<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/NCT03299946</url>
  </required_header>
  <id_info>
    <org_study_id>J17136</org_study_id>
    <secondary_id>IRB00149350</secondary_id>
    <nct_id>NCT03299946</nct_id>
  </id_info>
  <brief_title>Feasibility and Efficacy of Neoadjuvant Cabozantinib Plus Nivolumab (CaboNivo) Followed by Definitive Resection for Patients With Locally Advanced Hepatocellular Carcinoma (HCC)</brief_title>
  <official_title>Feasibility and Efficacy of Neoadjuvant Cabozantinib Plus Nivolumab (CaboNivo) Followed by Definitive Resection for Patients With Locally Advanced Hepatocellular Carcinoma (HCC)</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Exelixis</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
    <collaborator>
      <agency>Bristol-Myers Squibb</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins</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>
  </oversight_info>
  <brief_summary>
    <textblock>
      The proposed study is an open-label, single institution, single arm phase 1b study of&#xD;
      neoadjuvant cabozantinib plus nivolumab in patients with locally advanced HCC.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">May 14, 2018</start_date>
  <completion_date type="Actual">October 1, 2021</completion_date>
  <primary_completion_date type="Actual">December 9, 2019</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 adverse events in participants of neoadjuvant cabozantinib plus nivolumab.</measure>
    <time_frame>4 years</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Number of patients who complete pre-op treatment and proceed to surgery.</measure>
    <time_frame>4 years</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>Percentage of participants who obtain R0 resection.</measure>
    <time_frame>4 years</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percentage of participants who obtain a pathologic complete response (CR).</measure>
    <time_frame>4 years</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percentage of participants who obtain a major pathologic responses (MPR)</measure>
    <time_frame>4 years</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Objective response rate (ORR)</measure>
    <time_frame>4 years</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Median Overall Survival (OS)</measure>
    <time_frame>5 years</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Disease free survival (DFS)</measure>
    <time_frame>5 years</time_frame>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">15</enrollment>
  <condition>Locally Advanced Hepatocellular Carcinoma</condition>
  <arm_group>
    <arm_group_label>Arm 1</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Cabozantinib</intervention_name>
    <description>Cabozantinib (40mg) will be taken by mouth daily for 8 weeks.</description>
    <arm_group_label>Arm 1</arm_group_label>
    <other_name>XL184</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Nivolumab</intervention_name>
    <description>Nivolumab 240mg intravenously every 2 weeks (days 14, 28, 42, and 56 for a total of four doses), in combination with Cabozantinib 40mg by mouth daily for 8 weeks.</description>
    <arm_group_label>Arm 1</arm_group_label>
    <other_name>OPDIVO, BMS 936558, MDX-1106, ONO-4538</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Must have locally advanced/borderline resectable hepatocellular carcinoma.&#xD;
&#xD;
          2. Must have measurable disease.&#xD;
&#xD;
          3. Age ≥18 years.&#xD;
&#xD;
          4. Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1.&#xD;
&#xD;
          5. Patients must have adequate organ and marrow function defined by study-specified&#xD;
             laboratory tests.&#xD;
&#xD;
          6. Patients must have adequate liver remnant and function.&#xD;
&#xD;
          7. Antiviral therapy per local standard of care for hepatitis B.&#xD;
&#xD;
          8. Woman of child bearing potential must have a negative pregnancy test.&#xD;
&#xD;
          9. Must use acceptable form of birth control while on study.&#xD;
&#xD;
         10. Ability to understand and willingness to sign a written informed consent document.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Fibrolamellar carcinoma or mixed HCC.&#xD;
&#xD;
          2. Chemotherapy, radiotherapy, investigational therapy, or surgery less than 6 months&#xD;
             prior to trial registration.&#xD;
&#xD;
          3. Concomitant Anticoagulation therapy.&#xD;
&#xD;
          4. Any GI or pulmonary risks of bleeding.&#xD;
&#xD;
          5. History of HIV Infection.&#xD;
&#xD;
          6. Active co-infection with hepatitis B and hepatitis C.&#xD;
&#xD;
          7. Active co-infection with hepatitis B and hepatitis D.&#xD;
&#xD;
          8. Has a diagnosis of immunodeficiency, or is receiving systemic steroid therapy.&#xD;
&#xD;
          9. History of any autoimmune disease requiring systemic treatment within the past 2&#xD;
             years. Any patient bearing an allograft is not eligible.&#xD;
&#xD;
         10. Any additional malignancies with treatment or life-limiting cancers. Superficial&#xD;
             bladder cancer, non-melanoma skin cancers, or low grade prostate cancer not requiring&#xD;
             therapy would not exclude participation in this trial.&#xD;
&#xD;
         11. Uncontrolled intercurrent illness.&#xD;
&#xD;
         12. Corrected QT interval calculated by the Fridericia formula.&#xD;
&#xD;
         13. Uncontrolled high blood pressure.&#xD;
&#xD;
         14. Are pregnant or breastfeeding.&#xD;
&#xD;
         15. Any gastrointestinal (GI) disorders.&#xD;
&#xD;
         16. Any certain study-specified heart conditions 6 months prior to enrollment.&#xD;
&#xD;
         17. Major surgery within 2 months before enrollment.&#xD;
&#xD;
         18. Have any evidence of moderate or severe ascites.&#xD;
&#xD;
         19. Any untreated or incompletely treated varices with bleeding or high-risk bleeding.&#xD;
&#xD;
         20. Inability to swallow intact tablets.&#xD;
&#xD;
         21. Known or suspected hypersensitivity to study treatment.&#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>Daniel Laheru, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Sidney Kimmel Comprehensive Cancer Center</name>
      <address>
        <city>Baltimore</city>
        <state>Maryland</state>
        <zip>21231</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>March 2023</verification_date>
  <study_first_submitted>September 27, 2017</study_first_submitted>
  <study_first_submitted_qc>September 27, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">October 3, 2017</study_first_posted>
  <last_update_submitted>March 24, 2023</last_update_submitted>
  <last_update_submitted_qc>March 24, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">March 28, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Nivolumab</keyword>
  <keyword>Cabozantinib</keyword>
  <keyword>Neoadjuvant</keyword>
  <keyword>Immunotherapy</keyword>
  <keyword>Liver Cancer</keyword>
  <keyword>Borderline Resectable</keyword>
  <keyword>Advance Resectable</keyword>
  <keyword>Neoplasms</keyword>
  <keyword>Hepatocellular Carcinoma</keyword>
  <keyword>HCC</keyword>
  <keyword>Resection</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>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Nivolumab</mesh_term>
  </intervention_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/NCT03299946
org study id: J17136
secondary id: IRB00149350
nct id: NCT03299946
lead sponsor: 
collaborator: 
collaborator: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
The proposed study is an open-label, single institution, single arm phase 1b study of
      neoadjuvant cabozantinib plus nivolumab in patients with locally advanced HCC.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Number of adverse events in participants of neoadjuvant cabozantinib plus nivolumab.
time frame: 4 years
measure: Number of patients who complete pre-op treatment and proceed to surgery.
time frame: 4 years
measure: Percentage of participants who obtain R0 resection.
time frame: 4 years
measure: Percentage of participants who obtain a pathologic complete response (CR).
time frame: 4 years
measure: Percentage of participants who obtain a major pathologic responses (MPR)
time frame: 4 years
measure: Objective response rate (ORR)
time frame: 4 years
measure: Median Overall Survival (OS)
time frame: 5 years
measure: Disease free survival (DFS)
time frame: 5 years
arm group label: Arm 1
arm group type: Experimental
intervention type: Drug
intervention name: Cabozantinib
description: Cabozantinib (40mg) will be taken by mouth daily for 8 weeks.
arm group label: Arm 1
other name: XL184
intervention type: Drug
intervention name: Nivolumab
description: Nivolumab 240mg intravenously every 2 weeks (days 14, 28, 42, and 56 for a total of four doses), in combination with Cabozantinib 40mg by mouth daily for 8 weeks.
arm group label: Arm 1
other name: OPDIVO, BMS 936558, MDX-1106, ONO-4538
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Daniel Laheru, MD
role: Principal Investigator
affiliation: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
facility: 
country: United States
responsible party type: Sponsor
mesh term: Carcinoma
mesh term: Carcinoma, Hepatocellular
mesh term: Nivolumab
sharing ipd: Undecided