<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/NCT02200042</url>
  </required_header>
  <id_info>
    <org_study_id>NRG-GI001</org_study_id>
    <secondary_id>NCI-2014-00849</secondary_id>
    <secondary_id>PNRG-GI001_A02PAMDREVW01</secondary_id>
    <secondary_id>PNRG-GI001_A01PAMDREVW01</secondary_id>
    <secondary_id>NRG-GI001</secondary_id>
    <secondary_id>NRG-GI001</secondary_id>
    <secondary_id>U10CA180868</secondary_id>
    <nct_id>NCT02200042</nct_id>
  </id_info>
  <brief_title>Radiation Therapy vs. Observation Following Gemcitabine and Cisplatin for Inoperable Localized Liver Cancer</brief_title>
  <official_title>Randomized Phase III Study of Focal Radiation Therapy for Unresectable, Localized Intrahepatic Cholangiocarcinoma</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>NRG Oncology</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>National Cancer Institute (NCI)</agency>
      <agency_class>NIH</agency_class>
    </collaborator>
  </sponsors>
  <source>NRG Oncology</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      This randomized phase III trial studies how well gemcitabine hydrochloride and cisplatin with&#xD;
      or without radiation therapy work in treating patients with localized liver cancer that&#xD;
      cannot be removed by surgery. Drugs used in chemotherapy, such as gemcitabine hydrochloride&#xD;
      and cisplatin, work in different ways to stop the growth of tumor cells, either by killing&#xD;
      the cells, by stopping them from dividing, or by stopping them from spreading. Radiation&#xD;
      therapy uses high energy x rays to kill tumor cells. It is not yet known whether giving&#xD;
      gemcitabine and cisplatin is more effective with or without radiation therapy in this patient&#xD;
      population. Patients register to this study after receiving gemcitabine and cisplatin.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      PRIMARY OBJECTIVES:&#xD;
&#xD;
      I. To evaluate the addition of liver-directed radiation therapy with respect to overall&#xD;
      survival (OS) for patients with unresectable, localized intrahepatic cholangiocarcinoma.&#xD;
&#xD;
      SECONDARY OBJECTIVES:&#xD;
&#xD;
      I. To evaluate the addition of liver-directed radiation therapy with respect to local control&#xD;
      for patients with unresectable, localized intrahepatic cholangiocarcinoma.&#xD;
&#xD;
      II. To evaluate the addition of liver-directed radiation therapy with respect to adverse&#xD;
      events for patients with unresectable, localized intrahepatic cholangiocarcinoma.&#xD;
&#xD;
      III. To evaluate the addition of liver-directed radiation therapy with respect to regional&#xD;
      control for patients with unresectable, localized intrahepatic cholangiocarcinoma.&#xD;
&#xD;
      IV. To evaluate the addition of liver-directed radiation therapy with respect to distant&#xD;
      metastases for patients with unresectable, localized intrahepatic cholangiocarcinoma.&#xD;
&#xD;
      V. To evaluate the addition of liver-directed radiation therapy with respect to&#xD;
      progression-free survival for patients with unresectable, localized intrahepatic&#xD;
      cholangiocarcinoma.&#xD;
&#xD;
      After completion of study treatment, patients are followed up every 3 months for 3 years then&#xD;
      every 6 months for 2 years.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Terminated</overall_status>
  <start_date type="Actual">September 29, 2014</start_date>
  <completion_date type="Actual">July 2, 2018</completion_date>
  <primary_completion_date type="Actual">July 2, 2018</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>
    <intervention_model_description>Randomization ratio (Experimental:Observation) = 2:1</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Overall Survival</measure>
    <time_frame>From randomization to last follow-up. Analysis occurs after all patients have been on study for at least two years.</time_frame>
    <description>Overall survival time is defined as time from randomization to the date of death from any cause. Overall survival rates are estimated by the Kaplan-Meier method. Patients last known to be alive are censored at the date of last contact.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Distant Metastases</measure>
    <time_frame>From randomization to last follow-up. Analysis occurs after all patients have been on study for at least two years.</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Incidence of Adverse Events Evaluated Using National Cancer Institute Common Terminology Criteria for Adverse Events Version 4.0</measure>
    <time_frame>From randomization to last follow-up. Analysis occurs after all patients have been on study for at least two years.</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Local Progression</measure>
    <time_frame>From randomization to last follow-up. Analysis occurs after all patients have been on study for at least two years.</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Progression-free Survival (PFS)</measure>
    <time_frame>From randomization to last follow-up. Analysis occurs after all patients have been on study for at least two years.</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Regional Progression Defined as Progression or Existing or Appearance of New Nodal Disease</measure>
    <time_frame>From randomization to last follow-up. Analysis occurs after all patients have been on study for at least two years.</time_frame>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">1</enrollment>
  <condition>Stage III Intrahepatic Cholangiocarcinoma</condition>
  <condition>Stage IVA Intrahepatic Cholangiocarcinoma</condition>
  <arm_group>
    <arm_group_label>Radiation therapy</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Liver-directed radiation therapy</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Observation</arm_group_label>
    <arm_group_type>No Intervention</arm_group_type>
    <description>No radiation therapy</description>
  </arm_group>
  <intervention>
    <intervention_type>Radiation</intervention_type>
    <intervention_name>Image Guided Radiation Therapy</intervention_name>
    <description>Patients undergo 15 fractions of image-guided radiation therapy delivered over 19-26 or 27-34 days.</description>
    <arm_group_label>Radiation therapy</arm_group_label>
    <other_name>IGRT</other_name>
    <other_name>image-guided radiation therapy</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Pathologically (histologically or cytologically) proven diagnosis of intrahepatic&#xD;
             cholangiocarcinoma (IHC) without distant extrahepatic metastasis prior to study entry.&#xD;
             Patients with an adenocarcinoma suggestive of a pancreaticobiliary primary with&#xD;
             radiographic findings consistent with an intrahepatic cholangio-carcinoma are&#xD;
             eligible.&#xD;
&#xD;
          2. Patient must have 1 lesion with a maximum AXIAL diameter of 12cm at the time of study&#xD;
             entry. Up to 3 satellite lesions are permitted. Satellite lesions, are defined as&#xD;
             lesions less than 2 cm that are within 1 cm of the periphery of the dominant lesion&#xD;
             (gross tumor volume [GTV]) are permitted. The satellite lesions are NOT included in&#xD;
             the AXIAL diameter measurement. Regional Lymph Node involvement within the porta&#xD;
             hepatis (as medial as superior mesenteric vein [SMV] portal vein confluence) is&#xD;
             permitted if nodes are deemed clinically positive (i.e. FDG [Fluorine 18&#xD;
             fluorodeoxyglucose] avid);&#xD;
&#xD;
          3. Appropriate stage for protocol entry, including no distant metastases, based upon the&#xD;
             following minimum diagnostic workup:&#xD;
&#xD;
             • Pre-study entry Scan (REQUIRED for All Patients to confirm no progression): computed&#xD;
             tomography (CT) scan chest/abdomen/pelvis with multiphasic liver CT scan within 30&#xD;
             days prior to study entry. If CT contrast is contraindicated, CT chest without&#xD;
             contrast and MRI of abdomen and pelvis is permitted;&#xD;
&#xD;
          4. Zubrod Performance Status 0-1 at the time of study entry;&#xD;
&#xD;
          5. Age ≥ 18;&#xD;
&#xD;
          6. Complete blood count (CBC) / differential obtained within 21 days prior to study&#xD;
             entry, with adequate bone marrow function defined as follows:&#xD;
&#xD;
               -  Absolute neutrophil count (ANC) ≥ 1,000 cells/mm3;&#xD;
&#xD;
               -  Platelets ≥ 75,000 cells/mm3;&#xD;
&#xD;
               -  Total bilirubin &lt; 2.5 mg/dl;&#xD;
&#xD;
               -  Aspartate Aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT])&#xD;
                  and alanine aminotransferase (ALT) (Serum glutamic pyruvic transaminase [SGPT]) &lt;&#xD;
                  5.0 X institutional upper limit of normal;&#xD;
&#xD;
               -  Albumin ≥ 2.5mg/dl;&#xD;
&#xD;
               -  Creatinine within normal institutional limits or creatinine clearance ≥ 60&#xD;
                  mL/min/1.73 m2 for subject with creatinine levels above institutional normal;&#xD;
&#xD;
               -  Hemoglobin(Hgb) ≥ 9.0 g/dl. (Note: The use of transfusion or other intervention&#xD;
                  to achieve Hgb ≥ 9.0 g/dl is acceptable.)&#xD;
&#xD;
          7. Patient must provide study specific informed consent prior to study entry;&#xD;
&#xD;
          8. Negative Beta-Human Chorionic Gonadotropin (bHCG) prior to study entry if patient is&#xD;
             pre or peri-menopausal.&#xD;
&#xD;
          9. Must have received 6 months of Gemcitabine/Cisplatin chemotherapy without progression.&#xD;
             Disease response to chemotherapy is also permitted. If toxicity precludes 6 months of&#xD;
             chemotherapy at least 4 months of Gemcitabine/Cisplatin must have been administered.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Multiple lesions that don't meet the criteria as satellite lesions as defined in&#xD;
             protocol;&#xD;
&#xD;
          2. Extrahepatic metastases or malignant nodes beyond the periportal region. Celiac,&#xD;
             pancreaticoduodenal and para-aortic nodes&gt; 2 cm are ineligible. Note that benign&#xD;
             non-enhancing periportal lymphadenopathy is not unusual in the presence of hepatitis&#xD;
             and is permitted, even if the sum of enlarged nodes is &gt; 2.0 cm;&#xD;
&#xD;
          3. Hepatic insufficiency resulting in clinical jaundice, encephalopathy and/or variceal&#xD;
             bleed at the time of study entry;&#xD;
&#xD;
          4. Prior radiotherapy to the region of the liver that would result in overlap of&#xD;
             radiation therapy fields;&#xD;
&#xD;
          5. Prior selective internal radiotherapy/hepatic arterial Yttrium therapy, at any time;&#xD;
&#xD;
          6. Direct tumor extension into the stomach, duodenum, small bowel or large bowel;&#xD;
&#xD;
          7. Prior invasive malignancy, excluding the current diagnosis, (except non-melanomatous&#xD;
             skin cancer) unless disease free for a minimum of 3 years. (Note: carcinoma in situ of&#xD;
             the breast, oral cavity, or cervix is all permissible);&#xD;
&#xD;
          8. Prior systemic chemotherapy for the study cancer other than gemcitabine/cisplatin;&#xD;
             note that prior chemotherapy for a different cancer is allowable;&#xD;
&#xD;
          9. Currently receiving other anti-cancer agents;&#xD;
&#xD;
         10. Participants who require anticoagulation should receive low-molecular weight or&#xD;
             standard heparin and not warfarin;&#xD;
&#xD;
         11. Prior surgery for the IHC. (Liver resection is not allowed);&#xD;
&#xD;
         12. Severe, active co-morbidity, defined as follows:&#xD;
&#xD;
               -  Unstable angina and/or congestive heart failure requiring hospitalization within&#xD;
                  the last 6 months of study entry;&#xD;
&#xD;
               -  Transmural myocardial infarction within the last 6 months of study entry;&#xD;
&#xD;
               -  Acute bacterial or fungal infection requiring intravenous antibiotics at the time&#xD;
                  of study entry;&#xD;
&#xD;
               -  Chronic Obstructive Pulmonary Disease exacerbation or other respiratory illness&#xD;
                  requiring hospitalization or precluding study therapy within 30 days prior to&#xD;
                  study entry;&#xD;
&#xD;
               -  HIV positive with CD4 (cluster of differentiation 4) count &lt; 200&#xD;
                  cells/microliter. Note that patients who are HIV positive are eligible, provided&#xD;
                  they are under treatment with highly active antiretroviral therapy (HAART) and&#xD;
                  have a CD4 count ≥ 200 cells/microliter at the time of study entry. Note also&#xD;
                  that HIV testing is not required for eligibility for this protocol;&#xD;
&#xD;
               -  End-stage renal disease (ie, on dialysis or dialysis has been recommended).&#xD;
&#xD;
         13. 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;
         14. Grade 3 or higher peripheral neuropathy at the time of study entry.&#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>Theodore Hong</last_name>
    <role>Principal Investigator</role>
    <affiliation>NRG Oncology</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>University of Alabama at Birmingham Cancer Center</name>
      <address>
        <city>Birmingham</city>
        <state>Alabama</state>
        <zip>35233</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Arkansas for Medical Sciences</name>
      <address>
        <city>Little Rock</city>
        <state>Arkansas</state>
        <zip>72205</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Sutter Medical Center Sacramento</name>
      <address>
        <city>Sacramento</city>
        <state>California</state>
        <zip>95816</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Emory University Hospital Midtown</name>
      <address>
        <city>Atlanta</city>
        <state>Georgia</state>
        <zip>30308</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Piedmont Hospital</name>
      <address>
        <city>Atlanta</city>
        <state>Georgia</state>
        <zip>30309</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Emory University Hospital/Winship Cancer Institute</name>
      <address>
        <city>Atlanta</city>
        <state>Georgia</state>
        <zip>30322</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>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>OSF Saint Francis Medical Center</name>
      <address>
        <city>Peoria</city>
        <state>Illinois</state>
        <zip>61637</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>Maryland Proton Treatment Center</name>
      <address>
        <city>Baltimore</city>
        <state>Maryland</state>
        <zip>21201</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>Lahey Hospital and Medical Center</name>
      <address>
        <city>Burlington</city>
        <state>Massachusetts</state>
        <zip>01805</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>Missouri Baptist Medical Center</name>
      <address>
        <city>Saint Louis</city>
        <state>Missouri</state>
        <zip>63131</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Dartmouth Hitchcock Medical Center</name>
      <address>
        <city>Lebanon</city>
        <state>New Hampshire</state>
        <zip>03756</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of New Mexico Cancer Center</name>
      <address>
        <city>Albuquerque</city>
        <state>New Mexico</state>
        <zip>87102</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Mount Sinai Hospital</name>
      <address>
        <city>New York</city>
        <state>New York</state>
        <zip>10029</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>University of Cincinnati/Barrett Cancer Center</name>
      <address>
        <city>Cincinnati</city>
        <state>Ohio</state>
        <zip>45219</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>Legacy Good Samaritan Hospital and Medical Center</name>
      <address>
        <city>Portland</city>
        <state>Oregon</state>
        <zip>97210</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>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>West Virginia University Healthcare</name>
      <address>
        <city>Morgantown</city>
        <state>West Virginia</state>
        <zip>26506</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Wisconsin Hospital and Clinics</name>
      <address>
        <city>Madison</city>
        <state>Wisconsin</state>
        <zip>53792</zip>
        <country>United States</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_countries>
    <country>Canada</country>
    <country>United States</country>
  </location_countries>
  <verification_date>July 2019</verification_date>
  <study_first_submitted>July 8, 2014</study_first_submitted>
  <study_first_submitted_qc>July 23, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">July 25, 2014</study_first_posted>
  <results_first_submitted>July 31, 2019</results_first_submitted>
  <results_first_submitted_qc>July 31, 2019</results_first_submitted_qc>
  <results_first_posted type="Actual">August 28, 2019</results_first_posted>
  <last_update_submitted>July 31, 2019</last_update_submitted>
  <last_update_submitted_qc>July 31, 2019</last_update_submitted_qc>
  <last_update_posted type="Actual">August 28, 2019</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>Cholangiocarcinoma</mesh_term>
  </condition_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>March 20, 2017</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/42/NCT02200042/Prot_SAP_000.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <group_list>
        <group group_id="P1">
          <title>Radiation Therapy</title>
          <description>Liver-directed radiation therapy&#xD;
Radiation Therapy: Patients undergo 15 fractions of image-guided radiation therapy delivered over 19-26 or 27-34 days.</description>
        </group>
        <group group_id="P2">
          <title>Observation</title>
          <description>No radiation therapy</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="1"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="0"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="1"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Withdrawal by Subject</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <population>Patients with baseline data</population>
      <group_list>
        <group group_id="B1">
          <title>Radiation Therapy</title>
          <description>Liver-directed radiation therapy&#xD;
Radiation Therapy: Patients undergo 15 fractions of image-guided radiation therapy delivered over 19-26 or 27-34 days.</description>
        </group>
        <group group_id="B2">
          <title>Observation</title>
          <description>No radiation therapy</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="0"/>
            <count group_id="B2" value="1"/>
            <count group_id="B3" value="1"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>&lt;=18 years</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>Between 18 and 65 years</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>&gt;=65 years</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>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="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</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>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="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Not Hispanic or Latino</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>Unknown or Not Reported</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_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="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Asian</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>Native Hawaiian or Other Pacific Islander</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>Black or African American</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>White</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>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="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Overall Survival</title>
        <description>Overall survival time is defined as time from randomization to the date of death from any cause. Overall survival rates are estimated by the Kaplan-Meier method. Patients last known to be alive are censored at the date of last contact.</description>
        <time_frame>From randomization to last follow-up. Analysis occurs after all patients have been on study for at least two years.</time_frame>
        <population>No patients have outcome data.</population>
        <group_list>
          <group group_id="O1">
            <title>Radiation Therapy</title>
            <description>Liver-directed radiation therapy&#xD;
Radiation Therapy: Patients undergo 15 fractions of image-guided radiation therapy delivered over 19-26 or 27-34 days.</description>
          </group>
          <group group_id="O2">
            <title>Observation</title>
            <description>No radiation therapy</description>
          </group>
        </group_list>
        <measure>
          <title>Overall Survival</title>
          <description>Overall survival time is defined as time from randomization to the date of death from any cause. Overall survival rates are estimated by the Kaplan-Meier method. Patients last known to be alive are censored at the date of last contact.</description>
          <population>No patients have outcome data.</population>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="0"/>
                <count group_id="O2" value="0"/>
              </count_list>
            </analyzed>
          </analyzed_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Distant Metastases</title>
        <time_frame>From randomization to last follow-up. Analysis occurs after all patients have been on study for at least two years.</time_frame>
        <population>No patients have outcome data.</population>
        <group_list>
          <group group_id="O1">
            <title>Radiation Therapy</title>
            <description>Liver-directed radiation therapy&#xD;
Radiation Therapy: Patients undergo 15 fractions of image-guided radiation therapy delivered over 19-26 or 27-34 days.</description>
          </group>
          <group group_id="O2">
            <title>Observation</title>
            <description>No radiation therapy</description>
          </group>
        </group_list>
        <measure>
          <title>Distant Metastases</title>
          <population>No patients have outcome data.</population>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="0"/>
                <count group_id="O2" value="0"/>
              </count_list>
            </analyzed>
          </analyzed_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Incidence of Adverse Events Evaluated Using National Cancer Institute Common Terminology Criteria for Adverse Events Version 4.0</title>
        <time_frame>From randomization to last follow-up. Analysis occurs after all patients have been on study for at least two years.</time_frame>
        <population>No patients have outcome data.</population>
        <group_list>
          <group group_id="O1">
            <title>Radiation Therapy</title>
            <description>Liver-directed radiation therapy&#xD;
Radiation Therapy: Patients undergo 15 fractions of image-guided radiation therapy delivered over 19-26 or 27-34 days.</description>
          </group>
          <group group_id="O2">
            <title>Observation</title>
            <description>No radiation therapy</description>
          </group>
        </group_list>
        <measure>
          <title>Incidence of Adverse Events Evaluated Using National Cancer Institute Common Terminology Criteria for Adverse Events Version 4.0</title>
          <population>No patients have outcome data.</population>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="0"/>
                <count group_id="O2" value="0"/>
              </count_list>
            </analyzed>
          </analyzed_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Local Progression</title>
        <time_frame>From randomization to last follow-up. Analysis occurs after all patients have been on study for at least two years.</time_frame>
        <population>No patients have outcome data.</population>
        <group_list>
          <group group_id="O1">
            <title>Radiation Therapy</title>
            <description>Liver-directed radiation therapy&#xD;
Radiation Therapy: Patients undergo 15 fractions of image-guided radiation therapy delivered over 19-26 or 27-34 days.</description>
          </group>
          <group group_id="O2">
            <title>Observation</title>
            <description>No radiation therapy</description>
          </group>
        </group_list>
        <measure>
          <title>Local Progression</title>
          <population>No patients have outcome data.</population>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="0"/>
                <count group_id="O2" value="0"/>
              </count_list>
            </analyzed>
          </analyzed_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Progression-free Survival (PFS)</title>
        <time_frame>From randomization to last follow-up. Analysis occurs after all patients have been on study for at least two years.</time_frame>
        <population>No patients have outcome data.</population>
        <group_list>
          <group group_id="O1">
            <title>Radiation Therapy</title>
            <description>Liver-directed radiation therapy&#xD;
Radiation Therapy: Patients undergo 15 fractions of image-guided radiation therapy delivered over 19-26 or 27-34 days.</description>
          </group>
          <group group_id="O2">
            <title>Observation</title>
            <description>No radiation therapy</description>
          </group>
        </group_list>
        <measure>
          <title>Progression-free Survival (PFS)</title>
          <population>No patients have outcome data.</population>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="0"/>
                <count group_id="O2" value="0"/>
              </count_list>
            </analyzed>
          </analyzed_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Regional Progression Defined as Progression or Existing or Appearance of New Nodal Disease</title>
        <time_frame>From randomization to last follow-up. Analysis occurs after all patients have been on study for at least two years.</time_frame>
        <population>No patients have outcome data.</population>
        <group_list>
          <group group_id="O1">
            <title>Radiation Therapy</title>
            <description>Liver-directed radiation therapy&#xD;
Radiation Therapy: Patients undergo 15 fractions of image-guided radiation therapy delivered over 19-26 or 27-34 days.</description>
          </group>
          <group group_id="O2">
            <title>Observation</title>
            <description>No radiation therapy</description>
          </group>
        </group_list>
        <measure>
          <title>Regional Progression Defined as Progression or Existing or Appearance of New Nodal Disease</title>
          <population>No patients have outcome data.</population>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="0"/>
                <count group_id="O2" value="0"/>
              </count_list>
            </analyzed>
          </analyzed_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>No adverse event data was collected on this study due to early termination.</time_frame>
      <desc>No adverse event data was collected on this study due to early termination.</desc>
      <group_list>
        <group group_id="E1">
          <title>Radiation Therapy</title>
          <description>Liver-directed radiation therapy&#xD;
Radiation Therapy: Patients undergo 15 fractions of image-guided radiation therapy delivered over 19-26 or 27-34 days.</description>
        </group>
        <group group_id="E2">
          <title>Observation</title>
          <description>No radiation therapy</description>
        </group>
      </group_list>
      <serious_events>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, all-cause mortality</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="0"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="0"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="0"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="0"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>0</frequency_threshold>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, other adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="0"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="0"/>
              </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>This study stopped accrual early due to unmet targeted accrual goals with 1 subject accrued out of 146 planned. The registered subject withdrew consent the same day as randomization and therefore has no outcome data.</limitations_and_caveats>
    <point_of_contact>
      <name_or_title>Wendy Seiferheld</name_or_title>
      <organization>NRG Oncology</organization>
      <phone>215-574-3208</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/NCT02200042
org study id: NRG-GI001
secondary id: NCI-2014-00849
secondary id: PNRG-GI001_A02PAMDREVW01
secondary id: PNRG-GI001_A01PAMDREVW01
secondary id: NRG-GI001
secondary id: NRG-GI001
secondary id: U10CA180868
nct id: NCT02200042
lead sponsor: 
collaborator: 
has dmc: Yes
This randomized phase III trial studies how well gemcitabine hydrochloride and cisplatin with
      or without radiation therapy work in treating patients with localized liver cancer that
      cannot be removed by surgery. Drugs used in chemotherapy, such as gemcitabine hydrochloride
      and cisplatin, work in different ways to stop the growth of tumor cells, either by killing
      the cells, by stopping them from dividing, or by stopping them from spreading. Radiation
      therapy uses high energy x rays to kill tumor cells. It is not yet known whether giving
      gemcitabine and cisplatin is more effective with or without radiation therapy in this patient
      population. Patients register to this study after receiving gemcitabine and cisplatin.
PRIMARY OBJECTIVES:

      I. To evaluate the addition of liver-directed radiation therapy with respect to overall
      survival (OS) for patients with unresectable, localized intrahepatic cholangiocarcinoma.

      SECONDARY OBJECTIVES:

      I. To evaluate the addition of liver-directed radiation therapy with respect to local control
      for patients with unresectable, localized intrahepatic cholangiocarcinoma.

      II. To evaluate the addition of liver-directed radiation therapy with respect to adverse
      events for patients with unresectable, localized intrahepatic cholangiocarcinoma.

      III. To evaluate the addition of liver-directed radiation therapy with respect to regional
      control for patients with unresectable, localized intrahepatic cholangiocarcinoma.

      IV. To evaluate the addition of liver-directed radiation therapy with respect to distant
      metastases for patients with unresectable, localized intrahepatic cholangiocarcinoma.

      V. To evaluate the addition of liver-directed radiation therapy with respect to
      progression-free survival for patients with unresectable, localized intrahepatic
      cholangiocarcinoma.

      After completion of study treatment, patients are followed up every 3 months for 3 years then
      every 6 months for 2 years.
allocation: Randomized
intervention model: Parallel Assignment
intervention model description: Randomization ratio (Experimental:Observation) = 2:1
primary purpose: Treatment
masking: None (Open Label)
measure: Overall Survival
time frame: From randomization to last follow-up. Analysis occurs after all patients have been on study for at least two years.
description: Overall survival time is defined as time from randomization to the date of death from any cause. Overall survival rates are estimated by the Kaplan-Meier method. Patients last known to be alive are censored at the date of last contact.
measure: Distant Metastases
time frame: From randomization to last follow-up. Analysis occurs after all patients have been on study for at least two years.
measure: Incidence of Adverse Events Evaluated Using National Cancer Institute Common Terminology Criteria for Adverse Events Version 4.0
time frame: From randomization to last follow-up. Analysis occurs after all patients have been on study for at least two years.
measure: Local Progression
time frame: From randomization to last follow-up. Analysis occurs after all patients have been on study for at least two years.
measure: Progression-free Survival (PFS)
time frame: From randomization to last follow-up. Analysis occurs after all patients have been on study for at least two years.
measure: Regional Progression Defined as Progression or Existing or Appearance of New Nodal Disease
time frame: From randomization to last follow-up. Analysis occurs after all patients have been on study for at least two years.
arm group label: Radiation therapy
arm group type: Experimental
description: Liver-directed radiation therapy
arm group label: Observation
arm group type: No Intervention
description: No radiation therapy
intervention type: Radiation
intervention name: Image Guided Radiation Therapy
description: Patients undergo 15 fractions of image-guided radiation therapy delivered over 19-26 or 27-34 days.
arm group label: Radiation therapy
other name: IGRT
other name: image-guided radiation therapy
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Theodore Hong
role: Principal Investigator
affiliation: NRG Oncology
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country: Canada
country: United States
responsible party type: Sponsor
mesh term: Cholangiocarcinoma
provided document: 
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
limitations and caveats: This study stopped accrual early due to unmet targeted accrual goals with 1 subject accrued out of 146 planned. The registered subject withdrew consent the same day as randomization and therefore has no outcome data.
point of contact: 