<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/NCT02240433</url>
  </required_header>
  <id_info>
    <org_study_id>14856</org_study_id>
    <secondary_id>H9H-JE-JBAP</secondary_id>
    <nct_id>NCT02240433</nct_id>
  </id_info>
  <brief_title>A Study of LY2157299 in Participants With Unresectable Hepatocellular Cancer (HCC)</brief_title>
  <official_title>A Phase 1b Study of LY2157299 in Combination With Sorafenib in Patients With Unresectable Hepatocellular Carcinoma</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>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The main purpose of this study is to evaluate safety and tolerability of LY2157299 when&#xD;
      combined with sorafenib in Japanese hepatocellular carcinoma (HCC) participants.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">November 12, 2014</start_date>
  <completion_date type="Actual">December 25, 2019</completion_date>
  <primary_completion_date type="Actual">July 19, 2017</primary_completion_date>
  <phase>Phase 1</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>Number of Participants with LY2157299 Dose-Limiting Toxicities (DLT)</measure>
    <time_frame>Cycle 1 (28 days)</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>Pharmacokinetics (PK): Area Under the Plasma Concentration-time Curve (AUC) of LY2157299</measure>
    <time_frame>Cycle 1 Day1: predose through 6 hours post dose; Cycle1 Day14: predose through 24 hours post dose</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>PK: Maximum Observed Plasma Concentration (Cmax) of LY2157299</measure>
    <time_frame>Cycle 1 Day 1: Predose through 6 hours post dose; Cycle 1 Day 14: Predose through 24 hours post dose</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time to Progression (TTP)</measure>
    <time_frame>Baseline to objective progressive disease (estimated as 6 months)</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Progression-free Survival (PFS)</measure>
    <time_frame>Baseline to objective progressive disease or death (estimated as 6 months)</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>The Number of Participants with Best Response of Partial Response (PR), Complete Response (CR), Stable Disease (SD), or Progressive Disease (PD)</measure>
    <time_frame>Baseline to objective progressive disease (estimated as 6 months)</time_frame>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">9</enrollment>
  <condition>Hepatocellular Carcinoma</condition>
  <arm_group>
    <arm_group_label>LY2157299 + Sorafenib</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>LY2157299 will be administered orally twice daily for 14 days, followed by 14 days with no study drug per 28-day cycle. Sorafenib will be administered orally twice daily for 28 days, in each cycle.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>LY2157299</intervention_name>
    <description>LY2157299 administered orally</description>
    <arm_group_label>LY2157299 + Sorafenib</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Sorafenib</intervention_name>
    <description>Sorafenib administered orally</description>
    <arm_group_label>LY2157299 + Sorafenib</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Have histological evidence of a diagnosis of HCC (except HCC with fibrolamellar or&#xD;
             mixed histology) not amenable to curative surgery.&#xD;
&#xD;
          -  Have Child-Pugh Class A.&#xD;
&#xD;
          -  Have the presence of measurable or evaluable lesion as defined by the Response&#xD;
             Evaluation Criteria In Solid Tumors (RECIST) v1.1. A measurable or evaluable lesion&#xD;
             showing demonstrable progression after locoregional therapy could be also included.&#xD;
&#xD;
          -  Have not received sorafenib prior to enrollment.&#xD;
&#xD;
          -  Have resolution to Grade less than or equal 1 by the National Cancer Institute (NCI)&#xD;
             Common Terminology Criteria for Adverse Events (CTCAE) version 4.03 of all clinically&#xD;
             significant toxic effects of prior locoregional therapy, surgery, chemoembolization,&#xD;
             systemic chemotherapy.&#xD;
&#xD;
          -  Have a performance status of less than or equal 1 on the Eastern Cooperative Oncology&#xD;
             Group (ECOG) scale.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Are currently enrolled, or discontinued within 28 days prior to enrollment from, a&#xD;
             clinical trial involving an investigational product or nonapproved use of a drug or&#xD;
             device (other than the investigational product used in this study), or concurrently&#xD;
             enrolled in any other type of medical research judged not to be scientifically or&#xD;
             medically compatible with this study.&#xD;
&#xD;
          -  Have undergone major surgery within 28 days prior to enrollment.&#xD;
&#xD;
          -  Have undergone hepatic locoregional therapy (including radiation, surgery, hepatic&#xD;
             arterial embolization, chemoembolization, radiofrequency ablation, cryoablation,&#xD;
             percutaneous ethanol injection, or percutaneous microwave coagulation therapy) within&#xD;
             28 days prior to enrollment.&#xD;
&#xD;
          -  Have moderate or severe cardiac disease.&#xD;
&#xD;
               -  Myocardial infarction within 6 months prior to enrollment, unstable angina&#xD;
                  pectoris, New York Heart Association (NYHA) Class III/IV congestive heart&#xD;
                  failure, or uncontrolled hypertension.&#xD;
&#xD;
               -  Documented major electrocardiogram (ECG) abnormalities at the investigator's&#xD;
                  discretion within 28 days prior to enrollment.&#xD;
&#xD;
               -  Major abnormalities documented by echocardiography with Doppler at investigator's&#xD;
                  direction within 28 days prior to enrollment.&#xD;
&#xD;
               -  Have persistently elevated brain natriuretic peptide (BNP) or elevated troponin I&#xD;
                  within 14 days prior to enrollment.&#xD;
&#xD;
               -  Predisposing conditions that are consistent with development of aneurysms of the&#xD;
                  ascending aorta or aortic stress.&#xD;
&#xD;
               -  Have a history of cardiac or aortic surgery.&#xD;
&#xD;
          -  Have undergone liver transplant.&#xD;
&#xD;
          -  Are pregnant or breastfeeding.&#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 from 9 AM to 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>Kanagawa</city>
        <zip>241-8515</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>Suita-shi</city>
        <zip>565-0871</zip>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Japan</country>
  </location_countries>
  <verification_date>February 1, 2020</verification_date>
  <study_first_submitted>September 11, 2014</study_first_submitted>
  <study_first_submitted_qc>September 11, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">September 15, 2014</study_first_posted>
  <last_update_submitted>February 3, 2020</last_update_submitted>
  <last_update_submitted_qc>February 3, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">February 5, 2020</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>Carcinoma</mesh_term>
    <mesh_term>Carcinoma, Hepatocellular</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Sorafenib</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/NCT02240433
org study id: 14856
secondary id: H9H-JE-JBAP
nct id: NCT02240433
lead sponsor: 
has dmc: Yes
The main purpose of this study is to evaluate safety and tolerability of LY2157299 when
      combined with sorafenib in Japanese hepatocellular carcinoma (HCC) participants.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Number of Participants with LY2157299 Dose-Limiting Toxicities (DLT)
time frame: Cycle 1 (28 days)
measure: Pharmacokinetics (PK): Area Under the Plasma Concentration-time Curve (AUC) of LY2157299
time frame: Cycle 1 Day1: predose through 6 hours post dose; Cycle1 Day14: predose through 24 hours post dose
measure: PK: Maximum Observed Plasma Concentration (Cmax) of LY2157299
time frame: Cycle 1 Day 1: Predose through 6 hours post dose; Cycle 1 Day 14: Predose through 24 hours post dose
measure: Time to Progression (TTP)
time frame: Baseline to objective progressive disease (estimated as 6 months)
measure: Progression-free Survival (PFS)
time frame: Baseline to objective progressive disease or death (estimated as 6 months)
measure: The Number of Participants with Best Response of Partial Response (PR), Complete Response (CR), Stable Disease (SD), or Progressive Disease (PD)
time frame: Baseline to objective progressive disease (estimated as 6 months)
arm group label: LY2157299 + Sorafenib
arm group type: Experimental
description: LY2157299 will be administered orally twice daily for 14 days, followed by 14 days with no study drug per 28-day cycle. Sorafenib will be administered orally twice daily for 28 days, in each cycle.
intervention type: Drug
intervention name: LY2157299
description: LY2157299 administered orally
arm group label: LY2157299 + Sorafenib
intervention type: Drug
intervention name: Sorafenib
description: Sorafenib administered orally
arm group label: LY2157299 + Sorafenib
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 from 9 AM to 5 PM Eastern Time (UTC/GMT-5 hours, EST)
role: Study Director
affiliation: Eli Lilly and Company
facility: 
facility: 
facility: 
country: Japan
responsible party type: Sponsor
mesh term: Carcinoma
mesh term: Carcinoma, Hepatocellular
mesh term: Sorafenib