<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/NCT02970981</url>
  </required_header>
  <id_info>
    <org_study_id>16-00098</org_study_id>
    <nct_id>NCT02970981</nct_id>
  </id_info>
  <brief_title>Study of Combination of Ipilimumab and Nivolumab in Patients With Melanoma</brief_title>
  <official_title>A Pilot Trial of Ipilimumab With Nivolumab for Participants With Resected Stages IIIB/IIIC/ IV Melanoma</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>NYU Langone Health</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Bristol-Myers Squibb</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </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>Yes</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      The purpose of this study is to assess the safety and tolerability of treatment with&#xD;
      Nivolumab in combination with Ipilimumab in subjects with resected Stages IIIB/IIIC/ IV&#xD;
      melanoma.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The investigators hypothesize that PD-1 blockade combined with CTLA-4 blockade using&#xD;
      ipilimumab would have a favorable effect on the expansion and activity of human CD8+ T&#xD;
      cytotoxic lymphocytes (CTLs) specific for tumor-associated antigens (ie, self antigens),&#xD;
      which would translate into improved anti-cancer therapy.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">November 29, 2016</start_date>
  <completion_date type="Actual">May 2, 2022</completion_date>
  <primary_completion_date type="Actual">November 2018</primary_completion_date>
  <phase>Phase 2</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>N/A</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Number of Cases of Adverse Events Occurring During Study</measure>
    <time_frame>12 weeks post-treatment start</time_frame>
    <description>The adverse events are evaluated per Common Terminology Criteria for Adverse Events (CTCAE) V4.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Time to Relapse</measure>
    <time_frame>Up to 4 years</time_frame>
    <description>Time to relapse will be reported (in months post-treatment) to assess the preliminary efficacy of the study drugs.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Immune Response Assessment</measure>
    <time_frame>12 Weeks</time_frame>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">19</enrollment>
  <condition>Melanoma</condition>
  <arm_group>
    <arm_group_label>Nivolumab and Ipilimumab</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Dosing during cycle 1 will consist of: 3 mg/kg of Nivolumab+ Ipilimumab at 1 mg/kg. Each induction treatment cycle is comprised of 4 doses of Nivolumab and 4 doses of Ipilimumab given every three weeks for a total of 12 weeks (cycle 1)&#xD;
Dosing during cycles 2-5 will consist of flat dose Nivolumab at 480 mg every 4 weeks (Q4W) for 48 weeks.</description>
  </arm_group>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>Nivolumab</intervention_name>
    <arm_group_label>Nivolumab and Ipilimumab</arm_group_label>
    <other_name>Opdivo</other_name>
    <other_name>NSC 748726</other_name>
  </intervention>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>Ipilimumab</intervention_name>
    <arm_group_label>Nivolumab and Ipilimumab</arm_group_label>
    <other_name>Yervoy</other_name>
    <other_name>NSC 732442</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Be at least 16 years of age;&#xD;
&#xD;
          -  Histologic diagnosis of resected Stages IIIB/IIIC/ IV melanoma, with no evidence of&#xD;
             disease clinically and radiologically, and negative surgical margins. All melanomas&#xD;
             regardless of primary site of disease will be allowed;&#xD;
&#xD;
          -  Eastern Cooperative Oncology Group (ECOG) performance status score of 0 or 1.&#xD;
&#xD;
          -  Prior chemotherapy or immunotherapy (tumor vaccine, cytokine, or growth factor given&#xD;
             to control the cancer) must have been completed at least 4 weeks before study drug&#xD;
             administration, and all adverse events have either returned to baseline or stabilized;&#xD;
&#xD;
          -  Prior treated brain or meningeal metastases must be without magnetic resonance imaging&#xD;
             (MRI) evidence of progression for at least 8 weeks and off immunosuppressive doses of&#xD;
             systemic steroids (&gt; 10 mg/day prednisone or equivalent) for at least 2 weeks before&#xD;
             study drug administration;&#xD;
&#xD;
          -  Prior systemic radiation therapy must have been completed at least 4 weeks before&#xD;
             study drug administration. Prior focal radiotherapy completed at least 2 weeks before&#xD;
             study drug administration. No radiopharmaceuticals (strontium, samarium) within 8&#xD;
             weeks before study drug administration;&#xD;
&#xD;
          -  Immunosuppressive doses of systemic medications, such as steroids or absorbed topical&#xD;
             steroids (doses &gt; 10 mg/day prednisone or equivalent) must be discontinued at least 2&#xD;
             weeks before study drug administration;&#xD;
&#xD;
          -  Completed nitrosourea treatment at least 6 weeks before administration of any study&#xD;
             drug;&#xD;
&#xD;
          -  Prior surgery that required general anesthesia must be completed at least 4 weeks&#xD;
             before study drug administration. Surgery requiring local/epidural anesthesia must be&#xD;
             completed at least 72 hours before study drug administration and subjects should be&#xD;
             recovered;&#xD;
&#xD;
          -  Screening laboratory values must meet the following criteria:&#xD;
&#xD;
        white blood cells (WBCs) ≥ 2000 cells/μL&#xD;
&#xD;
          -  neutrophils ≥ 1500 cells/μL&#xD;
&#xD;
          -  platelets ≥ 100 x 103/μL&#xD;
&#xD;
          -  hemoglobin ≥ 9.0 g/dL&#xD;
&#xD;
          -  serum creatinine ≤ 2 mg/dL&#xD;
&#xD;
          -  AST ≤ 2.5 x upper limit of normal (ULN) without, and ≤ 5 x ULN with hepatic metastasis&#xD;
&#xD;
          -  ALT ≤ 2.5 x ULN without, and ≤ 5 x ULN with hepatic metastasis&#xD;
&#xD;
          -  bilirubin ≤ 2 x ULN (except subjects with Gilbert's syndrome, who must have total&#xD;
             bilirubin &lt; 3.0 mg/dL)&#xD;
&#xD;
          -  Females of childbearing potential must:&#xD;
&#xD;
          -  use appropriate method(s) of contraception. WOCBP should use an adequate method to&#xD;
             avoid pregnancy for 23 weeks (30 days plus the time required for nivolumab to undergo&#xD;
             five half-lives) after the last dose of investigational drug.&#xD;
&#xD;
          -  Women of childbearing potential must have a negative serum or urine pregnancy test&#xD;
             (minimum sensitivity 25 IU/L or equivalent units of HCG) within 24 hours prior to the&#xD;
             start of nivolumab.&#xD;
&#xD;
          -  For female subjects to be considered as not having childbearing potential, they must&#xD;
             meet 1 or more of the following criteria:&#xD;
&#xD;
          -  postmenopausal for at least 24 consecutive months;&#xD;
&#xD;
          -  surgically sterile (ie, have had a hysterectomy or bilateral oophorectomy);&#xD;
&#xD;
          -  females with irregular menstrual periods and/or on hormone replacement therapy must&#xD;
             have a documented serum follicle stimulating hormone level &gt; 35 mIU/mL;&#xD;
&#xD;
          -  Men who are sexually active with WOCBP must use any contraceptive method with a&#xD;
             failure rate of less than 1% per year Men receiving nivolumab and who are sexually&#xD;
             active with WOCBP will be instructed to adhere to contraception for a period of 31&#xD;
             weeks after the last dose of investigational product Women who are not of childbearing&#xD;
             potential (ie, who are postmenopausal or surgically sterile as well as azoospermic men&#xD;
             do not require contraception.&#xD;
&#xD;
          -  Subject must have read, understood, and provided written informed consent and HIPAA&#xD;
             authorization after the nature of the study has been fully explained; and&#xD;
&#xD;
          -  Willing to adhere to the study visit schedule and the prohibitions and restrictions&#xD;
             specified in this protocol.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Subjects who fulfill any of the following conditions at Screening will not be eligible&#xD;
             for admission into the study:&#xD;
&#xD;
          -  History of severe hypersensitivity reactions to other mAbs;&#xD;
&#xD;
          -  Prior non-melanoma malignancy active within the previous 2 years except for locally&#xD;
             curable cancers that have been apparently cured, such as basal or squamous cell skin&#xD;
             cancer, superficial bladder cancer, or carcinoma in situ of the prostate, cervix or&#xD;
             breast;&#xD;
&#xD;
          -  Subjects with any active autoimmune disease (Appendix 3) or a documented history of&#xD;
             autoimmune disease, or history of syndrome that required systemic steroids or&#xD;
             immunosuppressive medications, except for subjects with vitiligo or resolved childhood&#xD;
             asthma/atopy;&#xD;
&#xD;
          -  Known history of testing positive for human immunodeficiency virus (HIV) or known&#xD;
             acquired immunodeficiency syndrome (AIDS);&#xD;
&#xD;
          -  Positive tests for hepatitis B virus surface antigen (HBV SAg) or hepatitis C virus&#xD;
             ribonucleic acid (HCV RNA) indicating active or chronic infection;&#xD;
&#xD;
          -  Prior therapy with an anti-PD-1, anti-PD-L1, anti-PDL-2, or anti-CTLA-4 antibody (or&#xD;
             any other antibody targeting T cell co-stimulation pathways);&#xD;
&#xD;
          -  Concurrent medical condition requiring the use of immunosuppressive medications, or&#xD;
             immunosuppressive doses of systemic or absorbable topical corticosteroids;&#xD;
&#xD;
          -  Underlying medical condition (eg, a condition associated with diarrhea) that, in the&#xD;
             Investigator's opinion, would make the administration of either study drug or both&#xD;
             study drugs hazardous to the subject or obscure the interpretation of toxicity&#xD;
             determination or adverse events;&#xD;
&#xD;
          -  Pregnant or nursing; or&#xD;
&#xD;
          -  Current participation in another clinical study involving treatment with medications,&#xD;
             radiation or surgery, or prior participation in this 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 requirement&#xD;
             for immunosuppressive doses of systemic corticosteroids (&gt; 10 mg/day prednisone&#xD;
             equivalents) for at least 2 weeks prior to study drug administration.&#xD;
&#xD;
        As there is potential for hepatic toxicity with nivolumab or nivolumab/ipilimumab&#xD;
        combinations, drugs with a predisposition to hepatoxicity should be used with caution in&#xD;
        patients treated with nivolumab-containing regimen.&#xD;
&#xD;
          -  Allergies and Adverse Drug Reaction&#xD;
&#xD;
               1. History of allergy to study drug components&#xD;
&#xD;
               2. History of severe hypersensitivity reaction to any monoclonal antibody&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>16 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Jeffrey S Weber, MD, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>NYU Perlmutter Cancer Center</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Laura and Isaac Perlmutter Cancer Center</name>
      <address>
        <city>New York</city>
        <state>New York</state>
        <zip>10016</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>August 2022</verification_date>
  <study_first_submitted>November 18, 2016</study_first_submitted>
  <study_first_submitted_qc>November 21, 2016</study_first_submitted_qc>
  <study_first_posted type="Estimate">November 22, 2016</study_first_posted>
  <results_first_submitted>February 13, 2020</results_first_submitted>
  <results_first_submitted_qc>March 9, 2020</results_first_submitted_qc>
  <results_first_posted type="Actual">March 11, 2020</results_first_posted>
  <last_update_submitted>August 11, 2022</last_update_submitted>
  <last_update_submitted_qc>August 11, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">August 15, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Monoclonal antibody</keyword>
  <keyword>Programmed Death-1 (PD-1)</keyword>
  <keyword>Programmed Death-Ligand 1 (PD-L1)</keyword>
  <keyword>Cytotoxic T lymphocyte-associated antigen 4 (CTLA-4)</keyword>
  <keyword>Antigen</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Melanoma</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Nivolumab</mesh_term>
    <mesh_term>Ipilimumab</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>November 10, 2017</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/81/NCT02970981/Prot_SAP_000.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <group_list>
        <group group_id="P1">
          <title>Nivolumab and Ipilimumab</title>
          <description>Dosing during cycle 1 will consist of: 3 mg/kg of Nivolumab+ Ipilimumab at 1 mg/kg. Each induction treatment cycle is comprised of 4 doses of Nivolumab and 4 doses of Ipilimumab given every three weeks for a total of 12 weeks (cycle 1)&#xD;
Dosing during cycles 2-5 will consist of flat dose Nivolumab at 480 mg every 4 weeks (Q4W) for 48 weeks.&#xD;
Nivolumab&#xD;
Ipilimumab</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="16"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="16"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
              </participants_list>
            </milestone>
          </milestone_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>Nivolumab and Ipilimumab</title>
          <description>Dosing during cycle 1 will consist of: 3 mg/kg of Nivolumab+ Ipilimumab at 1 mg/kg. Each induction treatment cycle is comprised of 4 doses of Nivolumab and 4 doses of Ipilimumab given every three weeks for a total of 12 weeks (cycle 1)&#xD;
Dosing during cycles 2-5 will consist of flat dose Nivolumab at 480 mg every 4 weeks (Q4W) for 48 weeks.&#xD;
Nivolumab&#xD;
Ipilimumab</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="16"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age, Customized</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <title>&gt;= 16 years</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="16"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="16"/>
                  </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="16"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <title>Female</title>
                  <measurement_list>
                    <measurement group_id="B1" value="2"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="14"/>
                  </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>Disease Stage at Entry</title>
          <description>CT scans with contrast of the chest, abdomen, and pelvis as well as MRI scans of the brain with gadolinium were done for disease evaluation. The earliest stage melanomas are stage 0 (melanoma in situ), and then range from stages I (1) through IV (4). As a rule, the lower the number, the less the cancer has spread. A higher number, such as stage IV, means cancer has spread more. And within a stage, an earlier letter means a lower stage.</description>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <title>IIIB</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="16"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="6"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>IIIC</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="16"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>IV</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="16"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>IIB</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="16"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Number of Cases of Adverse Events Occurring During Study</title>
        <description>The adverse events are evaluated per Common Terminology Criteria for Adverse Events (CTCAE) V4.</description>
        <time_frame>12 weeks post-treatment start</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Nivolumab and Ipilimumab</title>
            <description>Dosing during cycle 1 will consist of: 3 mg/kg of Nivolumab+ Ipilimumab at 1 mg/kg. Each induction treatment cycle is comprised of 4 doses of Nivolumab and 4 doses of Ipilimumab given every three weeks for a total of 12 weeks (cycle 1)&#xD;
Dosing during cycles 2-5 will consist of flat dose Nivolumab at 480 mg every 4 weeks (Q4W) for 48 weeks.&#xD;
Nivolumab&#xD;
Ipilimumab</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Cases of Adverse Events Occurring During Study</title>
          <description>The adverse events are evaluated per Common Terminology Criteria for Adverse Events (CTCAE) V4.</description>
          <units>cases of adverse events</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="16"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="238"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Time to Relapse</title>
        <description>Time to relapse will be reported (in months post-treatment) to assess the preliminary efficacy of the study drugs.</description>
        <time_frame>Up to 4 years</time_frame>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Immune Response Assessment</title>
        <time_frame>12 Weeks</time_frame>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>12 weeks post-treatment</time_frame>
      <group_list>
        <group group_id="E1">
          <title>Nivolumab and Ipilimumab</title>
          <description>Dosing during cycle 1 will consist of: 3 mg/kg of Nivolumab+ Ipilimumab at 1 mg/kg. Each induction treatment cycle is comprised of 4 doses of Nivolumab and 4 doses of Ipilimumab given every three weeks for a total of 12 weeks (cycle 1)&#xD;
Dosing during cycles 2-5 will consist of flat dose Nivolumab at 480 mg every 4 weeks (Q4W) for 48 weeks.&#xD;
Nivolumab&#xD;
Ipilimumab</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="0" subjects_at_risk="16"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="16"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Blood and lymphatic system disorders</title>
            <event_list>
              <event>
                <sub_title>Hyponatremia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="16"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Enterocolitis</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="16"/>
              </event>
              <event>
                <sub_title>Diarrhea</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="16"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Fever</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="16"/>
              </event>
              <event>
                <sub_title>Fatigue</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="16"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Musculoskeletal and connective tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Generalized Muscle Weakness</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="16"/>
              </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="16" subjects_at_risk="16"/>
              </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="4" subjects_at_risk="16"/>
              </event>
              <event>
                <sub_title>Edema</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="16"/>
              </event>
              <event>
                <sub_title>Decrease in platelet count</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="16"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Eye disorders</title>
            <event_list>
              <event>
                <sub_title>Conjunctivitis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="16"/>
              </event>
              <event>
                <sub_title>Green floater in eye</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="16"/>
              </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="16"/>
              </event>
              <event>
                <sub_title>Bloating</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="16"/>
              </event>
              <event>
                <sub_title>Constipation</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="16"/>
              </event>
              <event>
                <sub_title>Diarrhea</sub_title>
                <counts group_id="E1" subjects_affected="6" subjects_at_risk="16"/>
              </event>
              <event>
                <sub_title>Enterocolitis</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="16"/>
              </event>
              <event>
                <sub_title>GERD</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="16"/>
              </event>
              <event>
                <sub_title>Loose stool</sub_title>
                <counts group_id="E1" subjects_affected="7" subjects_at_risk="16"/>
              </event>
              <event>
                <sub_title>Mucositis oral</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="16"/>
              </event>
              <event>
                <sub_title>Vomiting</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="16"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Increase in Alkalina Phosphatase</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="16"/>
              </event>
              <event>
                <sub_title>Allergic rhinitis</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="16"/>
              </event>
              <event>
                <sub_title>Blurred vision</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="16"/>
              </event>
              <event>
                <sub_title>Chills</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="16"/>
              </event>
              <event>
                <sub_title>Dehydration</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="16"/>
              </event>
              <event>
                <sub_title>Dry mouth</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="16"/>
              </event>
              <event>
                <sub_title>Fever</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="16"/>
              </event>
              <event>
                <sub_title>Alopecia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="16"/>
              </event>
              <event>
                <sub_title>Malaise</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="16"/>
              </event>
              <event>
                <sub_title>Nasal congestion</sub_title>
                <counts group_id="E1" subjects_affected="5" subjects_at_risk="16"/>
              </event>
              <event>
                <sub_title>Non productive cough</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="16"/>
              </event>
              <event>
                <sub_title>Nausea</sub_title>
                <counts group_id="E1" subjects_affected="6" subjects_at_risk="16"/>
              </event>
              <event>
                <sub_title>General pain</sub_title>
                <counts group_id="E1" subjects_affected="9" subjects_at_risk="16"/>
              </event>
              <event>
                <sub_title>Productive cough</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="16"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Hepatobiliary disorders</title>
            <event_list>
              <event>
                <sub_title>Increase in alanine aminotransferase</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="16"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Sore throat</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="16"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Metabolism and nutrition disorders</title>
            <event_list>
              <event>
                <sub_title>Increase in Creatinine</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="16"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Musculoskeletal and connective tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Cramping</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="16"/>
              </event>
              <event>
                <sub_title>Hernia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="16"/>
              </event>
              <event>
                <sub_title>Myalgia</sub_title>
                <counts group_id="E1" subjects_affected="5" subjects_at_risk="16"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Psychiatric disorders</title>
            <event_list>
              <event>
                <sub_title>Anorexia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="16"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Renal and urinary disorders</title>
            <event_list>
              <event>
                <sub_title>Urinary urgency</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="16"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Chest wall discomfort</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="16"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Skin and subcutaneous tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Papulopostular rash</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="16"/>
              </event>
              <event>
                <sub_title>Pruritis</sub_title>
                <counts group_id="E1" events="17" subjects_affected="16" subjects_at_risk="16"/>
              </event>
              <event>
                <sub_title>Rash maculopapular</sub_title>
                <counts group_id="E1" events="30" subjects_affected="16" subjects_at_risk="16"/>
              </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>Jeffrey S. Weber, MD, PhD</name_or_title>
      <organization>NYU Langone Health - Perlmutter Cancer Center</organization>
      <phone>212 731 6262</phone>
      <email>Jeffrey.Weber@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/NCT02970981
org study id: 16-00098
nct id: NCT02970981
lead sponsor: 
collaborator: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
is us export: Yes
The purpose of this study is to assess the safety and tolerability of treatment with
      Nivolumab in combination with Ipilimumab in subjects with resected Stages IIIB/IIIC/ IV
      melanoma.
The investigators hypothesize that PD-1 blockade combined with CTLA-4 blockade using
      ipilimumab would have a favorable effect on the expansion and activity of human CD8+ T
      cytotoxic lymphocytes (CTLs) specific for tumor-associated antigens (ie, self antigens),
      which would translate into improved anti-cancer therapy.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Number of Cases of Adverse Events Occurring During Study
time frame: 12 weeks post-treatment start
description: The adverse events are evaluated per Common Terminology Criteria for Adverse Events (CTCAE) V4.
measure: Time to Relapse
time frame: Up to 4 years
description: Time to relapse will be reported (in months post-treatment) to assess the preliminary efficacy of the study drugs.
measure: Immune Response Assessment
time frame: 12 Weeks
arm group label: Nivolumab and Ipilimumab
arm group type: Experimental
description: Dosing during cycle 1 will consist of: 3 mg/kg of Nivolumab+ Ipilimumab at 1 mg/kg. Each induction treatment cycle is comprised of 4 doses of Nivolumab and 4 doses of Ipilimumab given every three weeks for a total of 12 weeks (cycle 1)
Dosing during cycles 2-5 will consist of flat dose Nivolumab at 480 mg every 4 weeks (Q4W) for 48 weeks.
intervention type: Biological
intervention name: Nivolumab
arm group label: Nivolumab and Ipilimumab
other name: Opdivo
other name: NSC 748726
intervention type: Biological
intervention name: Ipilimumab
arm group label: Nivolumab and Ipilimumab
other name: Yervoy
other name: NSC 732442
criteria: 
gender: All
minimum age: 16 Years
maximum age: N/A
healthy volunteers: No
last name: Jeffrey S Weber, MD, PhD
role: Principal Investigator
affiliation: NYU Perlmutter Cancer Center
facility: 
country: United States
responsible party type: Sponsor
mesh term: Melanoma
mesh term: Nivolumab
mesh term: Ipilimumab
provided document: 
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 