<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/NCT03278106</url>
  </required_header>
  <id_info>
    <org_study_id>MC1642</org_study_id>
    <secondary_id>NCI-2017-01603</secondary_id>
    <secondary_id>MC1642</secondary_id>
    <secondary_id>P30CA015083</secondary_id>
    <nct_id>NCT03278106</nct_id>
  </id_info>
  <brief_title>TAS-102 in Treating Advanced Biliary Tract Cancers</brief_title>
  <official_title>Phase II Trial of Trifluridine/Tipiracil (FTD/TPI (TAS-102)) in Biliary Tract Cancers</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Mayo Clinic</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>National Cancer Institute (NCI)</agency>
      <agency_class>NIH</agency_class>
    </collaborator>
  </sponsors>
  <source>Mayo Clinic</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      This phase II trial studies how well trifluridine/tipiracil hydrochloride combination agent&#xD;
      TAS-102 (TAS-102) works in treating participants with biliary tract cancers that have spread&#xD;
      to other places in the body. Drugs used in the chemotherapy, such as trifluridine/tipiracil&#xD;
      hydrochloride combination agent TAS-102, work in different ways to stop the growth of tumor&#xD;
      cells, either by killing the cells, by stopping them from dividing, or by stopping them from&#xD;
      spreading.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      PRIMARY OBJECTIVES:&#xD;
&#xD;
      I. Determine the efficacy of trifluridine/tipiracil hydrochloride combination agent TAS-102&#xD;
      (FTD/TPI [TAS-102]) in patients with refractory cholangiocarcinoma using progression-free&#xD;
      survival at 16 weeks.&#xD;
&#xD;
      SECONDARY OBJECTIVES:&#xD;
&#xD;
      I. Assess the safety and tolerability of FTD/TPI (TAS-102) in patients with refractory&#xD;
      cholangiocarcinoma through adverse event monitoring.&#xD;
&#xD;
      II. Further explore the efficacy of FTD/TPI (TAS-102) in patients with refractory&#xD;
      cholangiocarcinoma by overall response rates, progression-free survival, and overall&#xD;
      survival.&#xD;
&#xD;
      TERTIARY OBJECTIVES:&#xD;
&#xD;
      I. Determine if circulating tumor cells (CTCs) or cell-free deoxyribonucleic acid (DNA)&#xD;
      (cfDNA) at baseline correlates with prognosis or response to therapy.&#xD;
&#xD;
      II. Determine if change in CTCs or cfDNA correlates with efficacy endpoints. III. Determine&#xD;
      if different mutational status of the tumor will affect efficacy endpoints.&#xD;
&#xD;
      OUTLINE:&#xD;
&#xD;
      Patients receive trifluridine/tipiracil hydrochloride combination agent TAS-102 orally (PO)&#xD;
      twice daily (BID) on days 1-5 and 8-12. Courses repeat every 28 days in the absence of&#xD;
      disease progression or unacceptable toxicity.&#xD;
&#xD;
      After completion of study treatment, patients are followed up at 30 days and then every 3&#xD;
      months for up to 2 years.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">October 20, 2017</start_date>
  <completion_date type="Actual">September 16, 2021</completion_date>
  <primary_completion_date type="Actual">November 30, 2018</primary_completion_date>
  <phase>Phase 2</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>N/A</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>16-Week Progression-free Survival (PFS) Rate</measure>
    <time_frame>16 weeks</time_frame>
    <description>16-Week Progression-free survival (PFS) rate is defined as the percentage of patients who are progression-free (stable disease, partial response, or complete response as defined by RECIST v1.1 criteria) at 16 weeks post registration.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Overall Response Rate (ORR)</measure>
    <time_frame>Up to 3 years</time_frame>
    <description>ORR defined as the percentage of patients who experience either a partial response or complete response by the given time point. Complete Response (CR):All of the following must be true: a. Disappearance of all target lesions. b. Each target lymph node must have reduction in short axis to &lt;1.0 cm. Partial Response (PR): At least a 30% decrease in PBSD (sum of the longest diameter for all target lesions plus the sum of the short axis of all the target lymph nodes at current evaluation) taking as reference the BSD.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Progression-free Survival (PFS)</measure>
    <time_frame>Time from study entry to the first of either disease progression or death from any cause, assessed up to 3 years</time_frame>
    <description>PFS will be estimated using the Kaplan-Meier method. Progression-Free Survival (PFS) is defined as the time from study entry to the first of either disease progression or death from any cause, where disease progression will be determined based on RECIST 1.1 criteria. Patients will be censored at the last disease assessment date. The median PFS and 95% confidence interval will be reported.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Overall Survival (OS)</measure>
    <time_frame>Time from study entry to death from any cause, assessed up to 3 years</time_frame>
    <description>OS will be estimated using the Kaplan-Meier method. OS is defined as the time from study entry to death from any cause. Patients will be censored at the date patient was last known to be alive. The median OS and 95% confidence interval will be reported.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Overall Toxicity Rates (Percentages) for Grade 3 or Higher Adverse Events Considered at Least Possibly Related to Treatment, Assessed Using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0 (v4)</measure>
    <time_frame>Up to 3 years</time_frame>
    <description>The maximum grade for each type of toxicity will be recorded for each patient, and frequency tables will be reviewed to determine toxicity patterns within patient groups. In addition, we will review all adverse event data that is graded as 3, 4, or 5 and classified as either &quot;unrelated&quot; or &quot;unlikely to be related&quot; to study treatment in the event of an actual relationship developing. The overall toxicity rates (percentages) for grade 3 or higher adverse events considered at least possibly related to treatment are reported below.</description>
  </secondary_outcome>
  <other_outcome>
    <measure>Change in Circulating Tumor Cells (CTCs) or Cell-free Deoxyribonucleic Acid (DNA) (cfDNA)</measure>
    <time_frame>Baseline up to 3 years</time_frame>
    <description>Will correlate with efficacy endpoints.</description>
  </other_outcome>
  <other_outcome>
    <measure>Circulating Tumor Cells (CTCs) or Cell-free Deoxyribonucleic Acid (DNA) (cfDNA) Analysis at Baseline</measure>
    <time_frame>Baseline</time_frame>
    <description>Will determine if CTCs or cfDNA at baseline will correlate with prognosis or response to therapy.</description>
  </other_outcome>
  <other_outcome>
    <measure>Mutation Status of the Tumor</measure>
    <time_frame>Up to 3 years</time_frame>
    <description>Will determine if different mutations status of the tumor will affect efficacy endpoints.</description>
  </other_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">28</enrollment>
  <condition>Cholangiocarcinoma</condition>
  <condition>Stage III Gallbladder Cancer AJCC v7</condition>
  <condition>Stage IIIA Gallbladder Cancer AJCC v7</condition>
  <condition>Stage IIIB Gallbladder Cancer AJCC v7</condition>
  <condition>Stage IV Gallbladder Cancer AJCC v7</condition>
  <condition>Stage IVA Gallbladder Cancer AJCC v7</condition>
  <condition>Stage IVB Gallbladder Cancer AJCC v7</condition>
  <arm_group>
    <arm_group_label>Treatment (TAS-102)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Patients receive trifluridine/tipiracil hydrochloride combination agent TAS-102 orally PO BID on days 1-5 and 8-12. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.</description>
  </arm_group>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Laboratory Biomarker Analysis</intervention_name>
    <description>Correlative studies</description>
    <arm_group_label>Treatment (TAS-102)</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Trifluridine/Tipiracil Hydrochloride Combination Agent TAS-102</intervention_name>
    <description>Given PO</description>
    <arm_group_label>Treatment (TAS-102)</arm_group_label>
    <other_name>Lonsurf</other_name>
    <other_name>TAS-102</other_name>
    <other_name>Trifluridine/Tipiracil</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Histological confirmation of advanced biliary tract cancers including cancers&#xD;
             originating in gallbladder who have received at least one line of systemic anticancer&#xD;
             therapy;&#xD;
&#xD;
               -  Note: Patients who have either progressed or intolerant to the prior therapy can&#xD;
                  be included in this study&#xD;
&#xD;
          -  Measurable disease&#xD;
&#xD;
          -  Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0 or 1&#xD;
&#xD;
          -  Absolute neutrophil count (ANC) &gt;= 1500/mm^3&#xD;
&#xD;
          -  Platelet count &gt;= 100,000/mm^3&#xD;
&#xD;
          -  Total bilirubin =&lt; 1.5 x upper limit of normal (ULN)&#xD;
&#xD;
          -  Aspartate transaminase (AST) or alanine transaminase (ALT) =&lt; 3 x ULN&#xD;
&#xD;
          -  Creatinine =&lt; 1.5 x ULN&#xD;
&#xD;
          -  Negative pregnancy test done =&lt; 7 days prior to registration, for persons of&#xD;
             childbearing potential only&#xD;
&#xD;
          -  Provide written informed consent&#xD;
&#xD;
          -  Willing to return to enrolling institution for follow-up (during the active monitoring&#xD;
             phase of the study)&#xD;
&#xD;
          -  Willing to provide blood samples for correlative research purposes&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Any of the following:&#xD;
&#xD;
               -  Pregnant persons&#xD;
&#xD;
               -  Nursing persons&#xD;
&#xD;
               -  Persons of childbearing potential who are unwilling to employ adequate&#xD;
                  contraception for at least 3 months after the last dose of the study drug&#xD;
&#xD;
          -  Co-morbid systemic illnesses or other severe concurrent disease which, in the judgment&#xD;
             of the investigator, would make the patient inappropriate for entry into this study or&#xD;
             interfere significantly with the proper assessment of safety and toxicity of the&#xD;
             prescribed regimens&#xD;
&#xD;
          -  Immunocompromised patients and patients known to be human immunodeficiency virus (HIV)&#xD;
             positive and currently receiving antiretroviral therapy; NOTE: patients known to be&#xD;
             HIV positive, but without clinical evidence of an immunocompromised state, are&#xD;
             eligible for this trial&#xD;
&#xD;
          -  Uncontrolled intercurrent illness including, but not limited to, ongoing or active&#xD;
             infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac&#xD;
             arrhythmia, or psychiatric illness/social situations that would limit compliance with&#xD;
             study requirements&#xD;
&#xD;
          -  Receiving any other investigational agent which would be considered as a treatment for&#xD;
             the primary neoplasm =&lt; 21 days prior to registration&#xD;
&#xD;
          -  Receiving any anticancer therapy for biliary tract cancer =&lt; 21 days prior to&#xD;
             registration&#xD;
&#xD;
          -  Other active malignancy requiring treatment in =&lt; 6 months prior to registration;&#xD;
             EXCEPTIONS: non-melanotic skin cancer or carcinoma-in-situ of the cervix; NOTE: if&#xD;
             there is a history of prior malignancy, they must not be receiving other specific&#xD;
             treatment for their cancer&#xD;
&#xD;
          -  History of myocardial infarction =&lt; 6 months prior to registration, or congestive&#xD;
             heart failure requiring use of ongoing maintenance therapy for life-threatening&#xD;
             ventricular arrhythmias&#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>Amit Mahipal</last_name>
    <role>Principal Investigator</role>
    <affiliation>Mayo Clinic</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Mayo Clinic in Arizona</name>
      <address>
        <city>Scottsdale</city>
        <state>Arizona</state>
        <zip>85259</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Mayo Clinic</name>
      <address>
        <city>Rochester</city>
        <state>Minnesota</state>
        <zip>55905</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>June 2023</verification_date>
  <study_first_submitted>September 7, 2017</study_first_submitted>
  <study_first_submitted_qc>September 7, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">September 11, 2017</study_first_posted>
  <results_first_submitted>September 11, 2019</results_first_submitted>
  <results_first_submitted_qc>September 11, 2019</results_first_submitted_qc>
  <results_first_posted type="Actual">October 1, 2019</results_first_posted>
  <last_update_submitted>June 22, 2023</last_update_submitted>
  <last_update_submitted_qc>June 22, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">June 28, 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>Cholangiocarcinoma</mesh_term>
    <mesh_term>Biliary Tract Neoplasms</mesh_term>
    <mesh_term>Gallbladder Neoplasms</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Trifluridine</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>August 2, 2018</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/06/NCT03278106/Prot_SAP_000.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <group_list>
        <group group_id="P1">
          <title>Treatment (TAS-102)</title>
          <description>Patients receive trifluridine/tipiracil hydrochloride combination agent TAS-102 orally PO BID on days 1-5 and 8-12. Courses repeat every 28 days 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="28"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="27"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>No protocol treatment</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>Treatment (TAS-102)</title>
          <description>Patients receive trifluridine/tipiracil hydrochloride combination agent TAS-102 orally PO BID on days 1-5 and 8-12. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="27"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>years</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="62.3" spread="8.3"/>
                  </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="13"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="14"/>
                  </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_list>
                </category>
                <category>
                  <title>Asian</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Native Hawaiian or Other Pacific Islander</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Black or African American</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>White</title>
                  <measurement_list>
                    <measurement group_id="B1" value="26"/>
                  </measurement_list>
                </category>
                <category>
                  <title>More than one race</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>ECOG Performance Status</title>
          <description>Eastern Cooperative Oncology Group PS Scale: 0)Fully active, able to carry on all pre-disease performance without restriction; 1)Restricted in physically strenuous activity but ambulatory and able to carry out work of a light or sedentary nature, e.g., light house work, office work; 2)Ambulatory and capable of all selfcare but unable to carry out any work activities. Up and about more than 50% of waking hours; 3)Capable of only limited selfcare, confined to bed or chair more than 50% of waking hours; 4)Completely disabled. Cannot carry on any selfcare. Totally confined to bed or chair.</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="12"/>
                  </measurement_list>
                </category>
                <category>
                  <title>1</title>
                  <measurement_list>
                    <measurement group_id="B1" value="15"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>16-Week Progression-free Survival (PFS) Rate</title>
        <description>16-Week Progression-free survival (PFS) rate is defined as the percentage of patients who are progression-free (stable disease, partial response, or complete response as defined by RECIST v1.1 criteria) at 16 weeks post registration.</description>
        <time_frame>16 weeks</time_frame>
        <population>Primary analysis population</population>
        <group_list>
          <group group_id="O1">
            <title>Treatment (TAS-102)</title>
            <description>Patients receive trifluridine/tipiracil hydrochloride combination agent TAS-102 orally PO BID on days 1-5 and 8-12. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.</description>
          </group>
        </group_list>
        <measure>
          <title>16-Week Progression-free Survival (PFS) Rate</title>
          <description>16-Week Progression-free survival (PFS) rate is defined as the percentage of patients who are progression-free (stable disease, partial response, or complete response as defined by RECIST v1.1 criteria) at 16 weeks post registration.</description>
          <population>Primary analysis population</population>
          <units>percentage of patients</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="25"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="32.0" lower_limit="14.9" upper_limit="53.5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Overall Response Rate (ORR)</title>
        <description>ORR defined as the percentage of patients who experience either a partial response or complete response by the given time point. Complete Response (CR):All of the following must be true: a. Disappearance of all target lesions. b. Each target lymph node must have reduction in short axis to &lt;1.0 cm. Partial Response (PR): At least a 30% decrease in PBSD (sum of the longest diameter for all target lesions plus the sum of the short axis of all the target lymph nodes at current evaluation) taking as reference the BSD.</description>
        <time_frame>Up to 3 years</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Treatment (TAS-102)</title>
            <description>Patients receive trifluridine/tipiracil hydrochloride combination agent TAS-102 orally PO BID on days 1-5 and 8-12. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.</description>
          </group>
        </group_list>
        <measure>
          <title>Overall Response Rate (ORR)</title>
          <description>ORR defined as the percentage of patients who experience either a partial response or complete response by the given time point. Complete Response (CR):All of the following must be true: a. Disappearance of all target lesions. b. Each target lymph node must have reduction in short axis to &lt;1.0 cm. Partial Response (PR): At least a 30% decrease in PBSD (sum of the longest diameter for all target lesions plus the sum of the short axis of all the target lymph nodes at current evaluation) taking as reference the BSD.</description>
          <units>percentage of patients</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="27"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0" lower_limit="0" upper_limit="12.8"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Progression-free Survival (PFS)</title>
        <description>PFS will be estimated using the Kaplan-Meier method. Progression-Free Survival (PFS) is defined as the time from study entry to the first of either disease progression or death from any cause, where disease progression will be determined based on RECIST 1.1 criteria. Patients will be censored at the last disease assessment date. The median PFS and 95% confidence interval will be reported.</description>
        <time_frame>Time from study entry to the first of either disease progression or death from any cause, assessed up to 3 years</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Treatment (TAS-102)</title>
            <description>Patients receive trifluridine/tipiracil hydrochloride combination agent TAS-102 orally PO BID on days 1-5 and 8-12. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.</description>
          </group>
        </group_list>
        <measure>
          <title>Progression-free Survival (PFS)</title>
          <description>PFS will be estimated using the Kaplan-Meier method. Progression-Free Survival (PFS) is defined as the time from study entry to the first of either disease progression or death from any cause, where disease progression will be determined based on RECIST 1.1 criteria. Patients will be censored at the last disease assessment date. The median PFS and 95% confidence interval will be reported.</description>
          <units>months</units>
          <param>Median</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="27"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3.8" lower_limit="2.0" upper_limit="5.8"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Overall Survival (OS)</title>
        <description>OS will be estimated using the Kaplan-Meier method. OS is defined as the time from study entry to death from any cause. Patients will be censored at the date patient was last known to be alive. The median OS and 95% confidence interval will be reported.</description>
        <time_frame>Time from study entry to death from any cause, assessed up to 3 years</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Treatment (TAS-102)</title>
            <description>Patients receive trifluridine/tipiracil hydrochloride combination agent TAS-102 orally PO BID on days 1-5 and 8-12. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.</description>
          </group>
        </group_list>
        <measure>
          <title>Overall Survival (OS)</title>
          <description>OS will be estimated using the Kaplan-Meier method. OS is defined as the time from study entry to death from any cause. Patients will be censored at the date patient was last known to be alive. The median OS and 95% confidence interval will be reported.</description>
          <units>months</units>
          <param>Median</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="27"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="6.1" lower_limit="4.4" upper_limit="11.4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Overall Toxicity Rates (Percentages) for Grade 3 or Higher Adverse Events Considered at Least Possibly Related to Treatment, Assessed Using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0 (v4)</title>
        <description>The maximum grade for each type of toxicity will be recorded for each patient, and frequency tables will be reviewed to determine toxicity patterns within patient groups. In addition, we will review all adverse event data that is graded as 3, 4, or 5 and classified as either &quot;unrelated&quot; or &quot;unlikely to be related&quot; to study treatment in the event of an actual relationship developing. The overall toxicity rates (percentages) for grade 3 or higher adverse events considered at least possibly related to treatment are reported below.</description>
        <time_frame>Up to 3 years</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Treatment (TAS-102)</title>
            <description>Patients receive trifluridine/tipiracil hydrochloride combination agent TAS-102 orally PO BID on days 1-5 and 8-12. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.</description>
          </group>
        </group_list>
        <measure>
          <title>Overall Toxicity Rates (Percentages) for Grade 3 or Higher Adverse Events Considered at Least Possibly Related to Treatment, Assessed Using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0 (v4)</title>
          <description>The maximum grade for each type of toxicity will be recorded for each patient, and frequency tables will be reviewed to determine toxicity patterns within patient groups. In addition, we will review all adverse event data that is graded as 3, 4, or 5 and classified as either &quot;unrelated&quot; or &quot;unlikely to be related&quot; to study treatment in the event of an actual relationship developing. The overall toxicity rates (percentages) for grade 3 or higher adverse events considered at least possibly related to treatment are reported below.</description>
          <units>percentage of patients</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="27"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Grade 3</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="48.1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Grade 4</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="11.1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Other Pre-specified</type>
        <title>Change in Circulating Tumor Cells (CTCs) or Cell-free Deoxyribonucleic Acid (DNA) (cfDNA)</title>
        <description>Will correlate with efficacy endpoints.</description>
        <time_frame>Baseline up to 3 years</time_frame>
      </outcome>
      <outcome>
        <type>Other Pre-specified</type>
        <title>Circulating Tumor Cells (CTCs) or Cell-free Deoxyribonucleic Acid (DNA) (cfDNA) Analysis at Baseline</title>
        <description>Will determine if CTCs or cfDNA at baseline will correlate with prognosis or response to therapy.</description>
        <time_frame>Baseline</time_frame>
      </outcome>
      <outcome>
        <type>Other Pre-specified</type>
        <title>Mutation Status of the Tumor</title>
        <description>Will determine if different mutations status of the tumor will affect efficacy endpoints.</description>
        <time_frame>Up to 3 years</time_frame>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>Up to 3 years</time_frame>
      <desc>All patient adverse events are summarized below.</desc>
      <group_list>
        <group group_id="E1">
          <title>Treatment (TAS-102)</title>
          <description>Patients receive trifluridine/tipiracil hydrochloride combination agent TAS-102 orally PO BID on days 1-5 and 8-12. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.</description>
        </group>
      </group_list>
      <serious_events>
        <default_vocab>MedDRA 12</default_vocab>
        <default_assessment>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="21" subjects_at_risk="27"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="10" subjects_at_risk="27"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Blood and lymphatic system disorders</title>
            <event_list>
              <event>
                <sub_title>Anemia</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="27"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Cardiac disorders</title>
            <event_list>
              <event>
                <sub_title>Sinus tachycardia</sub_title>
                <counts group_id="E1" events="2" subjects_affected="1" subjects_at_risk="27"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Abdominal pain</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="27"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Fever</sub_title>
                <counts group_id="E1" events="2" subjects_affected="1" subjects_at_risk="27"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Hepatobiliary disorders</title>
            <event_list>
              <event>
                <sub_title>Hepatobiliary disorders - Other, specify</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="27"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Biliary tract infection</sub_title>
                <counts group_id="E1" events="4" subjects_affected="1" subjects_at_risk="27"/>
              </event>
              <event>
                <sub_title>Hepatic infection</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="27"/>
              </event>
              <event>
                <sub_title>Infections and infestations - Other, specify</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="27"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Investigations</title>
            <event_list>
              <event>
                <sub_title>Blood bilirubin increased</sub_title>
                <counts group_id="E1" events="4" subjects_affected="4" subjects_at_risk="27"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Neoplasms benign, malignant and unspecified (incl cysts and polyps)</title>
            <event_list>
              <event>
                <sub_title>Neoplasms benign, malignant and unspecified (incl cysts and polyps) - Other, specify</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="27"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Cognitive disturbance</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="27"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>0</frequency_threshold>
        <default_vocab>MedDRA 12</default_vocab>
        <default_assessment>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="27" subjects_at_risk="27"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Blood and lymphatic system disorders</title>
            <event_list>
              <event>
                <sub_title>Anemia</sub_title>
                <counts group_id="E1" events="83" subjects_affected="25" subjects_at_risk="27"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Eye disorders</title>
            <event_list>
              <event>
                <sub_title>Watering eyes</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="27"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Abdominal pain</sub_title>
                <counts group_id="E1" events="66" subjects_affected="22" subjects_at_risk="27"/>
              </event>
              <event>
                <sub_title>Ascites</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="27"/>
              </event>
              <event>
                <sub_title>Constipation</sub_title>
                <counts group_id="E1" events="9" subjects_affected="5" subjects_at_risk="27"/>
              </event>
              <event>
                <sub_title>Diarrhea</sub_title>
                <counts group_id="E1" events="36" subjects_affected="12" subjects_at_risk="27"/>
              </event>
              <event>
                <sub_title>Mucositis oral</sub_title>
                <counts group_id="E1" events="3" subjects_affected="2" subjects_at_risk="27"/>
              </event>
              <event>
                <sub_title>Nausea</sub_title>
                <counts group_id="E1" events="52" subjects_affected="17" subjects_at_risk="27"/>
              </event>
              <event>
                <sub_title>Oral pain</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="27"/>
              </event>
              <event>
                <sub_title>Vomiting</sub_title>
                <counts group_id="E1" events="11" subjects_affected="9" subjects_at_risk="27"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Edema limbs</sub_title>
                <counts group_id="E1" events="4" subjects_affected="3" subjects_at_risk="27"/>
              </event>
              <event>
                <sub_title>Fatigue</sub_title>
                <counts group_id="E1" events="93" subjects_affected="27" subjects_at_risk="27"/>
              </event>
              <event>
                <sub_title>Fever</sub_title>
                <counts group_id="E1" events="2" subjects_affected="1" subjects_at_risk="27"/>
              </event>
              <event>
                <sub_title>General disorders and administration site conditions - Other, specify</sub_title>
                <counts group_id="E1" events="7" subjects_affected="5" subjects_at_risk="27"/>
              </event>
              <event>
                <sub_title>Neck edema</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="27"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Investigations</title>
            <event_list>
              <event>
                <sub_title>Alanine aminotransferase increased</sub_title>
                <counts group_id="E1" events="4" subjects_affected="2" subjects_at_risk="27"/>
              </event>
              <event>
                <sub_title>Alkaline phosphatase increased</sub_title>
                <counts group_id="E1" events="9" subjects_affected="6" subjects_at_risk="27"/>
              </event>
              <event>
                <sub_title>Aspartate aminotransferase increased</sub_title>
                <counts group_id="E1" events="6" subjects_affected="4" subjects_at_risk="27"/>
              </event>
              <event>
                <sub_title>Blood bilirubin increased</sub_title>
                <counts group_id="E1" events="5" subjects_affected="4" subjects_at_risk="27"/>
              </event>
              <event>
                <sub_title>Lymphocyte count decreased</sub_title>
                <counts group_id="E1" events="4" subjects_affected="3" subjects_at_risk="27"/>
              </event>
              <event>
                <sub_title>Neutrophil count decreased</sub_title>
                <counts group_id="E1" events="38" subjects_affected="15" subjects_at_risk="27"/>
              </event>
              <event>
                <sub_title>Platelet count decreased</sub_title>
                <counts group_id="E1" events="38" subjects_affected="16" subjects_at_risk="27"/>
              </event>
              <event>
                <sub_title>White blood cell decreased</sub_title>
                <counts group_id="E1" events="20" subjects_affected="12" subjects_at_risk="27"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Metabolism and nutrition disorders</title>
            <event_list>
              <event>
                <sub_title>Anorexia</sub_title>
                <counts group_id="E1" events="54" subjects_affected="20" subjects_at_risk="27"/>
              </event>
              <event>
                <sub_title>Hypoalbuminemia</sub_title>
                <counts group_id="E1" events="2" subjects_affected="1" subjects_at_risk="27"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Musculoskeletal and connective tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Arthralgia</sub_title>
                <counts group_id="E1" events="9" subjects_affected="2" subjects_at_risk="27"/>
              </event>
              <event>
                <sub_title>Back pain</sub_title>
                <counts group_id="E1" events="6" subjects_affected="4" subjects_at_risk="27"/>
              </event>
              <event>
                <sub_title>Generalized muscle weakness</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="27"/>
              </event>
              <event>
                <sub_title>Pain in extremity</sub_title>
                <counts group_id="E1" events="2" subjects_affected="1" subjects_at_risk="27"/>
              </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" events="2" subjects_affected="1" subjects_at_risk="27"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Headache</sub_title>
                <counts group_id="E1" events="8" subjects_affected="1" subjects_at_risk="27"/>
              </event>
              <event>
                <sub_title>Peripheral sensory neuropathy</sub_title>
                <counts group_id="E1" events="6" subjects_affected="3" subjects_at_risk="27"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Psychiatric disorders</title>
            <event_list>
              <event>
                <sub_title>Confusion</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="27"/>
              </event>
              <event>
                <sub_title>Insomnia</sub_title>
                <counts group_id="E1" events="4" subjects_affected="1" subjects_at_risk="27"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Dyspnea</sub_title>
                <counts group_id="E1" events="4" subjects_affected="2" subjects_at_risk="27"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Skin and subcutaneous tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Alopecia</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="27"/>
              </event>
              <event>
                <sub_title>Pruritus</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="27"/>
              </event>
              <event>
                <sub_title>Skin and subcutaneous tissue disorders - Other, specify</sub_title>
                <counts group_id="E1" events="2" subjects_affected="1" subjects_at_risk="27"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Vascular disorders</title>
            <event_list>
              <event>
                <sub_title>Hypertension</sub_title>
                <counts group_id="E1" events="4" subjects_affected="2" subjects_at_risk="27"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </other_events>
    </reported_events>

    <certain_agreements>
      <pi_employee>All Principal Investigators ARE employed by the organization sponsoring the study.</pi_employee>
      <restrictive_agreement>There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed. </restrictive_agreement>
    </certain_agreements>
    <point_of_contact>
      <name_or_title>Amit Mahipal MBBS</name_or_title>
      <organization>Mayo Clinic</organization>
      <phone>+1 (507) 293-0487</phone>
      <email>Mahipal.amit@mayo.edu</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/NCT03278106
org study id: MC1642
secondary id: NCI-2017-01603
secondary id: MC1642
secondary id: P30CA015083
nct id: NCT03278106
lead sponsor: 
collaborator: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
This phase II trial studies how well trifluridine/tipiracil hydrochloride combination agent
      TAS-102 (TAS-102) works in treating participants with biliary tract cancers that have spread
      to other places in the body. Drugs used in the chemotherapy, such as trifluridine/tipiracil
      hydrochloride combination agent TAS-102, 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.
PRIMARY OBJECTIVES:

      I. Determine the efficacy of trifluridine/tipiracil hydrochloride combination agent TAS-102
      (FTD/TPI [TAS-102]) in patients with refractory cholangiocarcinoma using progression-free
      survival at 16 weeks.

      SECONDARY OBJECTIVES:

      I. Assess the safety and tolerability of FTD/TPI (TAS-102) in patients with refractory
      cholangiocarcinoma through adverse event monitoring.

      II. Further explore the efficacy of FTD/TPI (TAS-102) in patients with refractory
      cholangiocarcinoma by overall response rates, progression-free survival, and overall
      survival.

      TERTIARY OBJECTIVES:

      I. Determine if circulating tumor cells (CTCs) or cell-free deoxyribonucleic acid (DNA)
      (cfDNA) at baseline correlates with prognosis or response to therapy.

      II. Determine if change in CTCs or cfDNA correlates with efficacy endpoints. III. Determine
      if different mutational status of the tumor will affect efficacy endpoints.

      OUTLINE:

      Patients receive trifluridine/tipiracil hydrochloride combination agent TAS-102 orally (PO)
      twice daily (BID) on days 1-5 and 8-12. Courses repeat every 28 days in the absence of
      disease progression or unacceptable toxicity.

      After completion of study treatment, patients are followed up at 30 days and then every 3
      months for up to 2 years.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: 16-Week Progression-free Survival (PFS) Rate
time frame: 16 weeks
description: 16-Week Progression-free survival (PFS) rate is defined as the percentage of patients who are progression-free (stable disease, partial response, or complete response as defined by RECIST v1.1 criteria) at 16 weeks post registration.
measure: Overall Response Rate (ORR)
time frame: Up to 3 years
description: ORR defined as the percentage of patients who experience either a partial response or complete response by the given time point. Complete Response (CR):All of the following must be true: a. Disappearance of all target lesions. b. Each target lymph node must have reduction in short axis to <1.0 cm. Partial Response (PR): At least a 30% decrease in PBSD (sum of the longest diameter for all target lesions plus the sum of the short axis of all the target lymph nodes at current evaluation) taking as reference the BSD.
measure: Progression-free Survival (PFS)
time frame: Time from study entry to the first of either disease progression or death from any cause, assessed up to 3 years
description: PFS will be estimated using the Kaplan-Meier method. Progression-Free Survival (PFS) is defined as the time from study entry to the first of either disease progression or death from any cause, where disease progression will be determined based on RECIST 1.1 criteria. Patients will be censored at the last disease assessment date. The median PFS and 95% confidence interval will be reported.
measure: Overall Survival (OS)
time frame: Time from study entry to death from any cause, assessed up to 3 years
description: OS will be estimated using the Kaplan-Meier method. OS is defined as the time from study entry to death from any cause. Patients will be censored at the date patient was last known to be alive. The median OS and 95% confidence interval will be reported.
measure: Overall Toxicity Rates (Percentages) for Grade 3 or Higher Adverse Events Considered at Least Possibly Related to Treatment, Assessed Using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0 (v4)
time frame: Up to 3 years
description: The maximum grade for each type of toxicity will be recorded for each patient, and frequency tables will be reviewed to determine toxicity patterns within patient groups. In addition, we will review all adverse event data that is graded as 3, 4, or 5 and classified as either "unrelated" or "unlikely to be related" to study treatment in the event of an actual relationship developing. The overall toxicity rates (percentages) for grade 3 or higher adverse events considered at least possibly related to treatment are reported below.
measure: Change in Circulating Tumor Cells (CTCs) or Cell-free Deoxyribonucleic Acid (DNA) (cfDNA)
time frame: Baseline up to 3 years
description: Will correlate with efficacy endpoints.
measure: Circulating Tumor Cells (CTCs) or Cell-free Deoxyribonucleic Acid (DNA) (cfDNA) Analysis at Baseline
time frame: Baseline
description: Will determine if CTCs or cfDNA at baseline will correlate with prognosis or response to therapy.
measure: Mutation Status of the Tumor
time frame: Up to 3 years
description: Will determine if different mutations status of the tumor will affect efficacy endpoints.
arm group label: Treatment (TAS-102)
arm group type: Experimental
description: Patients receive trifluridine/tipiracil hydrochloride combination agent TAS-102 orally PO BID on days 1-5 and 8-12. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
intervention type: Other
intervention name: Laboratory Biomarker Analysis
description: Correlative studies
arm group label: Treatment (TAS-102)
intervention type: Drug
intervention name: Trifluridine/Tipiracil Hydrochloride Combination Agent TAS-102
description: Given PO
arm group label: Treatment (TAS-102)
other name: Lonsurf
other name: TAS-102
other name: Trifluridine/Tipiracil
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Amit Mahipal
role: Principal Investigator
affiliation: Mayo Clinic
facility: 
facility: 
country: United States
responsible party type: Sponsor
mesh term: Cholangiocarcinoma
mesh term: Biliary Tract Neoplasms
mesh term: Gallbladder Neoplasms
mesh term: Trifluridine
provided document: 
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 