<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/NCT02234986</url>
  </required_header>
  <id_info>
    <org_study_id>2076-CL-006</org_study_id>
    <nct_id>NCT02234986</nct_id>
  </id_info>
  <brief_title>A Multi-center, Open-label Study of Oral ENMD-2076 for the Treatment of Patients With Advanced Fibrolamellar Carcinoma</brief_title>
  <official_title>A Phase 2, Multi-center, Open-label Study of Oral ENMD-2076 for the Treatment of Patients With Advanced Fibrolamellar Carcinoma (FLC)</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>CASI Pharmaceuticals, Inc.</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>CASI Pharmaceuticals, Inc.</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The purpose of the study is to determine whether once-daily dosing with ENMD-2076 will be a&#xD;
      safe and effective treatment in patients with FLC. Safety will be measured by looking at the&#xD;
      adverse events that may happen and the efficacy will look at the progression of the disease&#xD;
      over time.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Primary Objective:&#xD;
&#xD;
      • To determine the 6-month progression free survival (PFS6) rate when patients with advanced&#xD;
      fibrolamellar carcinoma (FLC) are treated with daily oral ENMD 2076&#xD;
&#xD;
      Secondary Objectives:&#xD;
&#xD;
        -  To evaluate the overall response rate using RECIST v 1.1 criteria when patients with FLC&#xD;
           are treated with daily oral ENMD 2076.&#xD;
&#xD;
        -  To evaluate the median Progression Free Survival (PFS), Time to Progression (TTP), and&#xD;
           Overall Survival (OS).&#xD;
&#xD;
        -  To determine the safety of ENMD-2076 as defined by the frequency and severity of adverse&#xD;
           events when patients with FLC are treated with daily oral ENMD-2076&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>October 2015</start_date>
  <completion_date type="Actual">June 30, 2018</completion_date>
  <primary_completion_date type="Actual">June 30, 2018</primary_completion_date>
  <phase>Phase 2</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>Overall Response Rate</measure>
    <time_frame>6 months</time_frame>
    <description>6-month overall response rate (ORR rate) using RECIST v1.1 criteria</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Progression Free Survival (PFS6) rate</measure>
    <time_frame>6 months</time_frame>
    <description>Overall response rate using RECIST v 1.1 criteria</description>
  </secondary_outcome>
  <other_outcome>
    <measure>Frequency and severity of adverse events</measure>
    <time_frame>6 months</time_frame>
    <description>Frequency and severity of adverse events</description>
  </other_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">37</enrollment>
  <condition>Advanced Adult Hepatocellular Carcinoma</condition>
  <condition>Advanced Fibrolamellar Carcinoma</condition>
  <arm_group>
    <arm_group_label>ENMD-2076</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>ENMD-2076, oral capsule Once daily dose 250 mg/day</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>ENMD-2076</intervention_name>
    <description>250 mg oral dose, QD for 28 day cycles</description>
    <arm_group_label>ENMD-2076</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Histologically or cytologically confirmed advanced fibrolamellar carcinoma (FLC).&#xD;
&#xD;
          -  All forms of prior local therapy are allowed as long as patients have either a target&#xD;
             lesion, which has not been treated with local therapy and/or the target lesion(s)&#xD;
             within the field of the local-regional therapy has shown an increase of ≥ 20% in size.&#xD;
             Local-regional therapy must be completed at least 4 weeks prior to the baseline CT&#xD;
             scan. Local therapies including chemoembolization do not count as prior systemic&#xD;
             therapy.&#xD;
&#xD;
          -  Are at least 4 weeks from major surgery and recovered.&#xD;
&#xD;
          -  At least one measureable lesion by RECIST 1.1.&#xD;
&#xD;
          -  Male or non-pregnant, non-breastfeeding female at least 18 years of age. Patients aged&#xD;
             at 12~18 years may be recruited but only at the site principle investigator's request&#xD;
             and subject to IRB approval.&#xD;
&#xD;
          -  Has a pre-study echocardiogram or multi-gated acquisition (MUGA) scan with an actual&#xD;
             left ventricular ejection fraction of greater than or equal to the institutional lower&#xD;
             limit of normal within one month of initiating therapy.&#xD;
&#xD;
          -  Have clinically acceptable laboratory screening results within certain limits&#xD;
             specified below:&#xD;
&#xD;
               -  AST and ALT ≤ 5 times upper limit of normal (ULN)&#xD;
&#xD;
               -  Total bilirubin ≤ 3.0 x ULN&#xD;
&#xD;
               -  Creatinine ≤ 1.5 x ULN or Cr Cl &gt; 60 cc/min&#xD;
&#xD;
               -  Absolute neutrophil count ≥ 1500 cells/mm3&#xD;
&#xD;
               -  Platelets ≥ 50,000/mm3&#xD;
&#xD;
          -  Have an ECOG performance status of 0-2 for ≥ 16 years of age and a Lansky performance&#xD;
             status of 70-100 for &lt; 16 years of age&#xD;
&#xD;
          -  Women and men of child producing potential must agree to use effective contraceptive&#xD;
             methods prior to study entry, during study participation, and for at least 30 days&#xD;
             after the last administration of study medication. A serum pregnancy test within 72&#xD;
             hours prior to the initiation of therapy will be required for women of childbearing&#xD;
             potential.&#xD;
&#xD;
          -  Have the ability to understand the requirements of the study, provide written informed&#xD;
             consent, which includes authorization for release of protected health information,&#xD;
             abide by the study restrictions, and agree to return for the required assessments.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Have active, acute, or chronic clinically significant infections or bleeding within&#xD;
             the last 6 months or previous thromboembolic or hemorrhagic events during anti&#xD;
             angiogenic therapy.&#xD;
&#xD;
          -  Have uncontrolled hypertension (systolic blood pressure greater than 150 or diastolic&#xD;
             blood pressure greater than 100) or history of congestive heart failure (AHA Grade 2&#xD;
             or higher).&#xD;
&#xD;
          -  Have active angina pectoris, stroke or recent myocardial infarction (within 6 months).&#xD;
&#xD;
          -  Have uncontrolled chronic atrial fibrillation.&#xD;
&#xD;
          -  Have chronic atrial fibrillation or QTc interval corrected for heart rate of greater&#xD;
             than 470 msec in adults and 450 msec in pediatrics (&lt; 18 years).&#xD;
&#xD;
          -  Have additional uncontrolled serious medical or psychiatric illness that in the point&#xD;
             of view of the investigator can render the patient unable to receive therapy or make&#xD;
             it unsafe to receive therapy.&#xD;
&#xD;
          -  Require treatment with any of the exclusionary medications listed in Appendix D.&#xD;
&#xD;
          -  Known untreated or unstable CNS metastatic disease.&#xD;
&#xD;
          -  Have persistent 2+ protein by urinalysis (patients with 2+ proteinuria that have a&#xD;
             spot protein:creatinine ratio of less than 0.3 may be enrolled) or a history of&#xD;
             nephrotic syndrome.&#xD;
&#xD;
          -  Subjects with history of another primary cancer, with the exception of: a) curatively&#xD;
             resected non-melanoma skin cancer; b) curatively treated cervical carcinoma in situ;&#xD;
             or c) other primary solid tumor with no known active disease present in the opinion of&#xD;
             the investigator will not affect patient outcome in the setting of current FLC&#xD;
             diagnosis.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>99 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Ken Ren, PhD</last_name>
    <role>Study Director</role>
    <affiliation>CASI Pharmaceuticals, Inc.</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Ghassan Abou-Alfa, MD</last_name>
    <role>Study Chair</role>
    <affiliation>MSKCC</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>CASI Site 03</name>
      <address>
        <city>San Francisco</city>
        <state>California</state>
        <zip>94158</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>CASI Site 04</name>
      <address>
        <city>Aurora</city>
        <state>Colorado</state>
        <zip>80045</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>CASI Site 02</name>
      <address>
        <city>Boston</city>
        <state>Massachusetts</state>
        <zip>01003</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Casi Site 01</name>
      <address>
        <city>New York</city>
        <state>New York</state>
        <zip>10065</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>CASI Site 05</name>
      <address>
        <city>Dallas</city>
        <state>Texas</state>
        <zip>75231</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>September 2018</verification_date>
  <study_first_submitted>September 5, 2014</study_first_submitted>
  <study_first_submitted_qc>September 5, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">September 9, 2014</study_first_posted>
  <last_update_submitted>September 4, 2018</last_update_submitted>
  <last_update_submitted_qc>September 4, 2018</last_update_submitted_qc>
  <last_update_posted type="Actual">September 6, 2018</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Advanced Fibrolamellar Carcinoma</keyword>
  <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>
  <patient_data>
    <sharing_ipd>Undecided</sharing_ipd>
  </patient_data>
  <!-- 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/NCT02234986
org study id: 2076-CL-006
nct id: NCT02234986
lead sponsor: 
has dmc: No
The purpose of the study is to determine whether once-daily dosing with ENMD-2076 will be a
      safe and effective treatment in patients with FLC. Safety will be measured by looking at the
      adverse events that may happen and the efficacy will look at the progression of the disease
      over time.
Primary Objective:

      • To determine the 6-month progression free survival (PFS6) rate when patients with advanced
      fibrolamellar carcinoma (FLC) are treated with daily oral ENMD 2076

      Secondary Objectives:

        -  To evaluate the overall response rate using RECIST v 1.1 criteria when patients with FLC
           are treated with daily oral ENMD 2076.

        -  To evaluate the median Progression Free Survival (PFS), Time to Progression (TTP), and
           Overall Survival (OS).

        -  To determine the safety of ENMD-2076 as defined by the frequency and severity of adverse
           events when patients with FLC are treated with daily oral ENMD-2076
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Overall Response Rate
time frame: 6 months
description: 6-month overall response rate (ORR rate) using RECIST v1.1 criteria
measure: Progression Free Survival (PFS6) rate
time frame: 6 months
description: Overall response rate using RECIST v 1.1 criteria
measure: Frequency and severity of adverse events
time frame: 6 months
description: Frequency and severity of adverse events
arm group label: ENMD-2076
arm group type: Experimental
description: ENMD-2076, oral capsule Once daily dose 250 mg/day
intervention type: Drug
intervention name: ENMD-2076
description: 250 mg oral dose, QD for 28 day cycles
arm group label: ENMD-2076
criteria: 
gender: All
minimum age: 18 Years
maximum age: 99 Years
healthy volunteers: No
last name: Ken Ren, PhD
role: Study Director
affiliation: CASI Pharmaceuticals, Inc.
last name: Ghassan Abou-Alfa, MD
role: Study Chair
affiliation: MSKCC
facility: 
facility: 
facility: 
facility: 
facility: 
country: United States
responsible party type: Sponsor
mesh term: Carcinoma
mesh term: Carcinoma, Hepatocellular
sharing ipd: Undecided