<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/NCT01661088</url>
  </required_header>
  <id_info>
    <org_study_id>UMCC 2011.007</org_study_id>
    <secondary_id>HUM 47389</secondary_id>
    <nct_id>NCT01661088</nct_id>
  </id_info>
  <brief_title>A Study of Neoadjuvant FOLFIRINOX and FDR-Gemcitabine With Concurrent IMRT in Patients</brief_title>
  <official_title>A Phase II Study of Neoadjuvant FOLFIRINOX and FDR-Gemcitabine With Concurrent IMRT in Patients With Borderline Resectable Pancreatic Cancer</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>
      The investigators hypothesize that the combination of the FOLFIRINOX regimen (a combination&#xD;
      of 5-fluorouracil, irinotecan and oxaliplatin chemotherapy) to provide maximal systemic&#xD;
      disease control and FDR-gemcitabine chemotherapy with concurrent IMRT (Radiation therapy) to&#xD;
      address local disease, will achieve a significant improvement R0 resection (Radiation&#xD;
      oncology repeat surgeries) rate in borderline resectable (surgical) pancreatic cancer and&#xD;
      enhance disease free and overall survival in this patient population.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Gemcitabine has been the cornerstone of systemic therapy for pancreas cancer over this past&#xD;
      decade. Recently, a combination of 5-fluorouracil, irinotecan and oxaliplatin (FOLFIRINOX)&#xD;
      was reported to have significant efficacy in advanced pancreatic cancer. Preclinical data&#xD;
      suggests synergy between irinotecan and 5FU as well as between oxaliplatin and 5FU. Results&#xD;
      of a phase II trial in advanced disease were reported in 2005 demonstrating a 26% confirmed&#xD;
      response rate and median overall survival of 10.2 months. A follow-up phase III trial&#xD;
      comparing FOLFIRINOX with gemcitabine for patients &lt;75 years of age with advanced pancreatic&#xD;
      cancer was presented at ASCO 2010 revealing improvement in PFS (6.4 vs 3.3 months, p=&lt;.0001)&#xD;
      and improved disease control rate (CR+PR+SD) (70.2% vs 50.9%, p=.0003). The most notable&#xD;
      result was an impressive improvement in median overall survival with FOLFIRINOX compared to&#xD;
      gemcitabine (11.1vs 6.8 months, p-value = &lt;.0001, HR=.57). The main toxicity was grade 3/4&#xD;
      neutropenia (45.7% vs 18.7%, p=.0001) and increased risk of febrile neutropenia (5.4% vs&#xD;
      0.6%, p=.009)31.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>June 2011</start_date>
  <completion_date type="Actual">August 30, 2019</completion_date>
  <primary_completion_date type="Actual">August 10, 2017</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 Patients That Underwent an R0 Resection</measure>
    <time_frame>6 months</time_frame>
    <description>To determine the frequency of achieving an R0 resection using a neoadjuvant regimen of FOLFIRINOX followed by IMRT concurrent with fixed dose rate (FDR)-gemcitabine in patients with borderline resectable pancreatic cancer. R0 resection indicates a microscopically margin-negative resection, in which no gross or microscopic tumor remains in the primary tumor bed.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Median Progression-free Survival Time</measure>
    <time_frame>up to 2 years</time_frame>
    <description>To estimate progression-free survival as a function of time from study enrollment. Progression is defined as at least a 20% increase in the LD (longest diameter) of the primary lesion or the appearance of one or more new lesions</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Median Overall Survival Time</measure>
    <time_frame>up to 2 years</time_frame>
    <description>To estimate overall survival as a function of time from study enrollment.</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">25</enrollment>
  <condition>Pancreatic Cancer</condition>
  <arm_group>
    <arm_group_label>Study Treatment</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Patients will receive FOLFIRINOX x 6 followed by IMRT concurrent with fixed dose rate (FDR)-gemcitabine (1g/m^2) on days 1, 8, 22, 29.&#xD;
Intensity-modulated radiotherapy (IMRT): The prescribed dose was 50.0Gy in 2.0Gy per fraction.&#xD;
Patients without metastatic disease will be offered surgical exploration.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>FOLFIRINOX</intervention_name>
    <description>Starting dose levels as following:&#xD;
Oxaliplatin 85mg/m2 intravenously over 120 minutes on day 1. Irinotecan 180mg/m2 intravenously over 90 minutes on day 1. NOTE: patients homozygous for the UGT1A1 (TA)7 promoter allele will be treated at an initial lower dose 140mg/m2 (please see Section 6.3.a) Leucovorin 400mg/m2 intravenously over 90 minutes on day 1. 5FU 400mg/m2 as bolus intravenous injection following leucovorin on day 1. 5FU 2,400mg/m2 infused intravenously as a continuous infusion over 46 hours following the bolus 5FU, beginning on day 1.</description>
    <arm_group_label>Study Treatment</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Radiation</intervention_type>
    <intervention_name>Intensity-modulated radiotherapy (IMRT)</intervention_name>
    <description>50.0Gy in 2.0Gy per fraction</description>
    <arm_group_label>Study Treatment</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Procedure</intervention_type>
    <intervention_name>Surgical Exploration</intervention_name>
    <description>Patients without metastatic disease will be offered surgical exploration.</description>
    <arm_group_label>Study Treatment</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Patients must have cytologic or histologic confirmation of carcinoma arising in the&#xD;
             pancreas.&#xD;
&#xD;
          -  Patients must be deemed to have borderline resectable disease with no radiologic&#xD;
             evidence of distant metastatic disease prior to registration.&#xD;
&#xD;
          -  Specifically, patients must have at least one designation of borderline resectable and&#xD;
             no designation of unresectable disease.&#xD;
&#xD;
          -  Patients must have a life expectancy of at least 12 weeks, a Zubrod performance status&#xD;
             of &lt; 1 and be willing and medically able to undergo surgical resection.&#xD;
&#xD;
          -  Patients must have adequate organ function defined as follows: absolute neutrophil&#xD;
             count of &gt; 1500/mm3, platelets &gt; 100,000/mm3, serum Cr &lt; 1.5 mg/dl, total bilirubin &lt;&#xD;
             2.0 mg/dl with relief of biliary obstruction if present (PTC tube or endobiliary&#xD;
             stent).&#xD;
&#xD;
          -  Patients must be free of other active systemic malignancy, ongoing infection, or any&#xD;
             other serious uncontrolled, concomitant systemic disorders or psychiatric condition&#xD;
             that would interfere with the safe delivery of protocol therapy.&#xD;
&#xD;
          -  Patients of reproductive potential must agree to use an effective contraceptive method&#xD;
             during participation in this trial due to the unacceptable teratogenic toxicity of&#xD;
             abdominal radiation and cytotoxic chemotherapy.&#xD;
&#xD;
          -  Patients must be aware of the investigational nature of the therapy and provide&#xD;
             written informed consent.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Patients with neuroendocrine tumors are excluded.&#xD;
&#xD;
          -  Active systemic malignancy, ongoing infection, or any other serious uncontrolled,&#xD;
             concomitant systemic disorders or psychiatric condition that would interfere with the&#xD;
             safe delivery of protocol therapy.&#xD;
&#xD;
          -  Patients with preexisting peripheral neuropathy &gt; grade 2 are ineligible&#xD;
&#xD;
          -  Pregnant or nursing women are ineligible.&#xD;
&#xD;
          -  Patients must have no history of previous chemotherapy for pancreatic cancer or any&#xD;
             abdominal radiation therapy.&#xD;
&#xD;
          -  Patients may not have used any investigational agent within 4 weeks prior to&#xD;
             enrollment into the study.&#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>
  <verification_date>October 2019</verification_date>
  <study_first_submitted>July 24, 2012</study_first_submitted>
  <study_first_submitted_qc>August 8, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">August 9, 2012</study_first_posted>
  <results_first_submitted>June 26, 2018</results_first_submitted>
  <results_first_submitted_qc>August 6, 2018</results_first_submitted_qc>
  <results_first_posted type="Actual">August 8, 2018</results_first_posted>
  <last_update_submitted>October 29, 2019</last_update_submitted>
  <last_update_submitted_qc>October 29, 2019</last_update_submitted_qc>
  <last_update_posted type="Actual">November 13, 2019</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Neoadjuvant FOLFIRINOX</keyword>
  <keyword>FDR-Gemcitabine</keyword>
  <keyword>Concurrent</keyword>
  <keyword>IMRT</keyword>
  <keyword>Borderline Resectable Pancreatic Cancer</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Pancreatic Neoplasms</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Folfirinox</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>October 14, 2016</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/88/NCT01661088/Prot_SAP_000.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <group_list>
        <group group_id="P1">
          <title>Study Treatment</title>
          <description>Patients received FOLFIRINOX x 6 followed by IMRT concurrent with fixed dose rate (FDR)-gemcitabine (1g/m^2) on days 1, 8, 22, 29.&#xD;
Intensity-modulated radiotherapy (IMRT): The prescribed dose was 50.0Gy in 2.0Gy per fraction.&#xD;
Patients without metastatic disease were offered surgical exploration.</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>FOLFIRINOX</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="25"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="21"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="4"/>
              </participants_list>
            </milestone>
          </milestone_list>
        </period>
        <period>
          <title>IMRT With FDR Gemcitabine</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="21"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="19"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="2"/>
              </participants_list>
            </milestone>
          </milestone_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>Study Treatment</title>
          <description>Patients received FOLFIRINOX x 6 followed by IMRT concurrent with fixed dose rate (FDR)-gemcitabine (1g/m^2) on days 1, 8, 22, 29.&#xD;
Intensity-modulated radiotherapy (IMRT): The prescribed dose was 50.0Gy in 2.0Gy per fraction.&#xD;
Patients without metastatic disease were offered surgical exploration.</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="25"/>
          </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="60" lower_limit="46" upper_limit="77"/>
                  </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="16"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Ethnicity (NIH/OMB)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="2"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Not Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="23"/>
                  </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_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>The Percentage of Patients That Underwent an R0 Resection</title>
        <description>To determine the frequency of achieving an R0 resection using a neoadjuvant regimen of FOLFIRINOX followed by IMRT concurrent with fixed dose rate (FDR)-gemcitabine in patients with borderline resectable pancreatic cancer. R0 resection indicates a microscopically margin-negative resection, in which no gross or microscopic tumor remains in the primary tumor bed.</description>
        <time_frame>6 months</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Study Treatment</title>
            <description>Patients received FOLFIRINOX x 6 followed by IMRT concurrent with fixed dose rate (FDR)-gemcitabine (1g/m^2) on days 1, 8, 22, 29.&#xD;
Intensity-modulated radiotherapy (IMRT): The prescribed dose was 50.0Gy in 2.0Gy per fraction.&#xD;
Patients without metastatic disease were offered surgical exploration.</description>
          </group>
        </group_list>
        <measure>
          <title>The Percentage of Patients That Underwent an R0 Resection</title>
          <description>To determine the frequency of achieving an R0 resection using a neoadjuvant regimen of FOLFIRINOX followed by IMRT concurrent with fixed dose rate (FDR)-gemcitabine in patients with borderline resectable pancreatic cancer. R0 resection indicates a microscopically margin-negative resection, in which no gross or microscopic tumor remains in the primary tumor bed.</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="25"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="52"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Median Progression-free Survival Time</title>
        <description>To estimate progression-free survival as a function of time from study enrollment. Progression is defined as at least a 20% increase in the LD (longest diameter) of the primary lesion or the appearance of one or more new lesions</description>
        <time_frame>up to 2 years</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Study Treatment</title>
            <description>Patients received FOLFIRINOX x 6 followed by IMRT concurrent with fixed dose rate (FDR)-gemcitabine (1g/m^2) on days 1, 8, 22, 29.&#xD;
Intensity-modulated radiotherapy (IMRT): The prescribed dose was 50.0Gy in 2.0Gy per fraction.&#xD;
Patients without metastatic disease were offered surgical exploration.</description>
          </group>
        </group_list>
        <measure>
          <title>Median Progression-free Survival Time</title>
          <description>To estimate progression-free survival as a function of time from study enrollment. Progression is defined as at least a 20% increase in the LD (longest diameter) of the primary lesion or the appearance of one or more new lesions</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="25"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="13.1" lower_limit="7.3" upper_limit="24.7"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Median Overall Survival Time</title>
        <description>To estimate overall survival as a function of time from study enrollment.</description>
        <time_frame>up to 2 years</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Study Treatment</title>
            <description>Patients received FOLFIRINOX x 6 followed by IMRT concurrent with fixed dose rate (FDR)-gemcitabine (1g/m^2) on days 1, 8, 22, 29.&#xD;
Intensity-modulated radiotherapy (IMRT): The prescribed dose was 50.0Gy in 2.0Gy per fraction.&#xD;
Patients without metastatic disease were offered surgical exploration.</description>
          </group>
        </group_list>
        <measure>
          <title>Median Overall Survival Time</title>
          <description>To estimate overall survival as a function of time from study enrollment.</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="25"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="24.4" lower_limit="12.6" upper_limit="40.0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>30 days post treatment</time_frame>
      <group_list>
        <group group_id="E1">
          <title>Study Treatment</title>
          <description>Patients received FOLFIRINOX x 6 followed by IMRT concurrent with fixed dose rate (FDR)-gemcitabine (1g/m^2) on days 1, 8, 22, 29.&#xD;
Intensity-modulated radiotherapy (IMRT): The prescribed dose was 50.0Gy in 2.0Gy per fraction.&#xD;
Patients without metastatic disease were offered surgical exploration.</description>
        </group>
      </group_list>
      <serious_events>
        <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="1" subjects_at_risk="25"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="6" subjects_at_risk="25"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Blood and lymphatic system disorders</title>
            <event_list>
              <event>
                <sub_title>Febrile neutropenia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="25"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Cardiac disorders</title>
            <event_list>
              <event>
                <sub_title>Cardiac arrest</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="25"/>
              </event>
              <event>
                <sub_title>Chest pain - cardiac</sub_title>
                <assessment>Non-systematic Assessment</assessment>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="25"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Esophagitis</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="25"/>
              </event>
              <event>
                <sub_title>Gastrointestinal disorders - Other</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="25"/>
              </event>
              <event>
                <sub_title>Lower gastrointestinal hemorrhage</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="25"/>
              </event>
              <event>
                <sub_title>Nausea</sub_title>
                <assessment>Non-systematic Assessment</assessment>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="25"/>
              </event>
              <event>
                <sub_title>Vomiting</sub_title>
                <assessment>Non-systematic Assessment</assessment>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="25"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Lung infection</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="25"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Dysphasia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="25"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>0</frequency_threshold>
        <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="21" subjects_at_risk="25"/>
              </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="6" subjects_affected="4" subjects_at_risk="25"/>
              </event>
              <event>
                <sub_title>Febrile neutropenia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="25"/>
              </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="25"/>
              </event>
              <event>
                <sub_title>Abdominal pain</sub_title>
                <assessment>Non-systematic Assessment</assessment>
                <counts group_id="E1" events="5" subjects_affected="5" subjects_at_risk="25"/>
              </event>
              <event>
                <sub_title>Diarrhea</sub_title>
                <assessment>Non-systematic Assessment</assessment>
                <counts group_id="E1" events="6" subjects_affected="6" subjects_at_risk="25"/>
              </event>
              <event>
                <sub_title>Mucositis oral</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="25"/>
              </event>
              <event>
                <sub_title>Nausea</sub_title>
                <assessment>Non-systematic Assessment</assessment>
                <counts group_id="E1" events="6" subjects_affected="4" subjects_at_risk="25"/>
              </event>
              <event>
                <sub_title>Stomach pain</sub_title>
                <assessment>Non-systematic Assessment</assessment>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="25"/>
              </event>
              <event>
                <sub_title>Vomiting</sub_title>
                <assessment>Non-systematic Assessment</assessment>
                <counts group_id="E1" events="4" subjects_affected="3" subjects_at_risk="25"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Chills</sub_title>
                <assessment>Non-systematic Assessment</assessment>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="25"/>
              </event>
              <event>
                <sub_title>Fatigue</sub_title>
                <assessment>Non-systematic Assessment</assessment>
                <counts group_id="E1" events="5" subjects_affected="4" subjects_at_risk="25"/>
              </event>
              <event>
                <sub_title>Fever</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="25"/>
              </event>
              <event>
                <sub_title>Non-cardiac chest pain</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="25"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Hepatobiliary disorders</title>
            <event_list>
              <event>
                <sub_title>Bile duct stenosis</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="25"/>
              </event>
              <event>
                <sub_title>Cholecystitis</sub_title>
                <counts group_id="E1" events="2" subjects_affected="1" subjects_at_risk="25"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Abdominal infection</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="25"/>
              </event>
              <event>
                <sub_title>Biliary tract infection</sub_title>
                <counts group_id="E1" events="3" subjects_affected="2" subjects_at_risk="25"/>
              </event>
              <event>
                <sub_title>Skin infection</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="25"/>
              </event>
              <event>
                <sub_title>Urinary tract infection</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="25"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Investigations</title>
            <event_list>
              <event>
                <sub_title>Alanine aminotransferase increased</sub_title>
                <counts group_id="E1" events="5" subjects_affected="4" subjects_at_risk="25"/>
              </event>
              <event>
                <sub_title>Alkaline phosphatase increased</sub_title>
                <counts group_id="E1" events="2" subjects_affected="1" subjects_at_risk="25"/>
              </event>
              <event>
                <sub_title>Aspartate aminotransferase increased</sub_title>
                <counts group_id="E1" events="4" subjects_affected="4" subjects_at_risk="25"/>
              </event>
              <event>
                <sub_title>Blood bilirubin increased</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="25"/>
              </event>
              <event>
                <sub_title>Lymphocyte count decreased</sub_title>
                <counts group_id="E1" events="14" subjects_affected="8" subjects_at_risk="25"/>
              </event>
              <event>
                <sub_title>Lymphocyte count increased</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="25"/>
              </event>
              <event>
                <sub_title>Neutrophil count decreased</sub_title>
                <counts group_id="E1" events="15" subjects_affected="10" subjects_at_risk="25"/>
              </event>
              <event>
                <sub_title>Platelet count decreased</sub_title>
                <counts group_id="E1" events="5" subjects_affected="3" subjects_at_risk="25"/>
              </event>
              <event>
                <sub_title>White blood cell decreased</sub_title>
                <counts group_id="E1" events="10" subjects_affected="9" subjects_at_risk="25"/>
              </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="25"/>
              </event>
              <event>
                <sub_title>Dehydration</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="25"/>
              </event>
              <event>
                <sub_title>Hyperglycemia</sub_title>
                <counts group_id="E1" events="10" subjects_affected="6" subjects_at_risk="25"/>
              </event>
              <event>
                <sub_title>Hypoalbuminemia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="25"/>
              </event>
              <event>
                <sub_title>Hypocalcemia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="25"/>
              </event>
              <event>
                <sub_title>Hypoglycemia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="25"/>
              </event>
              <event>
                <sub_title>Hypokalemia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="25"/>
              </event>
              <event>
                <sub_title>Hyponatremia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="25"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Musculoskeletal and connective tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Back pain</sub_title>
                <assessment>Non-systematic Assessment</assessment>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="25"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Ataxia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="25"/>
              </event>
              <event>
                <sub_title>Dysarthria</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="25"/>
              </event>
              <event>
                <sub_title>Dysgeusia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="25"/>
              </event>
              <event>
                <sub_title>Extrapyramidal disorder</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="25"/>
              </event>
              <event>
                <sub_title>Paresthesia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="25"/>
              </event>
              <event>
                <sub_title>Peripheral motor neuropathy</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="25"/>
              </event>
              <event>
                <sub_title>Peripheral sensory neuropathy</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="25"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Psychiatric disorders</title>
            <event_list>
              <event>
                <sub_title>Anxiety</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="25"/>
              </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="25"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Vascular disorders</title>
            <event_list>
              <event>
                <sub_title>Hypertension</sub_title>
                <counts group_id="E1" events="2" subjects_affected="1" subjects_at_risk="25"/>
              </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>Mark Zalupski, M.D.</name_or_title>
      <organization>University of Michigan Rogel Cancer Center</organization>
      <phone>734-647-8902</phone>
      <email>zalupski@med.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/NCT01661088
org study id: UMCC 2011.007
secondary id: HUM 47389
nct id: NCT01661088
lead sponsor: 
has dmc: Yes
The investigators hypothesize that the combination of the FOLFIRINOX regimen (a combination
      of 5-fluorouracil, irinotecan and oxaliplatin chemotherapy) to provide maximal systemic
      disease control and FDR-gemcitabine chemotherapy with concurrent IMRT (Radiation therapy) to
      address local disease, will achieve a significant improvement R0 resection (Radiation
      oncology repeat surgeries) rate in borderline resectable (surgical) pancreatic cancer and
      enhance disease free and overall survival in this patient population.
Gemcitabine has been the cornerstone of systemic therapy for pancreas cancer over this past
      decade. Recently, a combination of 5-fluorouracil, irinotecan and oxaliplatin (FOLFIRINOX)
      was reported to have significant efficacy in advanced pancreatic cancer. Preclinical data
      suggests synergy between irinotecan and 5FU as well as between oxaliplatin and 5FU. Results
      of a phase II trial in advanced disease were reported in 2005 demonstrating a 26% confirmed
      response rate and median overall survival of 10.2 months. A follow-up phase III trial
      comparing FOLFIRINOX with gemcitabine for patients <75 years of age with advanced pancreatic
      cancer was presented at ASCO 2010 revealing improvement in PFS (6.4 vs 3.3 months, p=<.0001)
      and improved disease control rate (CR+PR+SD) (70.2% vs 50.9%, p=.0003). The most notable
      result was an impressive improvement in median overall survival with FOLFIRINOX compared to
      gemcitabine (11.1vs 6.8 months, p-value = <.0001, HR=.57). The main toxicity was grade 3/4
      neutropenia (45.7% vs 18.7%, p=.0001) and increased risk of febrile neutropenia (5.4% vs
      0.6%, p=.009)31.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: The Percentage of Patients That Underwent an R0 Resection
time frame: 6 months
description: To determine the frequency of achieving an R0 resection using a neoadjuvant regimen of FOLFIRINOX followed by IMRT concurrent with fixed dose rate (FDR)-gemcitabine in patients with borderline resectable pancreatic cancer. R0 resection indicates a microscopically margin-negative resection, in which no gross or microscopic tumor remains in the primary tumor bed.
measure: Median Progression-free Survival Time
time frame: up to 2 years
description: To estimate progression-free survival as a function of time from study enrollment. Progression is defined as at least a 20% increase in the LD (longest diameter) of the primary lesion or the appearance of one or more new lesions
measure: Median Overall Survival Time
time frame: up to 2 years
description: To estimate overall survival as a function of time from study enrollment.
arm group label: Study Treatment
arm group type: Experimental
description: Patients will receive FOLFIRINOX x 6 followed by IMRT concurrent with fixed dose rate (FDR)-gemcitabine (1g/m^2) on days 1, 8, 22, 29.
Intensity-modulated radiotherapy (IMRT): The prescribed dose was 50.0Gy in 2.0Gy per fraction.
Patients without metastatic disease will be offered surgical exploration.
intervention type: Drug
intervention name: FOLFIRINOX
description: Starting dose levels as following:
Oxaliplatin 85mg/m2 intravenously over 120 minutes on day 1. Irinotecan 180mg/m2 intravenously over 90 minutes on day 1. NOTE: patients homozygous for the UGT1A1 (TA)7 promoter allele will be treated at an initial lower dose 140mg/m2 (please see Section 6.3.a) Leucovorin 400mg/m2 intravenously over 90 minutes on day 1. 5FU 400mg/m2 as bolus intravenous injection following leucovorin on day 1. 5FU 2,400mg/m2 infused intravenously as a continuous infusion over 46 hours following the bolus 5FU, beginning on day 1.
arm group label: Study Treatment
intervention type: Radiation
intervention name: Intensity-modulated radiotherapy (IMRT)
description: 50.0Gy in 2.0Gy per fraction
arm group label: Study Treatment
intervention type: Procedure
intervention name: Surgical Exploration
description: Patients without metastatic disease will be offered surgical exploration.
arm group label: Study Treatment
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
responsible party type: Sponsor
mesh term: Pancreatic Neoplasms
mesh term: Folfirinox
provided document: 
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 