<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/NCT01697514</url>
  </required_header>
  <id_info>
    <org_study_id>14492</org_study_id>
    <secondary_id>I4J-MC-HHBD</secondary_id>
    <nct_id>NCT01697514</nct_id>
  </id_info>
  <brief_title>A Study of LY2940680 in Pediatric Medulloblastoma or Rhabdomyosarcoma</brief_title>
  <official_title>A Phase 1 Trial of LY2940680 in Pediatric Patients With Recurrent or Refractory Rhabdomyosarcoma or Medulloblastoma</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Eli Lilly and Company</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Eli Lilly and Company</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The purpose of this study is to find a recommended dose level of LY2940680 that can be safely&#xD;
      given to children with medulloblastoma or rhabdomyosarcoma that has returned or doesn't&#xD;
      respond to initial treatment. The study will also explore the changes in a cancer marker&#xD;
      levels. Finally, the study will help document any antitumor activity.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Withdrawn</overall_status>
  <why_stopped>
    Trial stopped early for poor accrual.&#xD;
  </why_stopped>
  <start_date>July 2013</start_date>
  <completion_date type="Anticipated">July 2016</completion_date>
  <primary_completion_date type="Anticipated">July 2016</primary_completion_date>
  <phase>Phase 1</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Non-Randomized</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Maximum Tolerated Dose of LY2940680</measure>
    <time_frame>Baseline to Part A Completion (estimated as 12 months)</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>Pharmacokinetics: Area Under the Concentration - Time Curve (AUC) of LY2940680 and LSN2941091</measure>
    <time_frame>Predose up to 24 hours Postdose</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Pharmacokinetics: Maximum Concentration (Cmax) of LY2940680 and LSN2941091</measure>
    <time_frame>Predose up to 24 hours Postdose</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Pharmacokinetics: Time of Maximal Concentration (Tmax) of LY2940680 and LSN2941091</measure>
    <time_frame>Predose up to 24 hours Postdose</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of Participants with Tumor Response</measure>
    <time_frame>Baseline to Study Completion (estimated as 44 months)</time_frame>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">0</enrollment>
  <condition>Medulloblastoma, Childhood</condition>
  <condition>Rhabdomyosarcoma</condition>
  <arm_group>
    <arm_group_label>Part A: LY2940680 (Dose Escalation)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>LY2940680 administered orally once daily at escalating doses (92.5 milligrams per square meter [mg/m^2] up to 370 mg/m^2) for two 28 day cycles. Lower dose levels (23 mg/m^2 and 46 mg/m^2) may also be explored, if necessary. Participants receiving benefit may continue until disease progression, unacceptable toxicity, or discontinuation.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Part B: LY2940680 (Dose Confirmation)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>LY2940680 administered orally once daily for two 28 day cycles. Dose based on Part A. Participants receiving benefit may continue until disease progression, unacceptable toxicity, or discontinuation.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>LY2940680</intervention_name>
    <description>Capsule administered orally.</description>
    <arm_group_label>Part A: LY2940680 (Dose Escalation)</arm_group_label>
    <arm_group_label>Part B: LY2940680 (Dose Confirmation)</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>LY2940680</intervention_name>
    <description>Powder administered orally (may be sprinkled on soft food).</description>
    <arm_group_label>Part A: LY2940680 (Dose Escalation)</arm_group_label>
    <arm_group_label>Part B: LY2940680 (Dose Confirmation)</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  For Part A: Have a diagnosis of recurrent or refractory rhabdomyosarcoma or&#xD;
             medulloblastoma and have had histologic verification of malignancy at original&#xD;
             diagnosis or relapse.&#xD;
&#xD;
          -  For Part B: Have a diagnosis of recurrent or refractory medulloblastoma and have had&#xD;
             histologic verification of malignancy at original diagnosis or relapse.&#xD;
&#xD;
          -  Current disease state must be one for which there is no known curative therapy or&#xD;
             therapy proven to prolong survival with an acceptable quality of life.&#xD;
&#xD;
          -  Karnofsky score must be at least 50% for participants &gt;16 years of age, and Lansky&#xD;
             score must be at least 50% for participants 16 years of age or less. Participants who&#xD;
             are unable to walk because of paralysis, but who are in a wheelchair, will be&#xD;
             considered ambulatory for the purpose of assessing the performance score.&#xD;
&#xD;
          -  Have fully recovered from the acute toxic effects of all prior anticancer&#xD;
             chemotherapy.&#xD;
&#xD;
               -  Participants with solid tumors must not have received myelosuppressive&#xD;
                  chemotherapy within 3 weeks of enrollment in this study (6 weeks, if previously&#xD;
                  treated with nitrosourea).&#xD;
&#xD;
               -  Hematopoietic growth factors: At least 14 days after the last dose of a&#xD;
                  longacting growth factor (eg, Neulasta®) or 7 days for short-acting growth&#xD;
                  factor.&#xD;
&#xD;
               -  Biologic (antineoplastic agent): At least 7 days after the last dose of a&#xD;
                  biologic agent.&#xD;
&#xD;
               -  Immunotherapy: At least 6 weeks since the completion of any type of immunotherapy&#xD;
                  (eg, tumor vaccines).&#xD;
&#xD;
               -  Monoclonal antibodies: At least 3 half-lives of the antibody after the last dose&#xD;
                  of a monoclonal antibody.&#xD;
&#xD;
               -  Radiation therapy (XRT): ≥8 weeks for local irradiation to primary tumor;≥2 weeks&#xD;
                  prior to study entry for focal irradiation for symptomatic metastatic sites; ≥3&#xD;
                  months for craniospinal XRT, or ≥24 weeks if ≥50% radiation of pelvis; minimum of&#xD;
                  6 weeks must have elapsed if other substantial bone marrow radiation has been&#xD;
                  received.&#xD;
&#xD;
               -  Stem cell transplant: allowed if they have recovered from all acute toxicity and&#xD;
                  adequate bone marrow reserve is demonstrated. At least 8 weeks must have elapsed&#xD;
                  since autologous stem cell transplantation or ≥3 months for allogenic&#xD;
                  transplantation. Participants must be off all immunosuppressive therapy and have&#xD;
                  no evidence of active graft-versus-host disease.&#xD;
&#xD;
          -  Have adequate organ function, including:&#xD;
&#xD;
               -  Bone marrow: Peripheral absolute neutrophil count (ANC) ≥500/cubic millimeter&#xD;
                  (mm^3) and platelet count ≥100,000/mm^3 (transfusion independent, defined as not&#xD;
                  receiving platelet transfusions within a 7-day period prior to enrollment).&#xD;
&#xD;
               -  Hepatic: Bilirubin (sum of conjugated + unconjugated)≤1.5 × upper limit of normal&#xD;
                  (ULN) for age. Serum alanine aminotransferase (ALT) and aspartate&#xD;
                  aminotransferase (AST) ≤2.0 times ULN for age. Serum albumin ≥2 grams/deciliter&#xD;
                  (g/dL).&#xD;
&#xD;
               -  Renal: Creatinine clearance or radioisotope glomerular filtration rate (GFR)&#xD;
&#xD;
                  ≥70 milliliters/minute/1.73 square meters (mL/min/1.73 m^2), or a serum&#xD;
                  creatinine based on age/gender per the Schwartz formula for estimating GFR&#xD;
                  utilizing child length and stature data published by the Centers for Disease&#xD;
                  Control and Prevention (CDC).&#xD;
&#xD;
               -  Neurologic: Participants with seizure disorders may be enrolled if receiving&#xD;
                  nonenzyme-inducing anticonvulsants and if the symptoms are well controlled. They&#xD;
                  must have a stable neurologic status for at least 1 week prior to enrollment in&#xD;
                  the study.&#xD;
&#xD;
          -  Must be able to swallow powder or a capsule.&#xD;
&#xD;
          -  Have the presence of either measurable or nonmeasurable disease.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Have received treatment within 21 days of the initial dose of study drug with an&#xD;
             experimental agent for noncancer indications that has not received regulatory approval&#xD;
             for any indication.&#xD;
&#xD;
          -  Receiving corticosteroids and have not been on a stable or decreasing dose of&#xD;
             corticosteroid for the prior 7 days.&#xD;
&#xD;
          -  Receiving enzyme-inducing anticonvulsants.&#xD;
&#xD;
          -  Have serious preexisting medical conditions.&#xD;
&#xD;
          -  Have current hematologic malignancies or acute or chronic leukemia.&#xD;
&#xD;
          -  Have a known active fungal, bacterial, and/or known viral infection, including human&#xD;
             immunodeficiency virus (HIV) or viral (A, B, or C) hepatitis (screening is not&#xD;
             required).&#xD;
&#xD;
          -  Have a second primary malignancy that, in the judgment of the investigator and&#xD;
             sponsor, may affect the interpretation of results.&#xD;
&#xD;
          -  Have ≥Grade 2 QT prolongation, that is, QTc interval of &gt;480 milliseconds (msec) on&#xD;
             screening electrocardiography (ECG).&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>12 Months</minimum_age>
    <maximum_age>21 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon - Fri 9 AM - 5 PM Eastern time (UTC/GMT - 5 hours, EST)</last_name>
    <role>Study Director</role>
    <affiliation>Eli Lilly and Company</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.</name>
      <address>
        <city>San Diego</city>
        <state>California</state>
        <zip>92123</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.</name>
      <address>
        <city>Aurora</city>
        <state>Colorado</state>
        <zip>80045</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.</name>
      <address>
        <city>Cincinnati</city>
        <state>Ohio</state>
        <zip>45229</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.</name>
      <address>
        <city>Portland</city>
        <state>Oregon</state>
        <zip>97239</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>August 2013</verification_date>
  <study_first_submitted>September 28, 2012</study_first_submitted>
  <study_first_submitted_qc>September 28, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">October 2, 2012</study_first_posted>
  <last_update_submitted>August 26, 2013</last_update_submitted>
  <last_update_submitted_qc>August 26, 2013</last_update_submitted_qc>
  <last_update_posted type="Estimate">August 27, 2013</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>recurrent medulloblastoma</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Rhabdomyosarcoma</mesh_term>
    <mesh_term>Medulloblastoma</mesh_term>
  </condition_browse>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT01697514
org study id: 14492
secondary id: I4J-MC-HHBD
nct id: NCT01697514
lead sponsor: 
has dmc: No
The purpose of this study is to find a recommended dose level of LY2940680 that can be safely
      given to children with medulloblastoma or rhabdomyosarcoma that has returned or doesn't
      respond to initial treatment. The study will also explore the changes in a cancer marker
      levels. Finally, the study will help document any antitumor activity.
allocation: Non-Randomized
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Maximum Tolerated Dose of LY2940680
time frame: Baseline to Part A Completion (estimated as 12 months)
measure: Pharmacokinetics: Area Under the Concentration - Time Curve (AUC) of LY2940680 and LSN2941091
time frame: Predose up to 24 hours Postdose
measure: Pharmacokinetics: Maximum Concentration (Cmax) of LY2940680 and LSN2941091
time frame: Predose up to 24 hours Postdose
measure: Pharmacokinetics: Time of Maximal Concentration (Tmax) of LY2940680 and LSN2941091
time frame: Predose up to 24 hours Postdose
measure: Number of Participants with Tumor Response
time frame: Baseline to Study Completion (estimated as 44 months)
arm group label: Part A: LY2940680 (Dose Escalation)
arm group type: Experimental
description: LY2940680 administered orally once daily at escalating doses (92.5 milligrams per square meter [mg/m^2] up to 370 mg/m^2) for two 28 day cycles. Lower dose levels (23 mg/m^2 and 46 mg/m^2) may also be explored, if necessary. Participants receiving benefit may continue until disease progression, unacceptable toxicity, or discontinuation.
arm group label: Part B: LY2940680 (Dose Confirmation)
arm group type: Experimental
description: LY2940680 administered orally once daily for two 28 day cycles. Dose based on Part A. Participants receiving benefit may continue until disease progression, unacceptable toxicity, or discontinuation.
intervention type: Drug
intervention name: LY2940680
description: Capsule administered orally.
arm group label: Part A: LY2940680 (Dose Escalation)
arm group label: Part B: LY2940680 (Dose Confirmation)
intervention type: Drug
intervention name: LY2940680
description: Powder administered orally (may be sprinkled on soft food).
arm group label: Part A: LY2940680 (Dose Escalation)
arm group label: Part B: LY2940680 (Dose Confirmation)
criteria: 
gender: All
minimum age: 12 Months
maximum age: 21 Years
healthy volunteers: No
last name: Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon - Fri 9 AM - 5 PM Eastern time (UTC/GMT - 5 hours, EST)
role: Study Director
affiliation: Eli Lilly and Company
facility: 
facility: 
facility: 
facility: 
country: United States
responsible party type: Sponsor
mesh term: Rhabdomyosarcoma
mesh term: Medulloblastoma