<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/NCT02977754</url>
  </required_header>
  <id_info>
    <org_study_id>1458</org_study_id>
    <nct_id>NCT02977754</nct_id>
  </id_info>
  <brief_title>18F-FDG PET in HCC Patients Candidate to Treatment With Sorafenib</brief_title>
  <official_title>Exploring the Prognostic Role of 18F-FDG PET/CT Imaging in Patients Affected by Hepatocellular Carcinoma (HCC) and Candidate to Treatment With Sorafenib</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Istituto Clinico Humanitas</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Istituto Clinico Humanitas</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The principal objective of this study is to explore the role of 18F-FDG PET in identifying&#xD;
      sorafenib-induced metabolic shift in HCC, thus in predicting treatment response and disease&#xD;
      outcome in advanced HCC patients candidate to systemic treatment with sorafenib.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Aerobic glycolysis also called &quot;Warburg effect&quot;, represents one of the distinctive hallmarks&#xD;
      of the malignant cells. Although energetically less efficient than respiration, fermentative&#xD;
      metabolism is advantageous for cell growth due to the increased availability of anabolic&#xD;
      intermediates and the reduced cell dependence on oxygen. Moreover, by increasing&#xD;
      intracellular reducing equivalents and decreasing mitochondria-derived ROS, glycolysis&#xD;
      protects malignant cells from oxidant-induced senescence and apoptosis.&#xD;
&#xD;
      In diagnostic imaging, the &quot;Warburg effect&quot; is visualized thanks to the utilization of&#xD;
      ﬂuoro-2-deoxyglucose, a glucose analogue, labeled with the positron emitting nuclide&#xD;
      fluoride-18 (18F). F-2-ﬂuoro-2-deoxyglucose (18F-FDG) with positron emission tomography (PET)&#xD;
      has emerged useful in many tumor types and in HCC can help ruling out extra-hepatic&#xD;
      metastases or sites of recurrent disease, and giving prognostic information. Considering the&#xD;
      abovementioned premises, the investigators hypothesize a potential use of 18F-FDG PET for the&#xD;
      early assessment of sorafenib-induced metabolic shift in HCC, especially in&#xD;
      well-differentiated subtypes usually showing an uptake of the tracer not different or at&#xD;
      least not sufficiently increased compared to the normal liver.&#xD;
&#xD;
      For these reasons the investigators decided to conduct an explorative study for the&#xD;
      assessment of predictive and prognostic role of 18F-FDG PET in patients affected by advanced&#xD;
      HCC and candidate to systemic treatment with sorafenib.&#xD;
&#xD;
      The principal objective of this study is to explore the role of 18F-FDG PET in identifying&#xD;
      sorafenib-induced metabolic shift in HCC, thus in predicting treatment response and disease&#xD;
      outcome in advanced HCC patients candidate to systemic treatment with sorafenib.&#xD;
&#xD;
      More specifically the investigators will:&#xD;
&#xD;
        -  compare 18F-FDG uptake in HCC lesions, identified as target lesions (diam. min. 2cm), at&#xD;
           baseline, at 24 hours and 1 week after the first administration of sorafenib.&#xD;
&#xD;
        -  correlate the patterns of 18F-FDG uptake in HCC lesions with objective tumor response&#xD;
           assessed 8 weeks after the first administration of sorafenib according to mRECIST&#xD;
           criteria.&#xD;
&#xD;
        -  correlate the patterns of 18F-FDG uptake in HCC lesions with alpha-fetoprotein (AFP)&#xD;
           variation at baseline, at 24 hours and 1 week after the first administration of&#xD;
           sorafenib.&#xD;
&#xD;
        -  correlate the patterns of 18F-FDG uptake in HCC lesions with progression-free survival&#xD;
           (PFS) and overall survival (OS).&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>January 2016</start_date>
  <completion_date type="Actual">March 2019</completion_date>
  <primary_completion_date type="Actual">December 2018</primary_completion_date>
  <study_type>Observational</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <observational_model>Cohort</observational_model>
    <time_perspective>Prospective</time_perspective>
  </study_design_info>
  <primary_outcome>
    <measure>Early change of metabolic characteristics (i.e. SUVmax, SUVmean, MTV, TLG) of HCC lesions under Sorafenib</measure>
    <time_frame>Compare 18F-FDG uptake in HCC lesions at baseline and at 24 hours after the first administration of sorafenib.</time_frame>
    <description>Baseline parameters</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Change of metabolic characteristics (i.e. SUVmax, SUVmean, MTV, TLG) of HCC lesions under Sorafenib</measure>
    <time_frame>Compare 18F-FDG uptake in HCC lesions at baseline and 1 week after the first administration of sorafenib.</time_frame>
    <description>Variation of parameters</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Predictive role of metabolic characteristics of HCC (i.e. SUVmax, SUVmean, MTV, TLG) lesions under Sorafenib</measure>
    <time_frame>Correlate the patterns of 18F-FDG uptake in HCC lesions with objective tumor response assessed 8 weeks after the first administration of sorafenib according to mRECIST criteria</time_frame>
    <description>PET scan parameters compared to response</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Prognostic role of metabolic characteristics (i.e. SUVmax, SUVmean, MTV, TLG) of HCC lesions under Sorafenib</measure>
    <time_frame>Correlate the patterns of 18F-FDG uptake in HCC lesions with progression-free survival (PFS) and overall survival (OS) assessed during a minimun of 12 months of follow up</time_frame>
    <description>PET scan parameters compared to outcome</description>
  </secondary_outcome>
  <other_outcome>
    <measure>Correlate tumor markers with metabolic characteristics (i.e. SUVmax, SUVmean, MTV, TLG) of HCC lesions under Sorafenib</measure>
    <time_frame>Correlate the patterns of 18F-FDG uptake in HCC lesions with alpha-fetoprotein (AFP) measured at baseline and after 8 weeks of treatment</time_frame>
    <description>PET scan parameters compared to tumor markers</description>
  </other_outcome>
  <enrollment type="Actual">13</enrollment>
  <condition>HCC</condition>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>This is an observational study</intervention_name>
    <description>Imaging</description>
  </intervention>
  <eligibility>
    <study_pop>
      <textblock>
        This is a single-center, single-arm study, lasting 36 months including an estimated period&#xD;
        of 24 months for the enrolment and max 12 months of follow-up. All patients affected by HCC&#xD;
        and referred to our Institution for systemic treatment with sorafenib will be evaluated for&#xD;
        enrolment. A minimum number of 10 patients will be considered for the analysis.&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Non-Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  patients with an histological diagnosis of HCC and scheduled to undergo systemic&#xD;
             treatment with sorafenib;&#xD;
&#xD;
          -  obtained informed consent&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  patients age &lt;18 years&#xD;
&#xD;
          -  pregnancy or breast-feeding;&#xD;
&#xD;
          -  patients affected by other malignancies within the last 3 years, with the exception of&#xD;
             surgically cured carcinoma in situ of the cervix, in situ breast cancer, incidental&#xD;
             finding of stage T1a or T1b prostate cancer, and basal/squamous cell carcinoma of the&#xD;
             skin.&#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>Egesta Lopci</last_name>
    <role>Principal Investigator</role>
    <affiliation>Istituto Clinico Humanitas</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Istituto Clinico Humanitas</name>
      <address>
        <city>Rozzano</city>
        <state>Milano</state>
        <zip>20089</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Italy</country>
  </location_countries>
  <reference>
    <citation>Castello A, Rimassa L, Personeni N, Pressiani T, Smiroldo V, Lopci E. Metabolic Switch in Hepatocellular Carcinoma Patients Treated with Sorafenib: a Proof-of-Concept Trial. Mol Imaging Biol. 2020 Oct;22(5):1446-1454. doi: 10.1007/s11307-020-01489-6.</citation>
    <PMID>32206991</PMID>
  </reference>
  <verification_date>September 2020</verification_date>
  <study_first_submitted>November 18, 2016</study_first_submitted>
  <study_first_submitted_qc>November 26, 2016</study_first_submitted_qc>
  <study_first_posted type="Estimate">November 30, 2016</study_first_posted>
  <last_update_submitted>September 29, 2020</last_update_submitted>
  <last_update_submitted_qc>September 29, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">October 1, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <patient_data>
    <sharing_ipd>No</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/NCT02977754
org study id: 1458
nct id: NCT02977754
lead sponsor: 
has dmc: Yes
The principal objective of this study is to explore the role of 18F-FDG PET in identifying
      sorafenib-induced metabolic shift in HCC, thus in predicting treatment response and disease
      outcome in advanced HCC patients candidate to systemic treatment with sorafenib.
Aerobic glycolysis also called "Warburg effect", represents one of the distinctive hallmarks
      of the malignant cells. Although energetically less efficient than respiration, fermentative
      metabolism is advantageous for cell growth due to the increased availability of anabolic
      intermediates and the reduced cell dependence on oxygen. Moreover, by increasing
      intracellular reducing equivalents and decreasing mitochondria-derived ROS, glycolysis
      protects malignant cells from oxidant-induced senescence and apoptosis.

      In diagnostic imaging, the "Warburg effect" is visualized thanks to the utilization of
      ﬂuoro-2-deoxyglucose, a glucose analogue, labeled with the positron emitting nuclide
      fluoride-18 (18F). F-2-ﬂuoro-2-deoxyglucose (18F-FDG) with positron emission tomography (PET)
      has emerged useful in many tumor types and in HCC can help ruling out extra-hepatic
      metastases or sites of recurrent disease, and giving prognostic information. Considering the
      abovementioned premises, the investigators hypothesize a potential use of 18F-FDG PET for the
      early assessment of sorafenib-induced metabolic shift in HCC, especially in
      well-differentiated subtypes usually showing an uptake of the tracer not different or at
      least not sufficiently increased compared to the normal liver.

      For these reasons the investigators decided to conduct an explorative study for the
      assessment of predictive and prognostic role of 18F-FDG PET in patients affected by advanced
      HCC and candidate to systemic treatment with sorafenib.

      The principal objective of this study is to explore the role of 18F-FDG PET in identifying
      sorafenib-induced metabolic shift in HCC, thus in predicting treatment response and disease
      outcome in advanced HCC patients candidate to systemic treatment with sorafenib.

      More specifically the investigators will:

        -  compare 18F-FDG uptake in HCC lesions, identified as target lesions (diam. min. 2cm), at
           baseline, at 24 hours and 1 week after the first administration of sorafenib.

        -  correlate the patterns of 18F-FDG uptake in HCC lesions with objective tumor response
           assessed 8 weeks after the first administration of sorafenib according to mRECIST
           criteria.

        -  correlate the patterns of 18F-FDG uptake in HCC lesions with alpha-fetoprotein (AFP)
           variation at baseline, at 24 hours and 1 week after the first administration of
           sorafenib.

        -  correlate the patterns of 18F-FDG uptake in HCC lesions with progression-free survival
           (PFS) and overall survival (OS).
observational model: Cohort
time perspective: Prospective
measure: Early change of metabolic characteristics (i.e. SUVmax, SUVmean, MTV, TLG) of HCC lesions under Sorafenib
time frame: Compare 18F-FDG uptake in HCC lesions at baseline and at 24 hours after the first administration of sorafenib.
description: Baseline parameters
measure: Change of metabolic characteristics (i.e. SUVmax, SUVmean, MTV, TLG) of HCC lesions under Sorafenib
time frame: Compare 18F-FDG uptake in HCC lesions at baseline and 1 week after the first administration of sorafenib.
description: Variation of parameters
measure: Predictive role of metabolic characteristics of HCC (i.e. SUVmax, SUVmean, MTV, TLG) lesions under Sorafenib
time frame: Correlate the patterns of 18F-FDG uptake in HCC lesions with objective tumor response assessed 8 weeks after the first administration of sorafenib according to mRECIST criteria
description: PET scan parameters compared to response
measure: Prognostic role of metabolic characteristics (i.e. SUVmax, SUVmean, MTV, TLG) of HCC lesions under Sorafenib
time frame: Correlate the patterns of 18F-FDG uptake in HCC lesions with progression-free survival (PFS) and overall survival (OS) assessed during a minimun of 12 months of follow up
description: PET scan parameters compared to outcome
measure: Correlate tumor markers with metabolic characteristics (i.e. SUVmax, SUVmean, MTV, TLG) of HCC lesions under Sorafenib
time frame: Correlate the patterns of 18F-FDG uptake in HCC lesions with alpha-fetoprotein (AFP) measured at baseline and after 8 weeks of treatment
description: PET scan parameters compared to tumor markers
intervention type: Other
intervention name: This is an observational study
description: Imaging
study pop: 
sampling method: Non-Probability Sample
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Egesta Lopci
role: Principal Investigator
affiliation: Istituto Clinico Humanitas
facility: 
country: Italy
citation: Castello A, Rimassa L, Personeni N, Pressiani T, Smiroldo V, Lopci E. Metabolic Switch in Hepatocellular Carcinoma Patients Treated with Sorafenib: a Proof-of-Concept Trial. Mol Imaging Biol. 2020 Oct;22(5):1446-1454. doi: 10.1007/s11307-020-01489-6.
PMID: 32206991
responsible party type: Sponsor
sharing ipd: No