Other</sub_title>
                <counts group_id="E1" events="10" subjects_affected="6" subjects_at_risk="65"/>
              </event>
              <event>
                <sub_title>Hypomagnesemia</sub_title>
                <counts group_id="E1" events="7" subjects_affected="5" subjects_at_risk="65"/>
              </event>
              <event>
                <sub_title>Hypercalcemia</sub_title>
                <counts group_id="E1" events="4" subjects_affected="4" subjects_at_risk="65"/>
              </event>
              <event>
                <sub_title>Hyponatremia</sub_title>
                <counts group_id="E1" events="11" subjects_affected="4" subjects_at_risk="65"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Musculoskeletal and connective tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Pain in extremity</sub_title>
                <counts group_id="E1" events="5" subjects_affected="4" subjects_at_risk="65"/>
              </event>
              <event>
                <sub_title>Musculoskeletal and connective tissue disorder - Other</sub_title>
                <counts group_id="E1" events="5" subjects_affected="4" subjects_at_risk="65"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Headache</sub_title>
                <counts group_id="E1" events="36" subjects_affected="19" subjects_at_risk="65"/>
              </event>
              <event>
                <sub_title>Dizziness</sub_title>
                <counts group_id="E1" events="5" subjects_affected="5" subjects_at_risk="65"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Cough</sub_title>
                <counts group_id="E1" events="9" subjects_affected="7" subjects_at_risk="65"/>
              </event>
              <event>
                <sub_title>Sore throat</sub_title>
                <counts group_id="E1" events="10" subjects_affected="7" subjects_at_risk="65"/>
              </event>
              <event>
                <sub_title>Epistaxis</sub_title>
                <counts group_id="E1" events="7" subjects_affected="6" subjects_at_risk="65"/>
              </event>
              <event>
                <sub_title>Nasal congestion</sub_title>
                <counts group_id="E1" events="6" subjects_affected="5" subjects_at_risk="65"/>
              </event>
              <event>
                <sub_title>Respiratory, thoracic and mediastinal disorders - Other</sub_title>
                <counts group_id="E1" events="4" subjects_affected="4" subjects_at_risk="65"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Skin and subcutaneous tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Rash maculo-papular</sub_title>
                <counts group_id="E1" events="17" subjects_affected="12" subjects_at_risk="65"/>
              </event>
              <event>
                <sub_title>Dry skin</sub_title>
                <counts group_id="E1" events="5" subjects_affected="5" subjects_at_risk="65"/>
              </event>
              <event>
                <sub_title>Rash acneiform</sub_title>
                <counts group_id="E1" events="4" subjects_affected="4" subjects_at_risk="65"/>
              </event>
              <event>
                <sub_title>Skin and subcutaneous tissue disorders - Other</sub_title>
                <counts group_id="E1" events="4" subjects_affected="4" subjects_at_risk="65"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Vascular disorders</title>
            <event_list>
              <event>
                <sub_title>Hypertension</sub_title>
                <counts group_id="E1" events="15" subjects_affected="6" subjects_at_risk="65"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </other_events>
    </reported_events>

    <certain_agreements>
      <pi_employee>All Principal Investigators ARE employed by the organization sponsoring the study.</pi_employee>
      <restrictive_agreement>There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed. </restrictive_agreement>
    </certain_agreements>
    <point_of_contact>
      <name_or_title>Dr. Sabine Mueller, MD, PhD</name_or_title>
      <organization>University of California, San Francisco</organization>
      <phone>(415) 502-7301</phone>
      <email>sabine.mueller@ucsf.edu</email>
    </point_of_contact>
  </clinical_results>
</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/NCT01734512
org study id: 120817
secondary id: NCI-2012-02774
nct id: NCT01734512
lead sponsor: 
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has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
is us export: No
This is an open label study of everolimus in children with recurrent or progressive low-grade
      glioma.
This is an open label study of everolimus in children with recurrent or progressive low-grade
      glioma. All patients will receive everolimus at a dose of 5 mg/m2/dose daily. An adaptive
      Simon two-stage design for phase 2 studies of targeted therapies will be used to assess the
      efficacy primary objective. The proposed treatment with everolimus will be deemed not worthy
      of further investigation in this patient population if the true PFS at 6-months (PFS6) is
      less than 50%. If in the first stage, with a combined sample size of 25, there is preliminary
      evidence to suggest efficacy of everolimus is restricted to patients with PI3K/AKT/mTOR
      activation as measured by p-S6 positivity, a total of 45 patients will be enrolled and the
      design will have 81% statistical power to detect a true disease stabilization rate ≥70%. If
      in the first stage there is preliminary evidence to suggest efficacy of everolimus is
      independent of PI3K/AKT/mTOR activation, a total of 65 patients will be enrolled and the
      design will have >95% statistical power to detect a true disease stabilization rate ≥70%.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Percentage of Participants With Progression Free Survival at 6 Months
time frame: Up to 6 months
description: Response was be determined by bi-dimensional diameters. RECIST criteria will be collected and used for secondary evaluation. Patients will have brain MRI scans with and without gadolinium performed prior to therapy, after every second course in the first year, after every third course in the second year, and at the End of Study visit (if not done within prior 3 months). Spine MRIs should be performed prior to therapy and at the same time points as standard brain MRIs if clinically indicated.
measure: Proportion of Participants With Objective Response
time frame: Up to 6 months
description: The proportion of participants who demonstrated a complete or partial response as defined by Response Evaluation Criteria in Solid Tumors (RECIST) v1 Criteria where complete Response (CR) is defined as the complete disappearance of all known disease for >=8 weeks. Complete response is dated from time all lesions have disappeared on a stable or decreasing dose of corticosteroids. A Partial Response (PR) is a reduction of at least 50% in the size of all measurable tumor as quantitated by sum of the products of the largest diameters (SLD) of measurable lesions and maintained for >=8 weeks on a stable or decreasing dose of corticosteroids. Partial response is dated from the time of first observation. Overall response also takes into account the response in both the target and non-target lesion, and the appearance of new lesions, where applicable and depend on the achievement of both measurement and confirmation criteria.
measure: Median Progression Free Survival in Recurrent Pediatric Low-grade Glioma (LGGs)
time frame: Up to 5 years
description: Progression free survival will be calculated from date of first treatment to the date of first observation of progressive disease, non-reversible neurological progression or increasing steroid requirements (applies to stable disease only), death due to any cause, or early discontinuation of treatment
measure: Median Overall Survival in Recurrent Pediatric LGGs
time frame: Up to 5 years
description: Overall survival will be calculated from date of original diagnoses to death and also from the date of study registration to death. The latter will be an endpoint for assessment of benefit of this therapy.
arm group label: Everolimus
arm group type: Experimental
description: Everolimus tablet will be taken daily by mouth with water. Twenty-eight days will constitute one course and subsequent courses will immediately follow with no break in the administration of the drug. Dosing is based on the body surface area (BSA) calculated at the beginning of each course of therapy. Patients will also be provided with a drug diary for everolimus. The maximum time on study is 24-months, but if there is no disease progression or adverse events, the patient may speak with a doctor about continuing the treatment off-study.
intervention type: Drug
intervention name: Everolimus
description: Everolimus tablet will be taken daily by mouth with water. All patients will be given a dose of 5 mg/m2/dose daily.
arm group label: Everolimus
criteria: 
gender: All
minimum age: 3 Years
maximum age: 21 Years
healthy volunteers: No
last name: Daphne Haas-Kogan, MD
role: Study Chair
affiliation: Dana-Farber Cancer Institute
last name: Sabine Mueller, MD
role: Principal Investigator
affiliation: University of California, San Francisco
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country: United States
responsible party type: Sponsor
mesh term: Glioma
mesh term: Recurrence
mesh term: Everolimus
sharing ipd: No
provided document: 
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 