<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/NCT03278626</url>
  </required_header>
  <id_info>
    <org_study_id>16-00971</org_study_id>
    <nct_id>NCT03278626</nct_id>
  </id_info>
  <brief_title>Immune Checkpoint Therapy With Nivolumab Esophageal Squamous Cell Carcinoma</brief_title>
  <official_title>A Phase I/II Open Label Multi Center Study of Immune Checkpoint Therapy With Nivolumab for Patients With Locally Advanced Esophageal Squamous Cell Carcinoma</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>NYU Langone Health</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>NYU Langone Health</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>
      In this multi-institution phase I/II trial, the investigators have chosen paclitaxel and&#xD;
      carboplatin using a schedule and doses identical to those used in the CROSS trial. Following&#xD;
      a run-in with nivolumab alone at 240 mg IVPB every 2 weeks for 2 doses, nivolumab at 240 mg&#xD;
      every 2 weeks will be added to paclitaxel and carboplatin, which will be dosed according to&#xD;
      the standard of care established by the CROSS trial: paclitaxel 50 mg/m2 weekly for 6 weeks&#xD;
      and carboplatin AUC 2 weekly for 6 weeks. Concurrent radiation will be administered with&#xD;
      chemotherapy at 1.8 Gy/fraction × 28 fractions to a total dose of 50.4 Gy, the standard&#xD;
      radiation dose administered in the United States for trimodality therapy that includes&#xD;
      concurrent therapy with carboplatin and paclitaxel. A decrease in dose to 41.4 Gy per the&#xD;
      protocol established by van Hagen, et al. will be permitted before discontinuing therapy due&#xD;
      to unacceptable toxicity. While the CROSS study administered only 5 weekly doses of&#xD;
      chemotherapy during the 5 weeks of radiation, the higher dose of 50.4 Gy (1.8 Gy/fraction ×28&#xD;
      fractions over 5½ weeks) utilized in this study permits for a sixth dose during the&#xD;
      additional week of radiation.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Terminated</overall_status>
  <why_stopped>
    The study was stopped earlier than anticipated due to slow accrual&#xD;
  </why_stopped>
  <start_date type="Actual">June 27, 2017</start_date>
  <completion_date type="Actual">May 31, 2021</completion_date>
  <primary_completion_date type="Actual">November 7, 2019</primary_completion_date>
  <phase>Phase 1/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>Phase 1: Number of Unacceptable Toxicity (UT) Events</measure>
    <time_frame>92 days (up to 28 days after Day 64)</time_frame>
    <description>UT is defined as:&#xD;
Recurrent grade 3 or 4 hematologic toxicity (despite 1 prior dose reduction in chemotherapy)&#xD;
any toxicity that results in a &gt; 2-week delay in chemoradiation</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Phase 2: Number of Subjects Who Achieved cCR (Clinical Complete Response) or pCR (Pathological Complete Response)</measure>
    <time_frame>5-8 Weeks post radiation treatment (7-8 months after treatment start)</time_frame>
    <description>Clinical and pathological response after neoadjuvant therapy cCR by endoscopic + PET/CT evaluation; pCR for patients undergoing surgery Clinical Complete Response (cCR), no malignancy is found on clinical examination, imaging, endoscopy, and biopsy; Pathological Complete Response (pCR), no invasive and no in situ residual tumors in tissue</description>
  </primary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">12</enrollment>
  <condition>Esophageal Squamous Cell Carcinoma</condition>
  <arm_group>
    <arm_group_label>Nivolimumab+Carboplatin/paclitaxel+Radiation</arm_group_label>
    <arm_group_type>Other</arm_group_type>
    <description>240 mg IVPB every 2 weeks for 2 doses, nivolumab at 240 mg every 2 weeks will be added to paclitaxel and carboplatin, which will be dosed according to the standard of care: paclitaxel 50 mg/m2 weekly for 6 weeks and carboplatin AUC 2 weekly for 6 weeks and radiation</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Nivolimumab+Carboplatin/paclitaxel+Radiation</intervention_name>
    <description>In the phase I portion of the study, up to six patients will be treated (radiation will be 50.4 Gy (1.8 Gy/fraction × 28 fractions)) and then observed for 28 days (following last day of treatment (Day 64)).</description>
    <arm_group_label>Nivolimumab+Carboplatin/paclitaxel+Radiation</arm_group_label>
    <other_name>Opdivo</other_name>
    <other_name>Paraplatin</other_name>
    <other_name>Taxol</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Histologically or cytologically confirmed, treatment-naive esophageal squamous cell&#xD;
             carcinoma&#xD;
&#xD;
          -  Previously obtained archival tumor tissue, or tissue obtained by endoscopically guided&#xD;
             core biopsy at screening&#xD;
&#xD;
          -  TanyN1-3 or T3-4 N0as determined by EUS and PET/CT. All palpable or CT/PET visible&#xD;
             lymph nodes outside the usual surgical field must be biopsy-proven negative for&#xD;
             cancer.&#xD;
&#xD;
          -  All patients must have locoregional staging determined by endoscopic ultrasound (EUS)&#xD;
             if technically feasible. Endoscopy reports or subsequent GI clinic note should clearly&#xD;
             state both the T and N stage.&#xD;
&#xD;
          -  All patients must have initial PET/CT scans to document no evidence of metastatic or&#xD;
             unresectable squamous cell cancer&#xD;
&#xD;
          -  All patients with tumors involving the thoracic esophagus must undergo bronchoscopy to&#xD;
             document the absence of a fistula No known contraindication to the use of taxanes or&#xD;
             platinum compounds.&#xD;
&#xD;
          -  No history of severe hypersensitivity reaction to Cremophor® EL.&#xD;
&#xD;
          -  Patients who are ≥ 18 years old are eligible for this study. Neither specific gender&#xD;
             distribution, nor specific racial or ethnic origins are necessary for enrollment in&#xD;
             this study.&#xD;
&#xD;
          -  Eastern Cooperative Oncology Group (ECOG) Performance Status 0-1&#xD;
&#xD;
          -  A patient must be capable of giving informed consent or have an acceptable surrogate&#xD;
             capable of giving consent on the subject's behalf&#xD;
&#xD;
          -  Deemed a suitable candidate for esophagectomy by the treating surgeon as documented in&#xD;
             a pre-operative assessment visit per standard practice at each participating&#xD;
             institution.&#xD;
&#xD;
          -  Deemed a suitable candidate for radiation therapy by the treating radiation oncologist&#xD;
             as documented in a standard pretreatment visit per standard practice at each&#xD;
             participating institution.&#xD;
&#xD;
          -  Patient must be non-pregnant and non-nursing. Women of child bearing potential (WOCBP)&#xD;
             must have a negative serum or urine pregnancy test (minimum sensitivity 25 IU/L or&#xD;
             equivalent units of HCG) within 72 hours prior to C1D1.&#xD;
&#xD;
          -  Screening Laboratory Values must meet the following criteria and should be obtained&#xD;
             within 14 days prior to C1D1 (see Table 1 below)&#xD;
&#xD;
          -  Patients with a positive Hepatitis B core antibody (HBVcAb) must have negative viral&#xD;
             load measurement; Patients with HBV core positive, must have negative viral load&#xD;
             measurements&#xD;
&#xD;
          -  Screening Laboratory Values must meet the following criteria and should be obtained&#xD;
             within 14 days prior to randomization/registration (see Table 1 below) Test Acceptable&#xD;
             Result WBC ≥ 2000/µL Neutrophils ≥ 1500/µL Platelets ≥ 100,000 /µL Hemoglobin &gt; 9.0&#xD;
             g/dL Serum Creatinine ≤ 1.5 x ULN OR Creatinine Clearance (CrCl)* ≥ 40 mL/min AST ≤ 3&#xD;
             x ULN ALT ≤ 3 x ULN Total Bilirubin** ≤ 1.5 x ULN&#xD;
&#xD;
        Oxygen Saturation (O2 Sat.) ≥92% on ambient air Hepatitis B status HBV Surface Antigen&#xD;
        Negative HBV Surface Antibody Positive or Negative HBV Core Antibody Negative Hepatitis C&#xD;
        status Anti-HCV Total Antibody Negative HCV RNA analysis Negative HIV status Rapid HIV 1/2&#xD;
        Antibodies Negative *Creatinine Clearance Calculated using the Cockcroft-Gault formula&#xD;
&#xD;
        Female CrCl = (140- age in years) x weight in kg x 0.85 72 x serum creatinine in mg/dL&#xD;
&#xD;
        Male CrCl = (140- age in years) x weight in kg x 1.00 72 x serum creatinine in mg/dL&#xD;
&#xD;
        **Total Bilirubin ≤ 1.5 x ULN, except subjects with Gilbert Syndrome, who can have total&#xD;
        bilirubin &lt; 3.0 mg/dL&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  T1-2 N0 as determined by EUS and PET/CT.&#xD;
&#xD;
          -  Pregnant or lactating women&#xD;
&#xD;
          -  Active or prior documented autoimmune or inflammatory disorders including but not&#xD;
             limited to inflammatory bowel disease; systemic lupus erythematosus; type I diabetes&#xD;
             mellitus; Wegener syndrome [granulomatosis with polyangiitis]; myasthenia gravis;&#xD;
             Graves' disease; rheumatoid arthritis, hypophysitis, uveitis) within the past 3 years&#xD;
             prior to the start of treatment. The following are exceptions to this criterion:&#xD;
&#xD;
          -  Subjects with vitiligo or alopecia&#xD;
&#xD;
          -  Subjects with hypothyroidism (e.g., following Hashimoto syndrome) stable on hormone&#xD;
             replacement or psoriasis not requiring systemic treatment&#xD;
&#xD;
          -  History of idiopathic pulmonary fibrosis, organizing pneumonia, drug-induced&#xD;
             pneumonitis, idiopathic pneumonitis, or evidence of active pneumonitis on screening&#xD;
             chest Computed Tomography (CT) scan&#xD;
&#xD;
          -  The use of immunosuppressive medication within 28 days prior to the first dose of&#xD;
             nivolumab. The following are exceptions to this criterion:&#xD;
&#xD;
          -  Intranasal, topical, inhaled corticosteroids or local steroid injections (e.g.&#xD;
             intra-articular injection)&#xD;
&#xD;
          -  Systemic corticosteroids at physiologic doses ≤10 mg/day of prednisone or equivalent&#xD;
&#xD;
          -  Steroids as premedication for hypersensitivity reactions (e.g. CT scan premedication&#xD;
&#xD;
          -  Positive test for Human Immunodeficiency Virus (HIV) or known acquired&#xD;
             immunodeficiency syndrome (AIDS)&#xD;
&#xD;
          -  Active Hepatitis B or Hepatitis C (defined as positive-HBV surface antigen or&#xD;
             detectable HCV-antibody) indicating acute or chronic infection. Patients with a&#xD;
             positive Hepatitis B core antibody (HBVcAb) must have negative viral load measurement.&#xD;
&#xD;
          -  Prior treatment with any immunotherapy&#xD;
&#xD;
          -  Any other factors, including psychiatric or social, that in the opinion of the&#xD;
             treating physician makes the patient an inappropriate candidate for a study.&#xD;
&#xD;
          -  Patients are excluded if they have active brain metastases or leptomeningeal&#xD;
             metastases. Subjects with brain metastases are eligible if metastases have been&#xD;
             treated and there is no magnetic resonance imaging (MRI) evidence of progression for&#xD;
             [lowest minimum is 4 weeks or more] after treatment is complete and within 28 days&#xD;
             prior to the first dose of nivolumab administration. There must also be no ESCC&#xD;
             Nivolumab requirement for immunosuppressive doses of systemic corticosteroids (&gt; 10&#xD;
             mg/day prednisone equivalents) for at least 2 weeks prior to study drug&#xD;
             administration.&#xD;
&#xD;
          -  Patients should be excluded if they have an active, known or suspected autoimmune&#xD;
             disease. Subjects are permitted to enroll if they have vitiligo, residual&#xD;
             hypothyroidism due to autoimmune condition only requiring hormone replacement,&#xD;
             psoriasis not requiring systemic treatment, or conditions not expected to recur in the&#xD;
             absence of an external trigger&#xD;
&#xD;
          -  Patients should be excluded if they have a condition requiring systemic treatment with&#xD;
             either corticosteroids (&gt; 10 mg daily prednisone equivalents) or other&#xD;
             immunosuppressive medications within 14 days of study drug administration. Inhaled or&#xD;
             topical steroids and adrenal replacement doses &lt; 10 mg daily prednisone equivalents&#xD;
             are permitted in the absence of active autoimmune disease.&#xD;
&#xD;
          -  As there is potential for hepatic toxicity with nivolumab or nivolumab non-drugs with&#xD;
             a predisposition to hepatoxicity should be used with caution in patients treated with&#xD;
             nivolumab-containing regimen.&#xD;
&#xD;
          -  Patients with a history of allergy to the study drug components are excluded.&#xD;
&#xD;
          -  No herbal supplements are allowed in this protocol.&#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>Jennifer Wu, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>NYU Langone Health</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>University of Califonia, San Diego</name>
      <address>
        <city>La Jolla</city>
        <state>California</state>
        <zip>92093</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Southern California</name>
      <address>
        <city>Los Angeles</city>
        <state>California</state>
        <zip>90033</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>New York University School of Medicine</name>
      <address>
        <city>New York</city>
        <state>New York</state>
        <zip>10016</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Memorial Sloan Kettering Cancer Center</name>
      <address>
        <city>New York</city>
        <state>New York</state>
        <zip>10065</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Oregon Health Sciences University</name>
      <address>
        <city>Portland</city>
        <state>Oregon</state>
        <zip>97239</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>March 2022</verification_date>
  <study_first_submitted>August 31, 2017</study_first_submitted>
  <study_first_submitted_qc>September 8, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">September 11, 2017</study_first_posted>
  <results_first_submitted>February 9, 2022</results_first_submitted>
  <results_first_submitted_qc>March 2, 2022</results_first_submitted_qc>
  <results_first_posted type="Actual">March 28, 2022</results_first_posted>
  <last_update_submitted>March 2, 2022</last_update_submitted>
  <last_update_submitted_qc>March 2, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">March 28, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Locally Advanced Esophageal Squamous Cell Carcinoma</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Carcinoma</mesh_term>
    <mesh_term>Carcinoma, Squamous Cell</mesh_term>
    <mesh_term>Esophageal Squamous Cell Carcinoma</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Paclitaxel</mesh_term>
    <mesh_term>Carboplatin</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>January 22, 2020</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/26/NCT03278626/Prot_SAP_000.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <group_list>
        <group group_id="P1">
          <title>Nivolimumab+Carboplatin/Paclitaxel+Radiation</title>
          <description>240 mg IVPB every 2 weeks for 2 doses, nivolumab at 240 mg every 2 weeks will be added to paclitaxel and carboplatin, which will be dosed according to the standard of care: paclitaxel 50 mg/m2 weekly for 6 weeks and carboplatin AUC 2 weekly for 6 weeks and radiation&#xD;
Nivolimumab+Carboplatin/paclitaxel+Radiation: In the phase I portion of the study, up to six patients will be treated (radiation will be 50.4 Gy (1.8 Gy/fraction × 28 fractions)) and then observed for 28 days (following last day of treatment (Day 64)).</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="12"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="7"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="5"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Death</title>
              <participants_list>
                <participants group_id="P1" count="2"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Toxicity</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Disease Progression</title>
              <participants_list>
                <participants group_id="P1" count="2"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <population>6 subjects enrolled in Phase 1, and 6 subjects enrolled in Phase 2</population>
      <group_list>
        <group group_id="B1">
          <title>Nivolimumab+Carboplatin/Paclitaxel+Radiation</title>
          <description>240 mg IVPB every 2 weeks for 2 doses, nivolumab at 240 mg every 2 weeks will be added to paclitaxel and carboplatin, which will be dosed according to the standard of care: paclitaxel 50 mg/m2 weekly for 6 weeks and carboplatin AUC 2 weekly for 6 weeks and radiation&#xD;
Nivolimumab+Carboplatin/paclitaxel+Radiation: In the phase I portion of the study, up to six patients will be treated (radiation will be 50.4 Gy (1.8 Gy/fraction × 28 fractions)) and then observed for 28 days (following last day of treatment (Day 64)).</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="12"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>years</units>
          <param>Median</param>
          <dispersion>Full Range</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="63.95" lower_limit="47.03" upper_limit="86.17"/>
                  </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="5"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="7"/>
                  </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="12"/>
                  </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="3"/>
                  </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="2"/>
                  </measurement_list>
                </category>
                <category>
                  <title>White</title>
                  <measurement_list>
                    <measurement group_id="B1" value="7"/>
                  </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="12"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Phase 1: Number of Unacceptable Toxicity (UT) Events</title>
        <description>UT is defined as:&#xD;
Recurrent grade 3 or 4 hematologic toxicity (despite 1 prior dose reduction in chemotherapy)&#xD;
any toxicity that results in a &gt; 2-week delay in chemoradiation</description>
        <time_frame>92 days (up to 28 days after Day 64)</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Nivolimumab+Carboplatin/Paclitaxel+Radiation</title>
            <description>240 mg IVPB every 2 weeks for 2 doses, nivolumab at 240 mg every 2 weeks will be added to paclitaxel and carboplatin, which will be dosed according to the standard of care: paclitaxel 50 mg/m2 weekly for 6 weeks and carboplatin AUC 2 weekly for 6 weeks and radiation&#xD;
Nivolimumab+Carboplatin/paclitaxel+Radiation: In the phase I portion of the study, up to six patients will be treated (radiation will be 50.4 Gy (1.8 Gy/fraction × 28 fractions)) and then observed for 28 days (following last day of treatment (Day 64)).</description>
          </group>
        </group_list>
        <measure>
          <title>Phase 1: Number of Unacceptable Toxicity (UT) Events</title>
          <description>UT is defined as:&#xD;
Recurrent grade 3 or 4 hematologic toxicity (despite 1 prior dose reduction in chemotherapy)&#xD;
any toxicity that results in a &gt; 2-week delay in chemoradiation</description>
          <units>Unacceptable Toxicity Events</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="6"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Phase 2: Number of Subjects Who Achieved cCR (Clinical Complete Response) or pCR (Pathological Complete Response)</title>
        <description>Clinical and pathological response after neoadjuvant therapy cCR by endoscopic + PET/CT evaluation; pCR for patients undergoing surgery Clinical Complete Response (cCR), no malignancy is found on clinical examination, imaging, endoscopy, and biopsy; Pathological Complete Response (pCR), no invasive and no in situ residual tumors in tissue</description>
        <time_frame>5-8 Weeks post radiation treatment (7-8 months after treatment start)</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Nivolimumab+Carboplatin/Paclitaxel+Radiation</title>
            <description>240 mg IVPB every 2 weeks for 2 doses, nivolumab at 240 mg every 2 weeks will be added to paclitaxel and carboplatin, which will be dosed according to the standard of care: paclitaxel 50 mg/m2 weekly for 6 weeks and carboplatin AUC 2 weekly for 6 weeks and radiation&#xD;
Nivolimumab+Carboplatin/paclitaxel+Radiation: In the phase I portion of the study, up to six patients will be treated (radiation will be 50.4 Gy (1.8 Gy/fraction × 28 fractions)) and then observed for 28 days (following last day of treatment (Day 64)).</description>
          </group>
        </group_list>
        <measure>
          <title>Phase 2: Number of Subjects Who Achieved cCR (Clinical Complete Response) or pCR (Pathological Complete Response)</title>
          <description>Clinical and pathological response after neoadjuvant therapy cCR by endoscopic + PET/CT evaluation; pCR for patients undergoing surgery Clinical Complete Response (cCR), no malignancy is found on clinical examination, imaging, endoscopy, and biopsy; Pathological Complete Response (pCR), no invasive and no in situ residual tumors in tissue</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="3"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>100 days post-treatment</time_frame>
      <group_list>
        <group group_id="E1">
          <title>Nivolimumab+Carboplatin/Paclitaxel+Radiation</title>
          <description>240 mg IVPB every 2 weeks for 2 doses, nivolumab at 240 mg every 2 weeks will be added to paclitaxel and carboplatin, which will be dosed according to the standard of care: paclitaxel 50 mg/m2 weekly for 6 weeks and carboplatin AUC 2 weekly for 6 weeks and radiation&#xD;
Nivolimumab+Carboplatin/paclitaxel+Radiation: In the phase I portion of the study, up to six patients will be treated (radiation will be 50.4 Gy (1.8 Gy/fraction × 28 fractions)) and then observed for 28 days (following last day of treatment (Day 64)).</description>
        </group>
      </group_list>
      <serious_events>
        <default_assessment>Non-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="2" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="6" subjects_at_risk="12"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Cardiac disorders</title>
            <event_list>
              <event>
                <sub_title>Myocardial Infarction</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="12"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Abdominal Pain</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Colitis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Dysphagia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Esophagitis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="12"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Death</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Fever</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="12"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Lung Infection</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="12"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Psychiatric disorders</title>
            <event_list>
              <event>
                <sub_title>Confusion</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="12"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Aspiration</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="12"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Skin and subcutaneous tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Rash-Morbiliform</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="12"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>0</frequency_threshold>
        <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="12" subjects_at_risk="12"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Blood and lymphatic system disorders</title>
            <event_list>
              <event>
                <sub_title>Anemia</sub_title>
                <counts group_id="E1" subjects_affected="11" subjects_at_risk="12"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Cardiac disorders</title>
            <event_list>
              <event>
                <sub_title>Chest Pain After Stent</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Tachycardia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="12"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Ear and labyrinth disorders</title>
            <event_list>
              <event>
                <sub_title>Tinnitus</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="12"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Abdominal Pain</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Bloating</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Colitis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Constipation</sub_title>
                <counts group_id="E1" subjects_affected="6" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Diarrhea</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Dry Mouth</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Dyspepsia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Dysphagia</sub_title>
                <counts group_id="E1" subjects_affected="8" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Dyspnea</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Esophageal Discomfort</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Esophageal Pain</sub_title>
                <counts group_id="E1" subjects_affected="5" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Esophagitis</sub_title>
                <counts group_id="E1" subjects_affected="5" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Flatulence</sub_title>
                <counts group_id="E1" subjects_affected="6" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Gastrointestinal Pain</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Mucositis Oral</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Nausea</sub_title>
                <counts group_id="E1" subjects_affected="7" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Oral Pain</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Vomiting</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Vomiting After Stent</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="12"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Fatigue</sub_title>
                <counts group_id="E1" subjects_affected="6" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Fever</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Hyponatremia</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Infusion Related Reaction</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Intermittent Non Cardiac Chest Pain</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Night Sweats</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Nose Bleed</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Odynophagia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Pain</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Post Operation Pain</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Rectal Bleeding</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="12"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Upper Respiratory Infection</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Upper Respiratory Tract Infection</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="12"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Injury, poisoning and procedural complications</title>
            <event_list>
              <event>
                <sub_title>Bruising</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="12"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Investigations</title>
            <event_list>
              <event>
                <sub_title>Activated Partial Thromboplastin Time Prolonged</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Alanine Aminotransferase Increased</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Aspartate Aminotransferase Increased</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Decreased Lymphocyte Count</sub_title>
                <counts group_id="E1" subjects_affected="10" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Decreased Neutrophil Count</sub_title>
                <counts group_id="E1" subjects_affected="7" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Decreased Platelet Count</sub_title>
                <counts group_id="E1" subjects_affected="9" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Decreased Wbc Count</sub_title>
                <counts group_id="E1" subjects_affected="9" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Increased Blood Bilirubin</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Increased Wbc</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>INR Increased</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Low Tsh</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Weight Loss</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Alt Increased</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Ast Increased</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Increased Alk Phos</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="12"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Metabolism and nutrition disorders</title>
            <event_list>
              <event>
                <sub_title>Anorexia</sub_title>
                <counts group_id="E1" subjects_affected="5" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Dehydration</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Hypercalcemia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Hyperglycemia</sub_title>
                <counts group_id="E1" subjects_affected="5" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Hyperkalemia</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Hypernatremia</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Hypoalbuminemia</sub_title>
                <counts group_id="E1" subjects_affected="6" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Hypocalcemia</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Hypoglycemia</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Hypokalemia</sub_title>
                <counts group_id="E1" subjects_affected="7" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Hypomagnesemia</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Hypophosphatemia</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="12"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Musculoskeletal and connective tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Arthralgia</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Arthralgia Knee Pain</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Back Pain</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Generalized Muscle Weakness</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Left Hip Pain</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Leg Cramps</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Myositis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Upper Back Pain</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="12"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Ataxia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Dizziness</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Dysgeusia</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Peripheral Sensory Neuropathy</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Presyncope</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Syncope</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="12"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Aspiration</sub_title>
                <counts group_id="E1" subjects_affected="5" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Cough</sub_title>
                <counts group_id="E1" subjects_affected="5" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Hoarseness</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Nasal Congestion</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Pharyngolaryngeal Pain</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Productive Cough</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="12"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Skin and subcutaneous tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Alopecia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Dermatitis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Dermatitis Radiation</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Dry Skin</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Pruritus</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Rash Maculo-Papular</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Rash-Morbiliform</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="12"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Vascular disorders</title>
            <event_list>
              <event>
                <sub_title>Hypertension</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Hypotension</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="12"/>
              </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>Jennifer Wu, MD</name_or_title>
      <organization>NYU Langone Health - Perlmutter Cancer Center</organization>
      <phone>212-263-3809</phone>
      <email>Jennifer.Wu@nyulangone.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/NCT03278626
org study id: 16-00971
nct id: NCT03278626
lead sponsor: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
is us export: No
In this multi-institution phase I/II trial, the investigators have chosen paclitaxel and
      carboplatin using a schedule and doses identical to those used in the CROSS trial. Following
      a run-in with nivolumab alone at 240 mg IVPB every 2 weeks for 2 doses, nivolumab at 240 mg
      every 2 weeks will be added to paclitaxel and carboplatin, which will be dosed according to
      the standard of care established by the CROSS trial: paclitaxel 50 mg/m2 weekly for 6 weeks
      and carboplatin AUC 2 weekly for 6 weeks. Concurrent radiation will be administered with
      chemotherapy at 1.8 Gy/fraction × 28 fractions to a total dose of 50.4 Gy, the standard
      radiation dose administered in the United States for trimodality therapy that includes
      concurrent therapy with carboplatin and paclitaxel. A decrease in dose to 41.4 Gy per the
      protocol established by van Hagen, et al. will be permitted before discontinuing therapy due
      to unacceptable toxicity. While the CROSS study administered only 5 weekly doses of
      chemotherapy during the 5 weeks of radiation, the higher dose of 50.4 Gy (1.8 Gy/fraction ×28
      fractions over 5½ weeks) utilized in this study permits for a sixth dose during the
      additional week of radiation.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Phase 1: Number of Unacceptable Toxicity (UT) Events
time frame: 92 days (up to 28 days after Day 64)
description: UT is defined as:
Recurrent grade 3 or 4 hematologic toxicity (despite 1 prior dose reduction in chemotherapy)
any toxicity that results in a > 2-week delay in chemoradiation
measure: Phase 2: Number of Subjects Who Achieved cCR (Clinical Complete Response) or pCR (Pathological Complete Response)
time frame: 5-8 Weeks post radiation treatment (7-8 months after treatment start)
description: Clinical and pathological response after neoadjuvant therapy cCR by endoscopic + PET/CT evaluation; pCR for patients undergoing surgery Clinical Complete Response (cCR), no malignancy is found on clinical examination, imaging, endoscopy, and biopsy; Pathological Complete Response (pCR), no invasive and no in situ residual tumors in tissue
arm group label: Nivolimumab+Carboplatin/paclitaxel+Radiation
arm group type: Other
description: 240 mg IVPB every 2 weeks for 2 doses, nivolumab at 240 mg every 2 weeks will be added to paclitaxel and carboplatin, which will be dosed according to the standard of care: paclitaxel 50 mg/m2 weekly for 6 weeks and carboplatin AUC 2 weekly for 6 weeks and radiation
intervention type: Drug
intervention name: Nivolimumab+Carboplatin/paclitaxel+Radiation
description: In the phase I portion of the study, up to six patients will be treated (radiation will be 50.4 Gy (1.8 Gy/fraction × 28 fractions)) and then observed for 28 days (following last day of treatment (Day 64)).
arm group label: Nivolimumab+Carboplatin/paclitaxel+Radiation
other name: Opdivo
other name: Paraplatin
other name: Taxol
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Jennifer Wu, MD
role: Principal Investigator
affiliation: NYU Langone Health
facility: 
facility: 
facility: 
facility: 
facility: 
country: United States
responsible party type: Sponsor
mesh term: Carcinoma
mesh term: Carcinoma, Squamous Cell
mesh term: Esophageal Squamous Cell Carcinoma
mesh term: Paclitaxel
mesh term: Carboplatin
provided document: 
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 