<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/NCT02984566</url>
  </required_header>
  <id_info>
    <org_study_id>TROG1703 LARK</org_study_id>
    <nct_id>NCT02984566</nct_id>
  </id_info>
  <brief_title>Liver Ablative Radiotherapy Utilising Kilovoltage Intrafraction Monitoring (KIM)</brief_title>
  <acronym>TROG1703 LARK</acronym>
  <official_title>LARK: Liver Ablative Radiotherapy Utilising Kilovoltage Intrafraction Monitoring (KIM)</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of Sydney</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>University of Sydney</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      Primary and secondary liver cancer patients will receive liver SABR with or without KIM&#xD;
      intervention.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This is a single arm, phase II, two stage study designed to evaluate cancer targeting&#xD;
      accuracy, treatment outcomes and treatment efficiency in 46 patients eligible for SABR for&#xD;
      either primary or secondary liver malignancy with the incorporation of KIM.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">January 14, 2020</start_date>
  <completion_date type="Anticipated">December 2024</completion_date>
  <primary_completion_date type="Anticipated">July 2023</primary_completion_date>
  <phase>N/A</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>Difference in accumulated patient dose distribution with and without KIM</measure>
    <time_frame>15-60 minutes (time of individual fraction delivery)</time_frame>
    <description>Isodose distributions and dose volume histograms for each session will be calculated with KIM corrections as treated, and estimated without KIM corrections. The planning CT scan will be used for this assessment</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Difference in treatment time with and without KIM</measure>
    <time_frame>15-60 minutes (time of individual fraction delivery)</time_frame>
    <description>The time taken for the KIM treatments compared with the time taken for similar treatments from previous patients, accounting for the difference in the time and number of patient images acquired and the time taken to adjust the patient's position during treatment</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Difference in imaging dose with and without KIM</measure>
    <time_frame>15-60 minutes (time of individual fraction delivery)</time_frame>
    <description>The KIM procedure adds radiation dose with the kilovoltage images. However, there may be fewer volumetric cone beam computed tomography (CBCT) scans acquired. This difference in dose will be estimated and analysed</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Difference in PTV margins with and without KIM</measure>
    <time_frame>15-60 minutes (time of individual fraction delivery)</time_frame>
    <description>The clinical target volume (CTV) to planning target volume (PTV) margin with and without KIM will be recorded and analysed.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Difference in accumulated patient dose distribution with and without KIM based on the intra-treatment CBCT scans</measure>
    <time_frame>15-60 minutes (time of individual fraction delivery)</time_frame>
    <description>Isodose distributions and dose volume histograms for each session will be calculated with KIM corrections as treated, and estimated without KIM corrections. The intratreatment CBCT scans will be used for this assessment.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in dose when using KIM with and without using MLC tracking</measure>
    <time_frame>15-60 minutes (time of individual fraction delivery</time_frame>
    <description>Difference between dose delivered using KIM with or without MLC tracking</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Proportion of local failures at two years for patients treated</measure>
    <time_frame>2 years</time_frame>
    <description>Proportion of local failures at two years for patients treated as assessed using modified RECIST criteria</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>The proportion of grade 3 or higher toxicities</measure>
    <time_frame>2 years</time_frame>
    <description>The proportion of grade 3 or higher toxicities, assessed using CTCAE v4.03</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Patient-reported quality of life as measured by the European Organization for Research and Treatment of Cancer Quality-of-Life-Questionnaire-Core-30 (EORTC QLQ-C30)</measure>
    <time_frame>2 years</time_frame>
    <description>To compare change in Quality of Life, as defined by the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core-30 (EORTC QLQ-C30 (Version 3)) from baseline at completion of radiation therapy and at 6 weeks, 3, 6, 12, 18 and 24 months post-radiation therapy. The EORTC QLQ-C30 (Version 3) uses for the questions 1 to 28 a 4-point scale. The scale scores from 1 to 4: 1 (&quot;Not at all&quot;), 2 (&quot;A little&quot;), 3 (&quot;Quite a bit&quot;) and 4 (&quot;Very much&quot;). Half points are not allowed. The range is 3. For the raw score, less points are considered to have a better outcome. The EORTC QLQ-C30 (Version 3) uses for the questions 29 and 30 a 7-points scale. The scale scores from 1 to 7: 1 (&quot;very poor&quot;) to 7 (&quot;excellent&quot;). The questionnaire will be self-administered and will be given in patient's mother tongue.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Patient-reported quality of life as measured by the European Organization for Research and Treatment of Cancer Quality-of-Life-Questionnaire-Hepatocellular Carcinoma 18 Module (EORTC QLQ-HCC18)</measure>
    <time_frame>18 months</time_frame>
    <description>To compare change in Quality of Life related to hepatocellular carcinoma (HCC) as defined by the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire - Hepatocellular Carcinoma 18 Module (EORTC QLQ-HCC) from baseline at completion of radiation therapy and at 6 weeks, 3, 6, 12 and 18 months post-radiation therapy. The questionnaire will be self-administered and will be given to patients proficient in English. EORTC-QLQ-HCC18: includes HCC-specific symptoms or problems. Questions used 4-point Likert scale from 1 to 4: 1 (&quot;Not at all&quot;), 2 (&quot;A little&quot;), 3 (&quot;Quite a bit&quot;) and 4 (&quot;Very much&quot;). Scores averaged and transformed to 0-100 scale. High score for functional scale=high/healthy level of functioning. High score for single item=high level of symptomatology/problems.</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Anticipated">46</enrollment>
  <condition>Liver Cancer</condition>
  <arm_group>
    <arm_group_label>SABR with or without KIM</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>All patients will receive liver SABR. Kilovoltage Intrafraction Monitoring (KIM) tracking will be trialed during mock treatment. If KIM is successful, it will be used throughout treatment. If unsuccessful, cone beam CT will be used instead.</description>
  </arm_group>
  <intervention>
    <intervention_type>Device</intervention_type>
    <intervention_name>Kilovoltage Intrafraction Monitoring</intervention_name>
    <description>KIM is a novel intrafraction real-time tumour localization method. It involves a single gantry-mounted kV x-ray imager acquiring 2D projections of implanted fiducial markers. 3D positions are then reconstructed by maximum likelihood estimation of a 3D probability density function.</description>
    <arm_group_label>SABR with or without KIM</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  ECOG performance status 0-1&#xD;
&#xD;
          -  Life expectancy &gt;6 months&#xD;
&#xD;
          -  Number of lesions: ≤ 3&#xD;
&#xD;
          -  Lesion size : &lt; 10 cm for a single lesion (and up to 10 cm cumulative diameter for&#xD;
             multiple lesions)&#xD;
&#xD;
          -  Child-Pugh A or B7 within 6 weeks prior to study entry&#xD;
&#xD;
          -  Unsuitable for RFA or resection or transplant&#xD;
&#xD;
          -  Distance from GTV to luminal structures (i.e., oesophagus, stomach, duodenum, small or&#xD;
             large bowel) ≥ 10mm&#xD;
&#xD;
          -  All blood work obtained within 6 weeks prior to study entry with adequate organ&#xD;
             function&#xD;
&#xD;
          -  May have had previous surgery, RFA or ethanol injection&#xD;
&#xD;
          -  Patient must have been discussed at multidisciplinary tumour board with consensus&#xD;
             opinion for SBRT&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  HCC/cholangiocarcinoma with evidence of metastatic disease including nodal or distant&#xD;
             metastases&#xD;
&#xD;
          -  Metastatic disease with complete liver disease response to first-line chemotherapy&#xD;
             (i.e. no target for SBRT)&#xD;
&#xD;
          -  Previous radiation to the liver (including SIRTEX)&#xD;
&#xD;
          -  Untreated HIV or active hepatitis B/C&#xD;
&#xD;
          -  On systemic antineoplastic drug therapy within 7 days before inclusion&#xD;
&#xD;
          -  Pregnant or lactating women&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>85 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Tim Wang, Dr</last_name>
    <role>Principal Investigator</role>
    <affiliation>Westmead Hospital</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Doan Nguyen, PhD</last_name>
    <phone>+61 2 8627 1185</phone>
    <email>d.nguyen@sydney.edu.au</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Natalie Plant, Masters</last_name>
    <phone>+61 2 8627 1133</phone>
    <email>natalie.plant@sydney.edu.au</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>Nepean Hospital</name>
      <address>
        <city>Penrith</city>
        <state>New South Wales</state>
        <zip>2750</zip>
        <country>Australia</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Kirsten van Gysen</last_name>
    </contact>
    <investigator>
      <last_name>Kirsten van Gysen</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Westmead Hospital</name>
      <address>
        <city>Westmead</city>
        <state>New South Wales</state>
        <zip>2049</zip>
        <country>Australia</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Tracy Pearl-Larsson</last_name>
      <phone>02 8890 5200</phone>
      <email>Tracy.Pearl-Larson@health.nsw.gov.au</email>
    </contact>
    <investigator>
      <last_name>Tim Wang</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Princess Alexandra Hospital</name>
      <address>
        <city>Woolloongabba</city>
        <state>Queensland</state>
        <zip>4102</zip>
        <country>Australia</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Yoo Young Lee</last_name>
    </contact>
    <investigator>
      <last_name>Yoo Young Lee</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Peter MacCallum Cancer Centre</name>
      <address>
        <city>Melbourne</city>
        <state>Victoria</state>
        <zip>3000</zip>
        <country>Australia</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Julie Chu</last_name>
    </contact>
    <investigator>
      <last_name>Julie Chu</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location_countries>
    <country>Australia</country>
  </location_countries>
  <verification_date>January 2023</verification_date>
  <study_first_submitted>November 23, 2016</study_first_submitted>
  <study_first_submitted_qc>December 2, 2016</study_first_submitted_qc>
  <study_first_posted type="Estimate">December 7, 2016</study_first_posted>
  <last_update_submitted>January 23, 2023</last_update_submitted>
  <last_update_submitted_qc>January 23, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">January 25, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Primary liver cancer</keyword>
  <keyword>Secondary liver cancer</keyword>
  <keyword>Kilovoltage Intrafraction Monitoring</keyword>
  <keyword>Stereotactic Ablative Body Radiation</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Liver Neoplasms</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>Yes</sharing_ipd>
    <ipd_description>Anonymised data will be made available to researchers upon request, once evidence of ethical approval has been provided.</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/NCT02984566
org study id: TROG1703 LARK
nct id: NCT02984566
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
Primary and secondary liver cancer patients will receive liver SABR with or without KIM
      intervention.
This is a single arm, phase II, two stage study designed to evaluate cancer targeting
      accuracy, treatment outcomes and treatment efficiency in 46 patients eligible for SABR for
      either primary or secondary liver malignancy with the incorporation of KIM.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Difference in accumulated patient dose distribution with and without KIM
time frame: 15-60 minutes (time of individual fraction delivery)
description: Isodose distributions and dose volume histograms for each session will be calculated with KIM corrections as treated, and estimated without KIM corrections. The planning CT scan will be used for this assessment
measure: Difference in treatment time with and without KIM
time frame: 15-60 minutes (time of individual fraction delivery)
description: The time taken for the KIM treatments compared with the time taken for similar treatments from previous patients, accounting for the difference in the time and number of patient images acquired and the time taken to adjust the patient's position during treatment
measure: Difference in imaging dose with and without KIM
time frame: 15-60 minutes (time of individual fraction delivery)
description: The KIM procedure adds radiation dose with the kilovoltage images. However, there may be fewer volumetric cone beam computed tomography (CBCT) scans acquired. This difference in dose will be estimated and analysed
measure: Difference in PTV margins with and without KIM
time frame: 15-60 minutes (time of individual fraction delivery)
description: The clinical target volume (CTV) to planning target volume (PTV) margin with and without KIM will be recorded and analysed.
measure: Difference in accumulated patient dose distribution with and without KIM based on the intra-treatment CBCT scans
time frame: 15-60 minutes (time of individual fraction delivery)
description: Isodose distributions and dose volume histograms for each session will be calculated with KIM corrections as treated, and estimated without KIM corrections. The intratreatment CBCT scans will be used for this assessment.
measure: Change in dose when using KIM with and without using MLC tracking
time frame: 15-60 minutes (time of individual fraction delivery
description: Difference between dose delivered using KIM with or without MLC tracking
measure: Proportion of local failures at two years for patients treated
time frame: 2 years
description: Proportion of local failures at two years for patients treated as assessed using modified RECIST criteria
measure: The proportion of grade 3 or higher toxicities
time frame: 2 years
description: The proportion of grade 3 or higher toxicities, assessed using CTCAE v4.03
measure: Patient-reported quality of life as measured by the European Organization for Research and Treatment of Cancer Quality-of-Life-Questionnaire-Core-30 (EORTC QLQ-C30)
time frame: 2 years
description: To compare change in Quality of Life, as defined by the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core-30 (EORTC QLQ-C30 (Version 3)) from baseline at completion of radiation therapy and at 6 weeks, 3, 6, 12, 18 and 24 months post-radiation therapy. The EORTC QLQ-C30 (Version 3) uses for the questions 1 to 28 a 4-point scale. The scale scores from 1 to 4: 1 ("Not at all"), 2 ("A little"), 3 ("Quite a bit") and 4 ("Very much"). Half points are not allowed. The range is 3. For the raw score, less points are considered to have a better outcome. The EORTC QLQ-C30 (Version 3) uses for the questions 29 and 30 a 7-points scale. The scale scores from 1 to 7: 1 ("very poor") to 7 ("excellent"). The questionnaire will be self-administered and will be given in patient's mother tongue.
measure: Patient-reported quality of life as measured by the European Organization for Research and Treatment of Cancer Quality-of-Life-Questionnaire-Hepatocellular Carcinoma 18 Module (EORTC QLQ-HCC18)
time frame: 18 months
description: To compare change in Quality of Life related to hepatocellular carcinoma (HCC) as defined by the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire - Hepatocellular Carcinoma 18 Module (EORTC QLQ-HCC) from baseline at completion of radiation therapy and at 6 weeks, 3, 6, 12 and 18 months post-radiation therapy. The questionnaire will be self-administered and will be given to patients proficient in English. EORTC-QLQ-HCC18: includes HCC-specific symptoms or problems. Questions used 4-point Likert scale from 1 to 4: 1 ("Not at all"), 2 ("A little"), 3 ("Quite a bit") and 4 ("Very much"). Scores averaged and transformed to 0-100 scale. High score for functional scale=high/healthy level of functioning. High score for single item=high level of symptomatology/problems.
arm group label: SABR with or without KIM
arm group type: Experimental
description: All patients will receive liver SABR. Kilovoltage Intrafraction Monitoring (KIM) tracking will be trialed during mock treatment. If KIM is successful, it will be used throughout treatment. If unsuccessful, cone beam CT will be used instead.
intervention type: Device
intervention name: Kilovoltage Intrafraction Monitoring
description: KIM is a novel intrafraction real-time tumour localization method. It involves a single gantry-mounted kV x-ray imager acquiring 2D projections of implanted fiducial markers. 3D positions are then reconstructed by maximum likelihood estimation of a 3D probability density function.
arm group label: SABR with or without KIM
criteria: 
gender: All
minimum age: 18 Years
maximum age: 85 Years
healthy volunteers: No
last name: Tim Wang, Dr
role: Principal Investigator
affiliation: Westmead Hospital
last name: Doan Nguyen, PhD
phone: +61 2 8627 1185
email: d.nguyen@sydney.edu.au
last name: Natalie Plant, Masters
phone: +61 2 8627 1133
email: natalie.plant@sydney.edu.au
facility: 
status: Recruiting
contact: 
investigator: 
facility: 
status: Recruiting
contact: 
investigator: 
facility: 
status: Recruiting
contact: 
investigator: 
facility: 
status: Recruiting
contact: 
investigator: 
country: Australia
responsible party type: Sponsor
mesh term: Liver Neoplasms
sharing ipd: Yes
ipd description: Anonymised data will be made available to researchers upon request, once evidence of ethical approval has been provided.