<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/NCT01677988</url>
  </required_header>
  <id_info>
    <org_study_id>101822</org_study_id>
    <nct_id>NCT01677988</nct_id>
  </id_info>
  <brief_title>Neoadjuvant Folfirinox Followed by Capecitabine and Limited Field Radiation for Localized Pancreatic Head Adenocarcinoma</brief_title>
  <official_title>Phase II Study of Neoadjuvant Folfirinox Chemotherapy Followed by Capecitabine With Concurrent Limited Field Radiation Therapy in Patients With Localized Pancreatic Head Adenocarcinoma</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Medical University of South Carolina</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Medical University of South Carolina</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      This study is for subjects with adenocarcinoma of the pancreas. The purpose of this research&#xD;
      study is to determine the safety and effectiveness of modified Folfirinox and radiation&#xD;
      therapy as treatment for adenocarcinoma (cancer) of the pancreas before surgery. Screening&#xD;
      tests will be done to determine if subjects are eligible for participation in this study. If&#xD;
      subjects are eligible to participate and agree to participate they will begin chemotherapy.&#xD;
      After 3 cycles of chemotherapy, subjects will begin chemoradiation. Within 4 to 8 weeks of&#xD;
      completing radiation therapy, subjects will have surgery. There will also be post-treatment&#xD;
      and follow-up evaluations. Subjects will be followed for every 3 months for 3 years after&#xD;
      their initial registration.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Terminated</overall_status>
  <why_stopped>
    Study was terminated due to low accrual.&#xD;
  </why_stopped>
  <start_date>July 2012</start_date>
  <primary_completion_date type="Actual">October 2015</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>Estimate the R0/R1 Resection Rate</measure>
    <time_frame>at time of surgery</time_frame>
    <description>Estimate the R0/R1 resection rate as the proportion of patients with R0 or R1 resection status based on the ITT population. R0 resection status is macroscopic complete removal of tumor by non-contaminated operation, with neither macroscopic nor microscopic residual tumor. R1 resection status is macroscopic complete removal of tumor by non-contaminated operation, with microscopic residual tumor.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Radiographic Tumor Response</measure>
    <time_frame>From enrollment to Surgery</time_frame>
    <description>The rate of CR, PR, SD and PD will be estimated as described in Section 14B prior to chemoradiation start and prior to surgery. The analysis population for estimation of radiographic response rate will be the ITT population.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Histopathologic Tumor Response</measure>
    <time_frame>at the time of surgery</time_frame>
    <description>Estimate the rate of good histopathologic response as the proportion of grade I and II responders. The analysis population for this objective is the ITT population. Any patient for whom a surgical sample is not available will be considered a poor-responder.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time to Recurrence:</measure>
    <time_frame>2 years</time_frame>
    <description>Time to recurrence is defined as the time from surgical resection to disease recurrence or death from any cause. Patients who have not recurred at the end of follow up will have their recurrence time censored at the last date of contact.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Overall Survival:</measure>
    <time_frame>2 years</time_frame>
    <description>Overall survival is defined as the time from enrollment to death from any cause. Patients still alive at the end of follow up will have their survival time censored at the last date of contact.</description>
  </secondary_outcome>
  <other_outcome>
    <measure>Feasibility Objective</measure>
    <time_frame>From enrollment to end of chemotherapy part of the study</time_frame>
    <description>The feasibility of treating patients with localized pancreatic head adenocarcinoma with this neoadjuvant regimen will be evaluated by estimating the proportion of patients completing five of six planned doses. The analysis population will be the ITT population.</description>
  </other_outcome>
  <other_outcome>
    <measure>CTC Analysis</measure>
    <time_frame>End of study</time_frame>
    <description>To evaluate and describe CTC numbers, CTC phenotype characteristics and effectiveness/rate of CTC culturing techniques from patients with pancreatic adenocarcinoma.</description>
  </other_outcome>
  <other_outcome>
    <measure>CTC Expression</measure>
    <time_frame>2 years</time_frame>
    <description>To determine and evaluate the correlation between expression or biomarkers in the CTCs and expression of biomarkers in resected tissue specimens within the same cancer patient.</description>
  </other_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">3</enrollment>
  <condition>Adenocarcinoma of Head of Pancreas</condition>
  <arm_group>
    <arm_group_label>Chemotherapy, Chemoradiation, Surgery</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Neoadjuvant Chemotherapy- Modified FOLFIRINOX chemotherapy Day 1 and Day 15 of 28 day cycles for 3 cycles with growth factor support Chemoradiation Surgical Resection</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Neo-adjuvant Chemotherapy</intervention_name>
    <description>Modified FOLFIRINOX chemotherapy Day 1 and Day 15 of 28 day cycles, for three (3) cycles with growth factor support.&#xD;
Restaging # 1. (CT or MRI; use same modality as baseline staging unless otherwise indicated by Study Team)&#xD;
Progressive Disease (PD) → Off study. Subsequent treatment per patient's primary MD.&#xD;
Stable Disease (SD) or Tumor Response → Continue to Registration #2 for Chemoradiation.</description>
    <arm_group_label>Chemotherapy, Chemoradiation, Surgery</arm_group_label>
    <other_name>FOLFIRINOX chemotherapy</other_name>
  </intervention>
  <intervention>
    <intervention_type>Radiation</intervention_type>
    <intervention_name>Chemoradiation</intervention_name>
    <description>Chemoradiation may be administered at selected approved CTN sites.&#xD;
Determination of resectability as reviewed and documented by MUSC-HCC GI Tumor Board.&#xD;
Unresectable → Off study. Subsequent treatment per patient's primary MD.&#xD;
Resectable → Continue to Registration #3 for Surgical Resection</description>
    <arm_group_label>Chemotherapy, Chemoradiation, Surgery</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Procedure</intervention_type>
    <intervention_name>Surgical Resection</intervention_name>
    <description>Meets criteria for resectable* →pancreaticoduodenectomy (POD)&#xD;
At time of resection, snap frozen tumor specimen sent for correlative biomarker studies</description>
    <arm_group_label>Chemotherapy, Chemoradiation, Surgery</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Patient has histologically or cytologically confirmed borderline resectable&#xD;
             adenocarcinoma of the pancreas. Patients with islet cell or other neuroendocrine&#xD;
             neoplasms are excluded.&#xD;
&#xD;
          -  Borderline resectable disease as outlined in the protocol&#xD;
&#xD;
          -  ≥ 18 years of age.&#xD;
&#xD;
          -  Male or non-pregnant and non-lactating female. If a female patient is of childbearing&#xD;
             potential, she must have a negative serum pregnancy test (β hCG) documented within 72&#xD;
             hours of the first administration of study drug.&#xD;
&#xD;
          -  If sexually active, the patient must agree to use contraception considered adequate&#xD;
             and appropriate by the Investigator.&#xD;
&#xD;
          -  Patient must not have received prior chemotherapy or radiation for pancreatic cancer&#xD;
             and no exposure to systemic chemotherapy.&#xD;
&#xD;
          -  Patient have acceptable blood counts, chemistries &amp; coagulation at baseline as&#xD;
             outlined in the protocol&#xD;
&#xD;
          -  Patient has an ECOG performance status PS 0-1.&#xD;
&#xD;
          -  Patient has been informed about the nature of the study and has agreed to participate&#xD;
             in the study and signed the Informed Consent Form prior to participation in any&#xD;
             study-related activities.&#xD;
&#xD;
          -  Endoscopic ultrasound (EUS) with FNA for cytology.&#xD;
&#xD;
          -  Patients should not have any evidence of active or uncontrolled infection requiring&#xD;
             treatment with antibiotics.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Patient has localized resectable, locally advanced unresectable or advanced metastatic&#xD;
             disease. Patients with adenocarcinoma of the pancreatic body or tail are ineligible.&#xD;
&#xD;
          -  Patient has active, uncontrolled bacterial, viral, or fungal infection(s) requiring&#xD;
             systemic therapy.&#xD;
&#xD;
          -  Patient has known infection with HIV.&#xD;
&#xD;
          -  Patient has undergone major surgery, other than diagnostic surgery (i.e.surgery done&#xD;
             to obtain a biopsy for diagnosis without removal of an organ), within 4 weeks prior to&#xD;
             Day 1 of treatment in this study.&#xD;
&#xD;
          -  Prior chemotherapy, immunotherapy or radiation for pancreatic cancer.&#xD;
&#xD;
          -  Patient has a history of allergy or hypersensitivity to the study drugs.&#xD;
&#xD;
          -  Patient has serious medical risk factors involving any of the major organ systems such&#xD;
             that the Investigator considers it unsafe for the patient to receive chemotherapy&#xD;
             and/or radiation therapy.&#xD;
&#xD;
          -  Patients must not require chronic use of immunosuppressive agents (e.g. methotrexate,&#xD;
             cyclosporine).&#xD;
&#xD;
          -  No other prior malignancy is allowed except for the following: adequately treated&#xD;
             basal cell or squamous cell skin cancer, in situ cervical cancer, adequately treated&#xD;
             Stage I or II cancer from which the patient is currently in complete remission, or any&#xD;
             other cancer from which the patient has been disease-free for five years.&#xD;
&#xD;
          -  Patients must not have clinically significant cardiovascular disease (including&#xD;
             myocardial infarction, unstable angina, symptomatic congestive heart failure, serious&#xD;
             uncontrolled cardiac arrhythmia) &lt; 1 year before randomization.&#xD;
&#xD;
          -  Patients must not have a history of any medical or psychiatric condition or laboratory&#xD;
             abnormality that in the opinion of the investigator may increase the risks associated&#xD;
             with the study participation or investigational product(s) administration or may&#xD;
             interfere with the interpretation of the results.&#xD;
&#xD;
          -  Patient is unwilling or unable to comply with study procedures.&#xD;
&#xD;
          -  Patient is enrolled in any other therapeutic clinical protocol or investigational&#xD;
             trial.&#xD;
&#xD;
          -  Patients aged &gt; 70&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>80 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Paul E. O'Brien, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Medical University of South Carolina</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Medical University of South Carolina</name>
      <address>
        <city>Charleston</city>
        <state>South Carolina</state>
        <zip>29425</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>July 2015</verification_date>
  <study_first_submitted>August 29, 2012</study_first_submitted>
  <study_first_submitted_qc>August 29, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">September 3, 2012</study_first_posted>
  <results_first_submitted>October 28, 2015</results_first_submitted>
  <results_first_submitted_qc>December 11, 2015</results_first_submitted_qc>
  <results_first_posted type="Estimate">January 15, 2016</results_first_posted>
  <last_update_submitted>December 11, 2015</last_update_submitted>
  <last_update_submitted_qc>December 11, 2015</last_update_submitted_qc>
  <last_update_posted type="Estimate">January 15, 2016</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Medical University of South Carolina</investigator_affiliation>
    <investigator_full_name>Paul O'Brien</investigator_full_name>
    <investigator_title>Assistant Professor</investigator_title>
  </responsible_party>
  <keyword>NEOADJUVANT FOLFIRINOX CHEMOTHERAPY</keyword>
  <keyword>LOCALIZED PANCREATIC HEAD ADENOCARCINOMA</keyword>
  <keyword>RADIATION THERAPY</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Adenocarcinoma</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Folfirinox</mesh_term>
  </intervention_browse>

  <clinical_results>

    <participant_flow>
      <group_list>
        <group group_id="P1">
          <title>Chemotherapy, Chemoradiation, Surgery</title>
          <description>Neoadjuvant chemotherapy - modified FOLFIRINOX chemotherapy Day and and Day 15 of 28 days cycles for 3 cycles with growth factor support followed by chemoradiation for 6-8 weeks, then surgical resection</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="3"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="2"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Lack of Efficacy</title>
              <participants_list>
                <participants group_id="P1" count="2"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>Chemotherapy, Chemoradiation, Surgery</title>
          <description>Neoadjuvant chemotherapy - modified FOLFIRINOX chemotherapy Day and and Day 15 of 28 days cycles for 3 cycles with growth factor support followed by chemoradiation for 6-8 weeks, then surgical resection</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="3"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>&lt;=18 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Between 18 and 65 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="2"/>
                  </measurement_list>
                </category>
                <category>
                  <title>&gt;=65 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Sex: Female, Male</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Female</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Ethnicity (NIH/OMB)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Not Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="3"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Race (NIH/OMB)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>American Indian or Alaska Native</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Asian</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Native Hawaiian or Other Pacific Islander</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Black or African American</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                  </measurement_list>
                </category>
                <category>
                  <title>White</title>
                  <measurement_list>
                    <measurement group_id="B1" value="2"/>
                  </measurement_list>
                </category>
                <category>
                  <title>More than one race</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Estimate the R0/R1 Resection Rate</title>
        <description>Estimate the R0/R1 resection rate as the proportion of patients with R0 or R1 resection status based on the ITT population. R0 resection status is macroscopic complete removal of tumor by non-contaminated operation, with neither macroscopic nor microscopic residual tumor. R1 resection status is macroscopic complete removal of tumor by non-contaminated operation, with microscopic residual tumor.</description>
        <time_frame>at time of surgery</time_frame>
        <population>Only subjects who had surgery were included in the outcome measure data.</population>
        <group_list>
          <group group_id="O1">
            <title>Chemotherapy, Chemoradiation, Surgery</title>
            <description>Neoadjuvant chemotherapy - modified FOLFIRINOX chemotherapy Day and and Day 15 of 28 days cycles for 3 cycles with growth factor support followed by chemoradiation for -08 weeks, then surgical resection</description>
          </group>
        </group_list>
        <measure>
          <title>Estimate the R0/R1 Resection Rate</title>
          <description>Estimate the R0/R1 resection rate as the proportion of patients with R0 or R1 resection status based on the ITT population. R0 resection status is macroscopic complete removal of tumor by non-contaminated operation, with neither macroscopic nor microscopic residual tumor. R1 resection status is macroscopic complete removal of tumor by non-contaminated operation, with microscopic residual tumor.</description>
          <population>Only subjects who had surgery were included in the outcome measure data.</population>
          <units>participants</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="1"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>R0 resection status</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>R1 resection status</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Radiographic Tumor Response</title>
        <description>The rate of CR, PR, SD and PD will be estimated as described in Section 14B prior to chemoradiation start and prior to surgery. The analysis population for estimation of radiographic response rate will be the ITT population.</description>
        <time_frame>From enrollment to Surgery</time_frame>
        <population>All subjects enrolled and had a response assessment are included in the outcome measure below.</population>
        <group_list>
          <group group_id="O1">
            <title>Chemotherapy, Chemoradiation, Surgery</title>
            <description>Neoadjuvant chemotherapy - modified FOLFIRINOX chemotherapy Day and and Day 15 of 28 days cycles for 3 cycles with growth factor support followed by chemoradiation for 6-8 weeks, then surgical resection</description>
          </group>
        </group_list>
        <measure>
          <title>Radiographic Tumor Response</title>
          <description>The rate of CR, PR, SD and PD will be estimated as described in Section 14B prior to chemoradiation start and prior to surgery. The analysis population for estimation of radiographic response rate will be the ITT population.</description>
          <population>All subjects enrolled and had a response assessment are included in the outcome measure below.</population>
          <units>participants</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="3"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>SD before chemoradiation</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>PD before chemoradiation</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>SD before surgery</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Histopathologic Tumor Response</title>
        <description>Estimate the rate of good histopathologic response as the proportion of grade I and II responders. The analysis population for this objective is the ITT population. Any patient for whom a surgical sample is not available will be considered a poor-responder.</description>
        <time_frame>at the time of surgery</time_frame>
        <population>Only subjects who had surgery were included in this outcome measure.</population>
        <group_list>
          <group group_id="O1">
            <title>Chemotherapy, Chemoradiation, Surgery</title>
            <description>Neoadjuvant chemotherapy - modified FOLFIRINOX chemotherapy Day and and Day 15 of 28 days cycles for 3 cycles with growth factor support followed by chemoradiation for 6-8 weeks, then surgical resection</description>
          </group>
        </group_list>
        <measure>
          <title>Histopathologic Tumor Response</title>
          <description>Estimate the rate of good histopathologic response as the proportion of grade I and II responders. The analysis population for this objective is the ITT population. Any patient for whom a surgical sample is not available will be considered a poor-responder.</description>
          <population>Only subjects who had surgery were included in this outcome measure.</population>
          <units>grade II responder</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="1"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Time to Recurrence:</title>
        <description>Time to recurrence is defined as the time from surgical resection to disease recurrence or death from any cause. Patients who have not recurred at the end of follow up will have their recurrence time censored at the last date of contact.</description>
        <time_frame>2 years</time_frame>
        <population>The study terminated early, prior to the follow up period being completed. Only one subject had surgery and that subject is still alive at the time of study termination, so time to recurrence cannot be estimated.</population>
        <group_list>
          <group group_id="O1">
            <title>Chemotherapy, Chemoradiation, Surgery</title>
            <description>Neoadjuvant chemotherapy - modified FOLFIRINOX chemotherapy Day and and Day 15 of 28 days cycles for 3 cycles with growth factor support followed by chemoradiation for 6-8 weeks, then surgical resection</description>
          </group>
        </group_list>
        <measure>
          <title>Time to Recurrence:</title>
          <description>Time to recurrence is defined as the time from surgical resection to disease recurrence or death from any cause. Patients who have not recurred at the end of follow up will have their recurrence time censored at the last date of contact.</description>
          <population>The study terminated early, prior to the follow up period being completed. Only one subject had surgery and that subject is still alive at the time of study termination, so time to recurrence cannot be estimated.</population>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="0"/>
              </count_list>
            </analyzed>
          </analyzed_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Overall Survival:</title>
        <description>Overall survival is defined as the time from enrollment to death from any cause. Patients still alive at the end of follow up will have their survival time censored at the last date of contact.</description>
        <time_frame>2 years</time_frame>
        <population>The study terminated early, prior to the end of the follow up period for all subjects. At the time of study termination, one subject had expired and the time from enrollment to death for that subject is reported below.</population>
        <group_list>
          <group group_id="O1">
            <title>Chemotherapy, Chemoradiation, Surgery</title>
            <description>Neoadjuvant chemotherapy - modified FOLFIRINOX chemotherapy Day and and Day 15 of 28 days cycles for 3 cycles with growth factor support followed by chemoradiation for 6-8 weeks, then surgical resection</description>
          </group>
        </group_list>
        <measure>
          <title>Overall Survival:</title>
          <description>Overall survival is defined as the time from enrollment to death from any cause. Patients still alive at the end of follow up will have their survival time censored at the last date of contact.</description>
          <population>The study terminated early, prior to the end of the follow up period for all subjects. At the time of study termination, one subject had expired and the time from enrollment to death for that subject is reported below.</population>
          <units>days</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="1"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="256"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Other Pre-specified</type>
        <title>Feasibility Objective</title>
        <description>The feasibility of treating patients with localized pancreatic head adenocarcinoma with this neoadjuvant regimen will be evaluated by estimating the proportion of patients completing five of six planned doses. The analysis population will be the ITT population.</description>
        <time_frame>From enrollment to end of chemotherapy part of the study</time_frame>
        <population>The number of subjects who had 5-6 doses of neoadjuvant regimen</population>
        <group_list>
          <group group_id="O1">
            <title>Chemotherapy, Chemoradiation, Surgery</title>
            <description>Neoadjuvant chemotherapy - modified FOLFIRINOX chemotherapy Day and and Day 15 of 28 days cycles for 3 cycles with growth factor support followed by chemoradiation for 6-8 weeks, then surgical resection</description>
          </group>
        </group_list>
        <measure>
          <title>Feasibility Objective</title>
          <description>The feasibility of treating patients with localized pancreatic head adenocarcinoma with this neoadjuvant regimen will be evaluated by estimating the proportion of patients completing five of six planned doses. The analysis population will be the ITT population.</description>
          <population>The number of subjects who had 5-6 doses of neoadjuvant regimen</population>
          <units>participants</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="3"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Other Pre-specified</type>
        <title>CTC Analysis</title>
        <description>To evaluate and describe CTC numbers, CTC phenotype characteristics and effectiveness/rate of CTC culturing techniques from patients with pancreatic adenocarcinoma.</description>
        <time_frame>End of study</time_frame>
        <population>The CTC analysis was added as an amendment. No subjects were enrolled to the study after this amendment was approved, so data for this outcome was not collected or analyzed.</population>
        <group_list>
          <group group_id="O1">
            <title>Chemotherapy, Chemoradiation, Surgery</title>
            <description>Neoadjuvant chemotherapy - modified FOLFIRINOX chemotherapy Day and and Day 15 of 28 days cycles for 3 cycles with growth factor support followed by chemoradiation for 6-8 weeks, then surgical resection</description>
          </group>
        </group_list>
        <measure>
          <title>CTC Analysis</title>
          <description>To evaluate and describe CTC numbers, CTC phenotype characteristics and effectiveness/rate of CTC culturing techniques from patients with pancreatic adenocarcinoma.</description>
          <population>The CTC analysis was added as an amendment. No subjects were enrolled to the study after this amendment was approved, so data for this outcome was not collected or analyzed.</population>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="0"/>
              </count_list>
            </analyzed>
          </analyzed_list>
        </measure>
      </outcome>
      <outcome>
        <type>Other Pre-specified</type>
        <title>CTC Expression</title>
        <description>To determine and evaluate the correlation between expression or biomarkers in the CTCs and expression of biomarkers in resected tissue specimens within the same cancer patient.</description>
        <time_frame>2 years</time_frame>
        <population>The CTC expression endpoint was added as an amendment. No subjects were enrolled to the study after this amendment was approved, so data for this outcome was not collected or analyzed.</population>
        <group_list>
          <group group_id="O1">
            <title>Chemotherapy, Chemoradiation, Surgery</title>
            <description>Neoadjuvant chemotherapy - modified FOLFIRINOX chemotherapy Day and and Day 15 of 28 days cycles for 3 cycles with growth factor support followed by chemoradiation for 6-8 weeks, then surgical resection</description>
          </group>
        </group_list>
        <measure>
          <title>CTC Expression</title>
          <description>To determine and evaluate the correlation between expression or biomarkers in the CTCs and expression of biomarkers in resected tissue specimens within the same cancer patient.</description>
          <population>The CTC expression endpoint was added as an amendment. No subjects were enrolled to the study after this amendment was approved, so data for this outcome was not collected or analyzed.</population>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="0"/>
              </count_list>
            </analyzed>
          </analyzed_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>Start of treatment to end of treatment.</time_frame>
      <desc>AEs are reported from the start of chemotherapy to the end of study treatment. Any medically significant AEs, which are ongoing at the end of study treatment should be followed until the event is resolved or considered stable.</desc>
      <group_list>
        <group group_id="E1">
          <title>Chemotherapy, Chemoradiation, Surgery</title>
          <description>Neoadjuvant chemotherapy - modified FOLFIRINOX chemotherapy Day and and Day 15 of 28 days cycles for 3 cycles with growth factor support followed by chemoradiation for 6-8 weeks, then surgical resection</description>
        </group>
      </group_list>
      <serious_events>
        <default_vocab>CTCAE (4.0)</default_vocab>
        <default_assessment>Systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="3"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>abdominal pain</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="3"/>
              </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="3"/>
              </event>
              <event>
                <sub_title>fever</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="3"/>
              </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="3"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>0</frequency_threshold>
        <default_vocab>CTCAE (4.0)</default_vocab>
        <default_assessment>Systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, other adverse events</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="3"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Blood and lymphatic system disorders</title>
            <event_list>
              <event>
                <sub_title>anemia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>leukocytosis</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="3"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Ear and labyrinth disorders</title>
            <event_list>
              <event>
                <sub_title>ear infection</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="3"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>diarrhea</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>nausea</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>vomiting</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="3"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>fatigue</sub_title>
                <counts group_id="E1" events="3" subjects_affected="3" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>chills</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>fever</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>pain</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>non-cardiac chest pain</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="3"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Investigations</title>
            <event_list>
              <event>
                <sub_title>ALT increased</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>alkaline phosphatase increase</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>AST increased</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>blood bilirubin increase</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="3"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Metabolism and nutrition disorders</title>
            <event_list>
              <event>
                <sub_title>abnormal appetite</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>hyperglycemia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>hypoalbuminemia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>hypokalemia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="3"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>dizziness</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>syncope</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="3"/>
              </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="3"/>
              </event>
              <event>
                <sub_title>insomnia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="3"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>dyspnea</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>hiccups</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="3"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Surgical and medical procedures</title>
            <event_list>
              <event>
                <sub_title>ECRP</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="3"/>
              </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>Paul O'Brien, MD</name_or_title>
      <organization>Medical University of South Carolina</organization>
      <phone>843-792-4271</phone>
      <email>obrienpe@musc.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/NCT01677988
org study id: 101822
nct id: NCT01677988
lead sponsor: 
has dmc: Yes
This study is for subjects with adenocarcinoma of the pancreas. The purpose of this research
      study is to determine the safety and effectiveness of modified Folfirinox and radiation
      therapy as treatment for adenocarcinoma (cancer) of the pancreas before surgery. Screening
      tests will be done to determine if subjects are eligible for participation in this study. If
      subjects are eligible to participate and agree to participate they will begin chemotherapy.
      After 3 cycles of chemotherapy, subjects will begin chemoradiation. Within 4 to 8 weeks of
      completing radiation therapy, subjects will have surgery. There will also be post-treatment
      and follow-up evaluations. Subjects will be followed for every 3 months for 3 years after
      their initial registration.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Estimate the R0/R1 Resection Rate
time frame: at time of surgery
description: Estimate the R0/R1 resection rate as the proportion of patients with R0 or R1 resection status based on the ITT population. R0 resection status is macroscopic complete removal of tumor by non-contaminated operation, with neither macroscopic nor microscopic residual tumor. R1 resection status is macroscopic complete removal of tumor by non-contaminated operation, with microscopic residual tumor.
measure: Radiographic Tumor Response
time frame: From enrollment to Surgery
description: The rate of CR, PR, SD and PD will be estimated as described in Section 14B prior to chemoradiation start and prior to surgery. The analysis population for estimation of radiographic response rate will be the ITT population.
measure: Histopathologic Tumor Response
time frame: at the time of surgery
description: Estimate the rate of good histopathologic response as the proportion of grade I and II responders. The analysis population for this objective is the ITT population. Any patient for whom a surgical sample is not available will be considered a poor-responder.
measure: Time to Recurrence:
time frame: 2 years
description: Time to recurrence is defined as the time from surgical resection to disease recurrence or death from any cause. Patients who have not recurred at the end of follow up will have their recurrence time censored at the last date of contact.
measure: Overall Survival:
time frame: 2 years
description: Overall survival is defined as the time from enrollment to death from any cause. Patients still alive at the end of follow up will have their survival time censored at the last date of contact.
measure: Feasibility Objective
time frame: From enrollment to end of chemotherapy part of the study
description: The feasibility of treating patients with localized pancreatic head adenocarcinoma with this neoadjuvant regimen will be evaluated by estimating the proportion of patients completing five of six planned doses. The analysis population will be the ITT population.
measure: CTC Analysis
time frame: End of study
description: To evaluate and describe CTC numbers, CTC phenotype characteristics and effectiveness/rate of CTC culturing techniques from patients with pancreatic adenocarcinoma.
measure: CTC Expression
time frame: 2 years
description: To determine and evaluate the correlation between expression or biomarkers in the CTCs and expression of biomarkers in resected tissue specimens within the same cancer patient.
arm group label: Chemotherapy, Chemoradiation, Surgery
arm group type: Experimental
description: Neoadjuvant Chemotherapy- Modified FOLFIRINOX chemotherapy Day 1 and Day 15 of 28 day cycles for 3 cycles with growth factor support Chemoradiation Surgical Resection
intervention type: Drug
intervention name: Neo-adjuvant Chemotherapy
description: Modified FOLFIRINOX chemotherapy Day 1 and Day 15 of 28 day cycles, for three (3) cycles with growth factor support.
Restaging # 1. (CT or MRI; use same modality as baseline staging unless otherwise indicated by Study Team)
Progressive Disease (PD) → Off study. Subsequent treatment per patient's primary MD.
Stable Disease (SD) or Tumor Response → Continue to Registration #2 for Chemoradiation.
arm group label: Chemotherapy, Chemoradiation, Surgery
other name: FOLFIRINOX chemotherapy
intervention type: Radiation
intervention name: Chemoradiation
description: Chemoradiation may be administered at selected approved CTN sites.
Determination of resectability as reviewed and documented by MUSC-HCC GI Tumor Board.
Unresectable → Off study. Subsequent treatment per patient's primary MD.
Resectable → Continue to Registration #3 for Surgical Resection
arm group label: Chemotherapy, Chemoradiation, Surgery
intervention type: Procedure
intervention name: Surgical Resection
description: Meets criteria for resectable* →pancreaticoduodenectomy (POD)
At time of resection, snap frozen tumor specimen sent for correlative biomarker studies
arm group label: Chemotherapy, Chemoradiation, Surgery
criteria: 
gender: All
minimum age: 18 Years
maximum age: 80 Years
healthy volunteers: No
last name: Paul E. O'Brien, MD
role: Principal Investigator
affiliation: Medical University of South Carolina
facility: 
country: United States
responsible party type: Principal Investigator
investigator affiliation: Medical University of South Carolina
investigator full name: Paul O'Brien
investigator title: Assistant Professor
mesh term: Adenocarcinoma
mesh term: Folfirinox
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 