<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/NCT02265341</url>
  </required_header>
  <id_info>
    <org_study_id>MC1345</org_study_id>
    <secondary_id>NCI-2014-02075</secondary_id>
    <secondary_id>MC1345</secondary_id>
    <secondary_id>P30CA015083</secondary_id>
    <nct_id>NCT02265341</nct_id>
  </id_info>
  <brief_title>Ponatinib Hydrochloride in Treating Patients With Advanced Biliary Cancer With FGFR2 Fusions</brief_title>
  <official_title>Pilot Study of Ponatinib in Biliary Cancer Patients With FGFR2 Fusions</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>
  </oversight_info>
  <brief_summary>
    <textblock>
      This pilot phase II trial studies how well ponatinib hydrochloride works in treating patients&#xD;
      with biliary cancer that has spread to other places in the body and that have alterations&#xD;
      (fusions) in a gene known as fibroblast growth factor receptor 2 (FGFR2). Ponatinib&#xD;
      hydrochloride may stop the growth of tumor cells by blocking some of the enzymes needed for&#xD;
      cell growth.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      PRIMARY OBJECTIVES:&#xD;
&#xD;
      I. To assess the clinical benefit rate (confirmed complete or partial response or stable&#xD;
      disease for 4 or more cycles) of ponatinib (ponatinib hydrochloride) in fibroblast growth&#xD;
      factor receptor (FGFR) aberrant advanced biliary cancers.&#xD;
&#xD;
      SECONDARY OBJECTIVES:&#xD;
&#xD;
      I. To estimate progression free survival, overall survival, and cancer antigen 19-9 (CA19-9)&#xD;
      response rate of these patients.&#xD;
&#xD;
      II. To estimate the adverse event profile of ponatinib.&#xD;
&#xD;
      TERTIARY OBJECTIVES:&#xD;
&#xD;
      I. Establish preliminary correlations between FGFR2 fusions and evidence of any clinical&#xD;
      benefit.&#xD;
&#xD;
      II. Assess preliminary evaluation of FGFR2 pathway perturbation with ponatinib. III. To&#xD;
      describe patient-reported health-related quality of life and symptoms.&#xD;
&#xD;
      OUTLINE:&#xD;
&#xD;
      Patients receive ponatinib hydrochloride orally (PO) once daily (QD) on days 1-28. Courses&#xD;
      repeat every 28 days in the absence of disease progression or unacceptable toxicity.&#xD;
&#xD;
      After completion of study treatment, patients are followed up every 6 months for at least 2&#xD;
      years.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">December 2014</start_date>
  <completion_date type="Actual">June 14, 2019</completion_date>
  <primary_completion_date type="Actual">May 1, 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>Clinical Benefit Rate (Percentage), Which Includes Confirmed Tumor Response (Complete Response [CR] or Partial Response [PR]) or Stable Disease (SD)</measure>
    <time_frame>Up to 10 months of treatment</time_frame>
    <description>A confirmed tumor response is defined to be either a CR or PR noted as the objective status on 2 consecutive evaluations at least 8 weeks apart. The proportion of clinical benefit rate will be estimated by the number of patients with clinical benefit (confirmed CR, confirmed PR, or SD for 4 or more cycles) divided by the total number of evaluable patients. 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 (see Section 11.41). Stable Disease (SD): Neither sufficient shrinkage to qualify for PR, nor sufficient increase to qualify for PD taking as reference the MSD. Please refer to RECIST v1.1 response criteria for more details.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>CA 19-9 Response</measure>
    <time_frame>Up to 10 months of treatment</time_frame>
    <description>This test measures the amount of a protein called CA 19-9 (cancer antigen 19-9) in the blood. CA 19-9 is a type of tumor marker. Tumor markers are substances made by cancer cells or by normal cells in response to cancer in the body.CA 19-9 was collected at baseline and on day one of each cycle. A CA 19-9 response is defined to be a &gt;= 50% reduction from baseline. The CA 19-9 response rate (percentage) will be estimated by the number of CA 19-9 responses divided by the total number of evaluable patients.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Overall Toxicity Rate, Assessed Using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0 (v4)</measure>
    <time_frame>Up to 10 months of treatment</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>
  <secondary_outcome>
    <measure>Progression-free Survival</measure>
    <time_frame>Time from registration to the earliest date of documentation of disease progression, assessed up to maximum 3.3 years from registration.</time_frame>
    <description>Progression free survival (PFS) is defined as the time from the date of registration to the date of disease progression or death resulting from any cause, whichever comes first. Progression is defined according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. The median and 95% confidence intervals are estimated using the Kaplan-Meier estimator.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Survival Time</measure>
    <time_frame>Time from registration to death due to any cause, assessed up to a maximum of 3.3 years</time_frame>
    <description>Overall survival time is defined as the time from registration to death due to any cause. The median and 95% confidence intervals are estimated using the Kaplan-Meier estimator.</description>
  </secondary_outcome>
  <other_outcome>
    <measure>Changes in Patient-reported Outcomes (Quality of Life and Symptoms), Assessed by the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ)-C30, EORTC QLQ-BIL21, Skindex-16, and Bowel Function Questionnaire</measure>
    <time_frame>Up to a maximum follow-up of 3.3 years</time_frame>
    <description>The Uniscale assessment of overall quality of life will be used. The Was It Worth It questionnaire will determine patient's satisfaction with the study. Scale score trajectories over time will be examined using stream plots and mean plots with standard deviation error bars overall. Changes from baseline at each cycle will be statistically tested using paired t-tests, and standardized response means will be interpreted using Cohen's (1988) cut-offs. Correlation between outcomes will employ Pearson and/or Spearman correlations at individual time points.</description>
  </other_outcome>
  <other_outcome>
    <measure>Rate of Circulating-free Tumor Deoxyribonucleic Acid Mutations</measure>
    <time_frame>Up to a maximum follow-up of 3.3 years</time_frame>
    <description>Will be described, and association with confirmed tumor response and/or clinical benefit will be investigated using a Fisher's exact test.</description>
  </other_outcome>
  <other_outcome>
    <measure>Rate of FGFR Fusions</measure>
    <time_frame>Up to a maximum follow-up of 3.3 years</time_frame>
    <description>Will be described, and association with confirmed tumor response and/or clinical benefit will be investigated using a Fisher's exact test.</description>
  </other_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">12</enrollment>
  <condition>Malignant Hepatobiliary Neoplasm</condition>
  <arm_group>
    <arm_group_label>Treatment (ponatinib hydrochloride)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Patients receive ponatinib hydrochloride PO QD on days 1-28. 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 (ponatinib hydrochloride)</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Ponatinib Hydrochloride</intervention_name>
    <description>Given PO</description>
    <arm_group_label>Treatment (ponatinib hydrochloride)</arm_group_label>
    <other_name>AP24534 HCl</other_name>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Quality-of-Life Assessment</intervention_name>
    <description>Ancillary studies</description>
    <arm_group_label>Treatment (ponatinib hydrochloride)</arm_group_label>
    <other_name>Quality of Life Assessment</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Histological/cytological confirmation of biliary cancer&#xD;
&#xD;
          -  Confirmation of advanced biliary cancer that is refractory or intolerant to&#xD;
             gemcitabine or fluoropyrimidine based therapy with FGFR2 fusion [using next-gen&#xD;
             sequencing assays (such as Foundation One) or fluorescent in situ hybridization (FISH)&#xD;
             break-apart assays] or FGFR pathway mutation/amplification [using next-gen sequencing&#xD;
             assays (such as Foundation One)]; assays must be performed in a Clinical Laboratory&#xD;
             Improvement Amendments [CLIA] certified laboratory and done as a CLIA validated test&#xD;
             or research use only [RUO] in a CLIA laboratory&#xD;
&#xD;
          -  Measurable disease&#xD;
&#xD;
          -  Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0, 1 or 2&#xD;
&#xD;
          -  Absolute neutrophil count (ANC) &gt;= 1500/mm^3&#xD;
&#xD;
          -  Platelet count &gt;= 100,000/mm^3&#xD;
&#xD;
          -  Hemoglobin &gt;= 9.0 g/dL&#xD;
&#xD;
          -  Total bilirubin =&lt; 1.5 x upper limit of normal (ULN), unless due to Gilbert's syndrome&#xD;
&#xD;
          -  Aspartate transaminase (AST) and alanine aminotransferase (ALT) &lt; 3 x ULN&#xD;
&#xD;
          -  Creatinine =&lt; 1.5 x ULN&#xD;
&#xD;
          -  Serum lipase and amylase =&lt; 2.5 x ULN; NOTE: if subject has tumor involvement in the&#xD;
             liver =&lt; 3 x ULN&#xD;
&#xD;
          -  Negative pregnancy test done =&lt; 7 days prior to registration, for women of&#xD;
             childbearing potential only&#xD;
&#xD;
          -  Recovered from prior radiotherapy and/or systemic therapy related toxicities to grade&#xD;
             =&lt; 1&#xD;
&#xD;
          -  Provide informed written consent&#xD;
&#xD;
          -  Life expectancy &gt;= 3 months&#xD;
&#xD;
          -  Willing to return to enrolling institution for follow-up (during the Active Monitoring&#xD;
             Phase of the study); Note: during the Active Monitoring Phase of a study (i.e., active&#xD;
             treatment and observation), participants must be willing to return to the consenting&#xD;
             institution for follow-up&#xD;
&#xD;
          -  Female and male patients who are fertile agree to use an effective form of&#xD;
             contraception with their sexual partners from registration through 4 months after the&#xD;
             end of treatment&#xD;
&#xD;
          -  Ability to complete questionnaire(s) by themselves or with assistance&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Any of the following:&#xD;
&#xD;
               -  Pregnant women&#xD;
&#xD;
               -  Nursing women&#xD;
&#xD;
               -  Men or women of childbearing potential who are unwilling to employ adequate&#xD;
                  contraception&#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 with a known&#xD;
             history of HIV infection are not 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&#xD;
&#xD;
          -  Prior systemic chemotherapy, radiation therapy or major surgery =&lt; 30 days prior to&#xD;
             registration&#xD;
&#xD;
          -  Concurrent use of any other approved or investigational anticancer agents, including&#xD;
             hormonal agents&#xD;
&#xD;
          -  Prior nitrosourea or mitomycin C =&lt; 6 weeks prior to registration&#xD;
&#xD;
          -  Patients with gastrointestinal comorbidities that would affect intake or absorption of&#xD;
             ponatinib&#xD;
&#xD;
          -  Untreated or progressive brain metastases&#xD;
&#xD;
          -  Prior treatment with or allergic reactions attributed to compounds of similar chemical&#xD;
             or biologic composition to ponatinib&#xD;
&#xD;
          -  Clinically uncontrolled hypertension (diastolic blood pressure &gt; 90 mm mercury [Hg];&#xD;
             systolic &gt; 140 mm Hg); Note: patients with hypertension should be undergoing treatment&#xD;
             at study entry for blood pressure control&#xD;
&#xD;
          -  Previous or concurrent malignancy except adequately treated basal or squamous cell&#xD;
             skin cancer, in situ carcinoma of the cervix, or other solid tumor treated curatively&#xD;
             and without evidence of recurrence for at least 5 years&#xD;
&#xD;
          -  History of significant bleeding disorder unrelated to cancer&#xD;
&#xD;
          -  History of acute pancreatitis within 1 year prior to registration, chronic&#xD;
             pancreatitis, alcohol abuse or uncontrolled hypertriglyceridemia (triglycerides &gt; 450&#xD;
             mg/dL)&#xD;
&#xD;
          -  Clinically significant, uncontrolled, or active cardiovascular disease, specifically&#xD;
             including, but not restricted to:&#xD;
&#xD;
               -  Any history of myocardial infarction, stroke, or revascularization&#xD;
&#xD;
               -  Unstable angina or transient ischemic attack within 6 months prior to&#xD;
                  registration&#xD;
&#xD;
               -  Congestive heart failure within 6 months prior to registration, or left&#xD;
                  ventricular ejection fraction (LVEF) less than lower limit of normal per local&#xD;
                  institutional standards within 6 months prior to registration&#xD;
&#xD;
               -  History of clinically significant (as determined by the treating physician)&#xD;
                  atrial arrhythmia&#xD;
&#xD;
               -  Any history of ventricular arrhythmia&#xD;
&#xD;
               -  Active venous thromboembolism including deep venous thrombosis or pulmonary&#xD;
                  embolism that is not amenable to treatment with anticoagulants&#xD;
&#xD;
               -  Patients with congenital prolonged QT syndromes and abnormal baseline prolonged&#xD;
                  corrected QT (QTc) (&gt; 450 ms in men and &gt; 470 ms in women)&#xD;
&#xD;
               -  Patients with an ejection fraction =&lt; 50% as assessed by a baseline&#xD;
                  echocardiogram&#xD;
&#xD;
          -  Taking medications that are known to be associated with torsades de pointes&#xD;
&#xD;
          -  Taking any medications or herbal supplements that are known to be strong inhibitors of&#xD;
             cytochrome P450, family 3, subfamily A, polypeptide 4 (CYP3A4) =&lt; 14 days prior to&#xD;
             registration&#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>Mitesh Borad</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_countries>
    <country>United States</country>
  </location_countries>
  <link>
    <url>https://www.mayo.edu/research/clinical-trials</url>
    <description>Mayo Clinic Clinical Trials</description>
  </link>
  <verification_date>April 2019</verification_date>
  <study_first_submitted>October 9, 2014</study_first_submitted>
  <study_first_submitted_qc>October 9, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">October 15, 2014</study_first_posted>
  <results_first_submitted>June 3, 2019</results_first_submitted>
  <results_first_submitted_qc>July 12, 2019</results_first_submitted_qc>
  <results_first_posted type="Actual">August 6, 2019</results_first_posted>
  <last_update_submitted>November 10, 2020</last_update_submitted>
  <last_update_submitted_qc>November 10, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">November 25, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Ponatinib</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>April 13, 2016</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/41/NCT02265341/Prot_SAP_000.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <group_list>
        <group group_id="P1">
          <title>Treatment (Ponatinib Hydrochloride)</title>
          <description>Patients receive ponatinib hydrochloride PO QD on days 1-28. 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="12"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="12"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
              </participants_list>
            </milestone>
          </milestone_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>Treatment (Ponatinib Hydrochloride)</title>
          <description>Patients receive ponatinib hydrochloride PO QD on days 1-28. 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="12"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>years</units>
          <param>Median</param>
          <dispersion>Full Range</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="48.5" lower_limit="40.0" upper_limit="66.0"/>
                  </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="9"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="3"/>
                  </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="1"/>
                  </measurement_list>
                </category>
                <category>
                  <title>White</title>
                  <measurement_list>
                    <measurement group_id="B1" value="10"/>
                  </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="3"/>
                  </measurement_list>
                </category>
                <category>
                  <title>1</title>
                  <measurement_list>
                    <measurement group_id="B1" value="7"/>
                  </measurement_list>
                </category>
                <category>
                  <title>2</title>
                  <measurement_list>
                    <measurement group_id="B1" value="2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Clinical Benefit Rate (Percentage), Which Includes Confirmed Tumor Response (Complete Response [CR] or Partial Response [PR]) or Stable Disease (SD)</title>
        <description>A confirmed tumor response is defined to be either a CR or PR noted as the objective status on 2 consecutive evaluations at least 8 weeks apart. The proportion of clinical benefit rate will be estimated by the number of patients with clinical benefit (confirmed CR, confirmed PR, or SD for 4 or more cycles) divided by the total number of evaluable patients. 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 (see Section 11.41). Stable Disease (SD): Neither sufficient shrinkage to qualify for PR, nor sufficient increase to qualify for PD taking as reference the MSD. Please refer to RECIST v1.1 response criteria for more details.</description>
        <time_frame>Up to 10 months of treatment</time_frame>
        <population>Only patients who received treatment for at least 8 weeks are evaluable for this outcome (i.e. one patient refused further treatment and was therefore unevaluable for response at 8 weeks)</population>
        <group_list>
          <group group_id="O1">
            <title>Treatment (Ponatinib Hydrochloride)</title>
            <description>Patients receive ponatinib hydrochloride PO QD on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.</description>
          </group>
        </group_list>
        <measure>
          <title>Clinical Benefit Rate (Percentage), Which Includes Confirmed Tumor Response (Complete Response [CR] or Partial Response [PR]) or Stable Disease (SD)</title>
          <description>A confirmed tumor response is defined to be either a CR or PR noted as the objective status on 2 consecutive evaluations at least 8 weeks apart. The proportion of clinical benefit rate will be estimated by the number of patients with clinical benefit (confirmed CR, confirmed PR, or SD for 4 or more cycles) divided by the total number of evaluable patients. 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 (see Section 11.41). Stable Disease (SD): Neither sufficient shrinkage to qualify for PR, nor sufficient increase to qualify for PD taking as reference the MSD. Please refer to RECIST v1.1 response criteria for more details.</description>
          <population>Only patients who received treatment for at least 8 weeks are evaluable for this outcome (i.e. one patient refused further treatment and was therefore unevaluable for response at 8 weeks)</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="11"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="45.5" lower_limit="16.8" upper_limit="76.6"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>CA 19-9 Response</title>
        <description>This test measures the amount of a protein called CA 19-9 (cancer antigen 19-9) in the blood. CA 19-9 is a type of tumor marker. Tumor markers are substances made by cancer cells or by normal cells in response to cancer in the body.CA 19-9 was collected at baseline and on day one of each cycle. A CA 19-9 response is defined to be a &gt;= 50% reduction from baseline. The CA 19-9 response rate (percentage) will be estimated by the number of CA 19-9 responses divided by the total number of evaluable patients.</description>
        <time_frame>Up to 10 months of treatment</time_frame>
        <population>Only patients who had baseline and subsequent CA 19-9 levels measured in the study are evaluable for this analysis.</population>
        <group_list>
          <group group_id="O1">
            <title>Treatment (Ponatinib Hydrochloride)</title>
            <description>Patients receive ponatinib hydrochloride PO QD on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.</description>
          </group>
        </group_list>
        <measure>
          <title>CA 19-9 Response</title>
          <description>This test measures the amount of a protein called CA 19-9 (cancer antigen 19-9) in the blood. CA 19-9 is a type of tumor marker. Tumor markers are substances made by cancer cells or by normal cells in response to cancer in the body.CA 19-9 was collected at baseline and on day one of each cycle. A CA 19-9 response is defined to be a &gt;= 50% reduction from baseline. The CA 19-9 response rate (percentage) will be estimated by the number of CA 19-9 responses divided by the total number of evaluable patients.</description>
          <population>Only patients who had baseline and subsequent CA 19-9 levels measured in the study are evaluable for this analysis.</population>
          <units>percentage of patients</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="3"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Overall Toxicity Rate, 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 10 months of treatment</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Treatment (Ponatinib Hydrochloride)</title>
            <description>Patients receive ponatinib hydrochloride PO QD on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.</description>
          </group>
        </group_list>
        <measure>
          <title>Overall Toxicity Rate, 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="12"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="41.7"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Progression-free Survival</title>
        <description>Progression free survival (PFS) is defined as the time from the date of registration to the date of disease progression or death resulting from any cause, whichever comes first. Progression is defined according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. The median and 95% confidence intervals are estimated using the Kaplan-Meier estimator.</description>
        <time_frame>Time from registration to the earliest date of documentation of disease progression, assessed up to maximum 3.3 years from registration.</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Treatment (Ponatinib Hydrochloride)</title>
            <description>Patients receive ponatinib hydrochloride PO QD on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.</description>
          </group>
        </group_list>
        <measure>
          <title>Progression-free Survival</title>
          <description>Progression free survival (PFS) is defined as the time from the date of registration to the date of disease progression or death resulting from any cause, whichever comes first. Progression is defined according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. The median and 95% confidence intervals are estimated using the Kaplan-Meier estimator.</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="12"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2.4" lower_limit="1.9" upper_limit="9.2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Survival Time</title>
        <description>Overall survival time is defined as the time from registration to death due to any cause. The median and 95% confidence intervals are estimated using the Kaplan-Meier estimator.</description>
        <time_frame>Time from registration to death due to any cause, assessed up to a maximum of 3.3 years</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Treatment (Ponatinib Hydrochloride)</title>
            <description>Patients receive ponatinib hydrochloride PO QD on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.</description>
          </group>
        </group_list>
        <measure>
          <title>Survival Time</title>
          <description>Overall survival time is defined as the time from registration to death due to any cause. The median and 95% confidence intervals are estimated using the Kaplan-Meier estimator.</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="12"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="15.7" lower_limit="6.1" upper_limit="NA">The 95% Confidence interval upper limit was not able to be estimated due to an insufficient number of participants with events.</measurement>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Other Pre-specified</type>
        <title>Changes in Patient-reported Outcomes (Quality of Life and Symptoms), Assessed by the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ)-C30, EORTC QLQ-BIL21, Skindex-16, and Bowel Function Questionnaire</title>
        <description>The Uniscale assessment of overall quality of life will be used. The Was It Worth It questionnaire will determine patient's satisfaction with the study. Scale score trajectories over time will be examined using stream plots and mean plots with standard deviation error bars overall. Changes from baseline at each cycle will be statistically tested using paired t-tests, and standardized response means will be interpreted using Cohen's (1988) cut-offs. Correlation between outcomes will employ Pearson and/or Spearman correlations at individual time points.</description>
        <time_frame>Up to a maximum follow-up of 3.3 years</time_frame>
      </outcome>
      <outcome>
        <type>Other Pre-specified</type>
        <title>Rate of Circulating-free Tumor Deoxyribonucleic Acid Mutations</title>
        <description>Will be described, and association with confirmed tumor response and/or clinical benefit will be investigated using a Fisher's exact test.</description>
        <time_frame>Up to a maximum follow-up of 3.3 years</time_frame>
      </outcome>
      <outcome>
        <type>Other Pre-specified</type>
        <title>Rate of FGFR Fusions</title>
        <description>Will be described, and association with confirmed tumor response and/or clinical benefit will be investigated using a Fisher's exact test.</description>
        <time_frame>Up to a maximum follow-up of 3.3 years</time_frame>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>Up to a maximum of 10 months on treatment.</time_frame>
      <desc>Each CTCAE term is a representation of a specific event used for medical documentation &amp; analysis &amp; is a single MedDRA Lowest Level Term (LLT). All graded AEs are reported for all patients. Serious AE (SAE) reports may include any secondary serious or non-serious events considered related to the primary event (the reason for filing an expedited report); collectively, these events are referred to as Expedited AEs, &amp; appear in the SAE table.</desc>
      <group_list>
        <group group_id="E1">
          <title>Treatment (Ponatinib Hydrochloride)</title>
          <description>Patients receive ponatinib hydrochloride PO QD on days 1-28. 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="9" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="5" subjects_at_risk="12"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Pancreatitis</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="12"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Fatigue</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="12"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Sepsis</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="12"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Cough</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Pleural effusion</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="12"/>
              </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="11" subjects_at_risk="12"/>
              </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="1" subjects_affected="1" subjects_at_risk="12"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Abdominal pain</sub_title>
                <counts group_id="E1" events="17" subjects_affected="7" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Constipation</sub_title>
                <counts group_id="E1" events="21" subjects_affected="7" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Diarrhea</sub_title>
                <counts group_id="E1" events="7" subjects_affected="3" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Nausea</sub_title>
                <counts group_id="E1" events="18" subjects_affected="6" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Vomiting</sub_title>
                <counts group_id="E1" events="5" subjects_affected="2" subjects_at_risk="12"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Edema limbs</sub_title>
                <counts group_id="E1" events="11" subjects_affected="5" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Fatigue</sub_title>
                <counts group_id="E1" events="41" subjects_affected="9" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Fever</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="12"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Investigations</title>
            <event_list>
              <event>
                <sub_title>Alanine aminotransferase increased</sub_title>
                <counts group_id="E1" events="3" subjects_affected="2" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Alkaline phosphatase increased</sub_title>
                <counts group_id="E1" events="8" subjects_affected="4" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Blood bilirubin increased</sub_title>
                <counts group_id="E1" events="2" subjects_affected="1" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>CD4 lymphocytes decreased</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Lymphocyte count decreased</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Neutrophil count decreased</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Platelet count decreased</sub_title>
                <counts group_id="E1" events="22" subjects_affected="5" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>White blood cell decreased</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="12"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Metabolism and nutrition disorders</title>
            <event_list>
              <event>
                <sub_title>Anorexia</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Hyperglycemia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="12"/>
              </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="1" subjects_affected="1" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Back pain</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="12"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Headache</sub_title>
                <counts group_id="E1" events="2" subjects_affected="1" subjects_at_risk="12"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Cough</sub_title>
                <counts group_id="E1" events="3" subjects_affected="2" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Hoarseness</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Pneumonitis</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="12"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Skin and subcutaneous tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Dry skin</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Rash maculo-papular</sub_title>
                <counts group_id="E1" events="21" subjects_affected="7" subjects_at_risk="12"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Vascular disorders</title>
            <event_list>
              <event>
                <sub_title>Hypertension</sub_title>
                <counts group_id="E1" events="6" subjects_affected="3" subjects_at_risk="12"/>
              </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>Mitesh J. Borad, MD</name_or_title>
      <organization>Mayo Clinic</organization>
      <phone>480/301-8335</phone>
      <email>Borad.Mitesh@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/NCT02265341
org study id: MC1345
secondary id: NCI-2014-02075
secondary id: MC1345
secondary id: P30CA015083
nct id: NCT02265341
lead sponsor: 
collaborator: 
has dmc: Yes
This pilot phase II trial studies how well ponatinib hydrochloride works in treating patients
      with biliary cancer that has spread to other places in the body and that have alterations
      (fusions) in a gene known as fibroblast growth factor receptor 2 (FGFR2). Ponatinib
      hydrochloride may stop the growth of tumor cells by blocking some of the enzymes needed for
      cell growth.
PRIMARY OBJECTIVES:

      I. To assess the clinical benefit rate (confirmed complete or partial response or stable
      disease for 4 or more cycles) of ponatinib (ponatinib hydrochloride) in fibroblast growth
      factor receptor (FGFR) aberrant advanced biliary cancers.

      SECONDARY OBJECTIVES:

      I. To estimate progression free survival, overall survival, and cancer antigen 19-9 (CA19-9)
      response rate of these patients.

      II. To estimate the adverse event profile of ponatinib.

      TERTIARY OBJECTIVES:

      I. Establish preliminary correlations between FGFR2 fusions and evidence of any clinical
      benefit.

      II. Assess preliminary evaluation of FGFR2 pathway perturbation with ponatinib. III. To
      describe patient-reported health-related quality of life and symptoms.

      OUTLINE:

      Patients receive ponatinib hydrochloride orally (PO) once daily (QD) on days 1-28. Courses
      repeat every 28 days in the absence of disease progression or unacceptable toxicity.

      After completion of study treatment, patients are followed up every 6 months for at least 2
      years.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Clinical Benefit Rate (Percentage), Which Includes Confirmed Tumor Response (Complete Response [CR] or Partial Response [PR]) or Stable Disease (SD)
time frame: Up to 10 months of treatment
description: A confirmed tumor response is defined to be either a CR or PR noted as the objective status on 2 consecutive evaluations at least 8 weeks apart. The proportion of clinical benefit rate will be estimated by the number of patients with clinical benefit (confirmed CR, confirmed PR, or SD for 4 or more cycles) divided by the total number of evaluable patients. 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 (see Section 11.41). Stable Disease (SD): Neither sufficient shrinkage to qualify for PR, nor sufficient increase to qualify for PD taking as reference the MSD. Please refer to RECIST v1.1 response criteria for more details.
measure: CA 19-9 Response
time frame: Up to 10 months of treatment
description: This test measures the amount of a protein called CA 19-9 (cancer antigen 19-9) in the blood. CA 19-9 is a type of tumor marker. Tumor markers are substances made by cancer cells or by normal cells in response to cancer in the body.CA 19-9 was collected at baseline and on day one of each cycle. A CA 19-9 response is defined to be a >= 50% reduction from baseline. The CA 19-9 response rate (percentage) will be estimated by the number of CA 19-9 responses divided by the total number of evaluable patients.
measure: Overall Toxicity Rate, Assessed Using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0 (v4)
time frame: Up to 10 months of treatment
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: Progression-free Survival
time frame: Time from registration to the earliest date of documentation of disease progression, assessed up to maximum 3.3 years from registration.
description: Progression free survival (PFS) is defined as the time from the date of registration to the date of disease progression or death resulting from any cause, whichever comes first. Progression is defined according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. The median and 95% confidence intervals are estimated using the Kaplan-Meier estimator.
measure: Survival Time
time frame: Time from registration to death due to any cause, assessed up to a maximum of 3.3 years
description: Overall survival time is defined as the time from registration to death due to any cause. The median and 95% confidence intervals are estimated using the Kaplan-Meier estimator.
measure: Changes in Patient-reported Outcomes (Quality of Life and Symptoms), Assessed by the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ)-C30, EORTC QLQ-BIL21, Skindex-16, and Bowel Function Questionnaire
time frame: Up to a maximum follow-up of 3.3 years
description: The Uniscale assessment of overall quality of life will be used. The Was It Worth It questionnaire will determine patient's satisfaction with the study. Scale score trajectories over time will be examined using stream plots and mean plots with standard deviation error bars overall. Changes from baseline at each cycle will be statistically tested using paired t-tests, and standardized response means will be interpreted using Cohen's (1988) cut-offs. Correlation between outcomes will employ Pearson and/or Spearman correlations at individual time points.
measure: Rate of Circulating-free Tumor Deoxyribonucleic Acid Mutations
time frame: Up to a maximum follow-up of 3.3 years
description: Will be described, and association with confirmed tumor response and/or clinical benefit will be investigated using a Fisher's exact test.
measure: Rate of FGFR Fusions
time frame: Up to a maximum follow-up of 3.3 years
description: Will be described, and association with confirmed tumor response and/or clinical benefit will be investigated using a Fisher's exact test.
arm group label: Treatment (ponatinib hydrochloride)
arm group type: Experimental
description: Patients receive ponatinib hydrochloride PO QD on days 1-28. 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 (ponatinib hydrochloride)
intervention type: Drug
intervention name: Ponatinib Hydrochloride
description: Given PO
arm group label: Treatment (ponatinib hydrochloride)
other name: AP24534 HCl
intervention type: Other
intervention name: Quality-of-Life Assessment
description: Ancillary studies
arm group label: Treatment (ponatinib hydrochloride)
other name: Quality of Life Assessment
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Mitesh Borad
role: Principal Investigator
affiliation: Mayo Clinic
facility: 
country: United States
url: https://www.mayo.edu/research/clinical-trials
description: Mayo Clinic Clinical Trials
responsible party type: Sponsor
mesh term: Ponatinib
provided document: 
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 