<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/NCT03279237</url>
  </required_header>
  <id_info>
    <org_study_id>17-311</org_study_id>
    <secondary_id>U19CA021239-37</secondary_id>
    <nct_id>NCT03279237</nct_id>
  </id_info>
  <brief_title>A Pilot Study of FOLFIRINOX in Combination With Neoadjuvant Radiation for Gastric and GE Junction Cancers</brief_title>
  <official_title>A Pilot Study of FOLFIRINOX in Combination With Neoadjuvant Radiation for Gastric and GE Junction Cancers</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Massachusetts General Hospital</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>National Cancer Institute (NCI)</agency>
      <agency_class>NIH</agency_class>
    </collaborator>
  </sponsors>
  <source>Massachusetts General Hospital</source>
  <oversight_info>
    <has_dmc>Yes</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>
      This research study is studying a combination of interventions as a possible treatment for&#xD;
      gastroesophageal (GE) junction cancer.&#xD;
&#xD;
      The interventions involved in this study are:&#xD;
&#xD;
      -FOLFIRINOX which is made up of 4 different drugs:&#xD;
&#xD;
        -  5-Fluorouracil (5-FU)&#xD;
&#xD;
        -  Oxaliplatin&#xD;
&#xD;
        -  Irinotecan&#xD;
&#xD;
        -  Leucovorin&#xD;
&#xD;
        -  Paclitaxel&#xD;
&#xD;
        -  Carboplatin&#xD;
&#xD;
        -  Proton Beam Radiation Therapy&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This research study is a Pilot Study, which is the first time investigators are examining&#xD;
      this study intervention.&#xD;
&#xD;
      In this research study, the investigators are studying the combination of FOLFIRINOX followed&#xD;
      by radiation with paclitaxel and carboplatin before surgery. The investigators believe that&#xD;
      this intervention may help decrease the growth and spread of the cancer cells.&#xD;
&#xD;
      FOLFIRINOX has shown to be very effective in patients whom disease has spread. The&#xD;
      investigators are evaluating this regimen to see if there is an increase in curability when&#xD;
      the cancer has not spread.&#xD;
&#xD;
      The FDA (the U.S. Food and Drug Administration) has approved FOLFIRINOX as a treatment option&#xD;
      for this disease.&#xD;
&#xD;
      The FDA has not approved Paclitaxel or Carboplatin for this specific disease but they have&#xD;
      both been approved for other uses.&#xD;
&#xD;
      FOLFIRINOX is a combination of 4 chemotherapy agents that may help shrink the tumor before&#xD;
      surgery.&#xD;
&#xD;
      Carboplatin may stop the cancer cells from growing and paclitaxel may stop the cancer cells&#xD;
      from growing and spreading&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Active, not recruiting</overall_status>
  <start_date type="Actual">October 24, 2017</start_date>
  <completion_date type="Anticipated">September 2023</completion_date>
  <primary_completion_date type="Actual">November 20, 2018</primary_completion_date>
  <phase>Phase 1</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>N/A</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>The Completion Rate of Chemotherapy in Combination With Chemoradiation</measure>
    <time_frame>21 weeks</time_frame>
    <description>The number of participants that complete the assigned study intervention.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Number of Participants With Treatment-related Adverse Events as Assessed by CTCAE v4.0</measure>
    <time_frame>From the start of treatment until 30 days after the end of treatment (up to approximately 25 weeks)</time_frame>
    <description>The number of participants that experienced at least one treatment related adverse event as assessed by Common Terminology Criteria for Adverse Events (CTCAE v4.0).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Clinical Response Rate</measure>
    <time_frame>After 4 and 8 cycles of FOLFIRINOX (8 and 16 weeks); and 3-4 weeks after chemo radiation (24-25 weeks)</time_frame>
    <description>The number of participants that achieved a clinical response following treatment. Clinical response is defined as achieving a best overall response of a complete response (CR) or a partial response (PR).&#xD;
Complete Response (CR): Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to &lt;10 mm.&#xD;
Partial Response (PR): At least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Pathologic Complete Response Rate</measure>
    <time_frame>29 Weeks</time_frame>
    <description>The number of participants that achieve a pathologic complete response at surgery following FOLFIRINOX and chemoradiation. All patients will undergo a full pathological review of their surgical specimen according to the American Joint Committee on Cancer (AJCC) Staging Classification, 6th edition. Initial gross evaluation and identification of resection margins will be performed jointly by the surgeon and the pathologist. Pathological complete response will be defined as the absence of any viable tumor cells within the pathologic specimen.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Progression Free Survival</measure>
    <time_frame>5 Years</time_frame>
    <description>Progression-free survival (PFS) is defined as the time from the date of first dosing to the first documentation of radiographic disease progression per Response Evaluation Criteria In Solid Tumors (RECIST v1.1) or death due to any cause, whichever occurs first. Subjects who are alive with no documented progressive disease by the data cutoff date for PFS analysis will be censored at the date of their last evaluable disease assessment.&#xD;
Progressive Disease (PD) is defined as having at least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. (Note: the appearance of one or more new lesions is also considered progressions).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Overall Survival</measure>
    <time_frame>5 Years</time_frame>
    <description>The number of participants alive five years after the start of treatment. Overall survival (OS) is measured as the time from the date of first dosing until death due to any cause. If there is no death reported for a subject by the data cut-off date for overall survival analysis, OS will be censored at the last known alive date.</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">25</enrollment>
  <condition>GastroEsophageal Cancer</condition>
  <arm_group>
    <arm_group_label>FOLFIRINOX + pre-operative radiation</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>FOLFIRINOX is a combination of 4 drugs that is administered twice per cycle&#xD;
Oxaliplatin is administered intravenously&#xD;
Leucovorin is administered intravenously&#xD;
Irinotecan is administered intravenously&#xD;
5-Fluorouracil is administered intravenously&#xD;
Paclitaxel and Carboplatin will be given concurrently with radiation therapy every 7 days</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Irinotecan</intervention_name>
    <description>May help shrink tumor before surgery.</description>
    <arm_group_label>FOLFIRINOX + pre-operative radiation</arm_group_label>
    <other_name>Camptosar</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Oxaliplatin</intervention_name>
    <description>May help shrink tumor before surgery.</description>
    <arm_group_label>FOLFIRINOX + pre-operative radiation</arm_group_label>
    <other_name>Eloxatin</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Leucovorin</intervention_name>
    <description>May help shrink tumor before surgery.</description>
    <arm_group_label>FOLFIRINOX + pre-operative radiation</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>5-Fluorouracil</intervention_name>
    <description>May help shrink tumor before surgery.</description>
    <arm_group_label>FOLFIRINOX + pre-operative radiation</arm_group_label>
    <other_name>Efudex</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Paclitaxel</intervention_name>
    <description>Paclitaxel may stop cancer cells from growing and spreading.</description>
    <arm_group_label>FOLFIRINOX + pre-operative radiation</arm_group_label>
    <other_name>Abraxane</other_name>
  </intervention>
  <intervention>
    <intervention_type>Radiation</intervention_type>
    <intervention_name>Radiation Therapy</intervention_name>
    <description>May help shrink tumor.</description>
    <arm_group_label>FOLFIRINOX + pre-operative radiation</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Carboplatin</intervention_name>
    <description>Carboplatin may stop cancer cells from growing.</description>
    <arm_group_label>FOLFIRINOX + pre-operative radiation</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Histologically or cytologically confirmed T 3/4 or N+ (&gt; 1 cm in size or FDG avid)&#xD;
             gastric or gastroesophageal (GE) junction cancer. Diagnosis must be confirmed by the&#xD;
             Mass General Hospital pathology department.&#xD;
&#xD;
          -  Age 18 years or older. There will be no upper age restriction.&#xD;
&#xD;
          -  ECOG performance status ≤ 1&#xD;
&#xD;
          -  Life expectancy of greater than 3 months&#xD;
&#xD;
          -  Participants must have adequate organ and marrow function as defined below:&#xD;
&#xD;
               -  absolute neutrophil count ≥ 1,500 cells/mm3&#xD;
&#xD;
               -  platelets ≥ 75,000 cells/mm3&#xD;
&#xD;
               -  total bilirubin ≤ 1.5 x upper limit of normal, or, for patients who have&#xD;
&#xD;
               -  undergone biliary stenting, total bilirubin of ≤ 2 or two down trending values.&#xD;
&#xD;
               -  AST(SGOT) ≤ 2.5 × upper limit of normal&#xD;
&#xD;
               -  ALT (SGPT) ≤ 2.5 x upper limit of normal&#xD;
&#xD;
               -  creatinine ≤ 1.5 mg/dL, or&#xD;
&#xD;
               -  creatinine clearance ≥ 30 mL/min/1.73 m2 for participants with creatinine levels&#xD;
                  above institutional normal.&#xD;
&#xD;
          -  The effects of both radiation therapy and the chemotherapy agents used in this trial&#xD;
             are known to be teratogenic. Therefore, women of child-bearing potential and men must&#xD;
             agree to use adequate contraception (hormonal or barrier method of birth control;&#xD;
             abstinence) prior to study entry and for the duration of study participation plus 30&#xD;
             days from the last date of study drug administration. Should a woman become pregnant&#xD;
             or suspect she is pregnant while she or her partner is participating in this study,&#xD;
             she should inform her treating physician immediately.&#xD;
&#xD;
          -  Ability to understand and the willingness to sign a written informed consent document&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Evidence of metastatic disease as determined by chest CT scan, abdomen/pelvis CT scan&#xD;
             (or MRI with gadolinium and/or manganese) within six weeks of study entry. Distant&#xD;
             nodal disease is allowed if it is in the radiation port.&#xD;
&#xD;
          -  Any prior chemotherapy, targeted/biologic therapy, or radiation for treatment of the&#xD;
             participant's gastric or GE junction cancer.&#xD;
&#xD;
          -  Receipt of chemotherapy or radiotherapy within 4 weeks (6 weeks for nitrosoureas or&#xD;
             mitomycin C) prior to entering the study or those who have not recovered from adverse&#xD;
             events due to agents administered more than 4 weeks earlier.&#xD;
&#xD;
          -  Treatment of other invasive carcinomas within the last five years with greater than 5%&#xD;
             risk of recurrence at time of eligibility screening. Carcinoma in-situ and basal cell&#xD;
             carcinoma/ squamous cell carcinoma of the skin are allowed.&#xD;
&#xD;
          -  Receipt of any other investigational agents within 4 weeks preceding the start of&#xD;
             study treatment.&#xD;
&#xD;
          -  Serious concomitant systemic disorders incompatible with the study (at the discretion&#xD;
             of the investigator), such as significant cardiac or pulmonary morbidity (e.g.&#xD;
             congestive heart failure, symptomatic coronary artery disease and/or cardiac&#xD;
             arrhythmias not well controlled with medication) or myocardial infarction within the&#xD;
             last 12 months, or ongoing infection as manifested by fever.&#xD;
&#xD;
          -  History of uncontrolled seizures, central nervous system disorders or psychiatric&#xD;
             disability judged by the investigator to be clinically significant, precluding&#xD;
             informed consent, or interfering with compliance or drug intake.&#xD;
&#xD;
          -  Pregnant women are excluded from this study because radiation therapy and the&#xD;
             chemotherapy agents to be used have the potential for teratogenic or abortifacient&#xD;
             effects. Because there is an unknown but potential risk for adverse events in nursing&#xD;
             infants secondary to treatment of the mother with these agents, breastfeeding should&#xD;
             be discontinued while the mother is receiving protocol therapy.&#xD;
&#xD;
          -  Major surgery, excluding laparoscopy, within 4 weeks of the start of study treatment,&#xD;
             without complete recovery.&#xD;
&#xD;
          -  No concurrent administration of cimetidine (as it can decrease the clearance of 5-FU).&#xD;
             Another H2-blocker or proton pump inhibitor may be substituted before study entry.&#xD;
&#xD;
          -  Known, existing uncontrolled coagulopathy.&#xD;
&#xD;
          -  Prior systemic fluoropyrimidine therapy (unless given in an adjuvant setting and at&#xD;
             least six months earlier). Prior topical fluoropyrimidine use is allowed.&#xD;
&#xD;
          -  Known hypersensitivity to 5-fluorouracil or known DPD deficiency.&#xD;
&#xD;
          -  History of allergic reaction(s) attributed to compounds of similar chemical or&#xD;
             biologic composition to 5-fluorouracil, irinotecan, or oxaliplatin&#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>Theodore S. Hong, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Massachusetts General Hospital</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Massachusetts General Hospital</name>
      <address>
        <city>Boston</city>
        <state>Massachusetts</state>
        <zip>02214</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>September 2022</verification_date>
  <study_first_submitted>September 7, 2017</study_first_submitted>
  <study_first_submitted_qc>September 8, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">September 12, 2017</study_first_posted>
  <results_first_submitted>April 24, 2020</results_first_submitted>
  <results_first_submitted_qc>April 24, 2020</results_first_submitted_qc>
  <results_first_posted type="Actual">May 7, 2020</results_first_posted>
  <last_update_submitted>September 7, 2022</last_update_submitted>
  <last_update_submitted_qc>September 7, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">October 5, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Massachusetts General Hospital</investigator_affiliation>
    <investigator_full_name>Theodore Sunki Hong</investigator_full_name>
    <investigator_title>Principal Investigator</investigator_title>
  </responsible_party>
  <keyword>GastroEsophageal Cancer</keyword>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Leucovorin</mesh_term>
    <mesh_term>Paclitaxel</mesh_term>
    <mesh_term>Carboplatin</mesh_term>
    <mesh_term>Fluorouracil</mesh_term>
    <mesh_term>Oxaliplatin</mesh_term>
    <mesh_term>Irinotecan</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <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>August 14, 2019</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/37/NCT03279237/Prot_SAP_000.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <group_list>
        <group group_id="P1">
          <title>FOLFIRINOX + Pre-operative Radiation</title>
          <description>FOLFIRINOX is a combination of 4 drugs that is administered twice per cycle&#xD;
Oxaliplatin is administered intravenously&#xD;
Leucovorin is administered intravenously&#xD;
Irinotecan is administered intravenously&#xD;
5-Fluorouracil is administered intravenously&#xD;
Paclitaxel and Carboplatin will be given concurrently with radiation therapy every 7 days&#xD;
Irinotecan: May help shrink tumor before surgery.&#xD;
Oxaliplatin: May help shrink tumor before surgery.&#xD;
Leucovorin: May help shrink tumor before surgery.&#xD;
5-Fluorouracil: May help shrink tumor before surgery.&#xD;
Paclitaxel: Paclitaxel may stop cancer cells from growing and spreading.&#xD;
Radiation Therapy: May help shrink tumor.&#xD;
Carboplatin: Carboplatin may stop cancer cells from growing.</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="25"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>Chemo-radiation</title>
              <participants_list>
                <participants group_id="P1" count="23"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>Surgical Resection</title>
              <participants_list>
                <participants group_id="P1" count="20"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="20"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="5"/>
              </participants_list>
            </milestone>
          </milestone_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>FOLFIRINOX + Pre-operative Radiation</title>
          <description>FOLFIRINOX is a combination of 4 drugs that is administered twice per cycle&#xD;
Oxaliplatin is administered intravenously&#xD;
Leucovorin is administered intravenously&#xD;
Irinotecan is administered intravenously&#xD;
5-Fluorouracil is administered intravenously&#xD;
Paclitaxel and Carboplatin will be given concurrently with radiation therapy every 7 days&#xD;
Irinotecan: May help shrink tumor before surgery.&#xD;
Oxaliplatin: May help shrink tumor before surgery.&#xD;
Leucovorin: May help shrink tumor before surgery.&#xD;
5-Fluorouracil: May help shrink tumor before surgery.&#xD;
Paclitaxel: Paclitaxel may stop cancer cells from growing and spreading.&#xD;
Radiation Therapy: May help shrink tumor.&#xD;
Carboplatin: Carboplatin may stop cancer cells from growing.</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="25"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>years</units>
          <param>Median</param>
          <dispersion>Full Range</dispersion>
          <class_list>
            <class>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="25"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="60" lower_limit="30" upper_limit="76"/>
                  </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>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="25"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <title>Female</title>
                  <measurement_list>
                    <measurement group_id="B1" value="8"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="17"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Race and Ethnicity Not Collected</title>
          <population>Race and Ethnicity were not collected from any participant.</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="0"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Region of Enrollment</title>
          <units>participants</units>
          <param>Number</param>
          <class_list>
            <class>
              <title>United States</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="25"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="25"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>The Completion Rate of Chemotherapy in Combination With Chemoradiation</title>
        <description>The number of participants that complete the assigned study intervention.</description>
        <time_frame>21 weeks</time_frame>
        <group_list>
          <group group_id="O1">
            <title>FOLFIRINOX + Pre-operative Radiation</title>
            <description>FOLFIRINOX is a combination of 4 drugs that is administered twice per cycle&#xD;
Oxaliplatin is administered intravenously&#xD;
Leucovorin is administered intravenously&#xD;
Irinotecan is administered intravenously&#xD;
5-Fluorouracil is administered intravenously&#xD;
Paclitaxel and Carboplatin will be given concurrently with radiation therapy every 7 days&#xD;
Irinotecan: May help shrink tumor before surgery.&#xD;
Oxaliplatin: May help shrink tumor before surgery.&#xD;
Leucovorin: May help shrink tumor before surgery.&#xD;
5-Fluorouracil: May help shrink tumor before surgery.&#xD;
Paclitaxel: Paclitaxel may stop cancer cells from growing and spreading.&#xD;
Radiation Therapy: May help shrink tumor.&#xD;
Carboplatin: Carboplatin may stop cancer cells from growing.</description>
          </group>
        </group_list>
        <measure>
          <title>The Completion Rate of Chemotherapy in Combination With Chemoradiation</title>
          <description>The number of participants that complete the assigned study intervention.</description>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="25"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="23"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Number of Participants With Treatment-related Adverse Events as Assessed by CTCAE v4.0</title>
        <description>The number of participants that experienced at least one treatment related adverse event as assessed by Common Terminology Criteria for Adverse Events (CTCAE v4.0).</description>
        <time_frame>From the start of treatment until 30 days after the end of treatment (up to approximately 25 weeks)</time_frame>
        <group_list>
          <group group_id="O1">
            <title>FOLFIRINOX + Pre-operative Radiation</title>
            <description>FOLFIRINOX is a combination of 4 drugs that is administered twice per cycle&#xD;
Oxaliplatin is administered intravenously&#xD;
Leucovorin is administered intravenously&#xD;
Irinotecan is administered intravenously&#xD;
5-Fluorouracil is administered intravenously&#xD;
Paclitaxel and Carboplatin will be given concurrently with radiation therapy every 7 days&#xD;
Irinotecan: May help shrink tumor before surgery.&#xD;
Oxaliplatin: May help shrink tumor before surgery.&#xD;
Leucovorin: May help shrink tumor before surgery.&#xD;
5-Fluorouracil: May help shrink tumor before surgery.&#xD;
Paclitaxel: Paclitaxel may stop cancer cells from growing and spreading.&#xD;
Radiation Therapy: May help shrink tumor.&#xD;
Carboplatin: Carboplatin may stop cancer cells from growing.</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Participants With Treatment-related Adverse Events as Assessed by CTCAE v4.0</title>
          <description>The number of participants that experienced at least one treatment related adverse event as assessed by Common Terminology Criteria for Adverse Events (CTCAE v4.0).</description>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="25"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="25"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Clinical Response Rate</title>
        <description>The number of participants that achieved a clinical response following treatment. Clinical response is defined as achieving a best overall response of a complete response (CR) or a partial response (PR).&#xD;
Complete Response (CR): Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to &lt;10 mm.&#xD;
Partial Response (PR): At least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters.</description>
        <time_frame>After 4 and 8 cycles of FOLFIRINOX (8 and 16 weeks); and 3-4 weeks after chemo radiation (24-25 weeks)</time_frame>
        <group_list>
          <group group_id="O1">
            <title>FOLFIRINOX + Pre-operative Radiation</title>
            <description>FOLFIRINOX is a combination of 4 drugs that is administered twice per cycle&#xD;
Oxaliplatin is administered intravenously&#xD;
Leucovorin is administered intravenously&#xD;
Irinotecan is administered intravenously&#xD;
5-Fluorouracil is administered intravenously&#xD;
Paclitaxel and Carboplatin will be given concurrently with radiation therapy every 7 days&#xD;
Irinotecan: May help shrink tumor before surgery.&#xD;
Oxaliplatin: May help shrink tumor before surgery.&#xD;
Leucovorin: May help shrink tumor before surgery.&#xD;
5-Fluorouracil: May help shrink tumor before surgery.&#xD;
Paclitaxel: Paclitaxel may stop cancer cells from growing and spreading.&#xD;
Radiation Therapy: May help shrink tumor.&#xD;
Carboplatin: Carboplatin may stop cancer cells from growing.</description>
          </group>
        </group_list>
        <measure>
          <title>Clinical Response Rate</title>
          <description>The number of participants that achieved a clinical response following treatment. Clinical response is defined as achieving a best overall response of a complete response (CR) or a partial response (PR).&#xD;
Complete Response (CR): Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to &lt;10 mm.&#xD;
Partial Response (PR): At least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters.</description>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="25"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="20"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Pathologic Complete Response Rate</title>
        <description>The number of participants that achieve a pathologic complete response at surgery following FOLFIRINOX and chemoradiation. All patients will undergo a full pathological review of their surgical specimen according to the American Joint Committee on Cancer (AJCC) Staging Classification, 6th edition. Initial gross evaluation and identification of resection margins will be performed jointly by the surgeon and the pathologist. Pathological complete response will be defined as the absence of any viable tumor cells within the pathologic specimen.</description>
        <time_frame>29 Weeks</time_frame>
        <group_list>
          <group group_id="O1">
            <title>FOLFIRINOX + Pre-operative Radiation</title>
            <description>FOLFIRINOX is a combination of 4 drugs that is administered twice per cycle&#xD;
Oxaliplatin is administered intravenously&#xD;
Leucovorin is administered intravenously&#xD;
Irinotecan is administered intravenously&#xD;
5-Fluorouracil is administered intravenously&#xD;
Paclitaxel and Carboplatin will be given concurrently with radiation therapy every 7 days&#xD;
Irinotecan: May help shrink tumor before surgery.&#xD;
Oxaliplatin: May help shrink tumor before surgery.&#xD;
Leucovorin: May help shrink tumor before surgery.&#xD;
5-Fluorouracil: May help shrink tumor before surgery.&#xD;
Paclitaxel: Paclitaxel may stop cancer cells from growing and spreading.&#xD;
Radiation Therapy: May help shrink tumor.&#xD;
Carboplatin: Carboplatin may stop cancer cells from growing.</description>
          </group>
        </group_list>
        <measure>
          <title>Pathologic Complete Response Rate</title>
          <description>The number of participants that achieve a pathologic complete response at surgery following FOLFIRINOX and chemoradiation. All patients will undergo a full pathological review of their surgical specimen according to the American Joint Committee on Cancer (AJCC) Staging Classification, 6th edition. Initial gross evaluation and identification of resection margins will be performed jointly by the surgeon and the pathologist. Pathological complete response will be defined as the absence of any viable tumor cells within the pathologic specimen.</description>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="25"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="7"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Progression Free Survival</title>
        <description>Progression-free survival (PFS) is defined as the time from the date of first dosing to the first documentation of radiographic disease progression per Response Evaluation Criteria In Solid Tumors (RECIST v1.1) or death due to any cause, whichever occurs first. Subjects who are alive with no documented progressive disease by the data cutoff date for PFS analysis will be censored at the date of their last evaluable disease assessment.&#xD;
Progressive Disease (PD) is defined as having at least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. (Note: the appearance of one or more new lesions is also considered progressions).</description>
        <time_frame>5 Years</time_frame>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Overall Survival</title>
        <description>The number of participants alive five years after the start of treatment. Overall survival (OS) is measured as the time from the date of first dosing until death due to any cause. If there is no death reported for a subject by the data cut-off date for overall survival analysis, OS will be censored at the last known alive date.</description>
        <time_frame>5 Years</time_frame>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>From the start of treatment until 30 days after the end of treatment (up to approximately 25 weeks)</time_frame>
      <desc>Serious adverse events were defined as grade 3 or greater adverse events that were deemed to be at least possibly, probably, or definitely related to treatment. Non-serious adverse events were not captured.</desc>
      <group_list>
        <group group_id="E1">
          <title>FOLFIRINOX + Pre-operative Radiation</title>
          <description>FOLFIRINOX is a combination of 4 drugs that is administered twice per cycle&#xD;
Oxaliplatin is administered intravenously&#xD;
Leucovorin is administered intravenously&#xD;
Irinotecan is administered intravenously&#xD;
5-Fluorouracil is administered intravenously&#xD;
Paclitaxel and Carboplatin will be given concurrently with radiation therapy every 7 days&#xD;
Irinotecan: May help shrink tumor before surgery.&#xD;
Oxaliplatin: May help shrink tumor before surgery.&#xD;
Leucovorin: May help shrink tumor before surgery.&#xD;
5-Fluorouracil: May help shrink tumor before surgery.&#xD;
Paclitaxel: Paclitaxel may stop cancer cells from growing and spreading.&#xD;
Radiation Therapy: May help shrink tumor.&#xD;
Carboplatin: Carboplatin may stop cancer cells from growing.</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, all-cause mortality</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="25"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="24" subjects_at_risk="25"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Blood and lymphatic system disorders</title>
            <event_list>
              <event>
                <sub_title>Lymphopenia/Leukopenia/Neutropenia</sub_title>
                <counts group_id="E1" subjects_affected="21" subjects_at_risk="25"/>
              </event>
              <event>
                <sub_title>Febrile Neutropenia</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="25"/>
              </event>
              <event>
                <sub_title>Thrombocytopenia</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="25"/>
              </event>
              <event>
                <sub_title>Anemia</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="25"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Metabolism and nutrition disorders</title>
            <event_list>
              <event>
                <sub_title>Hypokalemia/Hyponatremia/Hypocalcemia</sub_title>
                <counts group_id="E1" subjects_affected="5" subjects_at_risk="25"/>
              </event>
              <event>
                <sub_title>Dehydration</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="25"/>
              </event>
              <event>
                <sub_title>Anorexia</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="25"/>
              </event>
              <event>
                <sub_title>Weight loss</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="25"/>
              </event>
              <event>
                <sub_title>Nausea/vomiting</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="25"/>
              </event>
              <event>
                <sub_title>Diarrhea</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="25"/>
              </event>
              <event>
                <sub_title>Dysphagia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="25"/>
              </event>
              <event>
                <sub_title>Mucositis, Oral</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="25"/>
              </event>
              <event>
                <sub_title>Gastrointestinal, Other</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="25"/>
              </event>
              <event>
                <sub_title>Infection</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="25"/>
              </event>
              <event>
                <sub_title>Hypotension</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="25"/>
              </event>
              <event>
                <sub_title>Fatigue</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="25"/>
              </event>
              <event>
                <sub_title>ALT/ALK phosphatase elevated</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="25"/>
              </event>
              <event>
                <sub_title>Cardiac</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="25"/>
              </event>
              <event>
                <sub_title>Acute kidney injury</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="25"/>
              </event>
              <event>
                <sub_title>Aspiration</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="25"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>0</frequency_threshold>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, other adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="0"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </other_events>
    </reported_events>

    <certain_agreements>
      <pi_employee>All Principal Investigators ARE employed by the organization sponsoring the study.</pi_employee>
      <restrictive_agreement>There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed. </restrictive_agreement>
    </certain_agreements>
    <point_of_contact>
      <name_or_title>Dr. Theodore Hong</name_or_title>
      <organization>Massachusetts General Hospital</organization>
      <phone>(617) 726-2000</phone>
      <email>TSHONG1@mgh.harvard.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/NCT03279237
org study id: 17-311
secondary id: U19CA021239-37
nct id: NCT03279237
lead sponsor: 
collaborator: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
is us export: No
This research study is studying a combination of interventions as a possible treatment for
      gastroesophageal (GE) junction cancer.

      The interventions involved in this study are:

      -FOLFIRINOX which is made up of 4 different drugs:

        -  5-Fluorouracil (5-FU)

        -  Oxaliplatin

        -  Irinotecan

        -  Leucovorin

        -  Paclitaxel

        -  Carboplatin

        -  Proton Beam Radiation Therapy
This research study is a Pilot Study, which is the first time investigators are examining
      this study intervention.

      In this research study, the investigators are studying the combination of FOLFIRINOX followed
      by radiation with paclitaxel and carboplatin before surgery. The investigators believe that
      this intervention may help decrease the growth and spread of the cancer cells.

      FOLFIRINOX has shown to be very effective in patients whom disease has spread. The
      investigators are evaluating this regimen to see if there is an increase in curability when
      the cancer has not spread.

      The FDA (the U.S. Food and Drug Administration) has approved FOLFIRINOX as a treatment option
      for this disease.

      The FDA has not approved Paclitaxel or Carboplatin for this specific disease but they have
      both been approved for other uses.

      FOLFIRINOX is a combination of 4 chemotherapy agents that may help shrink the tumor before
      surgery.

      Carboplatin may stop the cancer cells from growing and paclitaxel may stop the cancer cells
      from growing and spreading
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: The Completion Rate of Chemotherapy in Combination With Chemoradiation
time frame: 21 weeks
description: The number of participants that complete the assigned study intervention.
measure: Number of Participants With Treatment-related Adverse Events as Assessed by CTCAE v4.0
time frame: From the start of treatment until 30 days after the end of treatment (up to approximately 25 weeks)
description: The number of participants that experienced at least one treatment related adverse event as assessed by Common Terminology Criteria for Adverse Events (CTCAE v4.0).
measure: Clinical Response Rate
time frame: After 4 and 8 cycles of FOLFIRINOX (8 and 16 weeks); and 3-4 weeks after chemo radiation (24-25 weeks)
description: The number of participants that achieved a clinical response following treatment. Clinical response is defined as achieving a best overall response of a complete response (CR) or a partial response (PR).
Complete Response (CR): Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm.
Partial Response (PR): At least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters.
measure: Pathologic Complete Response Rate
time frame: 29 Weeks
description: The number of participants that achieve a pathologic complete response at surgery following FOLFIRINOX and chemoradiation. All patients will undergo a full pathological review of their surgical specimen according to the American Joint Committee on Cancer (AJCC) Staging Classification, 6th edition. Initial gross evaluation and identification of resection margins will be performed jointly by the surgeon and the pathologist. Pathological complete response will be defined as the absence of any viable tumor cells within the pathologic specimen.
measure: Progression Free Survival
time frame: 5 Years
description: Progression-free survival (PFS) is defined as the time from the date of first dosing to the first documentation of radiographic disease progression per Response Evaluation Criteria In Solid Tumors (RECIST v1.1) or death due to any cause, whichever occurs first. Subjects who are alive with no documented progressive disease by the data cutoff date for PFS analysis will be censored at the date of their last evaluable disease assessment.
Progressive Disease (PD) is defined as having at least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. (Note: the appearance of one or more new lesions is also considered progressions).
measure: Overall Survival
time frame: 5 Years
description: The number of participants alive five years after the start of treatment. Overall survival (OS) is measured as the time from the date of first dosing until death due to any cause. If there is no death reported for a subject by the data cut-off date for overall survival analysis, OS will be censored at the last known alive date.
arm group label: FOLFIRINOX + pre-operative radiation
arm group type: Experimental
description: FOLFIRINOX is a combination of 4 drugs that is administered twice per cycle
Oxaliplatin is administered intravenously
Leucovorin is administered intravenously
Irinotecan is administered intravenously
5-Fluorouracil is administered intravenously
Paclitaxel and Carboplatin will be given concurrently with radiation therapy every 7 days
intervention type: Drug
intervention name: Irinotecan
description: May help shrink tumor before surgery.
arm group label: FOLFIRINOX + pre-operative radiation
other name: Camptosar
intervention type: Drug
intervention name: Oxaliplatin
description: May help shrink tumor before surgery.
arm group label: FOLFIRINOX + pre-operative radiation
other name: Eloxatin
intervention type: Drug
intervention name: Leucovorin
description: May help shrink tumor before surgery.
arm group label: FOLFIRINOX + pre-operative radiation
intervention type: Drug
intervention name: 5-Fluorouracil
description: May help shrink tumor before surgery.
arm group label: FOLFIRINOX + pre-operative radiation
other name: Efudex
intervention type: Drug
intervention name: Paclitaxel
description: Paclitaxel may stop cancer cells from growing and spreading.
arm group label: FOLFIRINOX + pre-operative radiation
other name: Abraxane
intervention type: Radiation
intervention name: Radiation Therapy
description: May help shrink tumor.
arm group label: FOLFIRINOX + pre-operative radiation
intervention type: Drug
intervention name: Carboplatin
description: Carboplatin may stop cancer cells from growing.
arm group label: FOLFIRINOX + pre-operative radiation
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Theodore S. Hong, MD
role: Principal Investigator
affiliation: Massachusetts General Hospital
facility: 
country: United States
responsible party type: Principal Investigator
investigator affiliation: Massachusetts General Hospital
investigator full name: Theodore Sunki Hong
investigator title: Principal Investigator
mesh term: Leucovorin
mesh term: Paclitaxel
mesh term: Carboplatin
mesh term: Fluorouracil
mesh term: Oxaliplatin
mesh term: Irinotecan
sharing ipd: No
provided document: 
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 