<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/NCT03042780</url>
  </required_header>
  <id_info>
    <org_study_id>MCC-18675</org_study_id>
    <nct_id>NCT03042780</nct_id>
  </id_info>
  <brief_title>FOLFIRINOX in Metastatic High Grade Gastroenteropancreatic Neuroendocrine Carcinomas</brief_title>
  <official_title>Phase II Trial of FOLFIRINOX in Metastatic High Grade Gastroenteropancreatic Neuroendocrine Carcinomas</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>H. Lee Moffitt Cancer Center and Research Institute</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>H. Lee Moffitt Cancer Center and Research Institute</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
    <is_us_export>No</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      The purpose of this study is evaluate the efficacy and safety of FOLFIRINOX in patients with&#xD;
      gastroenteropancreatic high-grade neuroendocrine carcinomas.&#xD;
&#xD;
      This is a prospective Phase II open-label trial, stratifying gastroenteropancreatic high&#xD;
      grade neuroendocrine carcinomas participants equally into two cohorts (first-line versus&#xD;
      beyond first-line).&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Terminated</overall_status>
  <why_stopped>
    Slow accrual&#xD;
  </why_stopped>
  <start_date type="Actual">February 1, 2017</start_date>
  <completion_date type="Actual">September 7, 2018</completion_date>
  <primary_completion_date type="Actual">January 3, 2018</primary_completion_date>
  <phase>Phase 2</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>N/A</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Objective Radiographic Response Rate (ORR)</measure>
    <time_frame>Up to 36 months</time_frame>
    <description>The primary efficacy endpoint is objective response rate as determined by radiology review, as defined by Response Evaluation Criteria in Solid Tumors (RECIST) v1.1. Complete Response (CR): complete disappearance of all target lesions. Partial Response (PR): at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum longest diameter. Progressive disease (PD): at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this may include the baseline sum). Stable Disease (SD): neither sufficient decrease to qualify for partial response nor sufficient increase to qualify for progressive disease.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Progression Free Survival (PFS)</measure>
    <time_frame>Up to 36 months</time_frame>
    <description>PFS: from initiation date of therapy to disease progression or death. Progressive disease (PD): at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this may include the baseline sum).</description>
  </secondary_outcome>
  <other_outcome>
    <measure>Treatment Related Morbidity</measure>
    <time_frame>Up to 36 months</time_frame>
    <description>Safety analysis will be analyzed by collecting date on treatment-related morbidity and mortality. Investigators will collect data on frequency, type and severity of all adverse events that occur on or after Cycle 1, Day 1 according to National Cancer Institute Common Toxicity Criteria for Adverse Events (NCI CTCAE; Version 4.0).</description>
  </other_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">2</enrollment>
  <condition>Gastro-enteropancreatic Neuroendocrine Tumor</condition>
  <condition>Pancreatic Cancer</condition>
  <condition>Neuroendocrine Carcinomas of Pancreas</condition>
  <condition>Islet Cell Carcinoma</condition>
  <arm_group>
    <arm_group_label>FOLFIRINOX Treatment</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Participants will receive modified FOLFIRINOX which consists of 85 mg/m^2 of oxaliplatin, 400 mg/m^2 of leucovorin over the first 2 hours, 165 mg/m^2 of irinotecan in a 90-minute infusion on day 1, followed by a continuous, 46-hour infusion of 5-FU at a dosage of 2,400 mg/m^2. A cycle will be repeated every 14 days. Granulocyte colony-stimulating factor (G-CSF) prophylaxis will be allowed after each cycle. Participants will undergo re-staging studies every 8 weeks. Participants will receive up to 12 cycles during the study. Additional cycles will be determined per investigators' discretion.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>FOLFIRINOX</intervention_name>
    <description>The FOLFIRINOX regimen consists of oxaliplatin given as a 2-hour intravenous infusion, immediately followed by leucovorin given as a 2-hour intra-venous infusion, with the addition, after 30 minutes, of irinotecan given as a 90-minute intravenous infusion. This study treatment is immediately followed by a continuous intravenous infusion of 5-Fluorouracil (5-FU) over a 46-hour period every 2 weeks.</description>
    <arm_group_label>FOLFIRINOX Treatment</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Granulocyte colony-stimulating factor (G-CSF)</intervention_name>
    <description>The use of G-CSF will not be mandatory as primary prophylaxis, but will be allowed at investigators' discretion. If febrile neutropenia occurs, than the use of G-CSF will be mandatory after each following cycle of treatment.</description>
    <arm_group_label>FOLFIRINOX Treatment</arm_group_label>
    <other_name>Filgrastim</other_name>
    <other_name>Cytokine</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Histologically or cytologically confirmed neuroendocrine carcinoma of the&#xD;
             gastrointestinal (GI) tract. Potential participants with unknown origin for the&#xD;
             neuroendocrine carcinoma in which a gastroenteropancreatic origin is suspected (per&#xD;
             pathologist or investigator discretion) will be eligible for the study.&#xD;
&#xD;
          -  Tumors must have a Ki-67 index greater than 20% and/or &gt;20 mitotic figures/10&#xD;
             high-power fields.&#xD;
&#xD;
          -  Must have metastatic disease.&#xD;
&#xD;
          -  Must measurable disease, as defined by Response Evaluation Criteria in Solid Tumors&#xD;
             (RECIST) 1.1.&#xD;
&#xD;
          -  Any line of treatment (first line versus beyond first line).&#xD;
&#xD;
          -  Age &gt;18 years.&#xD;
&#xD;
          -  Life expectancy of greater than 12 weeks.&#xD;
&#xD;
          -  Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1 or 2.&#xD;
&#xD;
          -  Must have adequate organ and marrow function.&#xD;
&#xD;
          -  Ability to understand and the willingness to sign a written informed consent document.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Have had chemotherapy or radiotherapy within 3 weeks prior to entering the study.&#xD;
&#xD;
          -  Receiving any other investigational agents.&#xD;
&#xD;
          -  Untreated brain or meningeal metastases.&#xD;
&#xD;
          -  Prior treatment with 5-fluorouracil (5-FU), irinotecan or oxaliplatin.&#xD;
&#xD;
          -  Pre-treatment peripheral neuropathy greater than grade 1 per the CTCAE, version 4.0.&#xD;
&#xD;
          -  Uncontrolled intercurrent illness including, but not limited to, ongoing or active&#xD;
             infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac&#xD;
             arrhythmia, or psychiatric illness/social situations that would limit compliance with&#xD;
             study requirements.&#xD;
&#xD;
          -  A secondary primary cancer (excluding baso/squamous cell carcinoma of skin) within 1&#xD;
             year.&#xD;
&#xD;
          -  Active viral hepatitis or autoimmune hepatitis. The work-up to confirm active&#xD;
             hepatitis or autoimmune hepatitis will only be done if clinical suspicion based on&#xD;
             investigator discretion.&#xD;
&#xD;
          -  Potential participants with childbearing potential who are not willing to use adequate&#xD;
             contraception precautions during the study and for 3 months after stopping study&#xD;
             chemotherapy.&#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>Jonathan Strosberg, M.D.</last_name>
    <role>Principal Investigator</role>
    <affiliation>H. Lee Moffitt Cancer Center and Research Institute</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>H. Lee Moffitt Cancer Center and Research Institute</name>
      <address>
        <city>Tampa</city>
        <state>Florida</state>
        <zip>33612</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>November 2020</verification_date>
  <study_first_submitted>February 2, 2017</study_first_submitted>
  <study_first_submitted_qc>February 2, 2017</study_first_submitted_qc>
  <study_first_posted type="Estimate">February 3, 2017</study_first_posted>
  <results_first_submitted>November 19, 2018</results_first_submitted>
  <results_first_submitted_qc>November 19, 2018</results_first_submitted_qc>
  <results_first_posted type="Actual">December 11, 2018</results_first_posted>
  <last_update_submitted>November 24, 2020</last_update_submitted>
  <last_update_submitted_qc>November 24, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">November 27, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Gastroenteropancreatic neuroendocrine carcinomas (GEP-NECs)</keyword>
  <keyword>Metastatic</keyword>
  <keyword>High grade</keyword>
  <keyword>Pancreas</keyword>
  <keyword>Neuroendocrine carcinoma of gastrointestinal tract</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Carcinoma</mesh_term>
    <mesh_term>Pancreatic Neoplasms</mesh_term>
    <mesh_term>Neuroendocrine Tumors</mesh_term>
    <mesh_term>Carcinoma, Neuroendocrine</mesh_term>
    <mesh_term>Carcinoma, Islet Cell</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Folfirinox</mesh_term>
    <mesh_term>Lenograstim</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>June 14, 2017</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/80/NCT03042780/Prot_SAP_000.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <group_list>
        <group group_id="P1">
          <title>FOLFIRINOX Treatment</title>
          <description>Participants will receive modified FOLFIRINOX which consists of 85 mg/m^2 of oxaliplatin, 400 mg/m^2 of leucovorin over the first 2 hours, 165 mg/m^2 of irinotecan in a 90-minute infusion on day 1, followed by a continuous, 46-hour infusion of 5-FU at a dosage of 2,400 mg/m^2. A cycle will be repeated every 14 days. Granulocyte colony-stimulating factor (G-CSF) prophylaxis will be allowed after each cycle. Participants will undergo re-staging studies every 8 weeks. Participants will receive up to 12 cycles during the study. Additional cycles will be determined per investigators' discretion.&#xD;
FOLFIRINOX: The FOLFIRINOX regimen consists of oxaliplatin given as a 2-hour intravenous infusion, immediately followed by leucovorin given as a 2-hour intra-venous infusion, with the addition, after 30 minutes, of irinotecan given as a 90-minute intravenous infusion. This study treatment is immediately followed by a continuous intravenous infusion of 5-Fluorouracil (5-FU) over a 46-hour period</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="2"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="2"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
              </participants_list>
            </milestone>
          </milestone_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>FOLFIRINOX Treatment</title>
          <description>Participants will receive modified FOLFIRINOX which consists of 85 mg/m^2 of oxaliplatin, 400 mg/m^2 of leucovorin over the first 2 hours, 165 mg/m^2 of irinotecan in a 90-minute infusion on day 1, followed by a continuous, 46-hour infusion of 5-FU at a dosage of 2,400 mg/m^2. A cycle will be repeated every 14 days. Participants will receive up to 12 cycles during the study. Additional cycles will be determined per investigators' discretion.</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="2"/>
          </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="1"/>
                  </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="1"/>
                  </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="2"/>
                  </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="0"/>
                  </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>
          <title>Region of Enrollment</title>
          <units>participants</units>
          <param>Number</param>
          <class_list>
            <class>
              <title>United States</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Objective Radiographic Response Rate (ORR)</title>
        <description>The primary efficacy endpoint is objective response rate as determined by radiology review, as defined by Response Evaluation Criteria in Solid Tumors (RECIST) v1.1. Complete Response (CR): complete disappearance of all target lesions. Partial Response (PR): at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum longest diameter. Progressive disease (PD): at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this may include the baseline sum). Stable Disease (SD): neither sufficient decrease to qualify for partial response nor sufficient increase to qualify for progressive disease.</description>
        <time_frame>Up to 36 months</time_frame>
        <population>Due to low accrual, study was halted prematurely. No data, as no patients were analyzed.</population>
        <group_list>
          <group group_id="O1">
            <title>FOLFIRINOX Treatment</title>
            <description>Participants will receive modified FOLFIRINOX which consists of 85 mg/m^2 of oxaliplatin, 400 mg/m^2 of leucovorin over the first 2 hours, 165 mg/m^2 of irinotecan in a 90-minute infusion on day 1, followed by a continuous, 46-hour infusion of 5-FU at a dosage of 2,400 mg/m^2. A cycle will be repeated every 14 days. Granulocyte colony-stimulating factor (G-CSF) prophylaxis will be allowed after each cycle. Participants will undergo re-staging studies every 8 weeks. Participants will receive up to 12 cycles during the study. Additional cycles will be determined per investigators' discretion.&#xD;
FOLFIRINOX: The FOLFIRINOX regimen consists of oxaliplatin given as a 2-hour intravenous infusion, immediately followed by leucovorin given as a 2-hour intra-venous infusion, with the addition, after 30 minutes, of irinotecan given as a 90-minute intravenous infusion. This study treatment is immediately followed by a continuous intravenous infusion of 5-Fluorouracil (5-FU) over a 46-hour period</description>
          </group>
        </group_list>
        <measure>
          <title>Objective Radiographic Response Rate (ORR)</title>
          <description>The primary efficacy endpoint is objective response rate as determined by radiology review, as defined by Response Evaluation Criteria in Solid Tumors (RECIST) v1.1. Complete Response (CR): complete disappearance of all target lesions. Partial Response (PR): at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum longest diameter. Progressive disease (PD): at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this may include the baseline sum). Stable Disease (SD): neither sufficient decrease to qualify for partial response nor sufficient increase to qualify for progressive disease.</description>
          <population>Due to low accrual, study was halted prematurely. No data, as no patients were 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>Secondary</type>
        <title>Progression Free Survival (PFS)</title>
        <description>PFS: from initiation date of therapy to disease progression or death. Progressive disease (PD): at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this may include the baseline sum).</description>
        <time_frame>Up to 36 months</time_frame>
        <population>No data displayed because Outcome Measure has zero total participants analyzed.</population>
        <group_list>
          <group group_id="O1">
            <title>FOLFIRINOX Treatment</title>
            <description>Participants will receive modified FOLFIRINOX which consists of 85 mg/m^2 of oxaliplatin, 400 mg/m^2 of leucovorin over the first 2 hours, 165 mg/m^2 of irinotecan in a 90-minute infusion on day 1, followed by a continuous, 46-hour infusion of 5-FU at a dosage of 2,400 mg/m^2. A cycle will be repeated every 14 days. Granulocyte colony-stimulating factor (G-CSF) prophylaxis will be allowed after each cycle. Participants will undergo re-staging studies every 8 weeks. Participants will receive up to 12 cycles during the study. Additional cycles will be determined per investigators' discretion.&#xD;
FOLFIRINOX: The FOLFIRINOX regimen consists of oxaliplatin given as a 2-hour intravenous infusion, immediately followed by leucovorin given as a 2-hour intra-venous infusion, with the addition, after 30 minutes, of irinotecan given as a 90-minute intravenous infusion. This study treatment is immediately followed by a continuous intravenous infusion of 5-Fluorouracil (5-FU) over a 46-hour period</description>
          </group>
        </group_list>
        <measure>
          <title>Progression Free Survival (PFS)</title>
          <description>PFS: from initiation date of therapy to disease progression or death. Progressive disease (PD): at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this may include the baseline sum).</description>
          <population>No data displayed because Outcome Measure has zero total participants 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>Treatment Related Morbidity</title>
        <description>Safety analysis will be analyzed by collecting date on treatment-related morbidity and mortality. Investigators will collect data on frequency, type and severity of all adverse events that occur on or after Cycle 1, Day 1 according to National Cancer Institute Common Toxicity Criteria for Adverse Events (NCI CTCAE; Version 4.0).</description>
        <time_frame>Up to 36 months</time_frame>
        <population>No data displayed because Outcome Measure has zero total participants analyzed.</population>
        <group_list>
          <group group_id="O1">
            <title>FOLFIRINOX Treatment</title>
            <description>Participants will receive modified FOLFIRINOX which consists of 85 mg/m^2 of oxaliplatin, 400 mg/m^2 of leucovorin over the first 2 hours, 165 mg/m^2 of irinotecan in a 90-minute infusion on day 1, followed by a continuous, 46-hour infusion of 5-FU at a dosage of 2,400 mg/m^2. A cycle will be repeated every 14 days. Granulocyte colony-stimulating factor (G-CSF) prophylaxis will be allowed after each cycle. Participants will undergo re-staging studies every 8 weeks. Participants will receive up to 12 cycles during the study. Additional cycles will be determined per investigators' discretion.&#xD;
FOLFIRINOX: The FOLFIRINOX regimen consists of oxaliplatin given as a 2-hour intravenous infusion, immediately followed by leucovorin given as a 2-hour intra-venous infusion, with the addition, after 30 minutes, of irinotecan given as a 90-minute intravenous infusion. This study treatment is immediately followed by a continuous intravenous infusion of 5-Fluorouracil (5-FU) over a 46-hour period</description>
          </group>
        </group_list>
        <measure>
          <title>Treatment Related Morbidity</title>
          <description>Safety analysis will be analyzed by collecting date on treatment-related morbidity and mortality. Investigators will collect data on frequency, type and severity of all adverse events that occur on or after Cycle 1, Day 1 according to National Cancer Institute Common Toxicity Criteria for Adverse Events (NCI CTCAE; Version 4.0).</description>
          <population>No data displayed because Outcome Measure has zero total participants 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>1 year</time_frame>
      <group_list>
        <group group_id="E1">
          <title>FOLFIRINOX Treatment</title>
          <description>Participants received modified FOLFIRINOX which consists of 85 mg/m^2 of oxaliplatin, 400 mg/m^2 of leucovorin over the first 2 hours, 165 mg/m^2 of irinotecan in a 90-minute infusion on day 1, followed by a continuous, 46-hour infusion of 5-FU at a dosage of 2,400 mg/m^2. A cycle will be repeated every 14 days. Granulocyte colony-stimulating factor (G-CSF) prophylaxis will be allowed after each cycle.</description>
        </group>
      </group_list>
      <serious_events>
        <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="2"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="2"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>0</frequency_threshold>
        <default_vocab>CTCAE (4.0)</default_vocab>
        <default_assessment>Non-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="2" subjects_at_risk="2"/>
              </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="4" subjects_affected="1" subjects_at_risk="2"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Eye disorders</title>
            <event_list>
              <event>
                <sub_title>Blurred Vision</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="2"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Nausea</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="2"/>
              </event>
              <event>
                <sub_title>Diarrhea</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="2"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Fatigue</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="2"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Skin Infection</sub_title>
                <description>right forearm ant bite</description>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="2"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Investigations</title>
            <event_list>
              <event>
                <sub_title>Alanine aminotransferase increased</sub_title>
                <counts group_id="E1" events="7" subjects_affected="1" subjects_at_risk="2"/>
              </event>
              <event>
                <sub_title>Alkaline phosphatase increased</sub_title>
                <counts group_id="E1" events="4" subjects_affected="1" subjects_at_risk="2"/>
              </event>
              <event>
                <sub_title>Aspartate aminotransferase increased</sub_title>
                <counts group_id="E1" events="6" subjects_affected="1" subjects_at_risk="2"/>
              </event>
              <event>
                <sub_title>Lymphocyte count decreased</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="2"/>
              </event>
              <event>
                <sub_title>Neutrophil count decreased</sub_title>
                <counts group_id="E1" events="3" subjects_affected="2" subjects_at_risk="2"/>
              </event>
              <event>
                <sub_title>White blood cell decreased</sub_title>
                <counts group_id="E1" events="5" subjects_affected="2" subjects_at_risk="2"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Metabolism and nutrition disorders</title>
            <event_list>
              <event>
                <sub_title>Hyperglycemia</sub_title>
                <counts group_id="E1" events="2" subjects_affected="1" subjects_at_risk="2"/>
              </event>
              <event>
                <sub_title>Hypernatremia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="2"/>
              </event>
              <event>
                <sub_title>Hypokalemia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="2"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Musculoskeletal and connective tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Arthralgia</sub_title>
                <description>Body aches, joint pain</description>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="2"/>
              </event>
              <event>
                <sub_title>Back pain</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="2"/>
              </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="2"/>
              </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>
    <limitations_and_caveats>Study terminated early due to inability to accrue, leading to small number of participants analyzed.</limitations_and_caveats>
    <point_of_contact>
      <name_or_title>Jonathan Strosberg, MD</name_or_title>
      <organization>H Lee Moffitt Cancer Center and Research Institute</organization>
      <phone>813-745-7257</phone>
      <email>Jonathan.Strosberg@moffitt.org</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/NCT03042780
org study id: MCC-18675
nct id: NCT03042780
lead sponsor: 
has dmc: No
is fda regulated drug: Yes
is fda regulated device: No
is us export: No
The purpose of this study is evaluate the efficacy and safety of FOLFIRINOX in patients with
      gastroenteropancreatic high-grade neuroendocrine carcinomas.

      This is a prospective Phase II open-label trial, stratifying gastroenteropancreatic high
      grade neuroendocrine carcinomas participants equally into two cohorts (first-line versus
      beyond first-line).
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Objective Radiographic Response Rate (ORR)
time frame: Up to 36 months
description: The primary efficacy endpoint is objective response rate as determined by radiology review, as defined by Response Evaluation Criteria in Solid Tumors (RECIST) v1.1. Complete Response (CR): complete disappearance of all target lesions. Partial Response (PR): at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum longest diameter. Progressive disease (PD): at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this may include the baseline sum). Stable Disease (SD): neither sufficient decrease to qualify for partial response nor sufficient increase to qualify for progressive disease.
measure: Progression Free Survival (PFS)
time frame: Up to 36 months
description: PFS: from initiation date of therapy to disease progression or death. Progressive disease (PD): at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this may include the baseline sum).
measure: Treatment Related Morbidity
time frame: Up to 36 months
description: Safety analysis will be analyzed by collecting date on treatment-related morbidity and mortality. Investigators will collect data on frequency, type and severity of all adverse events that occur on or after Cycle 1, Day 1 according to National Cancer Institute Common Toxicity Criteria for Adverse Events (NCI CTCAE; Version 4.0).
arm group label: FOLFIRINOX Treatment
arm group type: Experimental
description: Participants will receive modified FOLFIRINOX which consists of 85 mg/m^2 of oxaliplatin, 400 mg/m^2 of leucovorin over the first 2 hours, 165 mg/m^2 of irinotecan in a 90-minute infusion on day 1, followed by a continuous, 46-hour infusion of 5-FU at a dosage of 2,400 mg/m^2. A cycle will be repeated every 14 days. Granulocyte colony-stimulating factor (G-CSF) prophylaxis will be allowed after each cycle. Participants will undergo re-staging studies every 8 weeks. Participants will receive up to 12 cycles during the study. Additional cycles will be determined per investigators' discretion.
intervention type: Drug
intervention name: FOLFIRINOX
description: The FOLFIRINOX regimen consists of oxaliplatin given as a 2-hour intravenous infusion, immediately followed by leucovorin given as a 2-hour intra-venous infusion, with the addition, after 30 minutes, of irinotecan given as a 90-minute intravenous infusion. This study treatment is immediately followed by a continuous intravenous infusion of 5-Fluorouracil (5-FU) over a 46-hour period every 2 weeks.
arm group label: FOLFIRINOX Treatment
intervention type: Drug
intervention name: Granulocyte colony-stimulating factor (G-CSF)
description: The use of G-CSF will not be mandatory as primary prophylaxis, but will be allowed at investigators' discretion. If febrile neutropenia occurs, than the use of G-CSF will be mandatory after each following cycle of treatment.
arm group label: FOLFIRINOX Treatment
other name: Filgrastim
other name: Cytokine
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Jonathan Strosberg, M.D.
role: Principal Investigator
affiliation: H. Lee Moffitt Cancer Center and Research Institute
facility: 
country: United States
responsible party type: Sponsor
mesh term: Carcinoma
mesh term: Pancreatic Neoplasms
mesh term: Neuroendocrine Tumors
mesh term: Carcinoma, Neuroendocrine
mesh term: Carcinoma, Islet Cell
mesh term: Folfirinox
mesh term: Lenograstim
provided document: 
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
limitations and caveats: Study terminated early due to inability to accrue, leading to small number of participants analyzed.
point of contact: 