<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/NCT03812289</url>
  </required_header>
  <id_info>
    <org_study_id>STUDY00018810</org_study_id>
    <secondary_id>NCI-2018-02864</secondary_id>
    <secondary_id>SOL-18142-L</secondary_id>
    <secondary_id>STUDY00018810</secondary_id>
    <nct_id>NCT03812289</nct_id>
  </id_info>
  <brief_title>Stereotactic Body Radiation Therapy in Treating Patients With Liver Cancer</brief_title>
  <official_title>A Pilot Study to Assess Feasibility of Hypofractionation and Stereotactic Body Radiation Therapy for Hepatocellular Carcinoma Patients Awaiting Liver Transplantation</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>OHSU Knight Cancer Institute</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Radiation Oncology Institute</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Oregon Health and Science University</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>OHSU Knight Cancer Institute</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>Yes</is_fda_regulated_device>
    <is_us_export>No</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      This trial studies how well stereotactic body radiation therapy works in treating patients&#xD;
      with liver cancer. Stereotactic body radiation therapy uses special equipment to position a&#xD;
      patient and deliver radiation to tumors with high precision. This method can kill tumor cells&#xD;
      with fewer doses over a shorter period and cause less damage to normal tissue.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      PRIMARY OBJECTIVE:&#xD;
&#xD;
      I. Assess the use of stereotactic body radiation therapy (SBRT) in hepatocellular carcinoma&#xD;
      (HCC) patients with advanced liver cirrhosis as a feasible approach to providing localized&#xD;
      disease control that adequately suffices liver transplant eligibility criteria.&#xD;
&#xD;
      SECONDARY OBJECTIVE:&#xD;
&#xD;
      I. Assess preliminary efficacy and toxicity in HCC patients with advanced cirrhosis following&#xD;
      liver SBRT.&#xD;
&#xD;
      EXPLORATORY OBJECTIVE:&#xD;
&#xD;
      I. Assess qualify of life in HCC patients with advanced cirrhosis following liver SBRT.&#xD;
&#xD;
      OUTLINE:&#xD;
&#xD;
      Patients undergo SBRT on days 1, 3, 5, 7, and 9 in the absence of disease progression or&#xD;
      unacceptable toxicity.&#xD;
&#xD;
      After completion of study treatment, patients are followed up at 6 weeks, then every 3 months&#xD;
      for up to 2 years.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">February 7, 2019</start_date>
  <completion_date type="Anticipated">March 23, 2024</completion_date>
  <primary_completion_date type="Anticipated">March 23, 2024</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>Proportion of participants who are transplanted or with localized disease control per Milan criteria</measure>
    <time_frame>Up to time of progression, or transplantation, or 1 year after last stereotactic body radiation therapy (SBRT) dose, whichever occurs first</time_frame>
    <description>Will be reported with 95% exact confidence interval (CI).</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Incidence of progressive disease within or at the planned tumor volume (PTV) margin</measure>
    <time_frame>Up to time of progression, transplantation, death or 2 years after last SBRT dose, whichever occurs first</time_frame>
    <description>The estimate of local control rate will be plotted using Kaplan-Meier curve and reported with median survival and 95% CI if available.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Incidence of intrahepatic progressive disease</measure>
    <time_frame>Up to time of progression, transplantation, death or 2-years after last SBRT dose, whichever occurs first</time_frame>
    <description>Will be plotted using Kaplan-Meier curve and reported with median survival and 95% CI if available.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Incidence of extrahepatic progressive disease</measure>
    <time_frame>Up to time of progression, transplantation, death or 2-years after last SBRT dose, whichever occurs first</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Proportion of participants that proceed to transplantation</measure>
    <time_frame>Up to time of progression, transplantation, death or 2-years after last SBRT dose, whichever occurs first</time_frame>
    <description>Will be measured and reported with 95% CI.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Overall survival</measure>
    <time_frame>Up to time of death or 2 years after last SBRT dose</time_frame>
    <description>Will be plotted using Kaplan-Meier curve and reported with median survival and 95% CI if available.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Incidence of non-classic radiation-induced liver disease (RILD) defined as grade 4 aspartate aminotransferase or alanine aminotransferase elevation, or an increase in Child Pugh (CP) score of &gt;= 2 within 1 week to 3 months after completing SBRT</measure>
    <time_frame>Up to 3 months after last SBRT dose</time_frame>
    <description>Will be estimated along with an exact CI using the safety analysis set.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Incidence of liver toxicity assessed per Common Terminology Criteria for Adverse Events (CTCAE) version (v) 5.0</measure>
    <time_frame>Within 1 week to 3 months after completing SBRT</time_frame>
    <description>Will be estimated along with an exact CI using the safety analysis set.</description>
  </secondary_outcome>
  <other_outcome>
    <measure>Change in quality of life (QoL) score using European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ)-C30 questionnaire</measure>
    <time_frame>From baseline to death or 2 years after the last SBRT dose, whichever occurs first</time_frame>
    <description>Summary of QoLs and its change over time will be presented graphically using box plot and spaghetti plot, in addition to a summary table of QoL over time.</description>
  </other_outcome>
  <other_outcome>
    <measure>Change in QoL scores for Functional Assessment of Cancer Therapy-Hepatobiliary (FACT-Hep) questionnaire</measure>
    <time_frame>From baseline to death or 2 years after the last SBRT dose, whichever occurs first</time_frame>
    <description>Summary of QoLs and its change over time will be presented graphically using box plot and spaghetti plot, in addition to a summary table of QoL over time.</description>
  </other_outcome>
  <other_outcome>
    <measure>Proportion of histopathologic changes in irradiated tumor sites relative to uninvolved liver tissue</measure>
    <time_frame>At transplantation</time_frame>
    <description>Descriptive statistical analysis, utilizing the efficacy analysis set, will be used to measure the proportion of histopathologic changes in irradiated tumor sites relative to uninvolved liver tissue will be measured.</description>
  </other_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Anticipated">15</enrollment>
  <condition>Hepatocellular Carcinoma</condition>
  <arm_group>
    <arm_group_label>Treatment (SBRT)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Patients undergo SBRT on days 1, 3, 5, 7, and 9 in the absence of disease progression or unacceptable toxicity.</description>
  </arm_group>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Quality-of-Life Assessment</intervention_name>
    <description>Ancillary studies</description>
    <arm_group_label>Treatment (SBRT)</arm_group_label>
    <other_name>Quality of Life Assessment</other_name>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Questionnaire Administration</intervention_name>
    <description>Ancillary studies</description>
    <arm_group_label>Treatment (SBRT)</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Radiation</intervention_type>
    <intervention_name>Stereotactic Body Radiation Therapy</intervention_name>
    <description>Undergo SBRT</description>
    <arm_group_label>Treatment (SBRT)</arm_group_label>
    <other_name>SABR</other_name>
    <other_name>SBRT</other_name>
    <other_name>Stereotactic Ablative Body Radiation Therapy</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Ability to understand and the willingness to sign a written informed consent document&#xD;
&#xD;
          -  Must be listed or recommended to be listed for orthotopic liver transplantation at the&#xD;
             participating institution&#xD;
&#xD;
          -  Have a Child-Pugh (CP) score &gt;= B8&#xD;
&#xD;
          -  Eastern Clinical Oncology Group (ECOG) performance status =&lt; 2, or Karnofsky&#xD;
             performance scale &gt; 60&#xD;
&#xD;
          -  Must have a life expectancy &gt; 12 weeks&#xD;
&#xD;
          -  Safe radiation treatment planning parameters that adhere to all organs at risk&#xD;
             constraints per section 5.1 of the protocol. If normal organs at risk constraints&#xD;
             (including at least 700cc of uninvolved liver) are unable to be met at the lowest dose&#xD;
             modification (30 Gy in 5 fractions), the patient is deemed ineligible for SBRT and&#xD;
             deemed a screen failure&#xD;
&#xD;
          -  Except for prior radiotherapy or radioembolization, other prior therapies to&#xD;
             previously treated lesions, are permitted&#xD;
&#xD;
          -  People of childbearing potential must have a negative urine or serum pregnancy test&#xD;
             within 72 hours prior to receiving the first dose of SBRT. If the urine test is&#xD;
             positive or cannot be confirmed as negative, a serum pregnancy test will be required&#xD;
&#xD;
          -  Participants of childbearing potential are those who have not been surgically&#xD;
             sterilized or have not been free from menses for &gt; 1 year without an alternative&#xD;
             medical cause&#xD;
&#xD;
               -  Note: Abstinence is acceptable if this is the preferred contraception for the&#xD;
                  participant&#xD;
&#xD;
          -  No other prior invasive malignancy is allowed except for the following: adequately&#xD;
             treated basal (or squamous cell) skin cancer, in situ breast or cervical cancer. Stage&#xD;
             I or II invasive cancer treated with a curative intent without evidence of disease&#xD;
             recurrence for at least five years&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Participants have any one of the following liver tumor characteristics:&#xD;
&#xD;
               -  Have &gt; 5 liver tumors, or&#xD;
&#xD;
               -  Maximal diameter &gt; 5 cm&#xD;
&#xD;
          -  Complete obstruction of portal venous flow to the segment of liver that includes the&#xD;
             target lesion&#xD;
&#xD;
          -  Prior radiotherapy to the upper abdomen or radioembolization of the liver, or prior&#xD;
             thermal ablation to the target lesion&#xD;
&#xD;
          -  For fiducial marker placement:&#xD;
&#xD;
               -  Have a gold allergy&#xD;
&#xD;
               -  Any coagulopathy preventing safe fiducial placement&#xD;
&#xD;
          -  Contraindication to both contrast enhanced magnetic resonance imaging (MRI) and&#xD;
             contrast enhanced computed tomography (CT) (i.e. unable to undergo follow-up imaging&#xD;
             or SBRT treatment planning)&#xD;
&#xD;
          -  Participation in another concurrent treatment protocol&#xD;
&#xD;
          -  Participant is pregnant or breastfeeding, or expecting to conceive or father children&#xD;
             within the projected duration of the trial, starting with the screening visit through&#xD;
             120 days after the last dose of trial treatment&#xD;
&#xD;
          -  Uncontrolled intercurrent illness, including but not limited to, ongoing or active&#xD;
             infection, symptomatic congestive heart failure, uncontrolled hypertension, unstable&#xD;
             angina pectoris, cardiac arrhythmia, interstitial lung disease, serious chronic&#xD;
             gastrointestinal conditions associated with diarrhea, or psychiatric illness/social&#xD;
             situations that would limit compliance with study requirement, substantially increase&#xD;
             risk of incurring adverse events (AEs) or compromise the ability of the patient to&#xD;
             give written informed consent&#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>Nima Nabavizadeh, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>OHSU Knight Cancer Institute</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>John Minger</last_name>
    <phone>503-418-3247</phone>
    <email>mingerj@ohsu.edu</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Nima Nabavizadeh, MD</last_name>
    <phone>503-418-3685</phone>
    <email>nabaviza@ohsu.edu</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>OHSU Knight Cancer Institute</name>
      <address>
        <city>Portland</city>
        <state>Oregon</state>
        <zip>97239</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>John Minger</last_name>
      <phone>503-494-8756</phone>
      <email>minger@ohsu.edu</email>
    </contact>
    <investigator>
      <last_name>Nima Nabavizadeh, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>August 2023</verification_date>
  <study_first_submitted>January 18, 2019</study_first_submitted>
  <study_first_submitted_qc>January 18, 2019</study_first_submitted_qc>
  <study_first_posted type="Actual">January 23, 2019</study_first_posted>
  <last_update_submitted>August 15, 2023</last_update_submitted>
  <last_update_submitted_qc>August 15, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">August 18, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>OHSU Knight Cancer Institute</investigator_affiliation>
    <investigator_full_name>Nima Nabavizadeh</investigator_full_name>
    <investigator_title>Principal Investigator</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>
  <!-- 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/NCT03812289
org study id: STUDY00018810
secondary id: NCI-2018-02864
secondary id: SOL-18142-L
secondary id: STUDY00018810
nct id: NCT03812289
lead sponsor: 
collaborator: 
collaborator: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: Yes
is us export: No
This trial studies how well stereotactic body radiation therapy works in treating patients
      with liver cancer. Stereotactic body radiation therapy uses special equipment to position a
      patient and deliver radiation to tumors with high precision. This method can kill tumor cells
      with fewer doses over a shorter period and cause less damage to normal tissue.
PRIMARY OBJECTIVE:

      I. Assess the use of stereotactic body radiation therapy (SBRT) in hepatocellular carcinoma
      (HCC) patients with advanced liver cirrhosis as a feasible approach to providing localized
      disease control that adequately suffices liver transplant eligibility criteria.

      SECONDARY OBJECTIVE:

      I. Assess preliminary efficacy and toxicity in HCC patients with advanced cirrhosis following
      liver SBRT.

      EXPLORATORY OBJECTIVE:

      I. Assess qualify of life in HCC patients with advanced cirrhosis following liver SBRT.

      OUTLINE:

      Patients undergo SBRT on days 1, 3, 5, 7, and 9 in the absence of disease progression or
      unacceptable toxicity.

      After completion of study treatment, patients are followed up at 6 weeks, then every 3 months
      for up to 2 years.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Proportion of participants who are transplanted or with localized disease control per Milan criteria
time frame: Up to time of progression, or transplantation, or 1 year after last stereotactic body radiation therapy (SBRT) dose, whichever occurs first
description: Will be reported with 95% exact confidence interval (CI).
measure: Incidence of progressive disease within or at the planned tumor volume (PTV) margin
time frame: Up to time of progression, transplantation, death or 2 years after last SBRT dose, whichever occurs first
description: The estimate of local control rate will be plotted using Kaplan-Meier curve and reported with median survival and 95% CI if available.
measure: Incidence of intrahepatic progressive disease
time frame: Up to time of progression, transplantation, death or 2-years after last SBRT dose, whichever occurs first
description: Will be plotted using Kaplan-Meier curve and reported with median survival and 95% CI if available.
measure: Incidence of extrahepatic progressive disease
time frame: Up to time of progression, transplantation, death or 2-years after last SBRT dose, whichever occurs first
measure: Proportion of participants that proceed to transplantation
time frame: Up to time of progression, transplantation, death or 2-years after last SBRT dose, whichever occurs first
description: Will be measured and reported with 95% CI.
measure: Overall survival
time frame: Up to time of death or 2 years after last SBRT dose
description: Will be plotted using Kaplan-Meier curve and reported with median survival and 95% CI if available.
measure: Incidence of non-classic radiation-induced liver disease (RILD) defined as grade 4 aspartate aminotransferase or alanine aminotransferase elevation, or an increase in Child Pugh (CP) score of >= 2 within 1 week to 3 months after completing SBRT
time frame: Up to 3 months after last SBRT dose
description: Will be estimated along with an exact CI using the safety analysis set.
measure: Incidence of liver toxicity assessed per Common Terminology Criteria for Adverse Events (CTCAE) version (v) 5.0
time frame: Within 1 week to 3 months after completing SBRT
description: Will be estimated along with an exact CI using the safety analysis set.
measure: Change in quality of life (QoL) score using European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ)-C30 questionnaire
time frame: From baseline to death or 2 years after the last SBRT dose, whichever occurs first
description: Summary of QoLs and its change over time will be presented graphically using box plot and spaghetti plot, in addition to a summary table of QoL over time.
measure: Change in QoL scores for Functional Assessment of Cancer Therapy-Hepatobiliary (FACT-Hep) questionnaire
time frame: From baseline to death or 2 years after the last SBRT dose, whichever occurs first
description: Summary of QoLs and its change over time will be presented graphically using box plot and spaghetti plot, in addition to a summary table of QoL over time.
measure: Proportion of histopathologic changes in irradiated tumor sites relative to uninvolved liver tissue
time frame: At transplantation
description: Descriptive statistical analysis, utilizing the efficacy analysis set, will be used to measure the proportion of histopathologic changes in irradiated tumor sites relative to uninvolved liver tissue will be measured.
arm group label: Treatment (SBRT)
arm group type: Experimental
description: Patients undergo SBRT on days 1, 3, 5, 7, and 9 in the absence of disease progression or unacceptable toxicity.
intervention type: Other
intervention name: Quality-of-Life Assessment
description: Ancillary studies
arm group label: Treatment (SBRT)
other name: Quality of Life Assessment
intervention type: Other
intervention name: Questionnaire Administration
description: Ancillary studies
arm group label: Treatment (SBRT)
intervention type: Radiation
intervention name: Stereotactic Body Radiation Therapy
description: Undergo SBRT
arm group label: Treatment (SBRT)
other name: SABR
other name: SBRT
other name: Stereotactic Ablative Body Radiation Therapy
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Nima Nabavizadeh, MD
role: Principal Investigator
affiliation: OHSU Knight Cancer Institute
last name: John Minger
phone: 503-418-3247
email: mingerj@ohsu.edu
last name: Nima Nabavizadeh, MD
phone: 503-418-3685
email: nabaviza@ohsu.edu
facility: 
status: Recruiting
contact: 
investigator: 
country: United States
responsible party type: Principal Investigator
investigator affiliation: OHSU Knight Cancer Institute
investigator full name: Nima Nabavizadeh
investigator title: Principal Investigator
mesh term: Carcinoma
mesh term: Carcinoma, Hepatocellular