<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/NCT03781960</url>
  </required_header>
  <id_info>
    <org_study_id>UPCC 35218</org_study_id>
    <nct_id>NCT03781960</nct_id>
  </id_info>
  <brief_title>Abemaciclib and Nivolumab for Subjects With Hepatocellular Carcinoma</brief_title>
  <official_title>Phase II Trial of Abemaciclib and Nivolumab for Subjects With Hepatocellular Carcinoma</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Abramson Cancer Center at Penn Medicine</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Abramson Cancer Center at Penn Medicine</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
    <is_us_export>No</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      The main purpose of this study is to evaluate the effectiveness of the combination of&#xD;
      nivolumab and abemaciclib for the treatment of hepatocellular carcinoma. Other goals of this&#xD;
      study are to learn about the side effects that this combination of drugs may cause and to&#xD;
      learn more about how these drugs work by studying blood and tissue.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Terminated</overall_status>
  <why_stopped>
    Safety letter from sponsor&#xD;
  </why_stopped>
  <start_date type="Actual">July 31, 2019</start_date>
  <completion_date type="Actual">April 29, 2022</completion_date>
  <primary_completion_date type="Actual">April 29, 2022</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>Objective Response Rate</measure>
    <time_frame>up to 2 years</time_frame>
    <description>The objective response rate is determined by the percentage of participants on study attaining a partial or complete response as noted per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), &gt;=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Progression-Free Survival</measure>
    <time_frame>From the start of study treatment until disease progression, death, whichever came first up to 2 years</time_frame>
    <description>Progression-Free survival is determined from the start of study treatment until the time of documented disease progression or death per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) and iRECIST criteria (guidelines for response criteria for use in trials testing immunotherapies)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Duration of Response</measure>
    <time_frame>up to 2 years</time_frame>
    <description>Time from the first recorded partial response or complete response (whichever comes first) defined Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), &gt;=30% decrease in the sum of the longest diameter of target lesions; until disease progression or death</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Overall Survival</measure>
    <time_frame>From the start of treatment to death, due to any cause or last patient contact alive, assessed up to 2 years</time_frame>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">7</enrollment>
  <condition>Hepatocellular Carcinoma</condition>
  <arm_group>
    <arm_group_label>Abemaciclib &amp; Nivolumab</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Subjects will receive abemaciclib monotherapy 150mg twice daily for seven days then will initiate nivolumab 480mg IV every 28 days while continuing twice daily abemaciclib.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Abemaciclib</intervention_name>
    <description>Abemaciclib will be given at a dose of 150mg by mouth twice daily continuously for the duration of trial therapy.</description>
    <arm_group_label>Abemaciclib &amp; Nivolumab</arm_group_label>
    <other_name>Verzenio</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Nivolumab</intervention_name>
    <description>Nivolumab will be administered at a dose of 480mg IV every 28 days. Treatment with nivolumab will begin after an initial 7-day treatment period with abemaciclib monotherapy.</description>
    <arm_group_label>Abemaciclib &amp; Nivolumab</arm_group_label>
    <other_name>Opdivo</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Subjects must have hepatocellular carcinoma (HCC) that is inoperable (where surgery is&#xD;
             not indicated due to disease extent, co-morbidities, or other technical reasons)&#xD;
&#xD;
          2. Histologic confirmation of HCC is not required for screening but is required prior to&#xD;
             initiation of study treatment. Subjects with hepatocholangiocarcinoma or&#xD;
             cholangiocarcinoma are not eligible.&#xD;
&#xD;
          3. Tumor must be positive for retinoblastoma (RB) expression by immunohistochemistry&#xD;
&#xD;
          4. Age &gt; 18 years and ability to understand and the willingness to sign a written&#xD;
             informed consent document.&#xD;
&#xD;
          5. ECOG performance status of 0 or 1&#xD;
&#xD;
          6. Childs-Pugh score of &lt;7&#xD;
&#xD;
          7. Life expectancy of at least 12 weeks&#xD;
&#xD;
          8. Must be able to swallow tablets&#xD;
&#xD;
          9. Must be willing to comply with protocol procedures (including completion of diaries&#xD;
             and outcome measures)&#xD;
&#xD;
         10. Local or loco-regional therapy to the liver (i.e. surgery, radiation therapy, hepatic&#xD;
             arterial embolization, chemoembolization, radiofrequency ablation, percutaneous&#xD;
             ethanol injection, or cryoablation) must have been completed &gt; 4 weeks prior to&#xD;
             enrollment&#xD;
&#xD;
         11. Must be willing to undergo a pretreatment and on-treatment biopsy and have a tumor&#xD;
             site that is accessible for core needle biopsy&#xD;
&#xD;
         12. Measurable or evaluable disease as defined by RECIST v. 1.1&#xD;
&#xD;
         13. Women of childbearing potential must have a negative serum pregnancy test performed&#xD;
             within 7 days of the first dose of abemaciclib (see Appendix A for definition of&#xD;
             childbearing potential). Female subjects of childbearing potential must use an&#xD;
             approved contraceptive method (detailed in Appendix A) for the duration of the study&#xD;
             and an additional 3 weeks after the final dose of abemaciclib.&#xD;
&#xD;
         14. Subjects with hepatitis B must have an HBV viral load &lt; 100 IU/mL by PCR during&#xD;
             screening&#xD;
&#xD;
         15. Must have adequate organ and hematopoietic function as defined below:&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Any history of a serious medical or psychiatric condition that would prevent the&#xD;
             subject from signing the informed consent form&#xD;
&#xD;
          2. Pregnant or breastfeeding&#xD;
&#xD;
          3. Use of any chemotherapy within 3 weeks prior to the first study treatment date&#xD;
&#xD;
          4. Use of any experimental therapy within 4 weeks or 5 half-lives, whichever is longer,&#xD;
             prior to the first study treatment date&#xD;
&#xD;
          5. Use of radiation within 2 weeks prior to the first study treatment date (4 weeks if&#xD;
             radiation to liver as per section 4.1)&#xD;
&#xD;
          6. Prior treatment with a CDK 4/6 inhibitor&#xD;
&#xD;
          7. Prior treatment with a PD-1 or PD-L1 inhibitor&#xD;
&#xD;
          8. Those who have not recovered from adverse events &lt; Grade 1 from prior therapy, with&#xD;
             the exceptions of alopecia of any grade or stable peripheral neuropathy &lt; Grade 2&#xD;
&#xD;
          9. Subjects may not receive concomitant anticancer agents or radiation. Antiviral agents&#xD;
             aimed at treating infectious hepatitis are permitted&#xD;
&#xD;
         10. History of or suspected hypersensitivity to nivolumab or abemaciclib&#xD;
&#xD;
         11. Uncontrolled ascites&#xD;
&#xD;
         12. Esophageal varices requiring treatment within the past 6 months (banding or&#xD;
             medication)&#xD;
&#xD;
         13. Subjects with uncontrolled brain metastases. Subjects with brain metastases must have&#xD;
             stable neurological status following local therapy (surgery or radiation) for at least&#xD;
             4 weeks prior to first study treatment and must be off of steroids related to the&#xD;
             brain metastases.&#xD;
&#xD;
         14. Any concurrent condition requiring the continued or anticipated use of systemic&#xD;
             steroids beyond physiologic replacement dosing (excluding non-systemic inhaled,&#xD;
             topical skin, nasal, and/or ophthalmic corticosteroids). All other systemic&#xD;
             corticosteroids above physiologic replacement dosing must be discontinued at least 4&#xD;
             weeks prior to first study treatment&#xD;
&#xD;
         15. Active drug or alcohol use or dependence as documented in the chart that, in the&#xD;
             opinion of the investigator, would interfere with adherence to study requirements&#xD;
&#xD;
         16. Active bacterial or fungal infection requiring IV therapy at the start of protocol&#xD;
             treatment&#xD;
&#xD;
         17. A second primary malignancy that, in the judgment of the investigator, may affect the&#xD;
             interpretation of results&#xD;
&#xD;
         18. Any illness or condition that in the opinion of the investigator may affect the safety&#xD;
             of the subject or the evaluation of any study endpoint (e.g. interstitial lung&#xD;
             disease, severe dyspnea at rest or requiring oxygen therapy, history of major surgical&#xD;
             resection involving the stomach or small bowel, or preexisting Crohn's disease or&#xD;
             ulcerative colitis or a preexisting chronic condition resulting in baseline Grade 2 or&#xD;
             higher diarrhea)&#xD;
&#xD;
         19. Personal history of ventricular tachycardia, ventricular fibrillation, or sudden&#xD;
             cardiac arrest&#xD;
&#xD;
         20. Prior organ allograft or allogeneic bone marrow transplantation&#xD;
&#xD;
         21. Pre-existing thyroid abnormality with thyroid function that cannot be maintained in&#xD;
             the normal range with medication&#xD;
&#xD;
         22. Active autoimmune disease, except for vitiligo, type 1 diabetes mellitus, asthma,&#xD;
             atopic dermatitis, or endocrinopathies manageable by hormone replacement; other&#xD;
             autoimmune conditions may be allowable at the discretion of the Principal Investigator&#xD;
&#xD;
         23. Any other conditions judged by the investigator that would limit the evaluation of the&#xD;
             subject&#xD;
&#xD;
         24. HIV positive by PCR&#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>Thomas Karasic, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Abramson Cancer Center at Penn Medicine</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Abramson Cancer Center of the University of Pennsylvania</name>
      <address>
        <city>Philadelphia</city>
        <state>Pennsylvania</state>
        <zip>19104</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>November 2022</verification_date>
  <study_first_submitted>December 17, 2018</study_first_submitted>
  <study_first_submitted_qc>December 18, 2018</study_first_submitted_qc>
  <study_first_posted type="Actual">December 20, 2018</study_first_posted>
  <results_first_submitted>October 21, 2022</results_first_submitted>
  <results_first_submitted_qc>November 17, 2022</results_first_submitted_qc>
  <results_first_posted type="Actual">December 14, 2022</results_first_posted>
  <last_update_submitted>November 17, 2022</last_update_submitted>
  <last_update_submitted_qc>November 17, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">December 14, 2022</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>Nivolumab</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <provided_document_section>
    <provided_document>
      <document_type>Study Protocol, Statistical Analysis Plan, and Informed Consent Form</document_type>
      <document_has_protocol>Yes</document_has_protocol>
      <document_has_icf>Yes</document_has_icf>
      <document_has_sap>Yes</document_has_sap>
      <document_date>December 14, 2019</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/60/NCT03781960/Prot_SAP_ICF_001.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <pre_assignment_details>7 met inclusion criteria and began treatment.</pre_assignment_details>
      <group_list>
        <group group_id="P1">
          <title>Abemaciclib &amp; Nivolumab</title>
          <description>Subjects will receive abemaciclib monotherapy 150mg twice daily for seven days then will initiate nivolumab 480mg IV every 28 days while continuing twice daily abemaciclib.&#xD;
Abemaciclib: Abemaciclib will be given at a dose of 150mg by mouth twice daily continuously for the duration of trial therapy.&#xD;
Nivolumab: Nivolumab will be administered at a dose of 480mg IV every 28 days. Treatment with nivolumab will begin after an initial 7-day treatment period with abemaciclib monotherapy.</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="7"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="7"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
              </participants_list>
            </milestone>
          </milestone_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>Abemaciclib &amp; Nivolumab</title>
          <description>Subjects will receive abemaciclib monotherapy 150mg twice daily for seven days then will initiate nivolumab 480mg IV every 28 days while continuing twice daily abemaciclib.&#xD;
Abemaciclib: Abemaciclib will be given at a dose of 150mg by mouth twice daily continuously for the duration of trial therapy.&#xD;
Nivolumab: Nivolumab will be administered at a dose of 480mg IV every 28 days. Treatment with nivolumab will begin after an initial 7-day treatment period with abemaciclib monotherapy.</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="7"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>&lt;=18 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Between 18 and 65 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="3"/>
                  </measurement_list>
                </category>
                <category>
                  <title>&gt;=65 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Sex: Female, Male</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Female</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="6"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Ethnicity (NIH/OMB)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Not Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="7"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Race (NIH/OMB)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>American Indian or Alaska Native</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Asian</title>
                  <measurement_list>
                    <measurement group_id="B1" value="2"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Native Hawaiian or Other Pacific Islander</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Black or African American</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                  </measurement_list>
                </category>
                <category>
                  <title>White</title>
                  <measurement_list>
                    <measurement group_id="B1" value="3"/>
                  </measurement_list>
                </category>
                <category>
                  <title>More than one race</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Region of Enrollment</title>
          <units>participants</units>
          <param>Number</param>
          <class_list>
            <class>
              <title>United States</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="7"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Objective Response Rate</title>
        <description>The objective response rate is determined by the percentage of participants on study attaining a partial or complete response as noted per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), &gt;=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR.</description>
        <time_frame>up to 2 years</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Abemaciclib &amp; Nivolumab</title>
            <description>Subjects will receive abemaciclib monotherapy 150mg twice daily for seven days then will initiate nivolumab 480mg IV every 28 days while continuing twice daily abemaciclib.&#xD;
Abemaciclib: Abemaciclib will be given at a dose of 150mg by mouth twice daily continuously for the duration of trial therapy.&#xD;
Nivolumab: Nivolumab will be administered at a dose of 480mg IV every 28 days. Treatment with nivolumab will begin after an initial 7-day treatment period with abemaciclib monotherapy.</description>
          </group>
        </group_list>
        <measure>
          <title>Objective Response Rate</title>
          <description>The objective response rate is determined by the percentage of participants on study attaining a partial or complete response as noted per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), &gt;=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR.</description>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="7"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Progression-Free Survival</title>
        <description>Progression-Free survival is determined from the start of study treatment until the time of documented disease progression or death per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) and iRECIST criteria (guidelines for response criteria for use in trials testing immunotherapies)</description>
        <time_frame>From the start of study treatment until disease progression, death, whichever came first up to 2 years</time_frame>
        <population>All subjects who received study therapy</population>
        <group_list>
          <group group_id="O1">
            <title>Abemaciclib &amp; Nivolumab</title>
            <description>Subjects will receive abemaciclib monotherapy 150mg twice daily for seven days then will initiate nivolumab 480mg IV every 28 days while continuing twice daily abemaciclib.&#xD;
Abemaciclib: Abemaciclib will be given at a dose of 150mg by mouth twice daily continuously for the duration of trial therapy.&#xD;
Nivolumab: Nivolumab will be administered at a dose of 480mg IV every 28 days. Treatment with nivolumab will begin after an initial 7-day treatment period with abemaciclib monotherapy.</description>
          </group>
        </group_list>
        <measure>
          <title>Progression-Free Survival</title>
          <description>Progression-Free survival is determined from the start of study treatment until the time of documented disease progression or death per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) and iRECIST criteria (guidelines for response criteria for use in trials testing immunotherapies)</description>
          <population>All subjects who received study therapy</population>
          <units>months</units>
          <param>Median</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="7"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2.1" lower_limit="1.6" upper_limit="5.6"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Duration of Response</title>
        <description>Time from the first recorded partial response or complete response (whichever comes first) defined Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), &gt;=30% decrease in the sum of the longest diameter of target lesions; until disease progression or death</description>
        <time_frame>up to 2 years</time_frame>
        <population>Subjects with objective response</population>
        <group_list>
          <group group_id="O1">
            <title>Abemaciclib &amp; Nivolumab</title>
            <description>Subjects will receive abemaciclib monotherapy 150mg twice daily for seven days then will initiate nivolumab 480mg IV every 28 days while continuing twice daily abemaciclib.&#xD;
Abemaciclib: Abemaciclib will be given at a dose of 150mg by mouth twice daily continuously for the duration of trial therapy.&#xD;
Nivolumab: Nivolumab will be administered at a dose of 480mg IV every 28 days. Treatment with nivolumab will begin after an initial 7-day treatment period with abemaciclib monotherapy.</description>
          </group>
        </group_list>
        <measure>
          <title>Duration of Response</title>
          <description>Time from the first recorded partial response or complete response (whichever comes first) defined Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), &gt;=30% decrease in the sum of the longest diameter of target lesions; until disease progression or death</description>
          <population>Subjects with objective response</population>
          <units>months</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="1"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="10.2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Overall Survival</title>
        <time_frame>From the start of treatment to death, due to any cause or last patient contact alive, assessed up to 2 years</time_frame>
        <population>All subjects who received study therapy</population>
        <group_list>
          <group group_id="O1">
            <title>Abemaciclib &amp; Nivolumab</title>
            <description>Subjects will receive abemaciclib monotherapy 150mg twice daily for seven days then will initiate nivolumab 480mg IV every 28 days while continuing twice daily abemaciclib.&#xD;
Abemaciclib: Abemaciclib will be given at a dose of 150mg by mouth twice daily continuously for the duration of trial therapy.&#xD;
Nivolumab: Nivolumab will be administered at a dose of 480mg IV every 28 days. Treatment with nivolumab will begin after an initial 7-day treatment period with abemaciclib monotherapy.</description>
          </group>
        </group_list>
        <measure>
          <title>Overall Survival</title>
          <population>All subjects who received study therapy</population>
          <units>months</units>
          <param>Median</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="7"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="7.9" lower_limit="2.6" upper_limit="22.7"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>From the initiation of any study procedures until 30 days following the last administration of study treatment, up to 2 years.</time_frame>
      <group_list>
        <group group_id="E1">
          <title>Abemaciclib &amp; Nivolumab</title>
          <description>Subjects will receive abemaciclib monotherapy 150mg twice daily for seven days then will initiate nivolumab 480mg IV every 28 days while continuing twice daily abemaciclib.&#xD;
Abemaciclib: Abemaciclib will be given at a dose of 150mg by mouth twice daily continuously for the duration of trial therapy.&#xD;
Nivolumab: Nivolumab will be administered at a dose of 480mg IV every 28 days. Treatment with nivolumab will begin after an initial 7-day treatment period with abemaciclib monotherapy.</description>
        </group>
      </group_list>
      <serious_events>
        <default_vocab>CTCAE 5.0</default_vocab>
        <default_assessment>Systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, all-cause mortality</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="7"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="7"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Abdominal Pain</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="7"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Sepsis</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="7"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Dyspnea</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="7"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>5</frequency_threshold>
        <default_vocab>CTCAE 5.0</default_vocab>
        <default_assessment>Systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, other adverse events</sub_title>
                <counts group_id="E1" subjects_affected="7" subjects_at_risk="7"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Blood and lymphatic system disorders</title>
            <event_list>
              <event>
                <sub_title>Anemia</sub_title>
                <counts group_id="E1" events="4" subjects_affected="4" subjects_at_risk="7"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Eye disorders</title>
            <event_list>
              <event>
                <sub_title>Blurred Vision</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="7"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Diarrhea</sub_title>
                <counts group_id="E1" events="6" subjects_affected="6" subjects_at_risk="7"/>
              </event>
              <event>
                <sub_title>Nausea</sub_title>
                <counts group_id="E1" events="3" subjects_affected="3" subjects_at_risk="7"/>
              </event>
              <event>
                <sub_title>constipation</sub_title>
                <counts group_id="E1" events="3" subjects_affected="3" subjects_at_risk="7"/>
              </event>
              <event>
                <sub_title>Abdominal Pain</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="7"/>
              </event>
              <event>
                <sub_title>Ascites</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="7"/>
              </event>
              <event>
                <sub_title>gastritis</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="7"/>
              </event>
              <event>
                <sub_title>Abdominal Distension</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="7"/>
              </event>
              <event>
                <sub_title>Vomiting</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="7"/>
              </event>
              <event>
                <sub_title>bloating</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="7"/>
              </event>
              <event>
                <sub_title>Edema Limbs</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="7"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Fatigue</sub_title>
                <counts group_id="E1" events="5" subjects_affected="5" subjects_at_risk="7"/>
              </event>
              <event>
                <sub_title>Fever</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="7"/>
              </event>
              <event>
                <sub_title>Chills</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="7"/>
              </event>
              <event>
                <sub_title>Non-cardiac chest pain</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="7"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Hepatobiliary disorders</title>
            <event_list>
              <event>
                <sub_title>Hepatic Failure</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="7"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Sepsis</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="7"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Investigations</title>
            <event_list>
              <event>
                <sub_title>AST Increased</sub_title>
                <counts group_id="E1" events="7" subjects_affected="7" subjects_at_risk="7"/>
              </event>
              <event>
                <sub_title>ALT Increased</sub_title>
                <counts group_id="E1" events="5" subjects_affected="5" subjects_at_risk="7"/>
              </event>
              <event>
                <sub_title>Blood bilirubin increased</sub_title>
                <counts group_id="E1" events="7" subjects_affected="7" subjects_at_risk="7"/>
              </event>
              <event>
                <sub_title>Alkaline Phosphate Increased</sub_title>
                <counts group_id="E1" events="6" subjects_affected="6" subjects_at_risk="7"/>
              </event>
              <event>
                <sub_title>Platelet Count Decreased</sub_title>
                <counts group_id="E1" events="6" subjects_affected="6" subjects_at_risk="7"/>
              </event>
              <event>
                <sub_title>Creatinine increased</sub_title>
                <counts group_id="E1" events="3" subjects_affected="3" subjects_at_risk="7"/>
              </event>
              <event>
                <sub_title>Neutrophil count decreased</sub_title>
                <counts group_id="E1" events="7" subjects_affected="7" subjects_at_risk="7"/>
              </event>
              <event>
                <sub_title>Weight loss</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="7"/>
              </event>
              <event>
                <sub_title>CPK increased</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="7"/>
              </event>
              <event>
                <sub_title>WBC Decreased</sub_title>
                <counts group_id="E1" events="7" subjects_affected="7" subjects_at_risk="7"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Metabolism and nutrition disorders</title>
            <event_list>
              <event>
                <sub_title>Anorexia</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="7"/>
              </event>
              <event>
                <sub_title>Hypokalemia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="7"/>
              </event>
              <event>
                <sub_title>Hyponatremia</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="7"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Musculoskeletal and connective tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Chest Wall Pain</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="7"/>
              </event>
              <event>
                <sub_title>Flank Pain</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="7"/>
              </event>
              <event>
                <sub_title>Back Pain</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="7"/>
              </event>
              <event>
                <sub_title>Bone Pain</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="7"/>
              </event>
              <event>
                <sub_title>Arthralgia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="7"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Dysgeusia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="7"/>
              </event>
              <event>
                <sub_title>Paresthesia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="7"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Psychiatric disorders</title>
            <event_list>
              <event>
                <sub_title>Depression</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="7"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Renal and urinary disorders</title>
            <event_list>
              <event>
                <sub_title>Acute Kidney Injury</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="7"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Cough</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="7"/>
              </event>
              <event>
                <sub_title>nasal congestion</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="7"/>
              </event>
              <event>
                <sub_title>rhinorrhea</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="7"/>
              </event>
              <event>
                <sub_title>Dyspnea</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="7"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Skin and subcutaneous tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Dry Skin</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="7"/>
              </event>
              <event>
                <sub_title>Nail Changes</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="7"/>
              </event>
              <event>
                <sub_title>Palmer-plantar erthrodysesthesia syndrome</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="7"/>
              </event>
              <event>
                <sub_title>Rash Maculopapular</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="7"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </other_events>
    </reported_events>

    <certain_agreements>
      <pi_employee>Principal Investigators are NOT employed by the organization sponsoring the study.</pi_employee>
      <restrictive_agreement>The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.</restrictive_agreement>
    </certain_agreements>
    <limitations_and_caveats>Early termination leading to small numbers of subjects analyzed</limitations_and_caveats>
    <point_of_contact>
      <name_or_title>Thomas Karasic, MD</name_or_title>
      <organization>University of Pennsylvania Hospital</organization>
      <phone>215-614-1858</phone>
      <email>thomas.karasic@pennmedicine.upenn.edu</email>
    </point_of_contact>
  </clinical_results>
</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/NCT03781960
org study id: UPCC 35218
nct id: NCT03781960
lead sponsor: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
is us export: No
The main purpose of this study is to evaluate the effectiveness of the combination of
      nivolumab and abemaciclib for the treatment of hepatocellular carcinoma. Other goals of this
      study are to learn about the side effects that this combination of drugs may cause and to
      learn more about how these drugs work by studying blood and tissue.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Objective Response Rate
time frame: up to 2 years
description: The objective response rate is determined by the percentage of participants on study attaining a partial or complete response as noted per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR.
measure: Progression-Free Survival
time frame: From the start of study treatment until disease progression, death, whichever came first up to 2 years
description: Progression-Free survival is determined from the start of study treatment until the time of documented disease progression or death per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) and iRECIST criteria (guidelines for response criteria for use in trials testing immunotherapies)
measure: Duration of Response
time frame: up to 2 years
description: Time from the first recorded partial response or complete response (whichever comes first) defined Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; until disease progression or death
measure: Overall Survival
time frame: From the start of treatment to death, due to any cause or last patient contact alive, assessed up to 2 years
arm group label: Abemaciclib & Nivolumab
arm group type: Experimental
description: Subjects will receive abemaciclib monotherapy 150mg twice daily for seven days then will initiate nivolumab 480mg IV every 28 days while continuing twice daily abemaciclib.
intervention type: Drug
intervention name: Abemaciclib
description: Abemaciclib will be given at a dose of 150mg by mouth twice daily continuously for the duration of trial therapy.
arm group label: Abemaciclib & Nivolumab
other name: Verzenio
intervention type: Drug
intervention name: Nivolumab
description: Nivolumab will be administered at a dose of 480mg IV every 28 days. Treatment with nivolumab will begin after an initial 7-day treatment period with abemaciclib monotherapy.
arm group label: Abemaciclib & Nivolumab
other name: Opdivo
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Thomas Karasic, MD
role: Principal Investigator
affiliation: Abramson Cancer Center at Penn Medicine
facility: 
country: United States
responsible party type: Sponsor
mesh term: Carcinoma
mesh term: Carcinoma, Hepatocellular
mesh term: Nivolumab
sharing ipd: No
provided document: 
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
limitations and caveats: Early termination leading to small numbers of subjects analyzed
point of contact: 