<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/NCT03027284</url>
  </required_header>
  <id_info>
    <org_study_id>16330</org_study_id>
    <secondary_id>I3O-JE-JSBG</secondary_id>
    <nct_id>NCT03027284</nct_id>
  </id_info>
  <brief_title>A Study of Merestinib (LY2801653) in Japanese Participants With Advanced or Metastatic Cancer</brief_title>
  <official_title>A Phase I Study of Merestinib Monotherapy or in Combination With Other Anti-Cancer Agents in Japanese Patients With Advanced and/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>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      The main purpose of this study is to evaluate tolerability of merestinib monotherapy or in&#xD;
      combination with other anti-cancer agents in Japanese participants with advanced and/or&#xD;
      metastatic cancer.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">February 3, 2017</start_date>
  <completion_date type="Actual">March 17, 2020</completion_date>
  <primary_completion_date type="Actual">June 20, 2019</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>Number of Participants with Merestinib Dose-Limiting Toxicities (DLTs)</measure>
    <time_frame>Cycle 1 (Part A = 28 Days or Part B = 21 Days)</time_frame>
    <description>Number of participants with DLTs</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Pharmacokinetics (PK): Maximum Concentration (Cmax) of Merestinib and its Metabolites</measure>
    <time_frame>Predose Cycle 1 Throughout the First 2 Cycles (Part A = 28-Day Cycles, Part B = 21-Day Cycles)</time_frame>
    <description>PK: Cmax of merestinib and its metabolites</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>PK: Area Under the Concentration Time Curve (AUC) of Merestinib and its Metabolites</measure>
    <time_frame>Predose Cycle 1 Throughout the First 2 Cycles (Part A = 28-Day Cycles, Part B = 21-Day Cycles)</time_frame>
    <description>PK: AUC of merestinib and its metabolites</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Objective Response Rate (ORR): Percentage of Participants With a Complete or Partial Response</measure>
    <time_frame>Baseline to Measured Progressive Disease or Start of New Anti-Cancer Therapy (Estimated as up to 8 Months)</time_frame>
    <description>ORR: Percentage of participants with a complete or partial response</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Disease Control Rate (DCR): Percentage of Participants with a Best Overall Response of Complete Response, Partial Response, and Stable Disease</measure>
    <time_frame>Baseline to Measured Progressive Disease or Start of New Anti-Cancer Therapy (Estimated as up to 8 Months)</time_frame>
    <description>DCR: Percentage of participants with a best overall response of complete response, partial response, and stable disease</description>
  </secondary_outcome>
  <number_of_arms>3</number_of_arms>
  <enrollment type="Actual">19</enrollment>
  <condition>Advanced Cancer</condition>
  <condition>Metastatic Cancer</condition>
  <condition>Biliary Tract Carcinoma</condition>
  <condition>Cholangiocarcinoma</condition>
  <condition>Gall Bladder Carcinoma</condition>
  <condition>Solid Tumor</condition>
  <condition>Non-Hodgkin's Lymphoma</condition>
  <arm_group>
    <arm_group_label>Merestinib (Part A Dose Level 1)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Merestinib administered orally. Treatment will continue until disease progression, development of unacceptable toxicity, or other discontinuation criteria are met.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Merestinib (Part A Dose Level 2)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Merestinib administered orally. Treatment will continue until disease progression, development of unacceptable toxicity, or other discontinuation criteria are met.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Merestinib + Cisplatin + Gemcitabine (Part B)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Merestinib administered orally with cisplatin and gemcitabine administered intravenously (IV). Treatment will continue until disease progression, development of unacceptable toxicity, or other discontinuation criteria are met, but Cisplatin and gemcitabine treatment will be limited to a maximum of 8 cycles.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Merestinib</intervention_name>
    <description>Administered orally</description>
    <arm_group_label>Merestinib (Part A Dose Level 1)</arm_group_label>
    <arm_group_label>Merestinib (Part A Dose Level 2)</arm_group_label>
    <arm_group_label>Merestinib + Cisplatin + Gemcitabine (Part B)</arm_group_label>
    <other_name>LY2801653</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Cisplatin</intervention_name>
    <description>Administered IV</description>
    <arm_group_label>Merestinib + Cisplatin + Gemcitabine (Part B)</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Gemcitabine</intervention_name>
    <description>Administered IV</description>
    <arm_group_label>Merestinib + Cisplatin + Gemcitabine (Part B)</arm_group_label>
    <other_name>LY188011</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Part A: Histological or cytological evidence of a diagnosis of cancer that is advanced&#xD;
             and/or metastatic (solid tumors or non-Hodgkin's lymphoma).&#xD;
&#xD;
          -  Part B: Biliary tract carcinoma that is unresectable, recurrent, or metastatic. The&#xD;
             participant must not have received prior systemic front-line therapy for metastatic or&#xD;
             resectable disease.&#xD;
&#xD;
          -  Part A: Measurable or nonmeasurable disease as defined by Response Evaluation Criteria&#xD;
             in Solid Tumors (RECIST) v1.1 or Cheson Criteria.&#xD;
&#xD;
          -  Part B: Measurable disease as defined by RECIST v1.1.&#xD;
&#xD;
          -  Adequate organ function including hematologic, hepatic and renal.&#xD;
&#xD;
          -  Eastern Cooperative Oncology Group (ECOG) scale of 0 or 1.&#xD;
&#xD;
          -  Are able to swallow tablets.&#xD;
&#xD;
          -  For participants in Part B, a tumor tissue sample is mandatory for biomarker analysis.&#xD;
&#xD;
          -  Males must agree to use medically approved barrier contraceptive precautions during&#xD;
             the study and for 3 months following the last dose of study drug.&#xD;
&#xD;
          -  Females with childbearing potential: Must agree to use medically approved&#xD;
             contraceptive precautions during the study and for 3 months following the last dose of&#xD;
             study drug, must have had a negative serum or urine pregnancy test ≤7 days before the&#xD;
             first dose of study drug.&#xD;
&#xD;
          -  A breastfeeding woman must not be breastfeeding. If a female who stops breastfeeding&#xD;
             enters the study, breastfeeding must cease from the day of the first study drug&#xD;
             administration until at least 3 months after the last administration.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Have serious pre-existing medical conditions.&#xD;
&#xD;
          -  Have a chronic underlying infection.&#xD;
&#xD;
          -  Have symptomatic central nervous system malignancy or metastasis.&#xD;
&#xD;
          -  Have an active fungal, bacterial, and/or known viral infection.&#xD;
&#xD;
          -  Part B: Have mixed hepatocellular biliary tract carcinoma histology.&#xD;
&#xD;
          -  Have liver cirrhosis with a Child-Pugh stage of B or higher, or have received a liver&#xD;
             transplant.&#xD;
&#xD;
          -  Have a history of congestive heart failure with New York Heart Association (NYHA)&#xD;
             class greater than 2, unstable angina, or have recent history of myocardial&#xD;
             infarction, transient ischemic attacks, stroke, or arterial or venous vascular&#xD;
             disease.&#xD;
&#xD;
          -  Have a corrected QT interval &gt;470 milliseconds as calculated be the Fredericia&#xD;
             equation.&#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 any evidence of clinically active interstitial lung disease (ILD).&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>20 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>Chiba</city>
        <zip>277 8577</zip>
        <country>Japan</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>Tokyo</city>
        <zip>104-0045</zip>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Japan</country>
  </location_countries>
  <verification_date>May 15, 2020</verification_date>
  <study_first_submitted>January 19, 2017</study_first_submitted>
  <study_first_submitted_qc>January 19, 2017</study_first_submitted_qc>
  <study_first_posted type="Estimate">January 23, 2017</study_first_posted>
  <last_update_submitted>May 18, 2020</last_update_submitted>
  <last_update_submitted_qc>May 18, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">May 19, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Neoplasm</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Carcinoma</mesh_term>
    <mesh_term>Cholangiocarcinoma</mesh_term>
    <mesh_term>Neoplasm Metastasis</mesh_term>
    <mesh_term>Neoplasms</mesh_term>
    <mesh_term>Neoplasms, Second Primary</mesh_term>
    <mesh_term>Urinary Bladder Neoplasms</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Gemcitabine</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/NCT03027284
org study id: 16330
secondary id: I3O-JE-JSBG
nct id: NCT03027284
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
The main purpose of this study is to evaluate tolerability of merestinib monotherapy or in
      combination with other anti-cancer agents in Japanese participants with advanced and/or
      metastatic cancer.
allocation: Non-Randomized
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Number of Participants with Merestinib Dose-Limiting Toxicities (DLTs)
time frame: Cycle 1 (Part A = 28 Days or Part B = 21 Days)
description: Number of participants with DLTs
measure: Pharmacokinetics (PK): Maximum Concentration (Cmax) of Merestinib and its Metabolites
time frame: Predose Cycle 1 Throughout the First 2 Cycles (Part A = 28-Day Cycles, Part B = 21-Day Cycles)
description: PK: Cmax of merestinib and its metabolites
measure: PK: Area Under the Concentration Time Curve (AUC) of Merestinib and its Metabolites
time frame: Predose Cycle 1 Throughout the First 2 Cycles (Part A = 28-Day Cycles, Part B = 21-Day Cycles)
description: PK: AUC of merestinib and its metabolites
measure: Objective Response Rate (ORR): Percentage of Participants With a Complete or Partial Response
time frame: Baseline to Measured Progressive Disease or Start of New Anti-Cancer Therapy (Estimated as up to 8 Months)
description: ORR: Percentage of participants with a complete or partial response
measure: Disease Control Rate (DCR): Percentage of Participants with a Best Overall Response of Complete Response, Partial Response, and Stable Disease
time frame: Baseline to Measured Progressive Disease or Start of New Anti-Cancer Therapy (Estimated as up to 8 Months)
description: DCR: Percentage of participants with a best overall response of complete response, partial response, and stable disease
arm group label: Merestinib (Part A Dose Level 1)
arm group type: Experimental
description: Merestinib administered orally. Treatment will continue until disease progression, development of unacceptable toxicity, or other discontinuation criteria are met.
arm group label: Merestinib (Part A Dose Level 2)
arm group type: Experimental
description: Merestinib administered orally. Treatment will continue until disease progression, development of unacceptable toxicity, or other discontinuation criteria are met.
arm group label: Merestinib + Cisplatin + Gemcitabine (Part B)
arm group type: Experimental
description: Merestinib administered orally with cisplatin and gemcitabine administered intravenously (IV). Treatment will continue until disease progression, development of unacceptable toxicity, or other discontinuation criteria are met, but Cisplatin and gemcitabine treatment will be limited to a maximum of 8 cycles.
intervention type: Drug
intervention name: Merestinib
description: Administered orally
arm group label: Merestinib (Part A Dose Level 1)
arm group label: Merestinib (Part A Dose Level 2)
arm group label: Merestinib + Cisplatin + Gemcitabine (Part B)
other name: LY2801653
intervention type: Drug
intervention name: Cisplatin
description: Administered IV
arm group label: Merestinib + Cisplatin + Gemcitabine (Part B)
intervention type: Drug
intervention name: Gemcitabine
description: Administered IV
arm group label: Merestinib + Cisplatin + Gemcitabine (Part B)
other name: LY188011
criteria: 
gender: All
minimum age: 20 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: 
country: Japan
responsible party type: Sponsor
mesh term: Carcinoma
mesh term: Cholangiocarcinoma
mesh term: Neoplasm Metastasis
mesh term: Neoplasms
mesh term: Neoplasms, Second Primary
mesh term: Urinary Bladder Neoplasms
mesh term: Gemcitabine