<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/NCT02967848</url>
  </required_header>
  <id_info>
    <org_study_id>RESP/16/129</org_study_id>
    <nct_id>NCT02967848</nct_id>
  </id_info>
  <brief_title>Liver Function Investigation With SPECT</brief_title>
  <acronym>LiverINSPECT</acronym>
  <official_title>Liver Function Investigation With Single Photon Emission Computed Tomography After Radiotherapy</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Royal North Shore Hospital</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Royal North Shore Hospital</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      This is a Phase 1 pilot study to assess feasibility and utility of 99mTc-mebrofenin&#xD;
      hepatobiliary scintigraphy for measurement of functional liver change due to radiotherapy.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Patients with cancers of the liver who are not suitable for surgery or chemo/radio&#xD;
      embolisation are often treated with stereotactic ablative body radiotherapy (SABR). SABR&#xD;
      results in high local control rates but, similar to other treatment modalities, carries risk&#xD;
      of damage to healthy surrounding liver. This study aims to use a novel nuclear medicine&#xD;
      imaging tracer, 99mTcMebrofenin, to evaluate liver function before and after radiotherapy.&#xD;
&#xD;
      Patients will have a 99mTcMebrofenin scan performed &lt; 2 weeks before radiotherapy and 1 and 6&#xD;
      months after radiotherapy. At the same time points, indocyanine green (ICG) and liver&#xD;
      elasticity tests will be performed. These are global measures of liver function, whereas&#xD;
      99mTcMebrofenin is both global and local. From the imaging data, the Investigators will be&#xD;
      able to correlate change in local liver function in each sub volume of the liver with the&#xD;
      radiotherapy dose it received. The Investigators will be able to thus measure the effect of&#xD;
      radiotherapy on global and local liver function.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Active, not recruiting</overall_status>
  <start_date type="Actual">October 19, 2016</start_date>
  <completion_date type="Anticipated">December 2022</completion_date>
  <primary_completion_date type="Actual">December 2020</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>Change in global and local liver function</measure>
    <time_frame>3 years</time_frame>
    <description>99mTC-mebrofenin hepatobiliary scintigraphy images after stereotactic ablative body radiotherapy to cancers of the liver. This will be reported as a change in function as a function of delivered radiotherapy dose.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Correlation between 99mTC mebrofenin HBS and various measures of global function</measure>
    <time_frame>3 years</time_frame>
    <description>This correlation will be measured using liver elasticity, Indocyanine Green (ICG) and Child-Pugh and Model for End stage Liver Disease (MELD) scores</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Relationship between radiological features on CT images and SPECT images</measure>
    <time_frame>2 years</time_frame>
    <description>Relationship between radiological features or changes visable on computed tomography (CT) image data and changes in local liver function as observed on 99mTC mebrofenin HBS.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Radiotherapy dose sparing of functional liver</measure>
    <time_frame>2 years</time_frame>
    <description>The amount of sparing of dose to functional liver that can be achieved using 99mTC Mebrofenin HBS to guide treatment plan optimisation will be evaluated.</description>
  </secondary_outcome>
  <number_of_groups>1</number_of_groups>
  <enrollment type="Anticipated">20</enrollment>
  <condition>Liver Cancer, Adult</condition>
  <arm_group>
    <arm_group_label>Patients with Cancers in Liver</arm_group_label>
    <description>Adult patients with primary liver cancer or liver metastases from any other histology who will be measured before and after Radiotherapy by '99mTc-mebrofenin hepatobiliary scintigraphy (HBS), Indocyanine Green and Liver Elasticity.</description>
  </arm_group>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>99mTc-mebrofenin hepatobiliary scintigraphy (HBS)</intervention_name>
    <description>99mTc-mebrofenin HBS is a SPECT imaging procedure that allows evaluation of global and local liver function. Mebrofenin, bound to albumin, is taken up by hepatocytes in a similar manner to organic anions such as bilirubin. After hepatic uptake, the mebrofenin is excreted into the bile canaliculi. Dynamic imaging tools allow measurement of clearance rates for global function, and 3D SPECT imaging with corresponding CT allows visualisation of the local liver function with respect to anatomy. HBS allows direct visualisation of hepatocyte function.</description>
    <arm_group_label>Patients with Cancers in Liver</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Indocyanine Green</intervention_name>
    <description>ICG is a fluorescent dye injected into the patient. The dye is exclusively excreted by the liver. The ICG clearance rate is measured in the finger of the subject.</description>
    <arm_group_label>Patients with Cancers in Liver</arm_group_label>
    <other_name>ICG</other_name>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Liver Elasticity</intervention_name>
    <description>This is an Ultrasound measurement of the elasticity of the liver.</description>
    <arm_group_label>Patients with Cancers in Liver</arm_group_label>
    <other_name>Liver FibroScan</other_name>
  </intervention>
  <eligibility>
    <study_pop>
      <textblock>
        Adult Liver Cancer patients attending the Northern Sydney Cancer Centre at the Royal North&#xD;
        Shore Hospital&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Non-Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Aged 18 or older&#xD;
&#xD;
          -  Has provided written Informed Consent for participation in this trial and is willing&#xD;
             to comply with the study&#xD;
&#xD;
          -  Patients undergoing external beam radiotherapy at Northern Sydney Cancer Centre&#xD;
&#xD;
          -  Histologically proven hepatocellular carcinoma or oligometastatic liver metastases (3&#xD;
             or less). Histological diagnosis will be obtained if clinically indicated.&#xD;
&#xD;
          -  ECOG performance status 0-2&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Previous high-dose radiotherapy to the liver&#xD;
&#xD;
          -  Previous SIRT&#xD;
&#xD;
          -  Women who are pregnant or lactating&#xD;
&#xD;
          -  Unwilling or unable to give informed consent&#xD;
&#xD;
          -  No venous access&#xD;
&#xD;
          -  Inability to lie supine and still for 30 minutes&#xD;
&#xD;
          -  History of allergic reactions attributed to compounds of similar chemical or biologic&#xD;
             composition to indocyanine green, including those patients with a history of iodide or&#xD;
             seafood allergy (excluded from ICG testing only)&#xD;
&#xD;
          -  Pacemaker (excluded from Fibroscan elasticity test only)&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>100 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <location>
    <facility>
      <name>Royal North Shore Hospital</name>
      <address>
        <city>St Leonards</city>
        <state>New South Wales</state>
        <zip>2065</zip>
        <country>Australia</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Australia</country>
  </location_countries>
  <verification_date>October 2022</verification_date>
  <study_first_submitted>November 16, 2016</study_first_submitted>
  <study_first_submitted_qc>November 17, 2016</study_first_submitted_qc>
  <study_first_posted type="Estimate">November 18, 2016</study_first_posted>
  <last_update_submitted>October 26, 2022</last_update_submitted>
  <last_update_submitted_qc>October 26, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">October 28, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Royal North Shore Hospital</investigator_affiliation>
    <investigator_full_name>Professor Andrew Kneebone</investigator_full_name>
    <investigator_title>Associate Professor Andrew Kneebone</investigator_title>
  </responsible_party>
  <keyword>Radiotherapy</keyword>
  <keyword>Mebrofenin</keyword>
  <keyword>Liver</keyword>
  <keyword>Cancer</keyword>
  <keyword>SPECT</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Carcinoma, Hepatocellular</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Technetium Tc 99m mebrofenin</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>Yes</sharing_ipd>
    <ipd_description>Data will be processed remotely at Peter MacCallum Cancer Centre, by the AI, Nicholas Hardcastle.</ipd_description>
  </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/NCT02967848
org study id: RESP/16/129
nct id: NCT02967848
lead sponsor: 
has dmc: No
This is a Phase 1 pilot study to assess feasibility and utility of 99mTc-mebrofenin
      hepatobiliary scintigraphy for measurement of functional liver change due to radiotherapy.
Patients with cancers of the liver who are not suitable for surgery or chemo/radio
      embolisation are often treated with stereotactic ablative body radiotherapy (SABR). SABR
      results in high local control rates but, similar to other treatment modalities, carries risk
      of damage to healthy surrounding liver. This study aims to use a novel nuclear medicine
      imaging tracer, 99mTcMebrofenin, to evaluate liver function before and after radiotherapy.

      Patients will have a 99mTcMebrofenin scan performed < 2 weeks before radiotherapy and 1 and 6
      months after radiotherapy. At the same time points, indocyanine green (ICG) and liver
      elasticity tests will be performed. These are global measures of liver function, whereas
      99mTcMebrofenin is both global and local. From the imaging data, the Investigators will be
      able to correlate change in local liver function in each sub volume of the liver with the
      radiotherapy dose it received. The Investigators will be able to thus measure the effect of
      radiotherapy on global and local liver function.
observational model: Cohort
time perspective: Prospective
measure: Change in global and local liver function
time frame: 3 years
description: 99mTC-mebrofenin hepatobiliary scintigraphy images after stereotactic ablative body radiotherapy to cancers of the liver. This will be reported as a change in function as a function of delivered radiotherapy dose.
measure: Correlation between 99mTC mebrofenin HBS and various measures of global function
time frame: 3 years
description: This correlation will be measured using liver elasticity, Indocyanine Green (ICG) and Child-Pugh and Model for End stage Liver Disease (MELD) scores
measure: Relationship between radiological features on CT images and SPECT images
time frame: 2 years
description: Relationship between radiological features or changes visable on computed tomography (CT) image data and changes in local liver function as observed on 99mTC mebrofenin HBS.
measure: Radiotherapy dose sparing of functional liver
time frame: 2 years
description: The amount of sparing of dose to functional liver that can be achieved using 99mTC Mebrofenin HBS to guide treatment plan optimisation will be evaluated.
arm group label: Patients with Cancers in Liver
description: Adult patients with primary liver cancer or liver metastases from any other histology who will be measured before and after Radiotherapy by '99mTc-mebrofenin hepatobiliary scintigraphy (HBS), Indocyanine Green and Liver Elasticity.
intervention type: Other
intervention name: 99mTc-mebrofenin hepatobiliary scintigraphy (HBS)
description: 99mTc-mebrofenin HBS is a SPECT imaging procedure that allows evaluation of global and local liver function. Mebrofenin, bound to albumin, is taken up by hepatocytes in a similar manner to organic anions such as bilirubin. After hepatic uptake, the mebrofenin is excreted into the bile canaliculi. Dynamic imaging tools allow measurement of clearance rates for global function, and 3D SPECT imaging with corresponding CT allows visualisation of the local liver function with respect to anatomy. HBS allows direct visualisation of hepatocyte function.
arm group label: Patients with Cancers in Liver
intervention type: Other
intervention name: Indocyanine Green
description: ICG is a fluorescent dye injected into the patient. The dye is exclusively excreted by the liver. The ICG clearance rate is measured in the finger of the subject.
arm group label: Patients with Cancers in Liver
other name: ICG
intervention type: Other
intervention name: Liver Elasticity
description: This is an Ultrasound measurement of the elasticity of the liver.
arm group label: Patients with Cancers in Liver
other name: Liver FibroScan
study pop: 
sampling method: Non-Probability Sample
criteria: 
gender: All
minimum age: 18 Years
maximum age: 100 Years
healthy volunteers: No
facility: 
country: Australia
responsible party type: Principal Investigator
investigator affiliation: Royal North Shore Hospital
investigator full name: Professor Andrew Kneebone
investigator title: Associate Professor Andrew Kneebone
mesh term: Carcinoma, Hepatocellular
mesh term: Technetium Tc 99m mebrofenin
sharing ipd: Yes
ipd description: Data will be processed remotely at Peter MacCallum Cancer Centre, by the AI, Nicholas Hardcastle.