<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/NCT01730937</url>
  </required_header>
  <id_info>
    <org_study_id>RTOG-1112</org_study_id>
    <secondary_id>NCI-2012-02057</secondary_id>
    <secondary_id>U10CA021661</secondary_id>
    <nct_id>NCT01730937</nct_id>
  </id_info>
  <brief_title>Sorafenib Tosylate With or Without Stereotactic Body Radiation Therapy in Treating Patients With Liver Cancer</brief_title>
  <official_title>Randomized Phase III Study of Sorafenib Versus Stereotactic Body Radiation Therapy Followed by Sorafenib in Hepatocellular Carcinoma</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Radiation Therapy Oncology Group</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>National Cancer Institute (NCI)</agency>
      <agency_class>NIH</agency_class>
    </collaborator>
    <collaborator>
      <agency>NRG Oncology</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Radiation Therapy Oncology Group</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      This randomized phase III trial studies sorafenib tosylate and stereotactic body radiation&#xD;
      therapy to see how well they work compared to sorafenib tosylate alone in treating patients&#xD;
      with liver cancer. Sorafenib tosylate may stop the growth of tumor cells by blocking some of&#xD;
      the enzymes needed for cell growth. Stereotactic body radiation therapy may be able to send&#xD;
      the radiation dose directly to the tumor and cause less damage to normal tissue. Giving&#xD;
      sorafenib tosylate together with stereotactic body radiation therapy may kill more tumor&#xD;
      cells.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      PRIMARY OBJECTIVES:&#xD;
&#xD;
      I. To determine if stereotactic body radiation therapy (SBRT) improves overall survival in&#xD;
      hepatocellular carcinoma (HCC) patients treated with sorafenib (sorafenib tosylate).&#xD;
&#xD;
      SECONDARY OBJECTIVES:&#xD;
&#xD;
      I. To determine the difference in time to progression (TTP) and progression-free survival&#xD;
      (PFS) in HCC patients treated with sorafenib compared to SBRT followed by sorafenib.&#xD;
&#xD;
      II. To measure differences in toxicity in HCC patients treated with sorafenib versus SBRT&#xD;
      followed by sorafenib.&#xD;
&#xD;
      III. To measure vascular thrombosis response post sorafenib versus SBRT followed by&#xD;
      sorafenib.&#xD;
&#xD;
      IV. To measure differences in health related quality of life (QOL) and quality-adjusted&#xD;
      survival in HCC patients treated with sorafenib compared to SBRT followed by sorafenib.&#xD;
&#xD;
      V. Collection of biospecimens for future correlative studies to investigate differences in&#xD;
      potential biomarkers in patients treated with sorafenib versus SBRT followed by sorafenib.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Active, not recruiting</overall_status>
  <start_date>April 2013</start_date>
  <completion_date type="Anticipated">July 1, 2027</completion_date>
  <primary_completion_date type="Actual">July 1, 2022</primary_completion_date>
  <phase>Phase 3</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Single (Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Overall Survival</measure>
    <time_frame>From randomization to last follow-up: weekly during SBRT, post-SBRT/pre-sorafenib, monthly during sorafenib, and overall, from study entry: every 3 months for 2 years, then every 6 months. Maximum follow-up at time of analysis was 7.6 years.</time_frame>
    <description>An event for overall survival (OS) is death due to any cause. Survival time is defined as time from randomization to the date of death or last known follow-up (censored). Rates are estimated by the Kaplan-Meier method. Analysis was to occur after 153 deaths were reported.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Time to Progression</measure>
    <time_frame>From randomization to last follow-up: weekly during SBRT, post-SBRT/pre-sorafenib, monthly during sorafenib, and overall, from study entry: every 3 months for 2 years, then every 6 months. Maximum follow-up at time of analysis was 7.6 years.</time_frame>
    <description>Progression (failure) is defined as any of the following events: new tumor thrombosis, progression of hepatocellular carcinoma (HCC) within liver excluding tumor thrombosis status, progression of distant metastases that were present at study entry, new HCC within the liver including tumor thrombosis, and vascular thrombosis events=progression-new enhancing tumor thrombosis/progression-Increase in the volume of enhancing portion of thrombosis. Time to progression was measured from the date of randomization to the date of first failure, death (competing risk), or last follow-up (censored). Progression rates are estimated by the cumulative incidence method. The protocol specifies only that the distributions of failure times be compared between the arms, which is reported in the statistical analysis results. Two-year estimates are provided as a summary of the distributions.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Progression-free Survival</measure>
    <time_frame>From randomization to last follow-up: weekly during SBRT, post-SBRT/pre-sorafenib, monthly during sorafenib, and overall, from study entry: every 3 months for 2 years, then every 6 months. Maximum follow-up at time of analysis was 7.6 years.</time_frame>
    <description>Failure for progression-free survival (PFS) include death, new tumor thrombosis, progression of hepatocellular carcinoma (HCC) within liver excluding tumor thrombosis status, progression of distant Mets that were present at study entry, new HCC within liver including tumor thrombosis, and vascular thrombosis events =progression-new enhancing tumor thrombosis/progression-Increase in the volume of enhancing portion of thrombosis. PFS time is defined as the time from randomization to the date of first failure, date of death, or last known follow-up (censored). PFS rates are estimated by the Kaplan-Meier method. The protocol specifies only that the distributions of failure times be compared between the arms, which is reported in the statistical analysis results. Two-year estimates are provided as a summary of the distributions.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of Participants by Highest Grade Adverse Event Reported</measure>
    <time_frame>From randomization to last follow-up: weekly during SBRT, post-SBRT/pre-sorafenib, monthly during sorafenib, and overall, from study entry: every 3 months for 2 years, then every 6 months. Maximum follow-up at time of analysis was 7.6 years.</time_frame>
    <description>Common Terminology Criteria for Adverse Events (version 4.0) grades adverse event severity from 1=mild to 5=death. Summary data is provided in this outcome measure; see Adverse Events Module for specific adverse event data.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percentage of Participants With Improvement in the Functional Assessment of Cancer Therapy - Hepatobiliary (FACT-Hep) Total Score 6 Months After the Start of Treatment</measure>
    <time_frame>Baseline and 6 months</time_frame>
    <description>The FACT-Hep total score measures quality of life in patients with hepatobiliary cancer. Possible scores range from 0 to 180, with higher scores indicating a better outcome. Improvement in FACT-Hep total score is defined as an increase from the baseline to 6-month score of at least 5 points.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Best Vascular Thrombosis Response up to the Time of Progressive Disease (if Applicable)</measure>
    <time_frame>From randomization to last follow-up. Imaging occurs every 3 months for two years then every six months. Maximum follow-up at time of analysis was 7.6 years.</time_frame>
    <description>Complete response: Complete resolution of thrombosis, with recanalization of vessel.&#xD;
Partial response (PR):&#xD;
Partial recanalization (if prior complete blockage)&#xD;
Unequivocal reduction in the maximal girth&#xD;
Unequivocal reduction in the volume, or elimination, of arterial enhancing portion&#xD;
Progressive disease (PD): any unequivocal, unambiguous&#xD;
New enhancing tumor thrombosis&#xD;
Increase in the volume of enhancing portion&#xD;
Unequivocal progression of thrombosis (non-measurable disease), the increase in overall tumor burden (enhancing thrombosis) must be comparable to the increase required for the Response Evaluation Criteria in Solid Tumor 1.1 definition of PD of measurable disease (e.g. ≥ 73% increase in volume, which is similar to 20% increase in diameter, and at least a 5 mm absolute increase).&#xD;
Stable disease:&#xD;
No/small changes that do not meet the above criteria for PR or PD&#xD;
Increase in the volume of non-enhancing thrombosis&#xD;
New bland non-enhancing thrombosis</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Quality Adjusted Life Years</measure>
    <time_frame>The EQ-5D-5L is administered at baseline, six months and one year.</time_frame>
    <description>Quality adjusted life years is calculated as the weighted sum of the number of years spent in different health states. The weight value is a utility score between 0 (worst health state) and 1 (best health state) derived from the EQ-5D-5L questionnaire, designed to describe and value health based on mobility, self-care, usual activities, pain/discomfort, and anxiety/depression.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">193</enrollment>
  <condition>Adult Primary Hepatocellular Carcinoma</condition>
  <condition>Advanced Adult Primary Liver Cancer</condition>
  <condition>Recurrent Adult Primary Liver Cancer</condition>
  <arm_group>
    <arm_group_label>Sorafenib Alone</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>400 mg sorafenib twice a day for 28-day cycle. Continue up to 5 years in the absence of disease progression or unacceptable toxicity.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>SBRT followed by Sorafenib</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>27.5 Gy to 50 Gy stereotactic body radiation therapy (SBRT) in 5 fractions 24-72 hours apart over 5-15 days followed within 1-5 days by one cycle of 200 mg sorafenib twice a day. Starting with second cycle, if tolerable, increase to 400 mg sorafenib twice a day. Continue up to 5 years in the absence of disease progression or unacceptable toxicity.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Sorafenib</intervention_name>
    <description>By mouth (PO)</description>
    <arm_group_label>SBRT followed by Sorafenib</arm_group_label>
    <arm_group_label>Sorafenib Alone</arm_group_label>
    <other_name>BAY 43-9006</other_name>
    <other_name>BAY 43-9006 Tosylate Salt</other_name>
    <other_name>BAY 54-9085</other_name>
    <other_name>Nexavar</other_name>
    <other_name>SFN</other_name>
    <other_name>Sorafenib Tosylate</other_name>
  </intervention>
  <intervention>
    <intervention_type>Radiation</intervention_type>
    <intervention_name>stereotactic body radiation therapy</intervention_name>
    <description>Intensity-modulated radiation therapy (IMRT), stereotactic body radiation therapy (SBRT), and proton therapy are allowed.</description>
    <arm_group_label>SBRT followed by Sorafenib</arm_group_label>
    <other_name>SBRT</other_name>
    <other_name>stereotactic radiation therapy</other_name>
    <other_name>stereotactic radiotherapy</other_name>
    <other_name>stereotactic ablative body radiation therapy,</other_name>
    <other_name>stereotactic ablative radiotherapy</other_name>
    <other_name>SABR</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Patients must have a diagnosis of HCC by at least one criterion listed below within&#xD;
             360 days prior to study entry:&#xD;
&#xD;
               -  Pathologically (histologically or cytologically) proven diagnosis of&#xD;
                  HCC,(biopsies are recommended, and are to be submitted for research evaluation if&#xD;
                  patients consent)&#xD;
&#xD;
               -  At least one solid liver lesion or vascular tumor thrombosis (involving portal&#xD;
                  vein, inferior vena cava (IVC) and/or hepatic vein) &gt; 1 cm with arterial&#xD;
                  enhancement and delayed washout on multi-phasic computerized tomography (CT) or&#xD;
                  magnetic resonance imaging (MRI) in the setting of cirrhosis or chronic hepatitis&#xD;
                  B or C without cirrhosis.&#xD;
&#xD;
               -  For patients whose CURRENT disease is vascular only: enhancing vascular&#xD;
                  thrombosis (involving portal vein, IVC and/or hepatic vein) demonstrating early&#xD;
                  arterial enhancement and delayed washout on multi-phasic CT or MRI in a patient&#xD;
                  with known HCC (diagnosed previously &lt;720 days) using the above criteria.&#xD;
&#xD;
          -  Measureable hepatic disease and/or presence of vascular tumor thrombosis (involving&#xD;
             portal vein, IVC and/or hepatic vein) which may not be measureable as per Response&#xD;
             Evaluation Criteria in Solid Tumors (RECIST) on liver CT or MRI, within 28 days of&#xD;
             registration&#xD;
&#xD;
          -  Appropriate for protocol entry based upon the following minimum diagnostic workup:&#xD;
&#xD;
               -  History/physical examination including examination for encephalopathy, ascites,&#xD;
                  weight, height, and blood pressure within 14 days prior to study entry&#xD;
&#xD;
               -  Assessment by radiation oncologist and medical oncologist or hepatologist who&#xD;
                  specializes in treatment of HCC within 28 days prior to study entry&#xD;
&#xD;
               -  Pre-randomization Scan (REQUIRED for All Patients): Within 28 days prior to study&#xD;
                  entry, multiphasic liver CT or multiphasic liver MR scan.&#xD;
&#xD;
               -  Within 28 days prior to study entry CT chest with CT or MR abdomen and CT or MR&#xD;
                  pelvis, or positron emission tomography (PET) CT chest/abdomen/pelvis.&#xD;
&#xD;
          -  Zubrod performance status 0-2 within 28 days prior to study entry&#xD;
&#xD;
          -  All blood work obtained within 14 days prior to study entry with adequate organ marrow&#xD;
             function defined as follows:&#xD;
&#xD;
               -  Absolute neutrophil count (ANC) &gt;= 1,500 cells/mm^3&#xD;
&#xD;
               -  Platelets &gt;= 60,000 cells/mm^3&#xD;
&#xD;
               -  Hemoglobin &gt;= 8.0 g/dl (note: the use of transfusion or other intervention to&#xD;
                  achieve hemoglobin [Hgb] &gt;= 8.0 g/dl is acceptable)&#xD;
&#xD;
               -  Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) &lt; 6 times&#xD;
                  upper limit of normal (ULN)&#xD;
&#xD;
               -  Serum creatinine =&lt; 2 x ULN or creatinine clearance &gt;= 60 mL/min&#xD;
&#xD;
          -  Barcelona Clinic Liver Cancer (BCLC) stage: intermediate (B) or advanced (C) within 28&#xD;
             days prior to study entry&#xD;
&#xD;
          -  Child-Pugh score A within 14 days prior to study entry&#xD;
&#xD;
          -  Women of childbearing potential and male participants must agree to practice adequate&#xD;
             contraception while on study and for at least 6 months following the last dose of&#xD;
             radiation therapy (RT) and for at least 28 days following the last dose of sorafenib&#xD;
             (whichever is later)&#xD;
&#xD;
          -  Unsuitable for resection or transplant or radiofrequency ablation (RFA)&#xD;
&#xD;
          -  Unsuitable for or refractory to transarterial hepatic chemo-embolization (TACE) or&#xD;
             drug eluting beads (DEB) for any of the following reasons, as described by Raoul et al&#xD;
             (2011):&#xD;
&#xD;
               -  Technical contraindications: arteriovenous fistula, including, surgical&#xD;
                  portosystemic shunt or spontaneous portosystemic shunt&#xD;
&#xD;
               -  Severe reduction in portal vein flow: due to tumor portal vein, IVC or atrial&#xD;
                  invasion or bland portal vein occlusion&#xD;
&#xD;
               -  Medical contraindications including congestive heart failure, angina, severe&#xD;
                  peripheral vascular disease&#xD;
&#xD;
               -  Presence of extrahepatic disease&#xD;
&#xD;
               -  No response post TACE (or DEB) or progressive HCC despite TACE; prior TACE or DEB&#xD;
                  is allowed but must be &gt; 28 days from study entry&#xD;
&#xD;
               -  Serious toxicity following prior TACE (or DEB); prior TACE or DEB must be &gt; 28&#xD;
                  days from study entry&#xD;
&#xD;
               -  Other medical comorbidities making TACE (or DEB) unsafe and/or risky (e.g.&#xD;
                  combination of relative contraindications including age &gt; 80 years, tumor &gt; 10&#xD;
                  cm, &gt; 50% replacement of the liver by HCC, extensive multinodular bilobar HCC,&#xD;
                  biliary drainage)&#xD;
&#xD;
          -  Patients treated with prior surgery are eligible for this study if they otherwise meet&#xD;
             eligibility criteria&#xD;
&#xD;
          -  Patient must be able to provide study-specific informed consent prior to study entry&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Prior invasive malignancy (except non-melanomatous skin cancer and T1 renal cell&#xD;
             carcinoma) unless disease free for a minimum of 2 years (note that carcinoma in situ&#xD;
             of the breast, oral cavity, or cervix are all permissible)&#xD;
&#xD;
          -  Prior sorafenib use &gt; 60 days and/or grade 3 or 4 sorafenib related toxicity. Note&#xD;
             that prior chemotherapy for HCC or a different cancer is allowable&#xD;
&#xD;
          -  Prior radiotherapy to the region of the liver that would result in overlap of&#xD;
             radiation therapy fields&#xD;
&#xD;
          -  Prior selective internal radiotherapy/hepatic arterial yttrium therapy, at any time&#xD;
&#xD;
          -  Severe, active co-morbidity, defined as follows:&#xD;
&#xD;
               -  Unstable angina and/or congestive heart failure requiring hospitalization within&#xD;
                  the last 6 months PRIOR TO registration&#xD;
&#xD;
               -  Transmural myocardial infarction within the last 6 months prior to study entry&#xD;
&#xD;
               -  Unstable ventricular arrhythmia within the last 6 months prior to study entry&#xD;
&#xD;
               -  Acute bacterial or fungal infection requiring intravenous antibiotics within 28&#xD;
                  days prior to study entry&#xD;
&#xD;
               -  Hepatic insufficiency resulting in clinical jaundice, encephalopathy and/or&#xD;
                  variceal bleed within 28 days prior to study entry&#xD;
&#xD;
               -  Bleeding within 28 days prior to study entry due to any cause, requiring&#xD;
                  transfusion&#xD;
&#xD;
               -  Thrombolytic therapy within 28 days prior to study entry. Subcutaneous heparin is&#xD;
                  permitted.&#xD;
&#xD;
               -  Known bleeding or clotting disorder&#xD;
&#xD;
               -  Uncontrolled psychotic disorder&#xD;
&#xD;
          -  Pregnancy or women of childbearing potential and men who are sexually active and not&#xD;
             willing/able to use medically acceptable forms of contraception; this exclusion is&#xD;
             necessary because the treatment involved in this study may be significantly&#xD;
             teratogenic&#xD;
&#xD;
          -  Maximal diameter of any one hepatocellular carcinoma &gt; 15 cm&#xD;
&#xD;
          -  Total sum of maximum diameters of each definite parenchymal hepatocellular carcinoma&#xD;
             within the liver or maximum diameter of a single conglomerate HCC &gt; 20 cm&#xD;
&#xD;
          -  More than 5 discrete intrahepatic parenchymal foci of HCC&#xD;
&#xD;
          -  Direct tumor extension into the stomach, duodenum, small bowel or large bowel&#xD;
&#xD;
          -  Measureable common or main branch biliary duct involvement with HCC&#xD;
&#xD;
          -  Extrahepatic metastases or malignant nodes (that enhance with typical features of HCC)&#xD;
             &gt; 3.0 cm, in sum of maximal diameters (e.g. presence of one 3.4 cm metastatic lymph&#xD;
             node or two 2 cm lung lesions); note that benign non-enhancing periportal&#xD;
             lymphadenopathy is not unusual in the presence of hepatitis and is permitted, even if&#xD;
             the sum of enlarged nodes is &gt; 2.0 cm&#xD;
&#xD;
          -  Prior liver transplant&#xD;
&#xD;
          -  HIV positive with CD4 (T-cell count) count &lt; (350) cells/microliter. Note that&#xD;
             patients who are HIV positive are eligible, provided they are under treatment with&#xD;
             highly active antiretroviral therapy (HAART) and have a CD4 count ≥ (350)&#xD;
             cells/microliter, and no known detectable viral load, at the time of study entry. Note&#xD;
             also that HIV testing is not required for eligibility for this protocol&#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>Laura Dawson</last_name>
    <role>Principal Investigator</role>
    <affiliation>Radiation Therapy Oncology Group</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Alta Bates Summit Medical Center-Herrick Campus</name>
      <address>
        <city>Berkeley</city>
        <state>California</state>
        <zip>94704</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>USC / Norris Comprehensive Cancer Center</name>
      <address>
        <city>Los Angeles</city>
        <state>California</state>
        <zip>90033</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>UCSF Medical Center-Mount Zion</name>
      <address>
        <city>San Francisco</city>
        <state>California</state>
        <zip>94115</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>UCSF Medical Center-Mission Bay</name>
      <address>
        <city>San Francisco</city>
        <state>California</state>
        <zip>94158</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Colorado Hospital</name>
      <address>
        <city>Aurora</city>
        <state>Colorado</state>
        <zip>80045</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Saint Vincent's Medical Center</name>
      <address>
        <city>Bridgeport</city>
        <state>Connecticut</state>
        <zip>06606</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Miami Miller School of Medicine-Sylvester Cancer Center</name>
      <address>
        <city>Miami</city>
        <state>Florida</state>
        <zip>33136</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Queen's Medical Center</name>
      <address>
        <city>Honolulu</city>
        <state>Hawaii</state>
        <zip>96813</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Northwestern University</name>
      <address>
        <city>Chicago</city>
        <state>Illinois</state>
        <zip>60611</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Illinois</name>
      <address>
        <city>Chicago</city>
        <state>Illinois</state>
        <zip>60612</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Decatur Memorial Hospital</name>
      <address>
        <city>Decatur</city>
        <state>Illinois</state>
        <zip>62526</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Loyola University Medical Center</name>
      <address>
        <city>Maywood</city>
        <state>Illinois</state>
        <zip>60153</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Northwestern Medicine Cancer Center Warrenville</name>
      <address>
        <city>Warrenville</city>
        <state>Illinois</state>
        <zip>60555</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Indiana University/Melvin and Bren Simon Cancer Center</name>
      <address>
        <city>Indianapolis</city>
        <state>Indiana</state>
        <zip>46202</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Iowa Methodist Medical Center</name>
      <address>
        <city>Des Moines</city>
        <state>Iowa</state>
        <zip>50309</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Ochsner Medical Center Jefferson</name>
      <address>
        <city>New Orleans</city>
        <state>Louisiana</state>
        <zip>70121</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Maryland/Greenebaum Cancer Center</name>
      <address>
        <city>Baltimore</city>
        <state>Maryland</state>
        <zip>21201</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Johns Hopkins University/Sidney Kimmel Cancer Center</name>
      <address>
        <city>Baltimore</city>
        <state>Maryland</state>
        <zip>21287</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Massachusetts General Hospital Cancer Center</name>
      <address>
        <city>Boston</city>
        <state>Massachusetts</state>
        <zip>02114</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Boston Medical Center</name>
      <address>
        <city>Boston</city>
        <state>Massachusetts</state>
        <zip>02118</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Michigan Comprehensive Cancer Center</name>
      <address>
        <city>Ann Arbor</city>
        <state>Michigan</state>
        <zip>48109</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Mississippi Medical Center</name>
      <address>
        <city>Jackson</city>
        <state>Mississippi</state>
        <zip>39216</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Washington University School of Medicine</name>
      <address>
        <city>Saint Louis</city>
        <state>Missouri</state>
        <zip>63110</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Rutgers Cancer Institute of New Jersey</name>
      <address>
        <city>New Brunswick</city>
        <state>New Jersey</state>
        <zip>08903</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Montefiore Medical Center - Moses Campus</name>
      <address>
        <city>Bronx</city>
        <state>New York</state>
        <zip>10467</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Columbia University/Herbert Irving Cancer Center</name>
      <address>
        <city>New York</city>
        <state>New York</state>
        <zip>10032</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Memorial Sloan Kettering Cancer Center</name>
      <address>
        <city>New York</city>
        <state>New York</state>
        <zip>10065</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Rochester</name>
      <address>
        <city>Rochester</city>
        <state>New York</state>
        <zip>14642</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Stony Brook University Medical Center</name>
      <address>
        <city>Stony Brook</city>
        <state>New York</state>
        <zip>11794</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Case Western Reserve University</name>
      <address>
        <city>Cleveland</city>
        <state>Ohio</state>
        <zip>44106</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Ohio State University Comprehensive Cancer Center</name>
      <address>
        <city>Columbus</city>
        <state>Ohio</state>
        <zip>43210</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Providence Portland Medical Center</name>
      <address>
        <city>Portland</city>
        <state>Oregon</state>
        <zip>97213</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Penn State Milton S Hershey Medical Center</name>
      <address>
        <city>Hershey</city>
        <state>Pennsylvania</state>
        <zip>17033-0850</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Pennsylvania/Abramson Cancer Center</name>
      <address>
        <city>Philadelphia</city>
        <state>Pennsylvania</state>
        <zip>19104</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>M D Anderson Cancer Center</name>
      <address>
        <city>Houston</city>
        <state>Texas</state>
        <zip>77030</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Huntsman Cancer Institute/University of Utah</name>
      <address>
        <city>Salt Lake City</city>
        <state>Utah</state>
        <zip>84112</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Vermont Medical Center</name>
      <address>
        <city>Burlington</city>
        <state>Vermont</state>
        <zip>05401</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hunter Holmes McGuire Veterans Administration Medical Center</name>
      <address>
        <city>Richmond</city>
        <state>Virginia</state>
        <zip>23249</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>ProCure Proton Therapy Center-Seattle</name>
      <address>
        <city>Seattle</city>
        <state>Washington</state>
        <zip>98133</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Washington Medical Center</name>
      <address>
        <city>Seattle</city>
        <state>Washington</state>
        <zip>98195</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Froedtert and the Medical College of Wisconsin</name>
      <address>
        <city>Milwaukee</city>
        <state>Wisconsin</state>
        <zip>53226</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Peter MacCallum Cancer Centre</name>
      <address>
        <city>Melbourne</city>
        <state>Victoria</state>
        <zip>3000</zip>
        <country>Australia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Tom Baker Cancer Centre</name>
      <address>
        <city>Calgary</city>
        <state>Alberta</state>
        <zip>T2N 4N2</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Juravinski Cancer Centre at Hamilton Health Sciences</name>
      <address>
        <city>Hamilton</city>
        <state>Ontario</state>
        <zip>L8V 5C2</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>London Regional Cancer Program</name>
      <address>
        <city>London</city>
        <state>Ontario</state>
        <zip>N6A 4L6</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University Health Network-Princess Margaret Hospital</name>
      <address>
        <city>Toronto</city>
        <state>Ontario</state>
        <zip>M5G 2M9</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>CHUM - Hopital Notre-Dame</name>
      <address>
        <city>Montreal</city>
        <state>Quebec</state>
        <zip>H2L 4M1</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>CHUM - Centre Hospitalier de l'Universite de Montreal</name>
      <address>
        <city>Montreal</city>
        <state>Quebec</state>
        <zip>H2X 3E4</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>The Research Institute of the McGill University Health Centre (MUHC)</name>
      <address>
        <city>Montreal</city>
        <state>Quebec</state>
        <zip>H3H 2R9</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Pamela Youde Nethersole Eastern Hospital</name>
      <address>
        <city>Chai Wan</city>
        <country>Hong Kong</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Samsung Medical Center</name>
      <address>
        <city>Seoul</city>
        <state>Korea</state>
        <zip>135-710</zip>
        <country>Korea, Republic of</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Australia</country>
    <country>Canada</country>
    <country>Hong Kong</country>
    <country>Korea, Republic of</country>
    <country>United States</country>
  </location_countries>
  <verification_date>May 2023</verification_date>
  <study_first_submitted>November 15, 2012</study_first_submitted>
  <study_first_submitted_qc>November 20, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">November 21, 2012</study_first_posted>
  <results_first_submitted>May 24, 2023</results_first_submitted>
  <results_first_submitted_qc>June 29, 2023</results_first_submitted_qc>
  <results_first_posted type="Actual">July 3, 2023</results_first_posted>
  <last_update_submitted>June 29, 2023</last_update_submitted>
  <last_update_submitted_qc>June 29, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">July 3, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </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>
    <mesh_term>Liver Neoplasms</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Sorafenib</mesh_term>
  </intervention_browse>
  <provided_document_section>
    <provided_document>
      <document_type>Study Protocol and Statistical Analysis Plan</document_type>
      <document_has_protocol>Yes</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>Yes</document_has_sap>
      <document_date>September 23, 2022</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/37/NCT01730937/Prot_SAP_000.pdf</document_url>
    </provided_document>
    <provided_document>
      <document_type>Informed Consent Form</document_type>
      <document_has_protocol>No</document_has_protocol>
      <document_has_icf>Yes</document_has_icf>
      <document_has_sap>No</document_has_sap>
      <document_date>September 23, 2022</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/37/NCT01730937/ICF_001.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <group_list>
        <group group_id="P1">
          <title>Sorafenib Alone</title>
          <description>400 mg sorafenib by mouth twice a day for 28-day cycle. Continue up to 5 years in the absence of disease progression or unacceptable toxicity.</description>
        </group>
        <group group_id="P2">
          <title>SBRT Followed by Sorafenib</title>
          <description>27.5 Gy to 50 Gy stereotactic body radiation therapy (SBRT) in 5 fractions 24-72 hours apart over 5-15 days followed within 1-5 days by one cycle of 200 mg sorafenib by mouth twice a day. Starting with second cycle, if tolerable, increase to 400 mg sorafenib by mouth twice a day. Continue up to 5 years in the absence of disease progression or unacceptable toxicity.</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="97"/>
                <participants group_id="P2" count="96"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>Eligible Population</title>
              <participants_list>
                <participants group_id="P1" count="92"/>
                <participants group_id="P2" count="85"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>Adverse Event Population</title>
              <participants_list>
                <participants group_id="P1" count="88"/>
                <participants group_id="P2" count="83"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>Quality of Life Population</title>
              <participants_list>
                <participants group_id="P1" count="46"/>
                <participants group_id="P2" count="37"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="92"/>
                <participants group_id="P2" count="85"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="5"/>
                <participants group_id="P2" count="11"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Protocol Violation</title>
              <participants_list>
                <participants group_id="P1" count="5"/>
                <participants group_id="P2" count="11"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <population>Eligible participants</population>
      <group_list>
        <group group_id="B1">
          <title>Sorafenib Alone</title>
          <description>400 mg sorafenib by mouth twice a day for 28-day cycle. Continue up to 5 years in the absence of disease progression or unacceptable toxicity.</description>
        </group>
        <group group_id="B2">
          <title>SBRT Followed by Sorafenib</title>
          <description>27.5 Gy to 50 Gy stereotactic body radiation therapy (SBRT) in 5 fractions 24-72 hours apart over 5-15 days followed within 1-5 days by one cycle of 200 mg sorafenib by mouth twice a day. Starting with second cycle, if tolerable, increase to 400 mg sorafenib by mouth twice a day. Continue up to 5 years in the absence of disease progression or unacceptable toxicity.</description>
        </group>
        <group group_id="B3">
          <title>Total</title>
          <description>Total of all reporting groups</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="92"/>
            <count group_id="B2" value="85"/>
            <count group_id="B3" value="177"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>years</units>
          <param>Median</param>
          <dispersion>Full Range</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="67" lower_limit="27" upper_limit="84"/>
                    <measurement group_id="B2" value="66" lower_limit="49" upper_limit="83"/>
                    <measurement group_id="B3" value="66" lower_limit="27" upper_limit="84"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Age, Customized</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>≤ 49 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="3"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="4"/>
                  </measurement_list>
                </category>
                <category>
                  <title>50 - 59 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="15"/>
                    <measurement group_id="B2" value="20"/>
                    <measurement group_id="B3" value="35"/>
                  </measurement_list>
                </category>
                <category>
                  <title>60 - 69 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="39"/>
                    <measurement group_id="B2" value="42"/>
                    <measurement group_id="B3" value="81"/>
                  </measurement_list>
                </category>
                <category>
                  <title>70 - 79 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="26"/>
                    <measurement group_id="B2" value="18"/>
                    <measurement group_id="B3" value="44"/>
                  </measurement_list>
                </category>
                <category>
                  <title>≥ 80 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="9"/>
                    <measurement group_id="B2" value="4"/>
                    <measurement group_id="B3" value="13"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Sex: Female, Male</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Female</title>
                  <measurement_list>
                    <measurement group_id="B1" value="10"/>
                    <measurement group_id="B2" value="17"/>
                    <measurement group_id="B3" value="27"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="82"/>
                    <measurement group_id="B2" value="68"/>
                    <measurement group_id="B3" value="150"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Ethnicity (NIH/OMB)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="6"/>
                    <measurement group_id="B2" value="2"/>
                    <measurement group_id="B3" value="8"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Not Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="54"/>
                    <measurement group_id="B2" value="47"/>
                    <measurement group_id="B3" value="101"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="32"/>
                    <measurement group_id="B2" value="36"/>
                    <measurement group_id="B3" value="68"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Race (NIH/OMB)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>American Indian or Alaska Native</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="1"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Asian</title>
                  <measurement_list>
                    <measurement group_id="B1" value="23"/>
                    <measurement group_id="B2" value="18"/>
                    <measurement group_id="B3" value="41"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Native Hawaiian or Other Pacific Islander</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="1"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Black or African American</title>
                  <measurement_list>
                    <measurement group_id="B1" value="5"/>
                    <measurement group_id="B2" value="3"/>
                    <measurement group_id="B3" value="8"/>
                  </measurement_list>
                </category>
                <category>
                  <title>White</title>
                  <measurement_list>
                    <measurement group_id="B1" value="58"/>
                    <measurement group_id="B2" value="59"/>
                    <measurement group_id="B3" value="117"/>
                  </measurement_list>
                </category>
                <category>
                  <title>More than one race</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="5"/>
                    <measurement group_id="B2" value="4"/>
                    <measurement group_id="B3" value="9"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Zubrod performance status</title>
          <description>0 - Asymptomatic; 1 - Symptomatic but completely ambulatory; 2 - Symptomatic, &lt;50% in bed during the day; 3 - Symptomatic, &gt;50% in bed, but not bedbound; 4 - Bedbound; 5 - Death</description>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>0</title>
                  <measurement_list>
                    <measurement group_id="B1" value="41"/>
                    <measurement group_id="B2" value="47"/>
                    <measurement group_id="B3" value="88"/>
                  </measurement_list>
                </category>
                <category>
                  <title>1</title>
                  <measurement_list>
                    <measurement group_id="B1" value="44"/>
                    <measurement group_id="B2" value="33"/>
                    <measurement group_id="B3" value="77"/>
                  </measurement_list>
                </category>
                <category>
                  <title>2</title>
                  <measurement_list>
                    <measurement group_id="B1" value="7"/>
                    <measurement group_id="B2" value="5"/>
                    <measurement group_id="B3" value="12"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>T Stage</title>
          <description>Tumor stage per the American Joint Committee on Cancer (AJCC) 7th ed. refers to the size and/or extent of the main tumor. The higher the number after the T, the larger the tumor or the more it has grown into nearby tissues. T's may be further divided to provide more detail, such as T3a and T3b.</description>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>T1</title>
                  <measurement_list>
                    <measurement group_id="B1" value="9"/>
                    <measurement group_id="B2" value="6"/>
                    <measurement group_id="B3" value="15"/>
                  </measurement_list>
                </category>
                <category>
                  <title>T2</title>
                  <measurement_list>
                    <measurement group_id="B1" value="17"/>
                    <measurement group_id="B2" value="19"/>
                    <measurement group_id="B3" value="36"/>
                  </measurement_list>
                </category>
                <category>
                  <title>T3a</title>
                  <measurement_list>
                    <measurement group_id="B1" value="12"/>
                    <measurement group_id="B2" value="16"/>
                    <measurement group_id="B3" value="28"/>
                  </measurement_list>
                </category>
                <category>
                  <title>T3b</title>
                  <measurement_list>
                    <measurement group_id="B1" value="49"/>
                    <measurement group_id="B2" value="38"/>
                    <measurement group_id="B3" value="87"/>
                  </measurement_list>
                </category>
                <category>
                  <title>T4</title>
                  <measurement_list>
                    <measurement group_id="B1" value="5"/>
                    <measurement group_id="B2" value="6"/>
                    <measurement group_id="B3" value="11"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>N Stage</title>
          <description>Regional lymph nodes staging per American Joint Committee on Cancer (AJCC) 7th ed. refers to the number and/or extent of spread of lymph nodes that contain cancer. The higher the number after the N, the greater the involvement of regional lymph nodes. (N0= no cancer in nearby lymph nodes; NX = cannot be measured.)</description>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>N0</title>
                  <measurement_list>
                    <measurement group_id="B1" value="89"/>
                    <measurement group_id="B2" value="80"/>
                    <measurement group_id="B3" value="169"/>
                  </measurement_list>
                </category>
                <category>
                  <title>N1</title>
                  <measurement_list>
                    <measurement group_id="B1" value="3"/>
                    <measurement group_id="B2" value="4"/>
                    <measurement group_id="B3" value="7"/>
                  </measurement_list>
                </category>
                <category>
                  <title>NX</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>M Stage</title>
          <description>Metastasis stage per the American Joint Committee on Cancer (AJCC) 7th ed. refers to the spread of the cancer to organs and tissues in other parts of the body. M0 = No distant metastasis; M1 = Distant metastasis; MX = Distant metastasis cannot be assessed.</description>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>M0</title>
                  <measurement_list>
                    <measurement group_id="B1" value="88"/>
                    <measurement group_id="B2" value="82"/>
                    <measurement group_id="B3" value="170"/>
                  </measurement_list>
                </category>
                <category>
                  <title>M1</title>
                  <measurement_list>
                    <measurement group_id="B1" value="4"/>
                    <measurement group_id="B2" value="3"/>
                    <measurement group_id="B3" value="7"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Child Pugh Score</title>
          <description>Child Pugh Classification uses the following to determine liver function: 1) bilirubin levels; 2) albumin levels; 3) how quickly the blood clots (prothrombin time); 4) if there is fluid in the abdomen (ascites); and 5) if there is encephalopathy (liver disease has affected brain function). Each one of the previous is given a score: 5 (Grade A) and 6 (Grade A) mean the liver is working normally.</description>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>5 (Grade A)</title>
                  <measurement_list>
                    <measurement group_id="B1" value="69"/>
                    <measurement group_id="B2" value="64"/>
                    <measurement group_id="B3" value="133"/>
                  </measurement_list>
                </category>
                <category>
                  <title>6 (Grade A)</title>
                  <measurement_list>
                    <measurement group_id="B1" value="23"/>
                    <measurement group_id="B2" value="21"/>
                    <measurement group_id="B3" value="44"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>BCLC Stage</title>
          <description>Barcelona Clinic Liver Cancer (BCLC) staging system helps doctors determine the best treatment using 1) the number and size of tumors in the liver, 2) general health status or Zubrod performance status, and 3) liver function using Child-Pugh score. Intermediate(B): many tumors in liver, but overall status is good (Zubrod=0) and liver function is good with Child Pugh A or B. Advanced(C): cancer has spread, Zubrod=1 or 2, but liver function is still good with Child Pugh A or B.</description>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Intermediate (B)</title>
                  <measurement_list>
                    <measurement group_id="B1" value="15"/>
                    <measurement group_id="B2" value="17"/>
                    <measurement group_id="B3" value="32"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Advanced (C)</title>
                  <measurement_list>
                    <measurement group_id="B1" value="77"/>
                    <measurement group_id="B2" value="68"/>
                    <measurement group_id="B3" value="145"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Hepatocellular carcinoma (HCC) tumor volume / liver volume</title>
          <description>The ratio of hepatocellular volume to the liver volume (as a percent).</description>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>&lt;10%</title>
                  <measurement_list>
                    <measurement group_id="B1" value="40"/>
                    <measurement group_id="B2" value="40"/>
                    <measurement group_id="B3" value="80"/>
                  </measurement_list>
                </category>
                <category>
                  <title>10-40%</title>
                  <measurement_list>
                    <measurement group_id="B1" value="42"/>
                    <measurement group_id="B2" value="39"/>
                    <measurement group_id="B3" value="81"/>
                  </measurement_list>
                </category>
                <category>
                  <title>&gt;40%</title>
                  <measurement_list>
                    <measurement group_id="B1" value="10"/>
                    <measurement group_id="B2" value="6"/>
                    <measurement group_id="B3" value="16"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Hepatitis Status</title>
          <description>Hepatitis is a type of liver disease that causes inflammation of the liver, which can be caused by alcohol, injury, autoimmune response, or a reaction to bacteria or virus. Hepatitis B may result in chronic liver disease or liver cancer. Hepatitis C may result in cirrhosis or liver cancer. Other (Hepatitis A) mostly likely will result in no liver damage.</description>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Hepatitis B or B and C</title>
                  <measurement_list>
                    <measurement group_id="B1" value="17"/>
                    <measurement group_id="B2" value="16"/>
                    <measurement group_id="B3" value="33"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Hepatitis C</title>
                  <measurement_list>
                    <measurement group_id="B1" value="38"/>
                    <measurement group_id="B2" value="35"/>
                    <measurement group_id="B3" value="73"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Other</title>
                  <measurement_list>
                    <measurement group_id="B1" value="37"/>
                    <measurement group_id="B2" value="34"/>
                    <measurement group_id="B3" value="71"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Enhancing vascular thrombosis</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Yes</title>
                  <measurement_list>
                    <measurement group_id="B1" value="66"/>
                    <measurement group_id="B2" value="62"/>
                    <measurement group_id="B3" value="128"/>
                  </measurement_list>
                </category>
                <category>
                  <title>No</title>
                  <measurement_list>
                    <measurement group_id="B1" value="26"/>
                    <measurement group_id="B2" value="23"/>
                    <measurement group_id="B3" value="49"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Region of Enrollment</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>North America</title>
                  <measurement_list>
                    <measurement group_id="B1" value="90"/>
                    <measurement group_id="B2" value="85"/>
                    <measurement group_id="B3" value="175"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Other</title>
                  <measurement_list>
                    <measurement group_id="B1" value="2"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Overall Survival</title>
        <description>An event for overall survival (OS) is death due to any cause. Survival time is defined as time from randomization to the date of death or last known follow-up (censored). Rates are estimated by the Kaplan-Meier method. Analysis was to occur after 153 deaths were reported.</description>
        <time_frame>From randomization to last follow-up: weekly during SBRT, post-SBRT/pre-sorafenib, monthly during sorafenib, and overall, from study entry: every 3 months for 2 years, then every 6 months. Maximum follow-up at time of analysis was 7.6 years.</time_frame>
        <population>Eligible participants</population>
        <group_list>
          <group group_id="O1">
            <title>Sorafenib Alone</title>
            <description>400 mg sorafenib by mouth twice a day for 28-day cycle. Continue up to 5 years in the absence of disease progression or unacceptable toxicity.</description>
          </group>
          <group group_id="O2">
            <title>SBRT Followed by Sorafenib</title>
            <description>27.5 Gy to 50 Gy stereotactic body radiation therapy (SBRT) in 5 fractions 24-72 hours apart over 5-15 days followed within 1-5 days by one cycle of 200 mg sorafenib by mouth twice a day. Starting with second cycle, if tolerable, increase to 400 mg sorafenib by mouth twice a day. Continue up to 5 years in the absence of disease progression or unacceptable toxicity.</description>
          </group>
        </group_list>
        <measure>
          <title>Overall Survival</title>
          <description>An event for overall survival (OS) is death due to any cause. Survival time is defined as time from randomization to the date of death or last known follow-up (censored). Rates are estimated by the Kaplan-Meier method. Analysis was to occur after 153 deaths were reported.</description>
          <population>Eligible participants</population>
          <units>months</units>
          <param>Median</param>
          <dispersion>90% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="92"/>
                <count group_id="O2" value="85"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="12.30" lower_limit="10.62" upper_limit="14.3"/>
                    <measurement group_id="O2" value="15.85" lower_limit="11.42" upper_limit="19.15"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>Original design: Hypothesized 28% reduction (HR=0.72) with SBRT (corresponds to median OS = 14.5 months). Assuming an exponential distribution and constant hazards, 292 patients were required to reach 238 OS events, with 80% statistical power, a 1-sided α of 0.05. Revised design (see limitations/caveats): For same above hypotheses, at least 155 OS events from 193 randomized patients provided 65% statistical power, with a 1-sided α of 0.05.</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.0554</p_value>
            <method>Log Rank</method>
            <param_type>Hazard Ratio (HR)</param_type>
            <param_value>0.77</param_value>
            <ci_percent>90</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>0.59</ci_lower_limit>
            <ci_upper_limit>1.01</ci_upper_limit>
            <estimate_desc>Reference arm = Sorafenib Alone</estimate_desc>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Time to Progression</title>
        <description>Progression (failure) is defined as any of the following events: new tumor thrombosis, progression of hepatocellular carcinoma (HCC) within liver excluding tumor thrombosis status, progression of distant metastases that were present at study entry, new HCC within the liver including tumor thrombosis, and vascular thrombosis events=progression-new enhancing tumor thrombosis/progression-Increase in the volume of enhancing portion of thrombosis. Time to progression was measured from the date of randomization to the date of first failure, death (competing risk), or last follow-up (censored). Progression rates are estimated by the cumulative incidence method. The protocol specifies only that the distributions of failure times be compared between the arms, which is reported in the statistical analysis results. Two-year estimates are provided as a summary of the distributions.</description>
        <time_frame>From randomization to last follow-up: weekly during SBRT, post-SBRT/pre-sorafenib, monthly during sorafenib, and overall, from study entry: every 3 months for 2 years, then every 6 months. Maximum follow-up at time of analysis was 7.6 years.</time_frame>
        <population>Eligible participants</population>
        <group_list>
          <group group_id="O1">
            <title>Sorafenib Alone</title>
            <description>400 mg sorafenib by mouth twice a day for 28-day cycle. Continue up to 5 years in the absence of disease progression or unacceptable toxicity.</description>
          </group>
          <group group_id="O2">
            <title>SBRT Followed by Sorafenib</title>
            <description>27.5 Gy to 50 Gy stereotactic body radiation therapy (SBRT) in 5 fractions 24-72 hours apart over 5-15 days followed within 1-5 days by one cycle of 200 mg sorafenib by mouth twice a day. Starting with second cycle, if tolerable, increase to 400 mg sorafenib by mouth twice a day. Continue up to 5 years in the absence of disease progression or unacceptable toxicity.</description>
          </group>
        </group_list>
        <measure>
          <title>Time to Progression</title>
          <description>Progression (failure) is defined as any of the following events: new tumor thrombosis, progression of hepatocellular carcinoma (HCC) within liver excluding tumor thrombosis status, progression of distant metastases that were present at study entry, new HCC within the liver including tumor thrombosis, and vascular thrombosis events=progression-new enhancing tumor thrombosis/progression-Increase in the volume of enhancing portion of thrombosis. Time to progression was measured from the date of randomization to the date of first failure, death (competing risk), or last follow-up (censored). Progression rates are estimated by the cumulative incidence method. The protocol specifies only that the distributions of failure times be compared between the arms, which is reported in the statistical analysis results. Two-year estimates are provided as a summary of the distributions.</description>
          <population>Eligible participants</population>
          <units>percentage of participants</units>
          <param>Number</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="92"/>
                <count group_id="O2" value="85"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="66.3" lower_limit="55.3" upper_limit="75.3"/>
                    <measurement group_id="O2" value="56.4" lower_limit="44.9" upper_limit="66.4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.034</p_value>
            <p_value_desc>Two-sided significance level = 0.05</p_value_desc>
            <method>Gray's test</method>
            <param_type>Hazard Ratio (HR)</param_type>
            <param_value>0.69</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>0.48</ci_lower_limit>
            <ci_upper_limit>0.99</ci_upper_limit>
            <estimate_desc>Reference arm = Sorafenib Alone</estimate_desc>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Progression-free Survival</title>
        <description>Failure for progression-free survival (PFS) include death, new tumor thrombosis, progression of hepatocellular carcinoma (HCC) within liver excluding tumor thrombosis status, progression of distant Mets that were present at study entry, new HCC within liver including tumor thrombosis, and vascular thrombosis events =progression-new enhancing tumor thrombosis/progression-Increase in the volume of enhancing portion of thrombosis. PFS time is defined as the time from randomization to the date of first failure, date of death, or last known follow-up (censored). PFS rates are estimated by the Kaplan-Meier method. The protocol specifies only that the distributions of failure times be compared between the arms, which is reported in the statistical analysis results. Two-year estimates are provided as a summary of the distributions.</description>
        <time_frame>From randomization to last follow-up: weekly during SBRT, post-SBRT/pre-sorafenib, monthly during sorafenib, and overall, from study entry: every 3 months for 2 years, then every 6 months. Maximum follow-up at time of analysis was 7.6 years.</time_frame>
        <population>Eligible participants</population>
        <group_list>
          <group group_id="O1">
            <title>Sorafenib Alone</title>
            <description>400 mg sorafenib by mouth twice a day for 28-day cycle. Continue up to 5 years in the absence of disease progression or unacceptable toxicity.</description>
          </group>
          <group group_id="O2">
            <title>SBRT Followed by Sorafenib</title>
            <description>27.5 Gy to 50 Gy stereotactic body radiation therapy (SBRT) in 5 fractions 24-72 hours apart over 5-15 days followed within 1-5 days by one cycle of 200 mg sorafenib by mouth twice a day. Starting with second cycle, if tolerable, increase to 400 mg sorafenib by mouth twice a day. Continue up to 5 years in the absence of disease progression or unacceptable toxicity.</description>
          </group>
        </group_list>
        <measure>
          <title>Progression-free Survival</title>
          <description>Failure for progression-free survival (PFS) include death, new tumor thrombosis, progression of hepatocellular carcinoma (HCC) within liver excluding tumor thrombosis status, progression of distant Mets that were present at study entry, new HCC within liver including tumor thrombosis, and vascular thrombosis events =progression-new enhancing tumor thrombosis/progression-Increase in the volume of enhancing portion of thrombosis. PFS time is defined as the time from randomization to the date of first failure, date of death, or last known follow-up (censored). PFS rates are estimated by the Kaplan-Meier method. The protocol specifies only that the distributions of failure times be compared between the arms, which is reported in the statistical analysis results. Two-year estimates are provided as a summary of the distributions.</description>
          <population>Eligible participants</population>
          <units>percentage of participants</units>
          <param>Number</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="92"/>
                <count group_id="O2" value="85"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="5.49" lower_limit="3.42" upper_limit="6.28"/>
                    <measurement group_id="O2" value="9.22" lower_limit="7.53" upper_limit="11.89"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.0001</p_value>
            <p_value_desc>Two-sided significance level=0.05</p_value_desc>
            <method>Log Rank</method>
            <param_type>Hazard Ratio (HR)</param_type>
            <param_value>0.55</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>0.40</ci_lower_limit>
            <ci_upper_limit>0.75</ci_upper_limit>
            <estimate_desc>Reference arm = Sorafenib Alone</estimate_desc>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Number of Participants by Highest Grade Adverse Event Reported</title>
        <description>Common Terminology Criteria for Adverse Events (version 4.0) grades adverse event severity from 1=mild to 5=death. Summary data is provided in this outcome measure; see Adverse Events Module for specific adverse event data.</description>
        <time_frame>From randomization to last follow-up: weekly during SBRT, post-SBRT/pre-sorafenib, monthly during sorafenib, and overall, from study entry: every 3 months for 2 years, then every 6 months. Maximum follow-up at time of analysis was 7.6 years.</time_frame>
        <population>Eligible, started treatment, and were assessed for adverse events.</population>
        <group_list>
          <group group_id="O1">
            <title>Sorafenib Alone</title>
            <description>400 mg sorafenib by mouth twice a day for 28-day cycle. Continue up to 5 years in the absence of disease progression or unacceptable toxicity.</description>
          </group>
          <group group_id="O2">
            <title>SBRT Followed by Sorafenib</title>
            <description>27.5 Gy to 50 Gy stereotactic body radiation therapy (SBRT) in 5 fractions 24-72 hours apart over 5-15 days followed within 1-5 days by one cycle of 200 mg sorafenib by mouth twice a day. Starting with second cycle, if tolerable, increase to 400 mg sorafenib by mouth twice a day. Continue up to 5 years in the absence of disease progression or unacceptable toxicity.</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Participants by Highest Grade Adverse Event Reported</title>
          <description>Common Terminology Criteria for Adverse Events (version 4.0) grades adverse event severity from 1=mild to 5=death. Summary data is provided in this outcome measure; see Adverse Events Module for specific adverse event data.</description>
          <population>Eligible, started treatment, and were assessed for adverse events.</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="88"/>
                <count group_id="O2" value="83"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Grade 1</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2"/>
                    <measurement group_id="O2" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Grade 2</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="21"/>
                    <measurement group_id="O2" value="20"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Grade 3</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="49"/>
                    <measurement group_id="O2" value="51"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Grade 4</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="10"/>
                    <measurement group_id="O2" value="9"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Grade 5</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="6"/>
                    <measurement group_id="O2" value="2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Percentage of Participants With Improvement in the Functional Assessment of Cancer Therapy - Hepatobiliary (FACT-Hep) Total Score 6 Months After the Start of Treatment</title>
        <description>The FACT-Hep total score measures quality of life in patients with hepatobiliary cancer. Possible scores range from 0 to 180, with higher scores indicating a better outcome. Improvement in FACT-Hep total score is defined as an increase from the baseline to 6-month score of at least 5 points.</description>
        <time_frame>Baseline and 6 months</time_frame>
        <population>Eligible participants who consented to the quality of life component and had data at baseline and six months.</population>
        <group_list>
          <group group_id="O1">
            <title>Sorafenib Alone</title>
            <description>400 mg sorafenib by mouth twice a day for 28-day cycle. Continue up to 5 years in the absence of disease progression or unacceptable toxicity.</description>
          </group>
          <group group_id="O2">
            <title>SBRT Followed by Sorafenib</title>
            <description>27.5 Gy to 50 Gy stereotactic body radiation therapy (SBRT) in 5 fractions 24-72 hours apart over 5-15 days followed within 1-5 days by one cycle of 200 mg sorafenib by mouth twice a day. Starting with second cycle, if tolerable, increase to 400 mg sorafenib by mouth twice a day. Continue up to 5 years in the absence of disease progression or unacceptable toxicity.</description>
          </group>
        </group_list>
        <measure>
          <title>Percentage of Participants With Improvement in the Functional Assessment of Cancer Therapy - Hepatobiliary (FACT-Hep) Total Score 6 Months After the Start of Treatment</title>
          <description>The FACT-Hep total score measures quality of life in patients with hepatobiliary cancer. Possible scores range from 0 to 180, with higher scores indicating a better outcome. Improvement in FACT-Hep total score is defined as an increase from the baseline to 6-month score of at least 5 points.</description>
          <population>Eligible participants who consented to the quality of life component and had data at baseline and six months.</population>
          <units>percentage of participants</units>
          <param>Number</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="20"/>
                <count group_id="O2" value="17"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="10" lower_limit="2" upper_limit="31"/>
                    <measurement group_id="O2" value="35" lower_limit="17" upper_limit="59"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Best Vascular Thrombosis Response up to the Time of Progressive Disease (if Applicable)</title>
        <description>Complete response: Complete resolution of thrombosis, with recanalization of vessel.&#xD;
Partial response (PR):&#xD;
Partial recanalization (if prior complete blockage)&#xD;
Unequivocal reduction in the maximal girth&#xD;
Unequivocal reduction in the volume, or elimination, of arterial enhancing portion&#xD;
Progressive disease (PD): any unequivocal, unambiguous&#xD;
New enhancing tumor thrombosis&#xD;
Increase in the volume of enhancing portion&#xD;
Unequivocal progression of thrombosis (non-measurable disease), the increase in overall tumor burden (enhancing thrombosis) must be comparable to the increase required for the Response Evaluation Criteria in Solid Tumor 1.1 definition of PD of measurable disease (e.g. ≥ 73% increase in volume, which is similar to 20% increase in diameter, and at least a 5 mm absolute increase).&#xD;
Stable disease:&#xD;
No/small changes that do not meet the above criteria for PR or PD&#xD;
Increase in the volume of non-enhancing thrombosis&#xD;
New bland non-enhancing thrombosis</description>
        <time_frame>From randomization to last follow-up. Imaging occurs every 3 months for two years then every six months. Maximum follow-up at time of analysis was 7.6 years.</time_frame>
        <population>Eligible participants who had vascular thrombosis at study entry</population>
        <group_list>
          <group group_id="O1">
            <title>Sorafenib Alone</title>
            <description>400 mg sorafenib by mouth twice a day for 28-day cycle. Continue up to 5 years in the absence of disease progression or unacceptable toxicity.</description>
          </group>
          <group group_id="O2">
            <title>SBRT Followed by Sorafenib</title>
            <description>27.5 Gy to 50 Gy stereotactic body radiation therapy (SBRT) in 5 fractions 24-72 hours apart over 5-15 days followed within 1-5 days by one cycle of 200 mg sorafenib by mouth twice a day. Starting with second cycle, if tolerable, increase to 400 mg sorafenib by mouth twice a day. Continue up to 5 years in the absence of disease progression or unacceptable toxicity.</description>
          </group>
        </group_list>
        <measure>
          <title>Best Vascular Thrombosis Response up to the Time of Progressive Disease (if Applicable)</title>
          <description>Complete response: Complete resolution of thrombosis, with recanalization of vessel.&#xD;
Partial response (PR):&#xD;
Partial recanalization (if prior complete blockage)&#xD;
Unequivocal reduction in the maximal girth&#xD;
Unequivocal reduction in the volume, or elimination, of arterial enhancing portion&#xD;
Progressive disease (PD): any unequivocal, unambiguous&#xD;
New enhancing tumor thrombosis&#xD;
Increase in the volume of enhancing portion&#xD;
Unequivocal progression of thrombosis (non-measurable disease), the increase in overall tumor burden (enhancing thrombosis) must be comparable to the increase required for the Response Evaluation Criteria in Solid Tumor 1.1 definition of PD of measurable disease (e.g. ≥ 73% increase in volume, which is similar to 20% increase in diameter, and at least a 5 mm absolute increase).&#xD;
Stable disease:&#xD;
No/small changes that do not meet the above criteria for PR or PD&#xD;
Increase in the volume of non-enhancing thrombosis&#xD;
New bland non-enhancing thrombosis</description>
          <population>Eligible participants who had vascular thrombosis at study entry</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="66"/>
                <count group_id="O2" value="62"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Complete Response</title>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="2"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Partial Response</title>
                  <measurement_list>
                    <measurement group_id="O1" value="6"/>
                    <measurement group_id="O2" value="22"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Stable Disease</title>
                  <measurement_list>
                    <measurement group_id="O1" value="25"/>
                    <measurement group_id="O2" value="23"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Progressive Disease</title>
                  <measurement_list>
                    <measurement group_id="O1" value="14"/>
                    <measurement group_id="O2" value="4"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown</title>
                  <measurement_list>
                    <measurement group_id="O1" value="21"/>
                    <measurement group_id="O2" value="11"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Quality Adjusted Life Years</title>
        <description>Quality adjusted life years is calculated as the weighted sum of the number of years spent in different health states. The weight value is a utility score between 0 (worst health state) and 1 (best health state) derived from the EQ-5D-5L questionnaire, designed to describe and value health based on mobility, self-care, usual activities, pain/discomfort, and anxiety/depression.</description>
        <time_frame>The EQ-5D-5L is administered at baseline, six months and one year.</time_frame>
        <posting_date>09/2023</posting_date>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>From randomization to last follow-up: weekly during SBRT, after SBRT and before starting sorafenib, monthly during sorafenib, and overall from study entry: every 3 months for 2 years, then every 6 months. Maximum follow-up at time of analysis was 7.6 years.</time_frame>
      <desc>All-cause mortality was assessed in eligible participants. Adverse events were assessed in eligible participants who started protocol treatment, and were assessed for adverse events.</desc>
      <group_list>
        <group group_id="E1">
          <title>Sorafenib Alone</title>
          <description>400 mg sorafenib by mouth twice a day for 28-day cycle. Continue up to 5 years in the absence of disease progression or unacceptable toxicity.</description>
        </group>
        <group group_id="E2">
          <title>SBRT Followed by Sorafenib</title>
          <description>27.5 Gy to 50 Gy stereotactic body radiation therapy (SBRT) in 5 fractions 24-72 hours apart over 5-15 days followed within 1-5 days by one cycle of 200 mg sorafenib by mouth twice a day. Starting with second cycle, if tolerable, increase to 400 mg sorafenib by mouth twice a day. Continue up to 5 years in the absence of disease progression or unacceptable toxicity.</description>
        </group>
      </group_list>
      <serious_events>
        <default_vocab>CTCAE (4.0)</default_vocab>
        <default_assessment>Non-systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, all-cause mortality</sub_title>
                <counts group_id="E1" subjects_affected="80" subjects_at_risk="92"/>
                <counts group_id="E2" subjects_affected="73" subjects_at_risk="85"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="20" subjects_at_risk="88"/>
                <counts group_id="E2" subjects_affected="19" subjects_at_risk="83"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Blood and lymphatic system disorders</title>
            <event_list>
              <event>
                <sub_title>Blood and lymphatic system disorders - Other, specify</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="88"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="83"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Cardiac disorders</title>
            <event_list>
              <event>
                <sub_title>Myocardial infarction</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="88"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="83"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Abdominal pain</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="88"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="83"/>
              </event>
              <event>
                <sub_title>Ascites</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="88"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="83"/>
              </event>
              <event>
                <sub_title>Duodenal perforation</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="88"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="83"/>
              </event>
              <event>
                <sub_title>Duodenal ulcer</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="88"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="83"/>
              </event>
              <event>
                <sub_title>Gastrointestinal disorders - Other, specify</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="88"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="83"/>
              </event>
              <event>
                <sub_title>Gastrointestinal pain</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="88"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="83"/>
              </event>
              <event>
                <sub_title>Lower gastrointestinal hemorrhage</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="88"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="83"/>
              </event>
              <event>
                <sub_title>Pancreatitis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="88"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="83"/>
              </event>
              <event>
                <sub_title>Upper gastrointestinal hemorrhage</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="88"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="83"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Death NOS</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="88"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="83"/>
              </event>
              <event>
                <sub_title>Flu like symptoms</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="88"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="83"/>
              </event>
              <event>
                <sub_title>General disorders and administration site conditions - Other, specify</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="88"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="83"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Hepatobiliary disorders</title>
            <event_list>
              <event>
                <sub_title>Cholecystitis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="88"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="83"/>
              </event>
              <event>
                <sub_title>Hepatic failure</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="88"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="83"/>
              </event>
              <event>
                <sub_title>Hepatic hemorrhage</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="88"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="83"/>
              </event>
              <event>
                <sub_title>Hepatobiliary disorders - Other, specify</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="88"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="83"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Bone infection</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="88"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="83"/>
              </event>
              <event>
                <sub_title>Infections and infestations - Other, specify</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="88"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="83"/>
              </event>
              <event>
                <sub_title>Lung infection</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="88"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="83"/>
              </event>
              <event>
                <sub_title>Peritoneal infection</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="88"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="83"/>
              </event>
              <event>
                <sub_title>Sepsis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="88"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="83"/>
              </event>
              <event>
                <sub_title>Upper respiratory infection</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="88"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="83"/>
              </event>
              <event>
                <sub_title>Urinary tract infection</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="88"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="83"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Injury, poisoning and procedural complications</title>
            <event_list>
              <event>
                <sub_title>Fall</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="88"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="83"/>
              </event>
              <event>
                <sub_title>Injury, poisoning and procedural complications - Other, specify</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="88"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="83"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Investigations</title>
            <event_list>
              <event>
                <sub_title>Alanine aminotransferase increased</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="88"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="83"/>
              </event>
              <event>
                <sub_title>Aspartate aminotransferase increased</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="88"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="83"/>
              </event>
              <event>
                <sub_title>Blood bilirubin increased</sub_title>
                <assessment>Systematic Assessment</assessment>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="88"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="83"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Metabolism and nutrition disorders</title>
            <event_list>
              <event>
                <sub_title>Hyperkalemia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="88"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="83"/>
              </event>
              <event>
                <sub_title>Hypoglycemia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="88"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="83"/>
              </event>
              <event>
                <sub_title>Hyponatremia</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="88"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="83"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Neoplasms benign, malignant and unspecified (incl cysts and polyps)</title>
            <event_list>
              <event>
                <sub_title>Tumor pain</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="88"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="83"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Encephalopathy</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="88"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="83"/>
              </event>
              <event>
                <sub_title>Nervous system disorders - Other, specify</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="88"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="83"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Renal and urinary disorders</title>
            <event_list>
              <event>
                <sub_title>Acute kidney injury</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="88"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="83"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Skin and subcutaneous tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Skin ulceration</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="88"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="83"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Vascular disorders</title>
            <event_list>
              <event>
                <sub_title>Hypotension</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="88"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="83"/>
              </event>
              <event>
                <sub_title>Thromboembolic event</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="88"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="83"/>
              </event>
              <event>
                <sub_title>Visceral arterial ischemia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="88"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="83"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>5</frequency_threshold>
        <default_vocab>CTCAE (4.0)</default_vocab>
        <default_assessment>Non-systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, other adverse events</sub_title>
                <counts group_id="E1" subjects_affected="88" subjects_at_risk="88"/>
                <counts group_id="E2" subjects_affected="83" subjects_at_risk="83"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Blood and lymphatic system disorders</title>
            <event_list>
              <event>
                <sub_title>Anemia</sub_title>
                <counts group_id="E1" subjects_affected="25" subjects_at_risk="88"/>
                <counts group_id="E2" subjects_affected="44" subjects_at_risk="83"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Abdominal distension</sub_title>
                <counts group_id="E1" subjects_affected="10" subjects_at_risk="88"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="83"/>
              </event>
              <event>
                <sub_title>Abdominal pain</sub_title>
                <counts group_id="E1" subjects_affected="29" subjects_at_risk="88"/>
                <counts group_id="E2" subjects_affected="28" subjects_at_risk="83"/>
              </event>
              <event>
                <sub_title>Ascites</sub_title>
                <counts group_id="E1" subjects_affected="7" subjects_at_risk="88"/>
                <counts group_id="E2" subjects_affected="11" subjects_at_risk="83"/>
              </event>
              <event>
                <sub_title>Bloating</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="88"/>
                <counts group_id="E2" subjects_affected="8" subjects_at_risk="83"/>
              </event>
              <event>
                <sub_title>Constipation</sub_title>
                <counts group_id="E1" subjects_affected="21" subjects_at_risk="88"/>
                <counts group_id="E2" subjects_affected="16" subjects_at_risk="83"/>
              </event>
              <event>
                <sub_title>Diarrhea</sub_title>
                <assessment>Systematic Assessment</assessment>
                <counts group_id="E1" subjects_affected="43" subjects_at_risk="88"/>
                <counts group_id="E2" subjects_affected="38" subjects_at_risk="83"/>
              </event>
              <event>
                <sub_title>Gastrointestinal disorders - Other, specify</sub_title>
                <counts group_id="E1" subjects_affected="15" subjects_at_risk="88"/>
                <counts group_id="E2" subjects_affected="19" subjects_at_risk="83"/>
              </event>
              <event>
                <sub_title>Gastrointestinal pain</sub_title>
                <counts group_id="E1" subjects_affected="5" subjects_at_risk="88"/>
                <counts group_id="E2" subjects_affected="5" subjects_at_risk="83"/>
              </event>
              <event>
                <sub_title>Mucositis oral</sub_title>
                <counts group_id="E1" subjects_affected="7" subjects_at_risk="88"/>
                <counts group_id="E2" subjects_affected="6" subjects_at_risk="83"/>
              </event>
              <event>
                <sub_title>Nausea</sub_title>
                <assessment>Systematic Assessment</assessment>
                <counts group_id="E1" subjects_affected="28" subjects_at_risk="88"/>
                <counts group_id="E2" subjects_affected="37" subjects_at_risk="83"/>
              </event>
              <event>
                <sub_title>Vomiting</sub_title>
                <assessment>Systematic Assessment</assessment>
                <counts group_id="E1" subjects_affected="9" subjects_at_risk="88"/>
                <counts group_id="E2" subjects_affected="18" subjects_at_risk="83"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Edema limbs</sub_title>
                <counts group_id="E1" subjects_affected="12" subjects_at_risk="88"/>
                <counts group_id="E2" subjects_affected="14" subjects_at_risk="83"/>
              </event>
              <event>
                <sub_title>Fatigue</sub_title>
                <counts group_id="E1" subjects_affected="55" subjects_at_risk="88"/>
                <counts group_id="E2" subjects_affected="54" subjects_at_risk="83"/>
              </event>
              <event>
                <sub_title>Fever</sub_title>
                <counts group_id="E1" subjects_affected="7" subjects_at_risk="88"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="83"/>
              </event>
              <event>
                <sub_title>General disorders and administration site conditions - Other, specify</sub_title>
                <counts group_id="E1" subjects_affected="10" subjects_at_risk="88"/>
                <counts group_id="E2" subjects_affected="14" subjects_at_risk="83"/>
              </event>
              <event>
                <sub_title>Pain</sub_title>
                <counts group_id="E1" subjects_affected="6" subjects_at_risk="88"/>
                <counts group_id="E2" subjects_affected="8" subjects_at_risk="83"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Infections and infestations - Other, specify</sub_title>
                <counts group_id="E1" subjects_affected="5" subjects_at_risk="88"/>
                <counts group_id="E2" subjects_affected="4" subjects_at_risk="83"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Investigations</title>
            <event_list>
              <event>
                <sub_title>Activated partial thromboplastin time prolonged</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="88"/>
                <counts group_id="E2" subjects_affected="5" subjects_at_risk="83"/>
              </event>
              <event>
                <sub_title>Alanine aminotransferase increased</sub_title>
                <counts group_id="E1" subjects_affected="31" subjects_at_risk="88"/>
                <counts group_id="E2" subjects_affected="40" subjects_at_risk="83"/>
              </event>
              <event>
                <sub_title>Alkaline phosphatase increased</sub_title>
                <counts group_id="E1" subjects_affected="14" subjects_at_risk="88"/>
                <counts group_id="E2" subjects_affected="22" subjects_at_risk="83"/>
              </event>
              <event>
                <sub_title>Aspartate aminotransferase increased</sub_title>
                <counts group_id="E1" subjects_affected="45" subjects_at_risk="88"/>
                <counts group_id="E2" subjects_affected="41" subjects_at_risk="83"/>
              </event>
              <event>
                <sub_title>Blood bilirubin increased</sub_title>
                <assessment>Systematic Assessment</assessment>
                <counts group_id="E1" subjects_affected="49" subjects_at_risk="88"/>
                <counts group_id="E2" subjects_affected="54" subjects_at_risk="83"/>
              </event>
              <event>
                <sub_title>Creatinine increased</sub_title>
                <counts group_id="E1" subjects_affected="8" subjects_at_risk="88"/>
                <counts group_id="E2" subjects_affected="4" subjects_at_risk="83"/>
              </event>
              <event>
                <sub_title>INR increased</sub_title>
                <counts group_id="E1" subjects_affected="8" subjects_at_risk="88"/>
                <counts group_id="E2" subjects_affected="19" subjects_at_risk="83"/>
              </event>
              <event>
                <sub_title>Investigations - Other, specify</sub_title>
                <counts group_id="E1" subjects_affected="17" subjects_at_risk="88"/>
                <counts group_id="E2" subjects_affected="24" subjects_at_risk="83"/>
              </event>
              <event>
                <sub_title>Lymphocyte count decreased</sub_title>
                <counts group_id="E1" subjects_affected="8" subjects_at_risk="88"/>
                <counts group_id="E2" subjects_affected="18" subjects_at_risk="83"/>
              </event>
              <event>
                <sub_title>Neutrophil count decreased</sub_title>
                <assessment>Systematic Assessment</assessment>
                <counts group_id="E1" subjects_affected="16" subjects_at_risk="88"/>
                <counts group_id="E2" subjects_affected="19" subjects_at_risk="83"/>
              </event>
              <event>
                <sub_title>Platelet count decreased</sub_title>
                <assessment>Systematic Assessment</assessment>
                <counts group_id="E1" subjects_affected="49" subjects_at_risk="88"/>
                <counts group_id="E2" subjects_affected="63" subjects_at_risk="83"/>
              </event>
              <event>
                <sub_title>Weight loss</sub_title>
                <counts group_id="E1" subjects_affected="22" subjects_at_risk="88"/>
                <counts group_id="E2" subjects_affected="19" subjects_at_risk="83"/>
              </event>
              <event>
                <sub_title>White blood cell decreased</sub_title>
                <counts group_id="E1" subjects_affected="16" subjects_at_risk="88"/>
                <counts group_id="E2" subjects_affected="38" subjects_at_risk="83"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Metabolism and nutrition disorders</title>
            <event_list>
              <event>
                <sub_title>Anorexia</sub_title>
                <counts group_id="E1" subjects_affected="39" subjects_at_risk="88"/>
                <counts group_id="E2" subjects_affected="34" subjects_at_risk="83"/>
              </event>
              <event>
                <sub_title>Hyperglycemia</sub_title>
                <counts group_id="E1" subjects_affected="10" subjects_at_risk="88"/>
                <counts group_id="E2" subjects_affected="17" subjects_at_risk="83"/>
              </event>
              <event>
                <sub_title>Hypoalbuminemia</sub_title>
                <counts group_id="E1" subjects_affected="40" subjects_at_risk="88"/>
                <counts group_id="E2" subjects_affected="41" subjects_at_risk="83"/>
              </event>
              <event>
                <sub_title>Hypocalcemia</sub_title>
                <counts group_id="E1" subjects_affected="20" subjects_at_risk="88"/>
                <counts group_id="E2" subjects_affected="18" subjects_at_risk="83"/>
              </event>
              <event>
                <sub_title>Hypokalemia</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="88"/>
                <counts group_id="E2" subjects_affected="5" subjects_at_risk="83"/>
              </event>
              <event>
                <sub_title>Hypomagnesemia</sub_title>
                <counts group_id="E1" subjects_affected="17" subjects_at_risk="88"/>
                <counts group_id="E2" subjects_affected="17" subjects_at_risk="83"/>
              </event>
              <event>
                <sub_title>Hyponatremia</sub_title>
                <counts group_id="E1" subjects_affected="28" subjects_at_risk="88"/>
                <counts group_id="E2" subjects_affected="16" subjects_at_risk="83"/>
              </event>
              <event>
                <sub_title>Hypophosphatemia</sub_title>
                <counts group_id="E1" subjects_affected="32" subjects_at_risk="88"/>
                <counts group_id="E2" subjects_affected="32" subjects_at_risk="83"/>
              </event>
              <event>
                <sub_title>Metabolism and nutrition disorders - Other, specify</sub_title>
                <counts group_id="E1" subjects_affected="15" subjects_at_risk="88"/>
                <counts group_id="E2" subjects_affected="15" subjects_at_risk="83"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Musculoskeletal and connective tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Back pain</sub_title>
                <counts group_id="E1" subjects_affected="9" subjects_at_risk="88"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="83"/>
              </event>
              <event>
                <sub_title>Generalized muscle weakness</sub_title>
                <counts group_id="E1" subjects_affected="5" subjects_at_risk="88"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="83"/>
              </event>
              <event>
                <sub_title>Musculoskeletal and connective tissue disorder - Other, specify</sub_title>
                <counts group_id="E1" subjects_affected="14" subjects_at_risk="88"/>
                <counts group_id="E2" subjects_affected="17" subjects_at_risk="83"/>
              </event>
              <event>
                <sub_title>Pain in extremity</sub_title>
                <counts group_id="E1" subjects_affected="7" subjects_at_risk="88"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="83"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Dysgeusia</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="88"/>
                <counts group_id="E2" subjects_affected="5" subjects_at_risk="83"/>
              </event>
              <event>
                <sub_title>Headache</sub_title>
                <counts group_id="E1" subjects_affected="12" subjects_at_risk="88"/>
                <counts group_id="E2" subjects_affected="7" subjects_at_risk="83"/>
              </event>
              <event>
                <sub_title>Nervous system disorders - Other, specify</sub_title>
                <counts group_id="E1" subjects_affected="5" subjects_at_risk="88"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="83"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Psychiatric disorders</title>
            <event_list>
              <event>
                <sub_title>Insomnia</sub_title>
                <counts group_id="E1" subjects_affected="13" subjects_at_risk="88"/>
                <counts group_id="E2" subjects_affected="7" subjects_at_risk="83"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Renal and urinary disorders</title>
            <event_list>
              <event>
                <sub_title>Renal and urinary disorders - Other, specify</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="88"/>
                <counts group_id="E2" subjects_affected="5" subjects_at_risk="83"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Cough</sub_title>
                <counts group_id="E1" subjects_affected="9" subjects_at_risk="88"/>
                <counts group_id="E2" subjects_affected="12" subjects_at_risk="83"/>
              </event>
              <event>
                <sub_title>Dyspnea</sub_title>
                <counts group_id="E1" subjects_affected="7" subjects_at_risk="88"/>
                <counts group_id="E2" subjects_affected="12" subjects_at_risk="83"/>
              </event>
              <event>
                <sub_title>Epistaxis</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="88"/>
                <counts group_id="E2" subjects_affected="5" subjects_at_risk="83"/>
              </event>
              <event>
                <sub_title>Respiratory, thoracic and mediastinal disorders - Other, specify</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="88"/>
                <counts group_id="E2" subjects_affected="6" subjects_at_risk="83"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Skin and subcutaneous tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Alopecia</sub_title>
                <counts group_id="E1" subjects_affected="5" subjects_at_risk="88"/>
                <counts group_id="E2" subjects_affected="6" subjects_at_risk="83"/>
              </event>
              <event>
                <sub_title>Dry skin</sub_title>
                <assessment>Systematic Assessment</assessment>
                <counts group_id="E1" subjects_affected="10" subjects_at_risk="88"/>
                <counts group_id="E2" subjects_affected="8" subjects_at_risk="83"/>
              </event>
              <event>
                <sub_title>Palmar-plantar erythrodysesthesia syndrome</sub_title>
                <assessment>Systematic Assessment</assessment>
                <counts group_id="E1" subjects_affected="28" subjects_at_risk="88"/>
                <counts group_id="E2" subjects_affected="21" subjects_at_risk="83"/>
              </event>
              <event>
                <sub_title>Pruritus</sub_title>
                <counts group_id="E1" subjects_affected="10" subjects_at_risk="88"/>
                <counts group_id="E2" subjects_affected="9" subjects_at_risk="83"/>
              </event>
              <event>
                <sub_title>Rash maculo-papular</sub_title>
                <assessment>Systematic Assessment</assessment>
                <counts group_id="E1" subjects_affected="21" subjects_at_risk="88"/>
                <counts group_id="E2" subjects_affected="17" subjects_at_risk="83"/>
              </event>
              <event>
                <sub_title>Skin and subcutaneous tissue disorders - Other, specify</sub_title>
                <counts group_id="E1" subjects_affected="23" subjects_at_risk="88"/>
                <counts group_id="E2" subjects_affected="14" subjects_at_risk="83"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Vascular disorders</title>
            <event_list>
              <event>
                <sub_title>Hypertension</sub_title>
                <assessment>Systematic Assessment</assessment>
                <counts group_id="E1" subjects_affected="24" subjects_at_risk="88"/>
                <counts group_id="E2" subjects_affected="20" subjects_at_risk="83"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </other_events>
    </reported_events>

    <certain_agreements>
      <pi_employee>Principal Investigators are NOT employed by the organization sponsoring the study.</pi_employee>
      <restrictive_agreement>PI's are required to abide by the sponsor's publication guidelines which require review by coauthors and subsequent review and approval by the sponsor.</restrictive_agreement>
    </certain_agreements>
    <limitations_and_caveats>The trial closed to accrual in March 2021 at 193 of 292 planned patients due to a change in the systemic standard of care for this disease, from sorafenib to atezolizumab and bevacizumab. As the original number of OS events (238) couldn't be met, the statistical analysis plan (SAP) was revised to report the study using available patients, with data through 7/1/2022. The changes were done by a statistician independent from the trial in accordance with the NCI Policy for Major Design Amendments.</limitations_and_caveats>
    <point_of_contact>
      <name_or_title>Wendy Seiferheld</name_or_title>
      <organization>NRG Oncology</organization>
      <phone>2155743208</phone>
      <email>seiferheldw@nrgoncology.org</email>
    </point_of_contact>
  </clinical_results>
</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/NCT01730937
org study id: RTOG-1112
secondary id: NCI-2012-02057
secondary id: U10CA021661
nct id: NCT01730937
lead sponsor: 
collaborator: 
collaborator: 
has dmc: Yes
This randomized phase III trial studies sorafenib tosylate and stereotactic body radiation
      therapy to see how well they work compared to sorafenib tosylate alone in treating patients
      with liver cancer. Sorafenib tosylate may stop the growth of tumor cells by blocking some of
      the enzymes needed for cell growth. Stereotactic body radiation therapy may be able to send
      the radiation dose directly to the tumor and cause less damage to normal tissue. Giving
      sorafenib tosylate together with stereotactic body radiation therapy may kill more tumor
      cells.
PRIMARY OBJECTIVES:

      I. To determine if stereotactic body radiation therapy (SBRT) improves overall survival in
      hepatocellular carcinoma (HCC) patients treated with sorafenib (sorafenib tosylate).

      SECONDARY OBJECTIVES:

      I. To determine the difference in time to progression (TTP) and progression-free survival
      (PFS) in HCC patients treated with sorafenib compared to SBRT followed by sorafenib.

      II. To measure differences in toxicity in HCC patients treated with sorafenib versus SBRT
      followed by sorafenib.

      III. To measure vascular thrombosis response post sorafenib versus SBRT followed by
      sorafenib.

      IV. To measure differences in health related quality of life (QOL) and quality-adjusted
      survival in HCC patients treated with sorafenib compared to SBRT followed by sorafenib.

      V. Collection of biospecimens for future correlative studies to investigate differences in
      potential biomarkers in patients treated with sorafenib versus SBRT followed by sorafenib.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Single (Outcomes Assessor)
measure: Overall Survival
time frame: From randomization to last follow-up: weekly during SBRT, post-SBRT/pre-sorafenib, monthly during sorafenib, and overall, from study entry: every 3 months for 2 years, then every 6 months. Maximum follow-up at time of analysis was 7.6 years.
description: An event for overall survival (OS) is death due to any cause. Survival time is defined as time from randomization to the date of death or last known follow-up (censored). Rates are estimated by the Kaplan-Meier method. Analysis was to occur after 153 deaths were reported.
measure: Time to Progression
time frame: From randomization to last follow-up: weekly during SBRT, post-SBRT/pre-sorafenib, monthly during sorafenib, and overall, from study entry: every 3 months for 2 years, then every 6 months. Maximum follow-up at time of analysis was 7.6 years.
description: Progression (failure) is defined as any of the following events: new tumor thrombosis, progression of hepatocellular carcinoma (HCC) within liver excluding tumor thrombosis status, progression of distant metastases that were present at study entry, new HCC within the liver including tumor thrombosis, and vascular thrombosis events=progression-new enhancing tumor thrombosis/progression-Increase in the volume of enhancing portion of thrombosis. Time to progression was measured from the date of randomization to the date of first failure, death (competing risk), or last follow-up (censored). Progression rates are estimated by the cumulative incidence method. The protocol specifies only that the distributions of failure times be compared between the arms, which is reported in the statistical analysis results. Two-year estimates are provided as a summary of the distributions.
measure: Progression-free Survival
time frame: From randomization to last follow-up: weekly during SBRT, post-SBRT/pre-sorafenib, monthly during sorafenib, and overall, from study entry: every 3 months for 2 years, then every 6 months. Maximum follow-up at time of analysis was 7.6 years.
description: Failure for progression-free survival (PFS) include death, new tumor thrombosis, progression of hepatocellular carcinoma (HCC) within liver excluding tumor thrombosis status, progression of distant Mets that were present at study entry, new HCC within liver including tumor thrombosis, and vascular thrombosis events =progression-new enhancing tumor thrombosis/progression-Increase in the volume of enhancing portion of thrombosis. PFS time is defined as the time from randomization to the date of first failure, date of death, or last known follow-up (censored). PFS rates are estimated by the Kaplan-Meier method. The protocol specifies only that the distributions of failure times be compared between the arms, which is reported in the statistical analysis results. Two-year estimates are provided as a summary of the distributions.
measure: Number of Participants by Highest Grade Adverse Event Reported
time frame: From randomization to last follow-up: weekly during SBRT, post-SBRT/pre-sorafenib, monthly during sorafenib, and overall, from study entry: every 3 months for 2 years, then every 6 months. Maximum follow-up at time of analysis was 7.6 years.
description: Common Terminology Criteria for Adverse Events (version 4.0) grades adverse event severity from 1=mild to 5=death. Summary data is provided in this outcome measure; see Adverse Events Module for specific adverse event data.
measure: Percentage of Participants With Improvement in the Functional Assessment of Cancer Therapy - Hepatobiliary (FACT-Hep) Total Score 6 Months After the Start of Treatment
time frame: Baseline and 6 months
description: The FACT-Hep total score measures quality of life in patients with hepatobiliary cancer. Possible scores range from 0 to 180, with higher scores indicating a better outcome. Improvement in FACT-Hep total score is defined as an increase from the baseline to 6-month score of at least 5 points.
measure: Best Vascular Thrombosis Response up to the Time of Progressive Disease (if Applicable)
time frame: From randomization to last follow-up. Imaging occurs every 3 months for two years then every six months. Maximum follow-up at time of analysis was 7.6 years.
description: Complete response: Complete resolution of thrombosis, with recanalization of vessel.
Partial response (PR):
Partial recanalization (if prior complete blockage)
Unequivocal reduction in the maximal girth
Unequivocal reduction in the volume, or elimination, of arterial enhancing portion
Progressive disease (PD): any unequivocal, unambiguous
New enhancing tumor thrombosis
Increase in the volume of enhancing portion
Unequivocal progression of thrombosis (non-measurable disease), the increase in overall tumor burden (enhancing thrombosis) must be comparable to the increase required for the Response Evaluation Criteria in Solid Tumor 1.1 definition of PD of measurable disease (e.g. ≥ 73% increase in volume, which is similar to 20% increase in diameter, and at least a 5 mm absolute increase).
Stable disease:
No/small changes that do not meet the above criteria for PR or PD
Increase in the volume of non-enhancing thrombosis
New bland non-enhancing thrombosis
measure: Quality Adjusted Life Years
time frame: The EQ-5D-5L is administered at baseline, six months and one year.
description: Quality adjusted life years is calculated as the weighted sum of the number of years spent in different health states. The weight value is a utility score between 0 (worst health state) and 1 (best health state) derived from the EQ-5D-5L questionnaire, designed to describe and value health based on mobility, self-care, usual activities, pain/discomfort, and anxiety/depression.
arm group label: Sorafenib Alone
arm group type: Active Comparator
description: 400 mg sorafenib twice a day for 28-day cycle. Continue up to 5 years in the absence of disease progression or unacceptable toxicity.
arm group label: SBRT followed by Sorafenib
arm group type: Experimental
description: 27.5 Gy to 50 Gy stereotactic body radiation therapy (SBRT) in 5 fractions 24-72 hours apart over 5-15 days followed within 1-5 days by one cycle of 200 mg sorafenib twice a day. Starting with second cycle, if tolerable, increase to 400 mg sorafenib twice a day. Continue up to 5 years in the absence of disease progression or unacceptable toxicity.
intervention type: Drug
intervention name: Sorafenib
description: By mouth (PO)
arm group label: SBRT followed by Sorafenib
arm group label: Sorafenib Alone
other name: BAY 43-9006
other name: BAY 43-9006 Tosylate Salt
other name: BAY 54-9085
other name: Nexavar
other name: SFN
other name: Sorafenib Tosylate
intervention type: Radiation
intervention name: stereotactic body radiation therapy
description: Intensity-modulated radiation therapy (IMRT), stereotactic body radiation therapy (SBRT), and proton therapy are allowed.
arm group label: SBRT followed by Sorafenib
other name: SBRT
other name: stereotactic radiation therapy
other name: stereotactic radiotherapy
other name: stereotactic ablative body radiation therapy,
other name: stereotactic ablative radiotherapy
other name: SABR
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Laura Dawson
role: Principal Investigator
affiliation: Radiation Therapy Oncology Group
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country: Australia
country: Canada
country: Hong Kong
country: Korea, Republic of
country: United States
responsible party type: Sponsor
mesh term: Carcinoma
mesh term: Carcinoma, Hepatocellular
mesh term: Liver Neoplasms
mesh term: Sorafenib
provided document: 
provided document: 
participant flow: 
baseline: 
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reported events: 
certain agreements: 
limitations and caveats: The trial closed to accrual in March 2021 at 193 of 292 planned patients due to a change in the systemic standard of care for this disease, from sorafenib to atezolizumab and bevacizumab. As the original number of OS events (238) couldn't be met, the statistical analysis plan (SAP) was revised to report the study using available patients, with data through 7/1/2022. The changes were done by a statistician independent from the trial in accordance with the NCI Policy for Major Design Amendments.
point of contact: 