<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/NCT01682187</url>
  </required_header>
  <id_info>
    <org_study_id>8660</org_study_id>
    <secondary_id>H9H-MC-JBAH</secondary_id>
    <nct_id>NCT01682187</nct_id>
  </id_info>
  <brief_title>A Dose-Escalation Study in Participants With Recurrent Malignant Glioma</brief_title>
  <official_title>Phase 1 Dose-Escalation Study of LY2157299 Monotherapy and in Combination With Lomustine in Patients With Recurrent Malignant Glioma</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>
      This is a study of oral LY2157299 as monotherapy and in combination with lomustine in&#xD;
      participants with recurrent malignant glioma.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Active, not recruiting</overall_status>
  <start_date type="Actual">December 15, 2005</start_date>
  <completion_date type="Anticipated">September 30, 2024</completion_date>
  <primary_completion_date type="Actual">May 22, 2012</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>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Recommended Dose for Phase 2 Studies</measure>
    <time_frame>Time of first dose to time of last dose (estimated up to 8 years)</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>Number of Participants with Tumor Response</measure>
    <time_frame>Time of first dose to time of last dose (estimated up to 8 years)</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Biologically Effective Dose Range</measure>
    <time_frame>Baseline, Days 1, 12, 13 of Cycle 1, Days 1 and 12 of Cycle 2 of Part A - LY2157299 as monotherapy</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Pharmacokinetics (PK): Area Under the Concentration-Time Curve (AUC)</measure>
    <time_frame>Part A Cycle 1: predose, up to 6 hours on Days 1, 3, 6, 12, 13, and 14; Part A Cycle 2: predose up to 6 hours on Days 1, 12, and 13. Part B Cycle 1: predose up to 6 hours on Days 1, 6, 7, 10, 12, 13, and 14</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Pharmacokinetics (PK): Maximum Concentration (Cmax)</measure>
    <time_frame>Part A Cycle 1: predose, up to 6 hours on Days 1, 3, 6, 12, 13, and 14; Part A Cycle 2: predose up to 6 hours on Days 1, 12, and 13. Part B Cycle 1: predose up to 6 hours on Days 1, 6, 7, 10, 12, 13, and 14</time_frame>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">66</enrollment>
  <condition>Glioma</condition>
  <arm_group>
    <arm_group_label>LY2157299 (Part A)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Administered orally by tablet twice daily for two weeks followed by two weeks of no treatment for two 28-day cycles. Part A dose escalation will have starting dose of 40 mg/day and may increase up to 360 mg/day.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>LY2157299 + Lomustine (Part B)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>LY21547299 will be administered orally by tablet twice daily for two weeks followed by two weeks of no treatment for two 28-day cycles. Part B dose expansion will have starting dose of 80 mg twice daily and may increase up to 150 mg twice daily.&#xD;
Lomustine will be administered orally by capsule once on Day 7 of Cycle 1 after receiving LY2157299, and once after receiving LY2157299 on Day 21 of Cycles 2, 5, 8, 11, and every 4th cycle thereafter.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>LY2157299</intervention_name>
    <description>Administered orally</description>
    <arm_group_label>LY2157299 (Part A)</arm_group_label>
    <arm_group_label>LY2157299 + Lomustine (Part B)</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Lomustine</intervention_name>
    <description>Administered orally</description>
    <arm_group_label>LY2157299 + Lomustine (Part B)</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Have given written informed consent&#xD;
&#xD;
          -  Have histological or cytological evidence of relapsed malignant glioma (such as&#xD;
             glioblastoma multiforme, anaplastic astrocytoma, anaplastic oligodendroglioma) for&#xD;
             which no treatment of higher priority exists&#xD;
&#xD;
               -  Available baseline tumor specimen is required prior to considering participant to&#xD;
                  be enrolled. The original diagnostic tumor tissue is sufficient for this&#xD;
                  inclusion criteria, but where possible, freshly obtained tumor biopsy material&#xD;
                  may be obtained&#xD;
&#xD;
               -  Measurable disease to allow assessment of tumor response based on radiographic&#xD;
                  assessment following Macdonald criteria and Response Evaluation Criteria In Solid&#xD;
                  Tumors (RECIST)&#xD;
&#xD;
          -  Have sufficient hepatic, renal, and hematological function&#xD;
&#xD;
          -  Have a performance status of ≤2 on the Eastern Cooperative Oncology Group (ECOG) scale&#xD;
&#xD;
          -  Have discontinued all previous therapies for cancer, including chemotherapy,&#xD;
             radiotherapy or other investigational therapy for at least 30 days prior to study&#xD;
             enrollment and recovered from the acute effects of therapy&#xD;
&#xD;
          -  Able to swallow tablets and capsules&#xD;
&#xD;
          -  For females, reproductive potential must be either terminated (by surgery, radiation,&#xD;
             or menopause) or attenuated by the use of an approved contraceptive method (including&#xD;
             intrauterine or barrier devices) during and for 3 to 6 months after the study&#xD;
&#xD;
          -  Male participants must be willing to use contraception during and for 3 to 6 months&#xD;
             after the study&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Have received treatment within the last 30 days with a drug that has not received&#xD;
             regulatory approval for any indication at the time of study entry&#xD;
&#xD;
          -  Have moderate or severe cardiac disease:&#xD;
&#xD;
               -  Have the presence of cardiac disease, including a myocardial infarction within 6&#xD;
                  months prior to study entry, unstable angina pectoris, New York Heart Association&#xD;
                  (NYHA) Class III/IV congestive heart failure, or uncontrolled hypertension&#xD;
&#xD;
               -  Have documented major electrocardiogram (ECG) abnormalities at the investigator's&#xD;
                  discretion (for example, symptomatic or sustained atrial or ventricular&#xD;
                  arrhythmias, second- or third-degree atrioventricular block, bundle branch&#xD;
                  blocks, ventricular hypertrophy, or recent myocardial infarction)&#xD;
&#xD;
               -  Have major abnormalities documented by echocardiography with Doppler (for&#xD;
                  example, moderate or severe heart valve function defect and/or left ventricular&#xD;
                  ejection fraction (LVEF) &lt;50%, evaluation based on the institutional lower limit&#xD;
                  of normal)&#xD;
&#xD;
               -  Have predisposing conditions that are consistent with development of aneurysms of&#xD;
                  the ascending aorta or aortic stress (for example, family history of aneurysms,&#xD;
                  Marfan syndrome, bicuspid aortic valve, evidence of damage to the large vessels&#xD;
                  of the heart documented by computerized tomography [CT] scan with contrast)&#xD;
&#xD;
          -  Have current acute or chronic leukemia&#xD;
&#xD;
          -  Women who are pregnant or lactating&#xD;
&#xD;
          -  Have received prior nitrosourea (including lomustine) therapy&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>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>Baltimore</city>
        <state>Maryland</state>
        <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>Barcelona</city>
        <country>Spain</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>Madrid</city>
        <country>Spain</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>Sevilla</city>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Spain</country>
    <country>United States</country>
  </location_countries>
  <verification_date>June 1, 2023</verification_date>
  <study_first_submitted>September 6, 2012</study_first_submitted>
  <study_first_submitted_qc>September 6, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">September 10, 2012</study_first_posted>
  <last_update_submitted>June 10, 2023</last_update_submitted>
  <last_update_submitted_qc>June 10, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">June 13, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Glioma</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Lomustine</mesh_term>
  </intervention_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/NCT01682187
org study id: 8660
secondary id: H9H-MC-JBAH
nct id: NCT01682187
lead sponsor: 
has dmc: No
This is a study of oral LY2157299 as monotherapy and in combination with lomustine in
      participants with recurrent malignant glioma.
allocation: Non-Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Recommended Dose for Phase 2 Studies
time frame: Time of first dose to time of last dose (estimated up to 8 years)
measure: Number of Participants with Tumor Response
time frame: Time of first dose to time of last dose (estimated up to 8 years)
measure: Biologically Effective Dose Range
time frame: Baseline, Days 1, 12, 13 of Cycle 1, Days 1 and 12 of Cycle 2 of Part A - LY2157299 as monotherapy
measure: Pharmacokinetics (PK): Area Under the Concentration-Time Curve (AUC)
time frame: Part A Cycle 1: predose, up to 6 hours on Days 1, 3, 6, 12, 13, and 14; Part A Cycle 2: predose up to 6 hours on Days 1, 12, and 13. Part B Cycle 1: predose up to 6 hours on Days 1, 6, 7, 10, 12, 13, and 14
measure: Pharmacokinetics (PK): Maximum Concentration (Cmax)
time frame: Part A Cycle 1: predose, up to 6 hours on Days 1, 3, 6, 12, 13, and 14; Part A Cycle 2: predose up to 6 hours on Days 1, 12, and 13. Part B Cycle 1: predose up to 6 hours on Days 1, 6, 7, 10, 12, 13, and 14
arm group label: LY2157299 (Part A)
arm group type: Experimental
description: Administered orally by tablet twice daily for two weeks followed by two weeks of no treatment for two 28-day cycles. Part A dose escalation will have starting dose of 40 mg/day and may increase up to 360 mg/day.
arm group label: LY2157299 + Lomustine (Part B)
arm group type: Experimental
description: LY21547299 will be administered orally by tablet twice daily for two weeks followed by two weeks of no treatment for two 28-day cycles. Part B dose expansion will have starting dose of 80 mg twice daily and may increase up to 150 mg twice daily.
Lomustine will be administered orally by capsule once on Day 7 of Cycle 1 after receiving LY2157299, and once after receiving LY2157299 on Day 21 of Cycles 2, 5, 8, 11, and every 4th cycle thereafter.
intervention type: Drug
intervention name: LY2157299
description: Administered orally
arm group label: LY2157299 (Part A)
arm group label: LY2157299 + Lomustine (Part B)
intervention type: Drug
intervention name: Lomustine
description: Administered orally
arm group label: LY2157299 + Lomustine (Part B)
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
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: Spain
country: United States
responsible party type: Sponsor
mesh term: Glioma
mesh term: Lomustine