<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/NCT02221778</url>
  </required_header>
  <id_info>
    <org_study_id>RT-02/2014</org_study_id>
    <nct_id>NCT02221778</nct_id>
  </id_info>
  <brief_title>SBRT for Hepatocellular Carcinoma Patients With Partial Response to TACE</brief_title>
  <official_title>Stereotactic Body Radiation Therapy for Hepatocellular Carcinoma Patients With Partial Response to Transarterial Chemoembolization</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of Sao Paulo</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>University of Sao Paulo</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      This is a pilot study where patients with Hepatocellular Carcinoma (HCC) that have failed&#xD;
      Transarterial Chemoembolization (TACE) will be treated with Stereotactic Body Radiation&#xD;
      Therapy (SBRT). The focus of the study will be to evaluate safety and efficacy in our&#xD;
      population of patients.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Active, not recruiting</overall_status>
  <start_date type="Actual">August 2014</start_date>
  <completion_date type="Anticipated">August 2024</completion_date>
  <primary_completion_date type="Anticipated">August 2024</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>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Local Progression Free Survival</measure>
    <time_frame>5 years</time_frame>
    <description>Local Progression Free Survival will be measured on triphasic Computerized Tomography (CT) or Magnetic Resonance Imaging (MRI) when clinically indicated.&#xD;
The exam will be performed every 3 months after the end of treatment. The tumor response will be measured according to the modified RECIST (mRECIST) directed to the HCC study.&#xD;
Local Progression Free Survival will be defined as increase of 20% in the sum of all diameters of the treated lesions.&#xD;
Time-to-event will be counted from the initiation of SBRT</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Distant Progression Free Survival</measure>
    <time_frame>5 years</time_frame>
    <description>Distant Progression Free Survival will be measured on triphasic Computerized Tomography (CT) or Magnetic Resonance Imaging (MRI) when clinically indicated.&#xD;
The exam will be performed every 3 months after the end of treatment. The tumor response will be measured according to the modified RECIST (mRECIST) directed to the HCC study.&#xD;
Distant Progression Free Survival will be defined as the appearance of a new hepatic lesion, tumoral thrombus or distant metastases.&#xD;
Time-to-event will be counted from the initiation of SBRT</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Toxicity</measure>
    <time_frame>5 years</time_frame>
    <description>Toxicity will be evaluated according to the Common Terminology Criteria for Adverse Events version 4.0 (CTCAE v.4.0). Toxicity will be evaluated weekly during treatment, monthly in the first 3 months after treatment and every 3 months after.&#xD;
Acute Toxicity will be defined as toxicity that develops within the first 3 months after initiation treatment.&#xD;
Chronic Toxicity will be defined as toxicity that develops after 3 months of initiation of treatment.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Overall Survival</measure>
    <time_frame>5 years</time_frame>
    <description>Time-to-event will be counted from the initiation of SBRT</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Anticipated">25</enrollment>
  <condition>Carcinoma, Hepatocellular</condition>
  <arm_group>
    <arm_group_label>SBRT</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>SBRT according to the intervention description</description>
  </arm_group>
  <intervention>
    <intervention_type>Radiation</intervention_type>
    <intervention_name>SBRT</intervention_name>
    <description>SBRT will be prescribed according to the Radiation Therapy Oncology Group (RTOG) 1112 protocol using Mean Liver Dose (MLD) as parameter. MLD will be calculated using Liver minus Gross Tumor Volume (GTV). Prescription dose will follow the scheme below:&#xD;
Prescription dose(Gy) / (MLD) (Gy)&#xD;
50 / 13&#xD;
45 / 15&#xD;
40 / 15&#xD;
35 / 15.5&#xD;
30 / 16&#xD;
27.5 / 17&#xD;
If the dose constraints cannot be met, prescription will be according to the level immediately bellow.&#xD;
Treatment will be delivered in 5 fractions in consecutive working days</description>
    <arm_group_label>SBRT</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  HCC diagnosis according to the American Association for the Study of Liver Diseases&#xD;
             (AASLD) 2010 criteria&#xD;
&#xD;
          -  Tumor Stage&#xD;
&#xD;
          -  liver only disease&#xD;
&#xD;
          -  tumor thrombus at segment is allowed&#xD;
&#xD;
          -  no extra hepatic metastases&#xD;
&#xD;
          -  tumor encompassing less than 50% of hepatic volume&#xD;
&#xD;
          -  previous treatment with Transarterial Chemo Embolization (TACE) - patient must have&#xD;
             performed at least 2 sessions of TACE and have signs of viable tumor in CT or MRI&#xD;
             performed 30-40 days after last TACE&#xD;
&#xD;
          -  presence of measurable lesion (at least one lesion that can be measured equal or more&#xD;
             than 1 cm in CT or MRI).&#xD;
&#xD;
          -  Maximum lesion size of 10 cm.&#xD;
&#xD;
          -  Liver residual volume equal or more than 700cc or 40% of total liver volume&#xD;
&#xD;
          -  Child-Pugh A or absence of hepatic cirrhosis&#xD;
&#xD;
          -  absence of encephalopathy or ascitis on clinical exam&#xD;
&#xD;
          -  Eastern Cooperative Oncology Group (ECOG) performance status 0-1&#xD;
&#xD;
          -  Lab exams:&#xD;
&#xD;
          -  hemoglobin &gt; or equal 8 mg/dl&#xD;
&#xD;
          -  neutrophils &gt; or equal 1.200/mm³&#xD;
&#xD;
          -  platelets &gt; or equal 45.000/mm³&#xD;
&#xD;
          -  alanine aminotransferase (ALT) and aspartate aminotransferase (AST) less than 6 times&#xD;
             the upper normal limit&#xD;
&#xD;
          -  bilirubin equal or &lt; 2 mg/dl&#xD;
&#xD;
          -  international normalized ratio (INR) &lt; 1.7&#xD;
&#xD;
          -  serum creatinine equal or &lt; 1.5 times the upper normal limit or creatinine clearance &gt;&#xD;
             or equal 60 ml/min&#xD;
&#xD;
          -  Albumin &gt;2.8 mg/dl&#xD;
&#xD;
          -  not being pregnant - a negative pregnancy test is required (for women). Patients in&#xD;
             fertile age should use a contraceptive method during treatment and 4 months after.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Patients with more than 5 discrete lesions in the liver&#xD;
&#xD;
          -  Main or common biliary duct invasion&#xD;
&#xD;
          -  Patients with main portal vein tumor thrombus or more than 2 portal branch thrombus&#xD;
&#xD;
          -  Patients in systemic treatment (sorafenib, chemotherapy). There should be an interval&#xD;
             of at least 4 weeks between any medication for treatment of HCC and the current study&#xD;
             treatment&#xD;
&#xD;
          -  Previous radiation to upper abdomen&#xD;
&#xD;
          -  Patients with other malignant neoplasms or previous malignant neoplasms will be&#xD;
             accepted in the study if HCC prognosis is worse&#xD;
&#xD;
          -  Patients with ischemic myocardial infarction within the last 6 months&#xD;
&#xD;
          -  Patients with large esophageal varices with red color sign or bleeding within the last&#xD;
             3 months&#xD;
&#xD;
          -  Patients with symptoms of colitis, enteritis, esophagitis, fistula, ileus, necrosis,&#xD;
             stenosis or ulcer&#xD;
&#xD;
          -  Patients with severe anorexy, constipation, dehydration, diarrhea or vomiting&#xD;
&#xD;
          -  Patients unable to understand and sign written informed consent&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>N/A</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Flair J Carrilho, MD, PhD</last_name>
    <role>Study Chair</role>
    <affiliation>University of Sao Paulo</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Andre T Chen, MD, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>University of Sao Paulo</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Instituto do Cancer do Estado de Sao Paulo, Hospital das Clinicas da Faculdade de Medicina da USP</name>
      <address>
        <city>Sao Paulo</city>
        <zip>01246000</zip>
        <country>Brazil</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Brazil</country>
  </location_countries>
  <verification_date>December 2021</verification_date>
  <study_first_submitted>August 19, 2014</study_first_submitted>
  <study_first_submitted_qc>August 19, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">August 20, 2014</study_first_posted>
  <last_update_submitted>December 15, 2021</last_update_submitted>
  <last_update_submitted_qc>December 15, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">December 16, 2021</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>University of Sao Paulo</investigator_affiliation>
    <investigator_full_name>Andre Tsin Chih Chen</investigator_full_name>
    <investigator_title>MD</investigator_title>
  </responsible_party>
  <keyword>Carcinoma, Hepatocellular</keyword>
  <keyword>SBRT</keyword>
  <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/NCT02221778
org study id: RT-02/2014
nct id: NCT02221778
lead sponsor: 
has dmc: No
This is a pilot study where patients with Hepatocellular Carcinoma (HCC) that have failed
      Transarterial Chemoembolization (TACE) will be treated with Stereotactic Body Radiation
      Therapy (SBRT). The focus of the study will be to evaluate safety and efficacy in our
      population of patients.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Local Progression Free Survival
time frame: 5 years
description: Local Progression Free Survival will be measured on triphasic Computerized Tomography (CT) or Magnetic Resonance Imaging (MRI) when clinically indicated.
The exam will be performed every 3 months after the end of treatment. The tumor response will be measured according to the modified RECIST (mRECIST) directed to the HCC study.
Local Progression Free Survival will be defined as increase of 20% in the sum of all diameters of the treated lesions.
Time-to-event will be counted from the initiation of SBRT
measure: Distant Progression Free Survival
time frame: 5 years
description: Distant Progression Free Survival will be measured on triphasic Computerized Tomography (CT) or Magnetic Resonance Imaging (MRI) when clinically indicated.
The exam will be performed every 3 months after the end of treatment. The tumor response will be measured according to the modified RECIST (mRECIST) directed to the HCC study.
Distant Progression Free Survival will be defined as the appearance of a new hepatic lesion, tumoral thrombus or distant metastases.
Time-to-event will be counted from the initiation of SBRT
measure: Toxicity
time frame: 5 years
description: Toxicity will be evaluated according to the Common Terminology Criteria for Adverse Events version 4.0 (CTCAE v.4.0). Toxicity will be evaluated weekly during treatment, monthly in the first 3 months after treatment and every 3 months after.
Acute Toxicity will be defined as toxicity that develops within the first 3 months after initiation treatment.
Chronic Toxicity will be defined as toxicity that develops after 3 months of initiation of treatment.
measure: Overall Survival
time frame: 5 years
description: Time-to-event will be counted from the initiation of SBRT
arm group label: SBRT
arm group type: Experimental
description: SBRT according to the intervention description
intervention type: Radiation
intervention name: SBRT
description: SBRT will be prescribed according to the Radiation Therapy Oncology Group (RTOG) 1112 protocol using Mean Liver Dose (MLD) as parameter. MLD will be calculated using Liver minus Gross Tumor Volume (GTV). Prescription dose will follow the scheme below:
Prescription dose(Gy) / (MLD) (Gy)
50 / 13
45 / 15
40 / 15
35 / 15.5
30 / 16
27.5 / 17
If the dose constraints cannot be met, prescription will be according to the level immediately bellow.
Treatment will be delivered in 5 fractions in consecutive working days
arm group label: SBRT
criteria: 
gender: All
minimum age: N/A
maximum age: N/A
healthy volunteers: No
last name: Flair J Carrilho, MD, PhD
role: Study Chair
affiliation: University of Sao Paulo
last name: Andre T Chen, MD, PhD
role: Principal Investigator
affiliation: University of Sao Paulo
facility: 
country: Brazil
responsible party type: Principal Investigator
investigator affiliation: University of Sao Paulo
investigator full name: Andre Tsin Chih Chen
investigator title: MD
mesh term: Carcinoma
mesh term: Carcinoma, Hepatocellular