<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/NCT01695005</url>
  </required_header>
  <id_info>
    <org_study_id>14547</org_study_id>
    <secondary_id>I6F-MC-JJCA</secondary_id>
    <nct_id>NCT01695005</nct_id>
  </id_info>
  <brief_title>A Study of LY3039478 in Participants With Advanced Cancer</brief_title>
  <official_title>A Phase 1 Study of LY3039478 in Patients With Advanced or Metastatic Cancer</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>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      The purpose of this study is to find a recommended dose level of LY3039478 that can safely be&#xD;
      taken by participants with advanced cancer or cancer that has spread to other parts of the&#xD;
      body, including but not limited to lymphoma. The study will also explore changes to various&#xD;
      markers in blood cells and tissue. Finally, the study will help to document any tumor&#xD;
      activity this drug may have.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      In Part A of this study, participants with advanced/metastatic cancer (including lymphoma)&#xD;
      will receive increasing doses of LY3039478 to define the dose level for Part B, C, D and E.&#xD;
      In Part B, C, D and E LY3039478 will be explored at a predefined fixed dose level.&#xD;
      Participants in Part B and D must have a defined alteration in a certain molecular pathway.&#xD;
      Enrollment of participants in Part B, C, D and E will start once Part A is completed. In Part&#xD;
      F participants will receive increasing doses of LY3039478 in combination with prednisone to&#xD;
      define the maximum tolerated dose level.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>October 2012</start_date>
  <completion_date type="Actual">June 26, 2018</completion_date>
  <primary_completion_date type="Actual">June 26, 2018</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>Part A and F: Number of Participants with Dose Limiting Toxicities (DLTs)</measure>
    <time_frame>Baseline to disease progression or participant discontinuation (estimated 8 -12 weeks)</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Part B, C, D, E and F: Number of Participants with Tumor Response</measure>
    <time_frame>Baseline to disease progression or participant discontinuation (estimated 8 -12 weeks)</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>Pharmacokinetics: Maximum Concentration (Cmax) of LY3039478</measure>
    <time_frame>Predose up to 30 hours post dose</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Pharmacokinetics: Time to Maximum Concentration (Tmax) of LY3039478</measure>
    <time_frame>Predose up to 30 hours post dose</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Part A: Number of Participants with Tumor Response</measure>
    <time_frame>Baseline to disease progression or participant discontinuation (estimated 8 -12 weeks)</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Part B, C, D, E and F: Duration of Response (DoR)</measure>
    <time_frame>Date of Complete Response or Partial Response to Date of Objective Disease Progression or Death Due to Any Cause (Estimated up to 6 Months)</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Part B, C, D, E and F: Progression Free Survival (PFS)</measure>
    <time_frame>Baseline to Objective Progression or Death from Any Cause (Estimated up to 6 Months)</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Part B, C, D, E and F: Overall Survival (OS)</measure>
    <time_frame>Baseline to Date of Death from Any Cause (Estimated up to 14 Months)</time_frame>
  </secondary_outcome>
  <number_of_arms>4</number_of_arms>
  <enrollment type="Actual">237</enrollment>
  <condition>Neoplasms</condition>
  <condition>Neoplasm Metastasis</condition>
  <condition>Lymphoma</condition>
  <arm_group>
    <arm_group_label>LY3039478 - Dose Escalation</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Part A: LY3039478 administered orally three times per week (TIW) at escalating doses (2.5 milligrams [mg] to 100 mg) for two 28 day cycles. Participants receiving benefit may continue until disease progression</description>
  </arm_group>
  <arm_group>
    <arm_group_label>LY3039478 - Cohort Expansion</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Part B, C, D and E: LY3039478 administered orally three times per week (TIW) at a fixed dose determined in Part A for two 28 day cycles. Participants receiving benefit may continue until disease progression.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Dose 1 LY3039478 + Prednisone</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Part F1: LY3039478 administered orally TIW for 28 day cycles. Prednisone will be co-administered with LY3039478 for the first 2 weeks in cycle 1 only (28 day cycles). Participants receiving benefit may continue until disease progression.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Dose 2 LY3039478 + Prednisone</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Part F2: LY3039478 administered orally TIW (twice a week in cycle 1) for 28 day cycles. Prednisone will be co-administered with LY3039478 for the first 2 weeks in cycle 1 only. Participants receiving benefit may continue until disease progression.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>LY3039478</intervention_name>
    <description>Administered orally</description>
    <arm_group_label>Dose 1 LY3039478 + Prednisone</arm_group_label>
    <arm_group_label>Dose 2 LY3039478 + Prednisone</arm_group_label>
    <arm_group_label>LY3039478 - Cohort Expansion</arm_group_label>
    <arm_group_label>LY3039478 - Dose Escalation</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Prednisone</intervention_name>
    <description>Administered orally</description>
    <arm_group_label>Dose 1 LY3039478 + Prednisone</arm_group_label>
    <arm_group_label>Dose 2 LY3039478 + Prednisone</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  For all parts: The participant must be, in the judgment of the investigator, an&#xD;
             appropriate candidate for experimental therapy after available standard therapies have&#xD;
             failed to provide clinical benefit for their advanced or metastatic cancer.&#xD;
&#xD;
          -  For Dose Escalation (Part A): The participant must have histological or cytological&#xD;
             evidence of cancer, either a solid tumor or a lymphoma, which is advanced or&#xD;
             metastatic.&#xD;
&#xD;
          -  For Part B: All participants must have a histological evidence of their advanced or&#xD;
             metastatic cancer and prescreened alterations in a defined pathway.&#xD;
&#xD;
          -  For Part C: All participants must have histological evidence of advanced or metastatic&#xD;
             specific subtypes of soft tissue sarcoma.&#xD;
&#xD;
          -  For Part D: All participants must have histological evidence of advanced or metastatic&#xD;
             cancer and prescreened alterations in a defined pathway.&#xD;
&#xD;
          -  Cohort 1: Participants must have triple negative breast cancer.&#xD;
&#xD;
          -  Cohort 2: Participants must have hepatocellular carcinoma (HCC). These participants&#xD;
             should have Child-Pugh stage A.&#xD;
&#xD;
          -  Cohort 3: Participants must have cholangiocarcinoma.&#xD;
&#xD;
          -  Cohort 4: Participants must have chronic lymphocytic leukemia.&#xD;
&#xD;
          -  Cohort 5: Participants must have a mature T cell, B cell, or natural killer (NK) cell&#xD;
             neoplasm.&#xD;
&#xD;
          -  For Part E: Participants must have adenoid cystic carcinoma (ACC).&#xD;
&#xD;
          -  For Part F dose confirmation: Participants must have leiomyosarcoma and prescreened&#xD;
             alterations in a defined pathway.&#xD;
&#xD;
          -  As defined by the Response Evaluation Criteria in Solid Tumors (RECIST 1.1), the&#xD;
             Revised Response Criteria for Malignant Lymphoma or the Response Assessment in Neuro&#xD;
             Oncology (RANO) criteria for glioblastoma:&#xD;
&#xD;
               -  For Dose Escalation (Part A): Have measurable or nonmeasurable disease.&#xD;
&#xD;
               -  For Parts B, C, D, E and F: Have measurable disease or reliable biomarker&#xD;
                  measure.&#xD;
&#xD;
          -  For Parts B, C, D, E and F: Have available tumor tissue.&#xD;
&#xD;
          -  Have adequate organ function.&#xD;
&#xD;
          -  Have a performance status of less than or equal to 1 on the Eastern Cooperative&#xD;
             Oncology Group (ECOG) scale and life expectancy of more than 12 weeks.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Have symptomatic or non stable central nervous system (CNS) malignancy.&#xD;
&#xD;
          -  Females who are pregnant or lactating.&#xD;
&#xD;
          -  Have active bacterial, fungal, and/or known viral infection.&#xD;
&#xD;
          -  Have malabsorptive syndromes, enteropathies, gastroenteritis (acute or chronic), or&#xD;
             diarrhea (acute or chronic).&#xD;
&#xD;
          -  Participants with HCC that:&#xD;
&#xD;
               -  Have known HCC with fibro-lamellar or mixed histology.&#xD;
&#xD;
               -  Have presence of clinically relevant ascites.&#xD;
&#xD;
               -  Have had a liver transplant.&#xD;
&#xD;
               -  Have active or uncontrolled clinically serious hepatitis B virus or hepatitis C&#xD;
                  virus infection.&#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>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>University of Miami School of Medicine</name>
      <address>
        <city>Miami</city>
        <state>Florida</state>
        <zip>33136</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Harvard Medical School</name>
      <address>
        <city>Boston</city>
        <state>Massachusetts</state>
        <zip>02215</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Michigan</name>
      <address>
        <city>Ann Arbor</city>
        <state>Michigan</state>
        <zip>48109</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Montefiore Medical Center</name>
      <address>
        <city>Bronx</city>
        <state>New York</state>
        <zip>10461</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Columbia University Medical Center</name>
      <address>
        <city>New York</city>
        <state>New York</state>
        <zip>10032</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>Kobenhavn</city>
        <zip>2100</zip>
        <country>Denmark</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>Paris</city>
        <zip>75248</zip>
        <country>France</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>Villejuif</city>
        <zip>94805</zip>
        <country>France</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>Tübingen</city>
        <zip>72076</zip>
        <country>Germany</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>
        <zip>08035</zip>
        <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>London</city>
        <zip>SE1 9RT</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Denmark</country>
    <country>France</country>
    <country>Germany</country>
    <country>Spain</country>
    <country>United Kingdom</country>
    <country>United States</country>
  </location_countries>
  <link>
    <url>https://www.lillytrialguide.com/en-US/studies/solid-tumor/JJCA#?postal=</url>
    <description>Click here for more information about this study: A Study of LY3039478 in Participants with Advanced Cancer</description>
  </link>
  <verification_date>August 2018</verification_date>
  <study_first_submitted>September 24, 2012</study_first_submitted>
  <study_first_submitted_qc>September 24, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">September 27, 2012</study_first_posted>
  <last_update_submitted>August 6, 2018</last_update_submitted>
  <last_update_submitted_qc>August 6, 2018</last_update_submitted_qc>
  <last_update_posted type="Actual">August 7, 2018</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>Neoplasms</mesh_term>
    <mesh_term>Neoplasm Metastasis</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Prednisone</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/NCT01695005
org study id: 14547
secondary id: I6F-MC-JJCA
nct id: NCT01695005
lead sponsor: 
has dmc: No
is fda regulated drug: Yes
is fda regulated device: No
The purpose of this study is to find a recommended dose level of LY3039478 that can safely be
      taken by participants with advanced cancer or cancer that has spread to other parts of the
      body, including but not limited to lymphoma. The study will also explore changes to various
      markers in blood cells and tissue. Finally, the study will help to document any tumor
      activity this drug may have.
In Part A of this study, participants with advanced/metastatic cancer (including lymphoma)
      will receive increasing doses of LY3039478 to define the dose level for Part B, C, D and E.
      In Part B, C, D and E LY3039478 will be explored at a predefined fixed dose level.
      Participants in Part B and D must have a defined alteration in a certain molecular pathway.
      Enrollment of participants in Part B, C, D and E will start once Part A is completed. In Part
      F participants will receive increasing doses of LY3039478 in combination with prednisone to
      define the maximum tolerated dose level.
allocation: Non-Randomized
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Part A and F: Number of Participants with Dose Limiting Toxicities (DLTs)
time frame: Baseline to disease progression or participant discontinuation (estimated 8 -12 weeks)
measure: Part B, C, D, E and F: Number of Participants with Tumor Response
time frame: Baseline to disease progression or participant discontinuation (estimated 8 -12 weeks)
measure: Pharmacokinetics: Maximum Concentration (Cmax) of LY3039478
time frame: Predose up to 30 hours post dose
measure: Pharmacokinetics: Time to Maximum Concentration (Tmax) of LY3039478
time frame: Predose up to 30 hours post dose
measure: Part A: Number of Participants with Tumor Response
time frame: Baseline to disease progression or participant discontinuation (estimated 8 -12 weeks)
measure: Part B, C, D, E and F: Duration of Response (DoR)
time frame: Date of Complete Response or Partial Response to Date of Objective Disease Progression or Death Due to Any Cause (Estimated up to 6 Months)
measure: Part B, C, D, E and F: Progression Free Survival (PFS)
time frame: Baseline to Objective Progression or Death from Any Cause (Estimated up to 6 Months)
measure: Part B, C, D, E and F: Overall Survival (OS)
time frame: Baseline to Date of Death from Any Cause (Estimated up to 14 Months)
arm group label: LY3039478 - Dose Escalation
arm group type: Experimental
description: Part A: LY3039478 administered orally three times per week (TIW) at escalating doses (2.5 milligrams [mg] to 100 mg) for two 28 day cycles. Participants receiving benefit may continue until disease progression
arm group label: LY3039478 - Cohort Expansion
arm group type: Experimental
description: Part B, C, D and E: LY3039478 administered orally three times per week (TIW) at a fixed dose determined in Part A for two 28 day cycles. Participants receiving benefit may continue until disease progression.
arm group label: Dose 1 LY3039478 + Prednisone
arm group type: Experimental
description: Part F1: LY3039478 administered orally TIW for 28 day cycles. Prednisone will be co-administered with LY3039478 for the first 2 weeks in cycle 1 only (28 day cycles). Participants receiving benefit may continue until disease progression.
arm group label: Dose 2 LY3039478 + Prednisone
arm group type: Experimental
description: Part F2: LY3039478 administered orally TIW (twice a week in cycle 1) for 28 day cycles. Prednisone will be co-administered with LY3039478 for the first 2 weeks in cycle 1 only. Participants receiving benefit may continue until disease progression.
intervention type: Drug
intervention name: LY3039478
description: Administered orally
arm group label: Dose 1 LY3039478 + Prednisone
arm group label: Dose 2 LY3039478 + Prednisone
arm group label: LY3039478 - Cohort Expansion
arm group label: LY3039478 - Dose Escalation
intervention type: Drug
intervention name: Prednisone
description: Administered orally
arm group label: Dose 1 LY3039478 + Prednisone
arm group label: Dose 2 LY3039478 + Prednisone
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: 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: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
country: Denmark
country: France
country: Germany
country: Spain
country: United Kingdom
country: United States
url: https://www.lillytrialguide.com/en-US/studies/solid-tumor/JJCA#?postal=
description: Click here for more information about this study: A Study of LY3039478 in Participants with Advanced Cancer
responsible party type: Sponsor
mesh term: Neoplasms
mesh term: Neoplasm Metastasis
mesh term: Prednisone