<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/NCT01661114</url>
  </required_header>
  <id_info>
    <org_study_id>UMCC 2011.036</org_study_id>
    <secondary_id>HUM 49518</secondary_id>
    <nct_id>NCT01661114</nct_id>
  </id_info>
  <brief_title>A Trial of Gemcitabine, Infusional 5-Fluorouracil and Cisplatin for Advanced Pancreatic and Biliary Cancers</brief_title>
  <official_title>A Trial of Gemcitabine, Infusional 5-Fluorouracil and Cisplatin for Advanced Pancreatic and Biliary Cancers</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of Michigan Rogel Cancer Center</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>University of Michigan Rogel Cancer Center</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      Multi-agent chemotherapy has value for patients with advanced pancreatic-biliary cancers&#xD;
      leading to responses in a substantial minority and increasing survival. The use of the&#xD;
      FOLFIRINOX regimen is limited by its' intensity and toxicity. Previous protocol and clinical&#xD;
      experience within the University of Michigan Pancreatic Program leads to an expectation of&#xD;
      tolerance and efficacy of the proposed regimen. Advantages of the proposed regimen relative&#xD;
      to FOLFIRINOX include:&#xD;
&#xD;
        1. Substitution of gemcitabine for irinotecan. Single agent activity of gemcitabine is at&#xD;
           least as good as irinotecan (probably better, especially when delivered by FDR&#xD;
           [fixed-dose rate] infusion) and gemcitabine is much better tolerated with less diarrhea,&#xD;
           nausea/emesis, myelosuppression and alopecia.&#xD;
&#xD;
        2. Deletion of leucovorin infusion and 5FU bolus injection will lessen myelosuppression,&#xD;
           mucositis and diarrhea.&#xD;
&#xD;
        3. Substitution of cisplatin for oxaliplatin will reduce cost of therapy and avoid cold&#xD;
           aggravated dysesthesia.&#xD;
&#xD;
      Presuming evidence of efficacy and confirmation of tolerance with the proposed regimen, the&#xD;
      investigators believe this treatment may be more widely applicable to pancreatic-biliary&#xD;
      cancer patients, including those with advanced disease as well as being considered for use in&#xD;
      locally advanced and neo- and adjuvant settings.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Gemcitabine combined with 5FU may enhance the activity of 5-FU in vivo. Gemcitabine is an&#xD;
      inhibitor of ribonucleotide reductase, an enzyme needed for synthesis of deoxynucleotides,&#xD;
      and 5-FU interferes with dTTP synthesis by inhibition of thymidylate synthase (TS). It is&#xD;
      likely that concomitant administration of gemcitabine and 5FU results in increased&#xD;
      cytotoxicity by reducing intracellular dTTP thru two different mechanisms, thereby inhibiting&#xD;
      DNA replication and repair. Platinum compounds lead to cell death by forming DNA adducts and&#xD;
      causing double strand breaks. By inhibiting DNA synthesis and repair, both gemcitabine and&#xD;
      5-FU potentiate the activity of cisplatin. These interactions underlie the clinical synergism&#xD;
      that has been observed with platinum/5FU and platinum/gemcitabine combinations.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>July 2011</start_date>
  <completion_date type="Actual">March 2016</completion_date>
  <primary_completion_date type="Actual">December 2014</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>The Percentage of Untreated and Previously Treated Patients That Had a Partial Response to Treatment</measure>
    <time_frame>28 days</time_frame>
    <description>The primary objective of this clinical trial is to estimate the response rate to treatment with the triplet chemotherapy regimen of gemcitabine, infusional 5-FU, and cisplatin, in untreated and previously treated advanced pancreatic and biliary cancer patients.&#xD;
Partial Response (PR) is defined as At least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Median Overall Survival of Previously Treated and Previously Untreated Patients</measure>
    <time_frame>1 year</time_frame>
    <description>To assess the overall survival following treatment with gemcitabine, 5-FU and cisplatin.</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">39</enrollment>
  <condition>Pancreatic Cancer</condition>
  <condition>Biliary Cancer</condition>
  <arm_group>
    <arm_group_label>Gemcitabine, 5-FU and Cisplatin</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>4 cycles - Gemcitabine, 5-FU and Cisplatin (2 months)-Continue treatment until progression of disease or intolerable toxicity</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Gemcitabine</intervention_name>
    <arm_group_label>Gemcitabine, 5-FU and Cisplatin</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>5-FU</intervention_name>
    <arm_group_label>Gemcitabine, 5-FU and Cisplatin</arm_group_label>
    <other_name>5-Fluorouracil</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Cisplatin</intervention_name>
    <arm_group_label>Gemcitabine, 5-FU and Cisplatin</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Patients must have histologic or cytologic diagnosis of pancreatic adenocarcinoma or&#xD;
             biliary tract cancer (intrahepatic or extrahepatic cholangiocarcinoma or gallbladder&#xD;
             carcinoma).&#xD;
&#xD;
          -  Patients must have clinical/radiologic evidence of metastatic disease.&#xD;
&#xD;
          -  Previous systemic therapy for metastatic disease limited to one cytotoxic chemotherapy&#xD;
             regimen not containing cisplatin. Previous therapy for metastatic disease might have&#xD;
             included gemcitabine or infusional 5-FU but not both agents.&#xD;
&#xD;
          -  ECOG (Eastern Cooperative Oncology Group) performance status &lt; 1 (A measure of quality&#xD;
             of life where 0 represents asymptomatic and 5 represents death).&#xD;
&#xD;
          -  Patients must have adequate bone marrow (absolute neutrophil count &gt;1,500/mm3,&#xD;
             platelet count &gt;100,000/mm3) and renal function (serum creatinine &lt; 1.25 x ULN).&#xD;
&#xD;
          -  Patients must have at least one measurable lesion per RECIST criteria.&#xD;
&#xD;
          -  Patients must be free of serious concomitant medical disorders incompatible with study&#xD;
             participation including active infection requiring systemic therapy.&#xD;
&#xD;
          -  Previous malignancies are permitted provided that they have been treated with curative&#xD;
             intent and patient is without evidence of active systemic disease.&#xD;
&#xD;
          -  Patients must be informed of the investigational nature of this study and provide&#xD;
             written informed consent prior to receiving protocol treatment.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Patients with pre-existing peripheral neuropathy &gt; grade 2 are ineligible.&#xD;
&#xD;
          -  Previous systemic therapy for metastatic disease limited to one cytotoxic chemotherapy&#xD;
             regimen not containing cisplatin.&#xD;
&#xD;
          -  Previous therapy for metastatic disease might have included gemcitabine or infusional&#xD;
             5-FU but not both agents.&#xD;
&#xD;
          -  Serious concomitant medical disorders incompatible with study participation including&#xD;
             active infection requiring systemic therapy.&#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>Mark Zalupski, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>University of Michigan Rogel Cancer Center</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>University of Michigan Comprehensive Cancer Center</name>
      <address>
        <city>Ann Arbor</city>
        <state>Michigan</state>
        <zip>48109</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <reference>
    <citation>Colucci et al., 2002, Louvet et al., 2005, Berlin et al., 2002, Cunningham et al., 2009, Heinemann et al., 2008, Valle et al., 2010</citation>
  </reference>
  <verification_date>September 2016</verification_date>
  <study_first_submitted>July 24, 2012</study_first_submitted>
  <study_first_submitted_qc>August 6, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">August 9, 2012</study_first_posted>
  <results_first_submitted>January 5, 2016</results_first_submitted>
  <results_first_submitted_qc>January 5, 2016</results_first_submitted_qc>
  <results_first_posted type="Estimate">February 4, 2016</results_first_posted>
  <last_update_submitted>September 1, 2016</last_update_submitted>
  <last_update_submitted_qc>September 1, 2016</last_update_submitted_qc>
  <last_update_posted type="Estimate">October 19, 2016</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Gemcitabine, Infusional 5-Fluorouracil,Cisplatin</keyword>
  <keyword>Advanced Pancreatic and Biliary Cancers</keyword>
  <keyword>untreated &amp; previously treated pancreatic &amp; biliary cancer.</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Biliary Tract Neoplasms</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Gemcitabine</mesh_term>
    <mesh_term>Fluorouracil</mesh_term>
  </intervention_browse>

  <clinical_results>

    <participant_flow>
      <group_list>
        <group group_id="P1">
          <title>Gemcitabine, 5-FU and Cisplatin</title>
          <description>4 cycles - Gemcitabine, 5-FU and Cisplatin (2 months)-Continue treatment until progression of disease or intolerable 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="39"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="39"/>
              </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>Gemcitabine, 5-FU and Cisplatin</title>
          <description>4 cycles - Gemcitabine, 5-FU and Cisplatin (2 months)-Continue treatment until progression of disease or intolerable toxicity</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="39"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>years</units>
          <param>Mean</param>
          <dispersion>Full Range</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="61" lower_limit="25" upper_limit="80"/>
                  </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="16"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="23"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>The Percentage of Untreated and Previously Treated Patients That Had a Partial Response to Treatment</title>
        <description>The primary objective of this clinical trial is to estimate the response rate to treatment with the triplet chemotherapy regimen of gemcitabine, infusional 5-FU, and cisplatin, in untreated and previously treated advanced pancreatic and biliary cancer patients.&#xD;
Partial Response (PR) is defined as At least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters.</description>
        <time_frame>28 days</time_frame>
        <population>Patients with metastatic adenocarcinoma of the pancreas or biliary tract, previously untreated or having received one cytotoxic regimen for advanced disease.</population>
        <group_list>
          <group group_id="O1">
            <title>Gemcitabine, 5-FU and Cisplatin</title>
            <description>4 cycles - Gemcitabine, 5-FU and Cisplatin (2 months)-Continue treatment until progression of disease or intolerable toxicity</description>
          </group>
        </group_list>
        <measure>
          <title>The Percentage of Untreated and Previously Treated Patients That Had a Partial Response to Treatment</title>
          <description>The primary objective of this clinical trial is to estimate the response rate to treatment with the triplet chemotherapy regimen of gemcitabine, infusional 5-FU, and cisplatin, in untreated and previously treated advanced pancreatic and biliary cancer patients.&#xD;
Partial Response (PR) is defined as At least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters.</description>
          <population>Patients with metastatic adenocarcinoma of the pancreas or biliary tract, previously untreated or having received one cytotoxic regimen for advanced disease.</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="39"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Untreated</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="40" lower_limit="21.1" upper_limit="61.3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Received Previous Treatment</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="7.1" lower_limit="1.8" upper_limit="33.9"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Median Overall Survival of Previously Treated and Previously Untreated Patients</title>
        <description>To assess the overall survival following treatment with gemcitabine, 5-FU and cisplatin.</description>
        <time_frame>1 year</time_frame>
        <population>Patients with metastatic adenocarcinoma of the pancreas or biliary tract, previously untreated or having received one cytotoxic regimen for advanced disease.</population>
        <group_list>
          <group group_id="O1">
            <title>Gemcitabine, 5-FU and Cisplatin</title>
            <description>4 cycles - Gemcitabine, 5-FU and Cisplatin (2 months)-Continue treatment until progression of disease or intolerable toxicity</description>
          </group>
        </group_list>
        <measure>
          <title>Median Overall Survival of Previously Treated and Previously Untreated Patients</title>
          <description>To assess the overall survival following treatment with gemcitabine, 5-FU and cisplatin.</description>
          <population>Patients with metastatic adenocarcinoma of the pancreas or biliary tract, previously untreated or having received one cytotoxic regimen for advanced disease.</population>
          <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="39"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Previously Untreated</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="10.3" lower_limit="8" upper_limit="19.4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Previously Treated</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="4.9" lower_limit="3.6" upper_limit="11.9"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <group_list>
        <group group_id="E1">
          <title>Gemcitabine, 5-FU and Cisplatin</title>
          <description>4 cycles - Gemcitabine, 5-FU and Cisplatin (2 months)-Continue treatment until progression of disease or intolerable toxicity</description>
        </group>
      </group_list>
      <serious_events>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="10" subjects_at_risk="39"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Anal Ulcer</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="39"/>
              </event>
              <event>
                <sub_title>Duodenal obstruction</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="39"/>
              </event>
              <event>
                <sub_title>Duodenal ulcer</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="39"/>
              </event>
              <event>
                <sub_title>Gastrointestinal disorders - Other</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="39"/>
              </event>
              <event>
                <sub_title>Lower gastrointestinal hemorrhage</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="39"/>
              </event>
              <event>
                <sub_title>Nausea</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="39"/>
              </event>
              <event>
                <sub_title>Vomiting</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="39"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Chills</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="39"/>
              </event>
              <event>
                <sub_title>Fatigue</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="39"/>
              </event>
              <event>
                <sub_title>Fever</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="39"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Infections and infestations - Other</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="39"/>
              </event>
              <event>
                <sub_title>Joint infection</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="39"/>
              </event>
              <event>
                <sub_title>Upper respiratory infection</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="39"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Injury, poisoning and procedural complications</title>
            <event_list>
              <event>
                <sub_title>Hip fracture</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="39"/>
              </event>
              <event>
                <sub_title>Spinal fracture</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="39"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Intracranial hemorrhage</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="39"/>
              </event>
              <event>
                <sub_title>Syncope</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="39"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Pneumonitis</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="39"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>0</frequency_threshold>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, other adverse events</sub_title>
                <counts group_id="E1" subjects_affected="39" subjects_at_risk="39"/>
              </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="49" subjects_affected="36" subjects_at_risk="39"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Cardiac disorders</title>
            <event_list>
              <event>
                <sub_title>Palpitations</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="39"/>
              </event>
              <event>
                <sub_title>Supraventricular tachycardia</sub_title>
                <counts group_id="E1" events="2" subjects_affected="1" subjects_at_risk="39"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Ear and labyrinth disorders</title>
            <event_list>
              <event>
                <sub_title>Ear and labyrinth disorders - Other</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="39"/>
              </event>
              <event>
                <sub_title>Hearing impaired</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="39"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Eye disorders</title>
            <event_list>
              <event>
                <sub_title>Blurred vision</sub_title>
                <counts group_id="E1" events="3" subjects_affected="3" subjects_at_risk="39"/>
              </event>
              <event>
                <sub_title>Eye pain</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="39"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Abdominal distension</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="39"/>
              </event>
              <event>
                <sub_title>Abdominal pain</sub_title>
                <counts group_id="E1" events="9" subjects_affected="8" subjects_at_risk="39"/>
              </event>
              <event>
                <sub_title>Anal ulcer</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="39"/>
              </event>
              <event>
                <sub_title>Bloating</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="39"/>
              </event>
              <event>
                <sub_title>Cheilitis</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="39"/>
              </event>
              <event>
                <sub_title>Constipation</sub_title>
                <counts group_id="E1" events="14" subjects_affected="12" subjects_at_risk="39"/>
              </event>
              <event>
                <sub_title>Diarrhea</sub_title>
                <counts group_id="E1" events="18" subjects_affected="13" subjects_at_risk="39"/>
              </event>
              <event>
                <sub_title>Dry mouth</sub_title>
                <counts group_id="E1" events="3" subjects_affected="3" subjects_at_risk="39"/>
              </event>
              <event>
                <sub_title>Duodenal obstruction</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="39"/>
              </event>
              <event>
                <sub_title>Duodenal ulcer</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="39"/>
              </event>
              <event>
                <sub_title>Dyspepsia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="39"/>
              </event>
              <event>
                <sub_title>Dysphagia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="39"/>
              </event>
              <event>
                <sub_title>Enterocolitis</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="39"/>
              </event>
              <event>
                <sub_title>Flatulence</sub_title>
                <counts group_id="E1" events="3" subjects_affected="3" subjects_at_risk="39"/>
              </event>
              <event>
                <sub_title>Gastroesophageal reflux disease</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="39"/>
              </event>
              <event>
                <sub_title>Gastrointestinal disorders - Other</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="39"/>
              </event>
              <event>
                <sub_title>Lower gastrointestinal hemorrhage</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="39"/>
              </event>
              <event>
                <sub_title>Mucositis oral</sub_title>
                <counts group_id="E1" events="6" subjects_affected="6" subjects_at_risk="39"/>
              </event>
              <event>
                <sub_title>Nausea</sub_title>
                <counts group_id="E1" events="38" subjects_affected="24" subjects_at_risk="39"/>
              </event>
              <event>
                <sub_title>Oral dysesthesia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="39"/>
              </event>
              <event>
                <sub_title>Oral pain</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="39"/>
              </event>
              <event>
                <sub_title>Pancreatitis</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="39"/>
              </event>
              <event>
                <sub_title>Vomiting</sub_title>
                <counts group_id="E1" events="23" subjects_affected="15" subjects_at_risk="39"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Chills</sub_title>
                <counts group_id="E1" events="4" subjects_affected="3" subjects_at_risk="39"/>
              </event>
              <event>
                <sub_title>Edema face</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="39"/>
              </event>
              <event>
                <sub_title>Edema limbs</sub_title>
                <counts group_id="E1" events="4" subjects_affected="4" subjects_at_risk="39"/>
              </event>
              <event>
                <sub_title>Facial pain</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="39"/>
              </event>
              <event>
                <sub_title>Fatigue</sub_title>
                <counts group_id="E1" events="36" subjects_affected="26" subjects_at_risk="39"/>
              </event>
              <event>
                <sub_title>Fever</sub_title>
                <counts group_id="E1" events="10" subjects_affected="9" subjects_at_risk="39"/>
              </event>
              <event>
                <sub_title>Flu like symptoms</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="39"/>
              </event>
              <event>
                <sub_title>Localized edema</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="39"/>
              </event>
              <event>
                <sub_title>Neck edema</sub_title>
                <counts group_id="E1" events="3" subjects_affected="3" subjects_at_risk="39"/>
              </event>
              <event>
                <sub_title>Non-cardiac chest pain</sub_title>
                <counts group_id="E1" events="4" subjects_affected="3" subjects_at_risk="39"/>
              </event>
              <event>
                <sub_title>Pain</sub_title>
                <counts group_id="E1" events="4" subjects_affected="4" subjects_at_risk="39"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Appendicitis</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="39"/>
              </event>
              <event>
                <sub_title>Eye infection</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="39"/>
              </event>
              <event>
                <sub_title>Infections and infestations - Other</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="39"/>
              </event>
              <event>
                <sub_title>Joint infection</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="39"/>
              </event>
              <event>
                <sub_title>Mucosal infection</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="39"/>
              </event>
              <event>
                <sub_title>Papulopustular rash</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="39"/>
              </event>
              <event>
                <sub_title>Tooth infection</sub_title>
                <counts group_id="E1" events="3" subjects_affected="2" subjects_at_risk="39"/>
              </event>
              <event>
                <sub_title>Upper respiratory infection</sub_title>
                <counts group_id="E1" events="5" subjects_affected="4" subjects_at_risk="39"/>
              </event>
              <event>
                <sub_title>Urinary tract infection</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="39"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Injury, poisoning and procedural complications</title>
            <event_list>
              <event>
                <sub_title>Hip fracture</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="39"/>
              </event>
              <event>
                <sub_title>Spinal fracture</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="39"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Investigations</title>
            <event_list>
              <event>
                <sub_title>Alanine aminotransferase increased</sub_title>
                <counts group_id="E1" events="12" subjects_affected="7" subjects_at_risk="39"/>
              </event>
              <event>
                <sub_title>Alkaline phosphatase increased</sub_title>
                <counts group_id="E1" events="12" subjects_affected="10" subjects_at_risk="39"/>
              </event>
              <event>
                <sub_title>Aspartate aminotransferase increased</sub_title>
                <counts group_id="E1" events="11" subjects_affected="8" subjects_at_risk="39"/>
              </event>
              <event>
                <sub_title>Blood bilirubin increased</sub_title>
                <counts group_id="E1" events="10" subjects_affected="6" subjects_at_risk="39"/>
              </event>
              <event>
                <sub_title>Creatinine increased</sub_title>
                <counts group_id="E1" events="6" subjects_affected="5" subjects_at_risk="39"/>
              </event>
              <event>
                <sub_title>Lipase increased</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="39"/>
              </event>
              <event>
                <sub_title>Lymphocyte count decreased</sub_title>
                <counts group_id="E1" events="44" subjects_affected="29" subjects_at_risk="39"/>
              </event>
              <event>
                <sub_title>Neutrophil count decreased</sub_title>
                <counts group_id="E1" events="50" subjects_affected="27" subjects_at_risk="39"/>
              </event>
              <event>
                <sub_title>Platelet count decreased</sub_title>
                <counts group_id="E1" events="53" subjects_affected="29" subjects_at_risk="39"/>
              </event>
              <event>
                <sub_title>Serum amylase increased</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="39"/>
              </event>
              <event>
                <sub_title>Weight gain</sub_title>
                <counts group_id="E1" events="3" subjects_affected="2" subjects_at_risk="39"/>
              </event>
              <event>
                <sub_title>Weight loss</sub_title>
                <counts group_id="E1" events="14" subjects_affected="11" subjects_at_risk="39"/>
              </event>
              <event>
                <sub_title>White blood cell decreased</sub_title>
                <counts group_id="E1" events="65" subjects_affected="31" subjects_at_risk="39"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Metabolism and nutrition disorders</title>
            <event_list>
              <event>
                <sub_title>Anorexia</sub_title>
                <counts group_id="E1" events="14" subjects_affected="13" subjects_at_risk="39"/>
              </event>
              <event>
                <sub_title>Hypercalcemia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="39"/>
              </event>
              <event>
                <sub_title>Hyperglycemia</sub_title>
                <counts group_id="E1" events="29" subjects_affected="21" subjects_at_risk="39"/>
              </event>
              <event>
                <sub_title>Hyperkalemia</sub_title>
                <counts group_id="E1" events="5" subjects_affected="4" subjects_at_risk="39"/>
              </event>
              <event>
                <sub_title>Hypoalbuminemia</sub_title>
                <counts group_id="E1" events="13" subjects_affected="11" subjects_at_risk="39"/>
              </event>
              <event>
                <sub_title>Hypocalcemia</sub_title>
                <counts group_id="E1" events="18" subjects_affected="13" subjects_at_risk="39"/>
              </event>
              <event>
                <sub_title>Hypoglycemia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="39"/>
              </event>
              <event>
                <sub_title>Hypokalemia</sub_title>
                <counts group_id="E1" events="8" subjects_affected="7" subjects_at_risk="39"/>
              </event>
              <event>
                <sub_title>Hypomagnesemia</sub_title>
                <counts group_id="E1" events="4" subjects_affected="4" subjects_at_risk="39"/>
              </event>
              <event>
                <sub_title>Hyponatremia</sub_title>
                <counts group_id="E1" events="19" subjects_affected="15" subjects_at_risk="39"/>
              </event>
              <event>
                <sub_title>Hypophosphatemia</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="39"/>
              </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="39"/>
              </event>
              <event>
                <sub_title>Back pain</sub_title>
                <counts group_id="E1" events="5" subjects_affected="5" subjects_at_risk="39"/>
              </event>
              <event>
                <sub_title>Bone pain</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="39"/>
              </event>
              <event>
                <sub_title>Flank pain</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="39"/>
              </event>
              <event>
                <sub_title>Generalized muscle weakness</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="39"/>
              </event>
              <event>
                <sub_title>Musculoskeletal and connective tissue disorder - Other</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="39"/>
              </event>
              <event>
                <sub_title>Neck pain</sub_title>
                <counts group_id="E1" events="3" subjects_affected="3" subjects_at_risk="39"/>
              </event>
              <event>
                <sub_title>Pain in extremity</sub_title>
                <counts group_id="E1" events="6" subjects_affected="5" subjects_at_risk="39"/>
              </event>
              <event>
                <sub_title>Trismus</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="39"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Dizziness</sub_title>
                <counts group_id="E1" events="7" subjects_affected="7" subjects_at_risk="39"/>
              </event>
              <event>
                <sub_title>Dysgeusia</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="39"/>
              </event>
              <event>
                <sub_title>Headache</sub_title>
                <counts group_id="E1" events="6" subjects_affected="6" subjects_at_risk="39"/>
              </event>
              <event>
                <sub_title>Intracranial hemorrhage</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="39"/>
              </event>
              <event>
                <sub_title>Memory impairment</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="39"/>
              </event>
              <event>
                <sub_title>Peripheral sensory neuropathy</sub_title>
                <counts group_id="E1" events="9" subjects_affected="9" subjects_at_risk="39"/>
              </event>
              <event>
                <sub_title>Syncope</sub_title>
                <counts group_id="E1" events="3" subjects_affected="3" subjects_at_risk="39"/>
              </event>
              <event>
                <sub_title>Tremor</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="39"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Psychiatric disorders</title>
            <event_list>
              <event>
                <sub_title>Agitation</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="39"/>
              </event>
              <event>
                <sub_title>Anxiety</sub_title>
                <counts group_id="E1" events="9" subjects_affected="7" subjects_at_risk="39"/>
              </event>
              <event>
                <sub_title>Depression</sub_title>
                <counts group_id="E1" events="4" subjects_affected="4" subjects_at_risk="39"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Renal and urinary disorders</title>
            <event_list>
              <event>
                <sub_title>Urinary retention</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="39"/>
              </event>
              <event>
                <sub_title>Urine discoloration</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="39"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Reproductive system and breast disorders</title>
            <event_list>
              <event>
                <sub_title>Irregular menstruation</sub_title>
                <counts group_id="E1" events="2" subjects_affected="1" subjects_at_risk="39"/>
              </event>
              <event>
                <sub_title>Pelvic pain</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="39"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Allergic rhinitis</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="39"/>
              </event>
              <event>
                <sub_title>Atelectasis</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="39"/>
              </event>
              <event>
                <sub_title>Cough</sub_title>
                <counts group_id="E1" events="8" subjects_affected="8" subjects_at_risk="39"/>
              </event>
              <event>
                <sub_title>Dyspnea</sub_title>
                <counts group_id="E1" events="9" subjects_affected="7" subjects_at_risk="39"/>
              </event>
              <event>
                <sub_title>Epistaxis</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="39"/>
              </event>
              <event>
                <sub_title>Hoarseness</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="39"/>
              </event>
              <event>
                <sub_title>Nasal congestion</sub_title>
                <counts group_id="E1" events="3" subjects_affected="3" subjects_at_risk="39"/>
              </event>
              <event>
                <sub_title>Pleural effusion</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="39"/>
              </event>
              <event>
                <sub_title>Pneumonitis</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="39"/>
              </event>
              <event>
                <sub_title>Pulmonary edema</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="39"/>
              </event>
              <event>
                <sub_title>Sore throat</sub_title>
                <counts group_id="E1" events="3" subjects_affected="3" subjects_at_risk="39"/>
              </event>
              <event>
                <sub_title>Wheezing</sub_title>
                <counts group_id="E1" events="3" subjects_affected="3" subjects_at_risk="39"/>
              </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="5" subjects_affected="3" subjects_at_risk="39"/>
              </event>
              <event>
                <sub_title>Scalp pain</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="39"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Vascular disorders</title>
            <event_list>
              <event>
                <sub_title>Hot flashes</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="39"/>
              </event>
              <event>
                <sub_title>Hypertension</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="39"/>
              </event>
              <event>
                <sub_title>Thromboembolic event</sub_title>
                <counts group_id="E1" events="9" subjects_affected="9" subjects_at_risk="39"/>
              </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>Dr. Mark Zalupski, M.D.</name_or_title>
      <organization>University of Michigan Comprehensive Cancer Center</organization>
      <phone>734-615-3969</phone>
      <email>zalupski@umich.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/NCT01661114
org study id: UMCC 2011.036
secondary id: HUM 49518
nct id: NCT01661114
lead sponsor: 
has dmc: Yes
Multi-agent chemotherapy has value for patients with advanced pancreatic-biliary cancers
      leading to responses in a substantial minority and increasing survival. The use of the
      FOLFIRINOX regimen is limited by its' intensity and toxicity. Previous protocol and clinical
      experience within the University of Michigan Pancreatic Program leads to an expectation of
      tolerance and efficacy of the proposed regimen. Advantages of the proposed regimen relative
      to FOLFIRINOX include:

        1. Substitution of gemcitabine for irinotecan. Single agent activity of gemcitabine is at
           least as good as irinotecan (probably better, especially when delivered by FDR
           [fixed-dose rate] infusion) and gemcitabine is much better tolerated with less diarrhea,
           nausea/emesis, myelosuppression and alopecia.

        2. Deletion of leucovorin infusion and 5FU bolus injection will lessen myelosuppression,
           mucositis and diarrhea.

        3. Substitution of cisplatin for oxaliplatin will reduce cost of therapy and avoid cold
           aggravated dysesthesia.

      Presuming evidence of efficacy and confirmation of tolerance with the proposed regimen, the
      investigators believe this treatment may be more widely applicable to pancreatic-biliary
      cancer patients, including those with advanced disease as well as being considered for use in
      locally advanced and neo- and adjuvant settings.
Gemcitabine combined with 5FU may enhance the activity of 5-FU in vivo. Gemcitabine is an
      inhibitor of ribonucleotide reductase, an enzyme needed for synthesis of deoxynucleotides,
      and 5-FU interferes with dTTP synthesis by inhibition of thymidylate synthase (TS). It is
      likely that concomitant administration of gemcitabine and 5FU results in increased
      cytotoxicity by reducing intracellular dTTP thru two different mechanisms, thereby inhibiting
      DNA replication and repair. Platinum compounds lead to cell death by forming DNA adducts and
      causing double strand breaks. By inhibiting DNA synthesis and repair, both gemcitabine and
      5-FU potentiate the activity of cisplatin. These interactions underlie the clinical synergism
      that has been observed with platinum/5FU and platinum/gemcitabine combinations.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: The Percentage of Untreated and Previously Treated Patients That Had a Partial Response to Treatment
time frame: 28 days
description: The primary objective of this clinical trial is to estimate the response rate to treatment with the triplet chemotherapy regimen of gemcitabine, infusional 5-FU, and cisplatin, in untreated and previously treated advanced pancreatic and biliary cancer patients.
Partial Response (PR) is defined as At least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters.
measure: Median Overall Survival of Previously Treated and Previously Untreated Patients
time frame: 1 year
description: To assess the overall survival following treatment with gemcitabine, 5-FU and cisplatin.
arm group label: Gemcitabine, 5-FU and Cisplatin
arm group type: Experimental
description: 4 cycles - Gemcitabine, 5-FU and Cisplatin (2 months)-Continue treatment until progression of disease or intolerable toxicity
intervention type: Drug
intervention name: Gemcitabine
arm group label: Gemcitabine, 5-FU and Cisplatin
intervention type: Drug
intervention name: 5-FU
arm group label: Gemcitabine, 5-FU and Cisplatin
other name: 5-Fluorouracil
intervention type: Drug
intervention name: Cisplatin
arm group label: Gemcitabine, 5-FU and Cisplatin
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Mark Zalupski, MD
role: Principal Investigator
affiliation: University of Michigan Rogel Cancer Center
facility: 
country: United States
citation: Colucci et al., 2002, Louvet et al., 2005, Berlin et al., 2002, Cunningham et al., 2009, Heinemann et al., 2008, Valle et al., 2010
responsible party type: Sponsor
mesh term: Biliary Tract Neoplasms
mesh term: Gemcitabine
mesh term: Fluorouracil
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 