<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/NCT03303469</url>
  </required_header>
  <id_info>
    <org_study_id>F170519002</org_study_id>
    <nct_id>NCT03303469</nct_id>
  </id_info>
  <brief_title>Hypoxic Changes in Hepatocellular Carcinoma (HCC) Following Trans Arterial Chemo Embolization and Stereotactic Radiation: Fluorine18 (18F) Fluoromisonidazole (FMISO) Imaging</brief_title>
  <official_title>Hypoxic Changes in Hepatocellular Carcinoma (HCC) Following Trans Arterial Chemo Embolization and Stereotactic Radiation: [18F]Fluoromisonidazole (FMISO) Imaging</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of Alabama at Birmingham</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>University of Alabama at Birmingham</source>
  <oversight_info>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      [18F] FMISO Positron Emission Tomography (PET) to determine hypoxia in patients with HCC&#xD;
      treated with TACE.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This Phase II study will investigate the utility of [18F] FMISO in patients with&#xD;
      hepatocellular carcinoma (HCC). This trial is designed to test the hypothesis that PET&#xD;
      determined [18F]FMISO uptake will indicate tumor hypoxia in patients with HCC treated with&#xD;
      trans-arterial chemo-embolization (TACE). We anticipate that [18F] FMISO PET/CT will advance&#xD;
      our understanding of the role of hypoxia in HCC prior to treatment and that this knowledge&#xD;
      will help design newer combination therapeutic trials for better treatment outcomes. [18F]&#xD;
      FMISO PET/CT provides three parameters, tissue hypoxic volume (HV), maximum tissue to blood&#xD;
      uptake ratio (T:Bmax) and tumor blood flow. Both pre-and post-therapy images will be examined&#xD;
      to investigate changes in these parameters during the course of TACE treatment.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Terminated</overall_status>
  <why_stopped>
    study was terminated due to poor enrollment&#xD;
  </why_stopped>
  <start_date type="Actual">October 30, 2017</start_date>
  <completion_date type="Actual">January 6, 2021</completion_date>
  <primary_completion_date type="Actual">January 6, 2021</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>Diagnostic</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Quantitate HCC Tumor Hypoxia at Baseline Using FMISO Positron Emission Tomography (PET).</measure>
    <time_frame>At baseline</time_frame>
    <description>Perform PET/CT imaging using FMISO at baseline to measure tumor hypoxia</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Measure Changes in HCC Tumor Hypoxia and Blood Flow After Trans-arterial Chemoembolization (TACE), Prior to Radiotherapy.</measure>
    <time_frame>1 month post-TACE procedures and prior to SBRT</time_frame>
    <description>Perform PET/CT imaging using FMISO post-TACE and prior to Stereotactic body radiation therapy (SBRT) to determine tumor hypoxia</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Measure Changes in Treated HCC Tumor Hypoxia Following TACE and Radiotherapy</measure>
    <time_frame>1 month post-SBRT</time_frame>
    <description>Perform PET/CT imaging using FMISO post-SBRT to determine tumor hypoxia</description>
  </primary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">3</enrollment>
  <condition>Hepatocellular Carcinoma</condition>
  <arm_group>
    <arm_group_label>FMISO PET imaging post TACE and Stereotactic body radiation therapy (SBRT)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>FMISO imaging at baseline, post-TACE and post-SBRT</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>FMISO</intervention_name>
    <description>FMISO PET/CT imaging at baseline</description>
    <arm_group_label>FMISO PET imaging post TACE and Stereotactic body radiation therapy (SBRT)</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>FMISO</intervention_name>
    <description>FMISO PET/CT post TACE</description>
    <arm_group_label>FMISO PET imaging post TACE and Stereotactic body radiation therapy (SBRT)</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>FMISO</intervention_name>
    <description>FMISO PET/CT post SBRT</description>
    <arm_group_label>FMISO PET imaging post TACE and Stereotactic body radiation therapy (SBRT)</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Adult (&gt; 18 years of age) patients with documented HCC tumor mass &gt;3cm, who are&#xD;
             scheduled to undergo TACE with additional selective internal radiation therapy (SIRT)&#xD;
&#xD;
          -  The appropriate criteria for inclusion for this patient population are:&#xD;
&#xD;
          -  Biopsy or radiological diagnosis of HCC (defined as Organ Procurement and&#xD;
             Transplantation Network (OPTN*) Category 5 lesion either on CT or MRI)&#xD;
&#xD;
          -  Scheduled for TACE (using doxorubicin-eluting beads) + SBRT&#xD;
&#xD;
          -  Willingness to undergo PET/CT&#xD;
&#xD;
          -  Able to lie on the imaging table for up to 1 hour.&#xD;
&#xD;
          -  Able to provide signed informed consent.&#xD;
&#xD;
          -  Women with childbearing potential must have a negative urine Beta-Human Chorionic&#xD;
             Gonadotropin (β-hCG) test day of procedure&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Estimated life expectancy &lt;12 months or serious medical co-morbidities that would&#xD;
             preclude definitive local therapy&#xD;
&#xD;
          -  Unable to lie on the imaging table&#xD;
&#xD;
          -  Age less than 18 years.&#xD;
&#xD;
          -  Pregnancy or lactation&#xD;
&#xD;
          -  Inability or unwillingness to provide informed consent.&#xD;
&#xD;
          -  Weight &gt;500 lbs (the weight limit of the tomograph gantry table)&#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>Janis P O'Malley, M.D.</last_name>
    <role>Principal Investigator</role>
    <affiliation>University of Alabama at Birmingham</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>UAB Advanced Imaging Facility</name>
      <address>
        <city>Birmingham</city>
        <state>Alabama</state>
        <zip>35294</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>February 2021</verification_date>
  <study_first_submitted>September 13, 2017</study_first_submitted>
  <study_first_submitted_qc>October 2, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">October 6, 2017</study_first_posted>
  <results_first_submitted>January 27, 2021</results_first_submitted>
  <results_first_submitted_qc>February 15, 2021</results_first_submitted_qc>
  <results_first_posted type="Actual">February 21, 2021</results_first_posted>
  <last_update_submitted>February 15, 2021</last_update_submitted>
  <last_update_submitted_qc>February 15, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">February 21, 2021</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>University of Alabama at Birmingham</investigator_affiliation>
    <investigator_full_name>Janis P. O'Malley, MD</investigator_full_name>
    <investigator_title>Principal Investigator, Professor of Radiology</investigator_title>
  </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>
  <provided_document_section>
    <provided_document>
      <document_type>Study Protocol and Statistical Analysis Plan</document_type>
      <document_has_protocol>Yes</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>Yes</document_has_sap>
      <document_date>July 30, 2020</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/69/NCT03303469/Prot_SAP_001.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <group_list>
        <group group_id="P1">
          <title>FMISO PET Imaging Post TACE and SBRT</title>
          <description>FMISO imaging at baseline, post-TACE and post-SBRT&#xD;
FMISO: FMISO PET/CT imaging at baseline&#xD;
FMISO: FMISO PET/CT post TACE&#xD;
FMISO: FMISO PET/CT post SBRT</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="3"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="2"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Lost to Follow-up</title>
              <participants_list>
                <participants group_id="P1" count="2"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>FMISO PET Imaging Post TACE and SBRT</title>
          <description>FMISO imaging at baseline, post-TACE and post-SBRT&#xD;
FMISO: FMISO PET/CT imaging at baseline&#xD;
FMISO: FMISO PET/CT post TACE&#xD;
FMISO: FMISO PET/CT post SBRT</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="3"/>
          </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="1"/>
                  </measurement_list>
                </category>
                <category>
                  <title>&gt;=65 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="2"/>
                  </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="2"/>
                  </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="3"/>
                  </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>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="3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Quantitate HCC Tumor Hypoxia at Baseline Using FMISO Positron Emission Tomography (PET).</title>
        <description>Perform PET/CT imaging using FMISO at baseline to measure tumor hypoxia</description>
        <time_frame>At baseline</time_frame>
        <population>We were unable to perform the statistical analysis due to insufficient data collection.</population>
        <group_list>
          <group group_id="O1">
            <title>FMISO PET Imaging Post TACE and SBRT</title>
            <description>FMISO imaging at baseline, post-TACE and post-SBRT&#xD;
FMISO: FMISO PET/CT imaging at baseline&#xD;
FMISO: FMISO PET/CT post TACE&#xD;
FMISO: FMISO PET/CT post SBRT</description>
          </group>
        </group_list>
        <measure>
          <title>Quantitate HCC Tumor Hypoxia at Baseline Using FMISO Positron Emission Tomography (PET).</title>
          <description>Perform PET/CT imaging using FMISO at baseline to measure tumor hypoxia</description>
          <population>We were unable to perform the statistical analysis due to insufficient data collection.</population>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="0"/>
              </count_list>
            </analyzed>
          </analyzed_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Measure Changes in HCC Tumor Hypoxia and Blood Flow After Trans-arterial Chemoembolization (TACE), Prior to Radiotherapy.</title>
        <description>Perform PET/CT imaging using FMISO post-TACE and prior to Stereotactic body radiation therapy (SBRT) to determine tumor hypoxia</description>
        <time_frame>1 month post-TACE procedures and prior to SBRT</time_frame>
        <population>We were unable to perform the statistical analysis due to insufficient data collection.</population>
        <group_list>
          <group group_id="O1">
            <title>FMISO PET Imaging Post TACE and SBRT</title>
            <description>FMISO imaging at baseline, post-TACE and post-SBRT&#xD;
FMISO: FMISO PET/CT imaging at baseline&#xD;
FMISO: FMISO PET/CT post TACE&#xD;
FMISO: FMISO PET/CT post SBRT</description>
          </group>
        </group_list>
        <measure>
          <title>Measure Changes in HCC Tumor Hypoxia and Blood Flow After Trans-arterial Chemoembolization (TACE), Prior to Radiotherapy.</title>
          <description>Perform PET/CT imaging using FMISO post-TACE and prior to Stereotactic body radiation therapy (SBRT) to determine tumor hypoxia</description>
          <population>We were unable to perform the statistical analysis due to insufficient data collection.</population>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="0"/>
              </count_list>
            </analyzed>
          </analyzed_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Measure Changes in Treated HCC Tumor Hypoxia Following TACE and Radiotherapy</title>
        <description>Perform PET/CT imaging using FMISO post-SBRT to determine tumor hypoxia</description>
        <time_frame>1 month post-SBRT</time_frame>
        <population>We were unable to perform the statistical analysis due to insufficient data collection.</population>
        <group_list>
          <group group_id="O1">
            <title>FMISO PET Imaging Post TACE and SBRT</title>
            <description>FMISO imaging at baseline, post-TACE and post-SBRT&#xD;
FMISO: FMISO PET/CT imaging at baseline&#xD;
FMISO: FMISO PET/CT post TACE&#xD;
FMISO: FMISO PET/CT post SBRT</description>
          </group>
        </group_list>
        <measure>
          <title>Measure Changes in Treated HCC Tumor Hypoxia Following TACE and Radiotherapy</title>
          <description>Perform PET/CT imaging using FMISO post-SBRT to determine tumor hypoxia</description>
          <population>We were unable to perform the statistical analysis due to insufficient data collection.</population>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="0"/>
              </count_list>
            </analyzed>
          </analyzed_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>Between 4 to 6 weeks.</time_frame>
      <group_list>
        <group group_id="E1">
          <title>FMISO PET Imaging Post TACE and SBRT</title>
          <description>FMISO imaging at baseline, post-TACE and post-SBRT&#xD;
FMISO: FMISO PET/CT imaging at baseline&#xD;
FMISO: FMISO PET/CT post TACE&#xD;
FMISO: FMISO PET/CT post SBRT</description>
        </group>
      </group_list>
      <serious_events>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, all-cause mortality</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="3"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>3</frequency_threshold>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, other adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="3"/>
              </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>There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed. </restrictive_agreement>
    </certain_agreements>
    <point_of_contact>
      <name_or_title>Janis O'Malley</name_or_title>
      <organization>The University of Alabama at Birmingham</organization>
      <phone>205-934-6504</phone>
      <email>jomalley@uabmc.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/NCT03303469
org study id: F170519002
nct id: NCT03303469
lead sponsor: 
is fda regulated drug: Yes
is fda regulated device: No
[18F] FMISO Positron Emission Tomography (PET) to determine hypoxia in patients with HCC
      treated with TACE.
This Phase II study will investigate the utility of [18F] FMISO in patients with
      hepatocellular carcinoma (HCC). This trial is designed to test the hypothesis that PET
      determined [18F]FMISO uptake will indicate tumor hypoxia in patients with HCC treated with
      trans-arterial chemo-embolization (TACE). We anticipate that [18F] FMISO PET/CT will advance
      our understanding of the role of hypoxia in HCC prior to treatment and that this knowledge
      will help design newer combination therapeutic trials for better treatment outcomes. [18F]
      FMISO PET/CT provides three parameters, tissue hypoxic volume (HV), maximum tissue to blood
      uptake ratio (T:Bmax) and tumor blood flow. Both pre-and post-therapy images will be examined
      to investigate changes in these parameters during the course of TACE treatment.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Diagnostic
masking: None (Open Label)
measure: Quantitate HCC Tumor Hypoxia at Baseline Using FMISO Positron Emission Tomography (PET).
time frame: At baseline
description: Perform PET/CT imaging using FMISO at baseline to measure tumor hypoxia
measure: Measure Changes in HCC Tumor Hypoxia and Blood Flow After Trans-arterial Chemoembolization (TACE), Prior to Radiotherapy.
time frame: 1 month post-TACE procedures and prior to SBRT
description: Perform PET/CT imaging using FMISO post-TACE and prior to Stereotactic body radiation therapy (SBRT) to determine tumor hypoxia
measure: Measure Changes in Treated HCC Tumor Hypoxia Following TACE and Radiotherapy
time frame: 1 month post-SBRT
description: Perform PET/CT imaging using FMISO post-SBRT to determine tumor hypoxia
arm group label: FMISO PET imaging post TACE and Stereotactic body radiation therapy (SBRT)
arm group type: Experimental
description: FMISO imaging at baseline, post-TACE and post-SBRT
intervention type: Drug
intervention name: FMISO
description: FMISO PET/CT imaging at baseline
arm group label: FMISO PET imaging post TACE and Stereotactic body radiation therapy (SBRT)
intervention type: Drug
intervention name: FMISO
description: FMISO PET/CT post TACE
arm group label: FMISO PET imaging post TACE and Stereotactic body radiation therapy (SBRT)
intervention type: Drug
intervention name: FMISO
description: FMISO PET/CT post SBRT
arm group label: FMISO PET imaging post TACE and Stereotactic body radiation therapy (SBRT)
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Janis P O'Malley, M.D.
role: Principal Investigator
affiliation: University of Alabama at Birmingham
facility: 
country: United States
responsible party type: Principal Investigator
investigator affiliation: University of Alabama at Birmingham
investigator full name: Janis P. O'Malley, MD
investigator title: Principal Investigator, Professor of Radiology
mesh term: Carcinoma
mesh term: Carcinoma, Hepatocellular
provided document: 
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 