<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/NCT02997956</url>
  </required_header>
  <id_info>
    <org_study_id>UMCC 2015.105</org_study_id>
    <secondary_id>HUM00104809</secondary_id>
    <nct_id>NCT02997956</nct_id>
  </id_info>
  <brief_title>Study of Tocilizumab in Patients With Hepatocellular Carcinoma (HCC) Undergoing Transarterial Chemoembolization (TACE)</brief_title>
  <official_title>Phase IB/II Study of Tocilizumab in Patients With Hepatocellular Carcinoma (HCC) Undergoing Transarterial Chemoembolization (TACE)</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of Michigan Rogel Cancer Center</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>University of Michigan Rogel Cancer Center</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>
      This is a phase IB study design planned to identify the MTD (Maximum Tolerated Dose) of&#xD;
      Tocilizumab in HCC (Hepatocellular Carcinoma) patients followed by a phase II design&#xD;
      whereupon the primary objective will be median progression free survival (PFS).&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      TACE (Transarterial Chemo Embolization) has shown to improve overall survival compared to&#xD;
      non-treated patients with intermediate HCC (Hepatocellular Carcinoma) tumors. However, TACE&#xD;
      is not considered a curative strategy and eventual local recurrence is observed in nearly all&#xD;
      (&gt;95%) of cases. Therefore, significant clinical equipoise exists in this large group of HCC&#xD;
      patients such that novel therapies can be tested in an adjuvant manner to TACE. Based on&#xD;
      pre-clinical data in HCC and the increasing identification that IL-6 signaling leads to tumor&#xD;
      progression or local recurrence in other solid malignancies, significant rationale exists for&#xD;
      the use of Tocilizumab, an IL-6 receptor inhibitor adjuvant to TACE. While Tocilizumab has&#xD;
      been demonstrated to be safe in RA patients and is FDA approved, limited data exists for the&#xD;
      maximum tolerated dose (MTD) in patients with cirrhosis and HCC. Therefore, a lead in phase&#xD;
      IB study design is planned to identify the MTD of Tocilizumab in HCC patients followed by&#xD;
      expansion to the phase II component whereupon the primary objective will be median&#xD;
      progression free survival (PFS).&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Withdrawn</overall_status>
  <why_stopped>
    funding issues&#xD;
  </why_stopped>
  <start_date type="Anticipated">July 2017</start_date>
  <completion_date type="Anticipated">July 2022</completion_date>
  <primary_completion_date type="Anticipated">July 2020</primary_completion_date>
  <phase>Phase 1/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>Maximum Tolerated Dose of Tocilizumab</measure>
    <time_frame>84 Days Post Treatment</time_frame>
    <description>The MTD is defined as the dose of Tocilizumab that induces dose-limiting toxicity in 20% of subjects or less when added to TACE. Patients must complete 84 days of treatment before the dose can be escalated.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Median Progression Free Survival</measure>
    <time_frame>2 Years Post Treatment</time_frame>
    <description>Patients will be followed every 3 months for 2 years post treatment. Progression-free survival (PFS) is defined as the duration of time from start of treatment to time of progression or death. Progressive disease is defined as at least a 20% increase in the sum of the LD or the appearance of one or more new lesions.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Number of patients that respond to treatment</measure>
    <time_frame>2 Years Post Treatment</time_frame>
    <description>Number of patients that respond to treatment</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of patients alive at two years post treatment</measure>
    <time_frame>2 Years Post Treatment</time_frame>
    <description>Number of patients alive at two years post treatment</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">0</enrollment>
  <condition>Hepatocellular Carcinoma</condition>
  <arm_group>
    <arm_group_label>Tocilizumab</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Participants will receive Tocilizumab (ACTEMRA®) at 4, 6, or 8 mg/kg IV dose escalation on days 1, 29 and 57.&#xD;
The first part of the trial will be Phase Ib and will enroll 18 participants. Participants will receive TACE on day 1 and Tocilizumab at dose level 1, 2, or 3 on days 1, 29 and 57. Maximum tolerated dose (MTD) of Tocilizumab will be determined.&#xD;
The second part of the trial will be a Phase II and will enroll 50 subjects. Participants will receive TACE on day 1 and Tocilizumab at the MTD on days 1, 29 and 57.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Tocilizumab</intervention_name>
    <description>Participants will receive Tocilizumab (ACTEMRA®) at 4, 6, or 8 mg/kg IV dose escalation on days 1, 29 and 57.</description>
    <arm_group_label>Tocilizumab</arm_group_label>
    <other_name>ACTEMRA</other_name>
  </intervention>
  <intervention>
    <intervention_type>Procedure</intervention_type>
    <intervention_name>Transcatheter Arterial Chemoembolization</intervention_name>
    <description>Minimally invasive procedure performed in interventional radiology to restrict a tumor's blood supply</description>
    <arm_group_label>Tocilizumab</arm_group_label>
    <other_name>TACE</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Histologic evidence of HCC, Barcelona-Clinic Liver Cancer (BCLC) stage B&#xD;
&#xD;
          -  FFPE (Fixed-paraffin Embedded) tumor tissue (two cores preferred) for biomarker&#xD;
             analysis&#xD;
&#xD;
          -  Prior radioembolization, local ablative therapies (radiofrequency, microwave or&#xD;
             cryoablation), radiation (external beam or stereotactic), or hepatic resection&#xD;
             permitted if completed ≥ 4 weeks prior to study enrollment and if patient has&#xD;
             recovered with ≤ grade 1 toxicity and if untreated measurable disease is present.&#xD;
&#xD;
          -  Radiographically measurable disease by mRECIST in at least one site not previously&#xD;
             treated by local therapies.&#xD;
&#xD;
          -  Must not be receiving treatment with other investigational agents and must not have&#xD;
             received any other investigational agent's ≤ 4 weeks prior to registration.&#xD;
&#xD;
          -  Age ≥ 18 years.&#xD;
&#xD;
          -  Eastern Cooperative Oncology Group (ECOG) performance status of 0-1&#xD;
&#xD;
          -  Required lab and acceptable range criteria.&#xD;
&#xD;
          -  Women of child-bearing potential and men must agree to use 2 methods of adequate&#xD;
             contraception.&#xD;
&#xD;
          -  No contraindications to TACE therapy&#xD;
&#xD;
          -  Child-Pugh Score A-B&#xD;
&#xD;
          -  Ability to understand and the willingness to sign a written informed consent, and the&#xD;
             willingness to comply with the requirements of the protocol.&#xD;
&#xD;
          -  Life expectancy greater than 3 months.&#xD;
&#xD;
          -  Adequate baseline organ and marrow function&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  History of hepatitis B&#xD;
&#xD;
          -  Women must not be pregnant or breastfeeding&#xD;
&#xD;
          -  Presence of other malignancies&#xD;
&#xD;
          -  Active or history of Tuberculosis&#xD;
&#xD;
          -  Patients with known HIV positive status&#xD;
&#xD;
          -  Conditions with impaired immunity or on immunosuppressive medications such as oral&#xD;
             steroids, calcineurin inhibitors, or anti-proliferative agents.&#xD;
&#xD;
          -  Must have no evidence of significant, uncontrolled concomitant diseases&#xD;
&#xD;
          -  Must have no ongoing or active, uncontrolled infections&#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>Theodore Welling, M.D.</last_name>
    <role>Principal Investigator</role>
    <affiliation>University of Michigan Rogel Cancer Center</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>The University of Michigan Comprehensive Cancer Center</name>
      <address>
        <city>Ann Arbor</city>
        <state>Michigan</state>
        <zip>48109</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>April 2017</verification_date>
  <study_first_submitted>December 16, 2016</study_first_submitted>
  <study_first_submitted_qc>December 19, 2016</study_first_submitted_qc>
  <study_first_posted type="Estimate">December 20, 2016</study_first_posted>
  <last_update_submitted>April 21, 2017</last_update_submitted>
  <last_update_submitted_qc>April 21, 2017</last_update_submitted_qc>
  <last_update_posted type="Actual">April 25, 2017</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>
  <!-- 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/NCT02997956
org study id: UMCC 2015.105
secondary id: HUM00104809
nct id: NCT02997956
lead sponsor: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
This is a phase IB study design planned to identify the MTD (Maximum Tolerated Dose) of
      Tocilizumab in HCC (Hepatocellular Carcinoma) patients followed by a phase II design
      whereupon the primary objective will be median progression free survival (PFS).
TACE (Transarterial Chemo Embolization) has shown to improve overall survival compared to
      non-treated patients with intermediate HCC (Hepatocellular Carcinoma) tumors. However, TACE
      is not considered a curative strategy and eventual local recurrence is observed in nearly all
      (>95%) of cases. Therefore, significant clinical equipoise exists in this large group of HCC
      patients such that novel therapies can be tested in an adjuvant manner to TACE. Based on
      pre-clinical data in HCC and the increasing identification that IL-6 signaling leads to tumor
      progression or local recurrence in other solid malignancies, significant rationale exists for
      the use of Tocilizumab, an IL-6 receptor inhibitor adjuvant to TACE. While Tocilizumab has
      been demonstrated to be safe in RA patients and is FDA approved, limited data exists for the
      maximum tolerated dose (MTD) in patients with cirrhosis and HCC. Therefore, a lead in phase
      IB study design is planned to identify the MTD of Tocilizumab in HCC patients followed by
      expansion to the phase II component whereupon the primary objective will be median
      progression free survival (PFS).
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Maximum Tolerated Dose of Tocilizumab
time frame: 84 Days Post Treatment
description: The MTD is defined as the dose of Tocilizumab that induces dose-limiting toxicity in 20% of subjects or less when added to TACE. Patients must complete 84 days of treatment before the dose can be escalated.
measure: Median Progression Free Survival
time frame: 2 Years Post Treatment
description: Patients will be followed every 3 months for 2 years post treatment. Progression-free survival (PFS) is defined as the duration of time from start of treatment to time of progression or death. Progressive disease is defined as at least a 20% increase in the sum of the LD or the appearance of one or more new lesions.
measure: Number of patients that respond to treatment
time frame: 2 Years Post Treatment
description: Number of patients that respond to treatment
measure: Number of patients alive at two years post treatment
time frame: 2 Years Post Treatment
description: Number of patients alive at two years post treatment
arm group label: Tocilizumab
arm group type: Experimental
description: Participants will receive Tocilizumab (ACTEMRA®) at 4, 6, or 8 mg/kg IV dose escalation on days 1, 29 and 57.
The first part of the trial will be Phase Ib and will enroll 18 participants. Participants will receive TACE on day 1 and Tocilizumab at dose level 1, 2, or 3 on days 1, 29 and 57. Maximum tolerated dose (MTD) of Tocilizumab will be determined.
The second part of the trial will be a Phase II and will enroll 50 subjects. Participants will receive TACE on day 1 and Tocilizumab at the MTD on days 1, 29 and 57.
intervention type: Drug
intervention name: Tocilizumab
description: Participants will receive Tocilizumab (ACTEMRA®) at 4, 6, or 8 mg/kg IV dose escalation on days 1, 29 and 57.
arm group label: Tocilizumab
other name: ACTEMRA
intervention type: Procedure
intervention name: Transcatheter Arterial Chemoembolization
description: Minimally invasive procedure performed in interventional radiology to restrict a tumor's blood supply
arm group label: Tocilizumab
other name: TACE
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Theodore Welling, M.D.
role: Principal Investigator
affiliation: University of Michigan Rogel Cancer Center
facility: 
country: United States
responsible party type: Sponsor
mesh term: Carcinoma
mesh term: Carcinoma, Hepatocellular