<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/NCT03041181</url>
  </required_header>
  <id_info>
    <org_study_id>HCRN LUN15-233</org_study_id>
    <nct_id>NCT03041181</nct_id>
  </id_info>
  <brief_title>Single Agent Chemotherapy +/- Nivolumab in Patients With Advanced Squamous or Non-squamous NSCLC With Primary Resistance to Prior PD-1 or PDL-1 Inhibitor</brief_title>
  <official_title>Randomized Phase II Trial of Single Agent Chemotherapy Plus Nivolumab or Single Agent Chemotherapy Alone in Patients With Advanced Squamous or Non-squamous NSCLC With Primary Resistance to Prior PD-1 or PDL-1 Inhibitor</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Nasser Hanna, M.D.</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Hoosier Cancer Research Network</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Bristol-Myers Squibb</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>Hoosier Cancer Research Network</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>
      This is a randomized phase II study assessing the activity of single agent chemotherapy&#xD;
      combined with nivolumab (Arm A) compared to single agent chemotherapy alone (Arm B) in&#xD;
      squamous or non-squamous NSCLC subjects with primary resistance to prior PD-1 or PDL-1&#xD;
      inhibitor. The single agent chemotherapy chosen is at the discretion of the site investigator&#xD;
      and may include pemetrexed, gemcitabine or taxotere. Institutional standards should be used&#xD;
      for administration of the single agent chemotherapy. For both treatment arms, 21 days equals&#xD;
      1 cycle of therapy and subjects will be eligible to continue treatment until progressive&#xD;
      disease by RECIST v1.1 or unacceptable toxicity.&#xD;
&#xD;
      Upon registration, subjects will be randomized in a 1:1 ratio to either treatment with single&#xD;
      agent chemotherapy or single agent chemotherapy in combination with nivolumab. Randomization&#xD;
      is un-blinded and open-label; therefore there will be no placebo treatment for subjects&#xD;
      randomized to single agent chemotherapy&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Terminated</overall_status>
  <why_stopped>
    Funder decision - lack of accrual&#xD;
  </why_stopped>
  <start_date type="Actual">January 27, 2017</start_date>
  <completion_date type="Actual">May 23, 2019</completion_date>
  <primary_completion_date type="Actual">May 23, 2019</primary_completion_date>
  <phase>Phase 2</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
    <masking_description>Open-Label</masking_description>
  </study_design_info>
  <primary_outcome>
    <measure>Progression Free Survival (PFS), as Defined by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1.</measure>
    <time_frame>24 months</time_frame>
    <description>Compare PFS rates for subjects on each treatment arm, per RECIST 1.1. Subjects who have not progressed will be right-censored at the date of the last follow up.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Overall Response Rate (ORR) for Subjects on Each Treatment Arm, as Defined by RECIST 1.1 and Immune-related Response Criteria (irRECIST)</measure>
    <time_frame>Every 6 weeks beginning with C3D1 and every odd numbered cycle thereafter, assessed for up to 24 months</time_frame>
    <description>Proportion of subjects on each arm with complete response or partial response, per RECIST 1.1 and irRECIST</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Clinical Benefit Rate (CBR) for Subjects on Each Treatment Arm, as Defined by RECIST 1.1 and irRECIST</measure>
    <time_frame>From D1 of treatment until documented disease progression/recurrence, assessed for up to 24 months</time_frame>
    <description>Proportion of subjects on each arm with complete response, partial response or stable disease for at least 3 months, per RECIST 1.1 and irRECIST</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Progression Free Survival (PFS), as Defined by irRECIST</measure>
    <time_frame>24 months</time_frame>
    <description>Compare PFS rates for subjects on each treatment arm, per irRECIST. From date of randomization until the criteria for disease progression is met or death as a result of any cause, assessed up to 24 months</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of Participants With Grade 3 or Grade 4 Adverse Events</measure>
    <time_frame>6 months</time_frame>
    <description>Assess toxicity of Nivolumab plus single agent chemotherapy compared with single agent chemotherapy alone. Number of grade 3 and 4 toxicities as defined by the NCI Common Terminology Criteria for Adverse Events (NCI CTCAE) v4.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">3</enrollment>
  <condition>Non-Squamous Non-Small Cell Lung Cancer (NSCLC)</condition>
  <condition>Adenocarcinoma of the Lung</condition>
  <condition>Lung Cancer</condition>
  <condition>Squamous Cell Lung Cancer</condition>
  <arm_group>
    <arm_group_label>Arm A - Single Agent Chemotherapy + Nivolumab</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Single Agent Chemotherapy of choice plus nivolumab:&#xD;
Taxotere Pemetrexed Gemcitabine</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Arm B - Single Agent Chemotherapy</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Single Agent Chemotherapy of choice Taxotere Pemetrexed Gemcitabine</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Docetaxel</intervention_name>
    <description>Docetaxel 75 mg/m2 IV Day 1 of each cycle (21 days = 1 cycle)</description>
    <arm_group_label>Arm A - Single Agent Chemotherapy + Nivolumab</arm_group_label>
    <arm_group_label>Arm B - Single Agent Chemotherapy</arm_group_label>
    <other_name>Taxotere</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Nivolumab</intervention_name>
    <description>Nivolumab 360 mg IV Day 1 of each cycle (21 days = 1 cycle)</description>
    <arm_group_label>Arm A - Single Agent Chemotherapy + Nivolumab</arm_group_label>
    <other_name>BMS-936558-01</other_name>
    <other_name>Opdivo</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Gemcitabine</intervention_name>
    <description>Gemcitabine 1000 mg/m2 IV Day 1 and Day 8 of each cycle (21 days = 1 cycle)</description>
    <arm_group_label>Arm A - Single Agent Chemotherapy + Nivolumab</arm_group_label>
    <arm_group_label>Arm B - Single Agent Chemotherapy</arm_group_label>
    <other_name>Gemzar</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Pemetrexed</intervention_name>
    <description>Pemetrexed 500 mg/m2 IV Day 1 of each cycle (21 days = 1 cycle)</description>
    <arm_group_label>Arm A - Single Agent Chemotherapy + Nivolumab</arm_group_label>
    <arm_group_label>Arm B - Single Agent Chemotherapy</arm_group_label>
    <other_name>Alimta</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
        Subject must meet all of the following applicable inclusion criteria to participate in this&#xD;
        study:&#xD;
&#xD;
          1. Written informed consent and HIPAA authorization for release of personal health&#xD;
             information prior to registration. NOTE: HIPAA authorization may be included in the&#xD;
             informed consent or obtained separately.&#xD;
&#xD;
          2. Age ≥ 18 years at the time of consent.&#xD;
&#xD;
          3. ECOG Performance Status of 0-2 within 28 days prior to randomization.&#xD;
&#xD;
          4. Histological or cytological confirmed squamous or non-squamous non-small cell lung&#xD;
             cancer.&#xD;
&#xD;
          5. Measurable disease according to RECIST 1.1 within 28 days prior to randomization.&#xD;
&#xD;
          6. A subject with prior brain metastasis may be considered if they have completed their&#xD;
             treatment for brain metastasis at least 4 weeks prior to randomization, have been off&#xD;
             of corticosteroids for ≥ 2 weeks, and are asymptomatic.&#xD;
&#xD;
          7. Subjects must have primary resistance to PD-1 or PDL-1 inhibitors; defined as PD after&#xD;
             3 or fewer treatments with a PD-1 or PDL-1 inhibitor&#xD;
&#xD;
          8. Subjects must have progressed on or after previous platinum-based chemotherapy.&#xD;
             Chemotherapy may have previously been given with a PD-1 or PD-L1 inhibitor. Subjects&#xD;
             must have also progressed on or after receiving any PD-1 or PD-L1 inhibitor (including&#xD;
             nivolumab) as their most recent therapy.&#xD;
&#xD;
          9. Most recent PD-1 or PD-L1 inhibitor infusion must be completed at least 6 weeks of&#xD;
             randomization. The subject must have recovered from all reversible acute toxic effects&#xD;
             (other than alopecia) to ≤ Grade 1 or baseline.&#xD;
&#xD;
         10. Demonstrate adequate organ function as defined in the table below. All screening labs&#xD;
             to be obtained within 28 days prior to randomization.&#xD;
&#xD;
             White blood cell (WBC) ≥ 2 k/mm3 Absolute Neutrophil Count (ANC) ≥ 1.5 K/mm3&#xD;
             Hemoglobin (Hgb) ≥ 9 g/dL Platelet &gt;100k Estimated creatinine clearance OR ≥ 40 cc/min&#xD;
             Serum creatinine ≤ 1.5 x upper limit of normal (ULN) Bilirubin 1.5 ≤ (ULN)2 Aspartate&#xD;
             aminotransferase (AST) ≤ 1.5 × ULN Alanine aminotransferase (ALT) ≤ 1.5 × ULN&#xD;
             International Normalized Ratio (INR) or Prothrombin Time (PT) Activated Partial&#xD;
             Thromboplastin Time (aPTT) ≤ 2 × ULN (Note: use of vitamin K antagonist is not&#xD;
             allowed)&#xD;
&#xD;
         11. Women of childbearing potential (WOCBP) must have a negative serum pregnancy test&#xD;
             within 14 days prior to registration. These women must also have a negative serum or&#xD;
             urine pregnancy test (minimum sensitivity 25 IU/L or equivalent units of HCG) within&#xD;
             24 hours prior to the start of Nivolumab then every 6 weeks thereafter. NOTE: Women&#xD;
             are considered of child bearing potential unless they are surgically sterile (have&#xD;
             undergone a hysterectomy, bilateral tubal ligation, or bilateral oophorectomy) or are&#xD;
             post-menopausal. Menopause is defined clinically as 12 months of amenorrhea in a woman&#xD;
             over 45 in the absence of other biological or physiological causes. In addition, women&#xD;
             under the age of 62 must have a documented serum follicle stimulating hormone (FSH)&#xD;
             level less than 40 mIU/mL.&#xD;
&#xD;
         12. Women of childbearing potential must be willing to abstain from heterosexual activity&#xD;
             or use an effective method of contraception from the time of informed consent until 5&#xD;
             months after treatment discontinuation. Women cannot breast feed from the time of&#xD;
             informed consent to 5 months after last dose of study treatment. See below for&#xD;
             adequate methods of contraception.&#xD;
&#xD;
         13. 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 7&#xD;
             months after the last dose of investigational product. See below for methods of&#xD;
             contraception.&#xD;
&#xD;
         14. As determined by the enrolling physician or protocol designee, ability of the subject&#xD;
             to understand and comply with study procedures for the entire length of the study&#xD;
&#xD;
        Exclusion Criteria&#xD;
&#xD;
          1. Prior treatment with the single agent chemotherapy the site investigator chooses to&#xD;
             use for this protocol (pemetrexed, taxotere or gemcitabine).&#xD;
&#xD;
          2. Previous autoimmune complication from PD-1 or PD-L1 requiring discontinuation of&#xD;
             therapy or treatment with steroids (ongoing treatment with more than 10 mg of&#xD;
             prednisone or steroid equivalent daily, excluding inhaled or topical steroids).&#xD;
&#xD;
          3. Previous discontinuation from PD-1 or PD-L1 due to an adverse event.&#xD;
&#xD;
          4. Any serious or uncontrolled medical disorder or active infection that would impair the&#xD;
             ability of the subject to receive protocol therapy.&#xD;
&#xD;
          5. Pregnant or breastfeeding (NOTE: breast milk cannot be stored for future use while the&#xD;
             mother is being treated on study).&#xD;
&#xD;
          6. Known additional malignancy that is active and/or progressive requiring treatment;&#xD;
             exceptions include basal cell or squamous cell skin cancer, in situ cervical or&#xD;
             bladder cancer, or other cancer for which the subject has been disease-free for at&#xD;
             least five years.&#xD;
&#xD;
          7. Active central nervous system (CNS) metastases. Subjects with brain metastases are&#xD;
             eligible if metastases have been treated and there is no magnetic resonance imaging&#xD;
             (MRI) evidence of progression for [lowest minimum is 4 weeks or more] after treatment&#xD;
             is complete and within 28 days prior to the first dose of Nivolumab administration.&#xD;
             There must also be no requirement for immunosuppressive doses of systemic&#xD;
             corticosteroids (&gt; 10 mg/day prednisone equivalents) for at least 2 weeks prior to&#xD;
             study drug administration.&#xD;
&#xD;
          8. Treatment with any investigational drug within 30 days prior to registration.&#xD;
&#xD;
          9. Subjects whose tumors express EGFR mutations on exons 19 and 21, ALK rearrangement, or&#xD;
             ROS1 rearrangement who still have other FDA approved targeted agents available for&#xD;
             treatment.&#xD;
&#xD;
         10. Subjects with an active or recent history of a known or suspected autoimmune disease&#xD;
             or recent history of a syndrome that required systemic&#xD;
             corticosteroids/immunosuppressive medications EXCEPT for syndromes which would not be&#xD;
             expected to recur in the absence of an external trigger. (Subjects with vitiligo,&#xD;
             autoimmune thyroiditis, or type I diabetes mellitus are permitted to enroll.)&#xD;
&#xD;
         11. As there is potential for hepatic toxicity with Nivolumab, drugs with a predisposition&#xD;
             to hepatoxicity should be used with caution in subjects treated with&#xD;
             Nivolumab-containing regimen.&#xD;
&#xD;
         12. Subjects should be excluded if they are positive test for hepatitis B virus surface&#xD;
             antigen (HBV sAg) or hepatitis C virus ribonucleic acid (HCV antibody) indicating&#xD;
             acute or chronic infection.&#xD;
&#xD;
         13. Subjects should be excluded if they have known history of testing positive for human&#xD;
             immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome (AIDS).&#xD;
&#xD;
         14. History of allergy to study drug components.&#xD;
&#xD;
         15. Prior solid organ or stem cell transplant&#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>Nasser Hanna, M.D.</last_name>
    <role>Principal Investigator</role>
    <affiliation>Hoosier Cancer Research Network</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>St. Vincent Anderson Regional Hospital</name>
      <address>
        <city>Anderson</city>
        <state>Indiana</state>
        <zip>46016</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Indiana University Melvin and Bren Simon Cancer Center</name>
      <address>
        <city>Indianapolis</city>
        <state>Indiana</state>
        <zip>46202</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>IU Health Central Indiana Cancer Center</name>
      <address>
        <city>Indianapolis</city>
        <state>Indiana</state>
        <zip>46219</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Community Regional Cancer Care</name>
      <address>
        <city>Indianapolis</city>
        <state>Indiana</state>
        <zip>46256</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>IU Health Ball Memorial Hospital Cancer Center</name>
      <address>
        <city>Muncie</city>
        <state>Indiana</state>
        <zip>47303</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Community Healthcare System</name>
      <address>
        <city>Munster</city>
        <state>Indiana</state>
        <zip>46321</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>HealthPartners Institute</name>
      <address>
        <city>Minneapolis</city>
        <state>Minnesota</state>
        <zip>55440</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Texas Medical Branch at Galveston</name>
      <address>
        <city>Galveston</city>
        <state>Texas</state>
        <zip>77555</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Virginia Health System</name>
      <address>
        <city>Charlottesville</city>
        <state>Virginia</state>
        <zip>22908</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <link>
    <url>https://hoosiercancer.org/</url>
    <description>Hoosier Cancer Research Network Website</description>
  </link>
  <verification_date>July 2022</verification_date>
  <study_first_submitted>January 31, 2017</study_first_submitted>
  <study_first_submitted_qc>January 31, 2017</study_first_submitted_qc>
  <study_first_posted type="Estimate">February 2, 2017</study_first_posted>
  <results_first_submitted>July 10, 2019</results_first_submitted>
  <results_first_submitted_qc>November 11, 2019</results_first_submitted_qc>
  <results_first_posted type="Actual">November 29, 2019</results_first_posted>
  <last_update_submitted>July 7, 2022</last_update_submitted>
  <last_update_submitted_qc>July 7, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">July 11, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor-Investigator</responsible_party_type>
    <investigator_affiliation>Hoosier Cancer Research Network</investigator_affiliation>
    <investigator_full_name>Nasser Hanna, M.D.</investigator_full_name>
    <investigator_title>Sponsor-Investigator</investigator_title>
  </responsible_party>
  <keyword>Nivolumab</keyword>
  <keyword>BMS-936558-01</keyword>
  <keyword>Anti-PD-1 Antibody</keyword>
  <keyword>Docetaxel</keyword>
  <keyword>Pemetrexed</keyword>
  <keyword>Gemcitabine</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Lung Neoplasms</mesh_term>
    <mesh_term>Carcinoma, Non-Small-Cell Lung</mesh_term>
    <mesh_term>Adenocarcinoma of Lung</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Gemcitabine</mesh_term>
    <mesh_term>Docetaxel</mesh_term>
    <mesh_term>Nivolumab</mesh_term>
    <mesh_term>Pemetrexed</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <provided_document_section>
    <provided_document>
      <document_type>Study Protocol and Statistical Analysis Plan</document_type>
      <document_has_protocol>Yes</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>Yes</document_has_sap>
      <document_date>October 16, 2018</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/81/NCT03041181/Prot_SAP_000.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <group_list>
        <group group_id="P1">
          <title>Arm A - Single Agent Chemotherapy + Nivolumab</title>
          <description>Single Agent Chemotherapy of choice plus nivolumab:&#xD;
Taxotere Pemetrexed Gemcitabine&#xD;
Docetaxel: Docetaxel 75 mg/m2 IV Day 1 of each cycle (21 days = 1 cycle)&#xD;
Nivolumab: Nivolumab 360 mg IV Day 1 of each cycle (21 days = 1 cycle)&#xD;
Gemcitabine: Gemcitabine 1000 mg/m2 IV Day 1 and Day 8 of each cycle (21 days = 1 cycle)&#xD;
Pemetrexed: Pemetrexed 500 mg/m2 IV Day 1 of each cycle (21 days = 1 cycle)</description>
        </group>
        <group group_id="P2">
          <title>Arm B - Single Agent Chemotherapy</title>
          <description>Single Agent Chemotherapy of choice Taxotere Pemetrexed Gemcitabine&#xD;
Docetaxel: Docetaxel 75 mg/m2 IV Day 1 of each cycle (21 days = 1 cycle)&#xD;
Gemcitabine: Gemcitabine 1000 mg/m2 IV Day 1 and Day 8 of each cycle (21 days = 1 cycle)&#xD;
Pemetrexed: Pemetrexed 500 mg/m2 IV Day 1 of each cycle (21 days = 1 cycle)</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="2"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="0"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="2"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Disease Progression</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="2"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>Arm A</title>
          <description>Single Agent Chemotherapy of choice plus nivolumab:&#xD;
Taxotere Pemetrexed Gemcitabine&#xD;
Docetaxel: Docetaxel 75 mg/m2 IV Day 1 of each cycle (21 days = 1 cycle)&#xD;
Nivolumab: Nivolumab 360 mg IV Day 1 of each cycle (21 days = 1 cycle)&#xD;
Gemcitabine: Gemcitabine 1000 mg/m2 IV Day 1 and Day 8 of each cycle (21 days = 1 cycle)&#xD;
Pemetrexed: Pemetrexed 500 mg/m2 IV Day 1 of each cycle (21 days = 1 cycle)</description>
        </group>
        <group group_id="B2">
          <title>Arm B</title>
          <description>Single Agent Chemotherapy of choice Taxotere Pemetrexed Gemcitabine&#xD;
Docetaxel: Docetaxel 75 mg/m2 IV Day 1 of each cycle (21 days = 1 cycle)&#xD;
Gemcitabine: Gemcitabine 1000 mg/m2 IV Day 1 and Day 8 of each cycle (21 days = 1 cycle)&#xD;
Pemetrexed: Pemetrexed 500 mg/m2 IV Day 1 of each cycle (21 days = 1 cycle)</description>
        </group>
        <group group_id="B3">
          <title>Total</title>
          <description>Total of all reporting groups</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="1"/>
            <count group_id="B2" value="2"/>
            <count group_id="B3" value="3"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>&lt;=18 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Between 18 and 65 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                    <measurement group_id="B2" value="2"/>
                    <measurement group_id="B3" value="3"/>
                  </measurement_list>
                </category>
                <category>
                  <title>&gt;=65 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Sex: Female, Male</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Female</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="1"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="2"/>
                    <measurement group_id="B3" value="2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Ethnicity (NIH/OMB)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Not Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                    <measurement group_id="B2" value="2"/>
                    <measurement group_id="B3" value="3"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" 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 group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Asian</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Native Hawaiian or Other Pacific Islander</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Black or African American</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="1"/>
                  </measurement_list>
                </category>
                <category>
                  <title>White</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="2"/>
                  </measurement_list>
                </category>
                <category>
                  <title>More than one race</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" 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="1"/>
                    <measurement group_id="B2" value="2"/>
                    <measurement group_id="B3" value="3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Histology</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Adenocarcinoma</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                    <measurement group_id="B2" value="2"/>
                    <measurement group_id="B3" value="3"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Large Cell Carcinoma</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Mixed Histology</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Non-small Cell Carcinoma</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Sqamous</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Progression Free Survival (PFS), as Defined by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1.</title>
        <description>Compare PFS rates for subjects on each treatment arm, per RECIST 1.1. Subjects who have not progressed will be right-censored at the date of the last follow up.</description>
        <time_frame>24 months</time_frame>
        <population>Data for this objective was neither collected or analyzed due to the early termination of the study.</population>
        <group_list>
          <group group_id="O1">
            <title>Arm A</title>
            <description>Single Agent Chemotherapy of choice plus nivolumab:&#xD;
Taxotere Pemetrexed Gemcitabine&#xD;
Docetaxel: Docetaxel 75 mg/m2 IV Day 1 of each cycle (21 days = 1 cycle)&#xD;
Nivolumab: Nivolumab 360 mg IV Day 1 of each cycle (21 days = 1 cycle)&#xD;
Gemcitabine: Gemcitabine 1000 mg/m2 IV Day 1 and Day 8 of each cycle (21 days = 1 cycle)&#xD;
Pemetrexed: Pemetrexed 500 mg/m2 IV Day 1 of each cycle (21 days = 1 cycle)</description>
          </group>
          <group group_id="O2">
            <title>Arm B</title>
            <description>Single Agent Chemotherapy of choice Taxotere Pemetrexed Gemcitabine&#xD;
Docetaxel: Docetaxel 75 mg/m2 IV Day 1 of each cycle (21 days = 1 cycle)&#xD;
Gemcitabine: Gemcitabine 1000 mg/m2 IV Day 1 and Day 8 of each cycle (21 days = 1 cycle)&#xD;
Pemetrexed: Pemetrexed 500 mg/m2 IV Day 1 of each cycle (21 days = 1 cycle)</description>
          </group>
        </group_list>
        <measure>
          <title>Progression Free Survival (PFS), as Defined by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1.</title>
          <description>Compare PFS rates for subjects on each treatment arm, per RECIST 1.1. Subjects who have not progressed will be right-censored at the date of the last follow up.</description>
          <population>Data for this objective was neither collected or analyzed due to the early termination of the study.</population>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="0"/>
                <count group_id="O2" value="0"/>
              </count_list>
            </analyzed>
          </analyzed_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Overall Response Rate (ORR) for Subjects on Each Treatment Arm, as Defined by RECIST 1.1 and Immune-related Response Criteria (irRECIST)</title>
        <description>Proportion of subjects on each arm with complete response or partial response, per RECIST 1.1 and irRECIST</description>
        <time_frame>Every 6 weeks beginning with C3D1 and every odd numbered cycle thereafter, assessed for up to 24 months</time_frame>
        <population>Data for this objective was neither collected or analyzed due to the early termination of the study.</population>
        <group_list>
          <group group_id="O1">
            <title>Arm A</title>
            <description>Single Agent Chemotherapy of choice plus nivolumab:&#xD;
Taxotere Pemetrexed Gemcitabine&#xD;
Docetaxel: Docetaxel 75 mg/m2 IV Day 1 of each cycle (21 days = 1 cycle)&#xD;
Nivolumab: Nivolumab 360 mg IV Day 1 of each cycle (21 days = 1 cycle)&#xD;
Gemcitabine: Gemcitabine 1000 mg/m2 IV Day 1 and Day 8 of each cycle (21 days = 1 cycle)&#xD;
Pemetrexed: Pemetrexed 500 mg/m2 IV Day 1 of each cycle (21 days = 1 cycle)</description>
          </group>
          <group group_id="O2">
            <title>Arm B</title>
            <description>Single Agent Chemotherapy of choice Taxotere Pemetrexed Gemcitabine&#xD;
Docetaxel: Docetaxel 75 mg/m2 IV Day 1 of each cycle (21 days = 1 cycle)&#xD;
Gemcitabine: Gemcitabine 1000 mg/m2 IV Day 1 and Day 8 of each cycle (21 days = 1 cycle)&#xD;
Pemetrexed: Pemetrexed 500 mg/m2 IV Day 1 of each cycle (21 days = 1 cycle)</description>
          </group>
        </group_list>
        <measure>
          <title>Overall Response Rate (ORR) for Subjects on Each Treatment Arm, as Defined by RECIST 1.1 and Immune-related Response Criteria (irRECIST)</title>
          <description>Proportion of subjects on each arm with complete response or partial response, per RECIST 1.1 and irRECIST</description>
          <population>Data for this objective was neither collected or analyzed due to the early termination of the study.</population>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="0"/>
                <count group_id="O2" value="0"/>
              </count_list>
            </analyzed>
          </analyzed_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Clinical Benefit Rate (CBR) for Subjects on Each Treatment Arm, as Defined by RECIST 1.1 and irRECIST</title>
        <description>Proportion of subjects on each arm with complete response, partial response or stable disease for at least 3 months, per RECIST 1.1 and irRECIST</description>
        <time_frame>From D1 of treatment until documented disease progression/recurrence, assessed for up to 24 months</time_frame>
        <population>Data for this objective was neither collected or analyzed due to the early termination of the study.</population>
        <group_list>
          <group group_id="O1">
            <title>Arm A</title>
            <description>Single Agent Chemotherapy of choice plus nivolumab:&#xD;
Taxotere Pemetrexed Gemcitabine&#xD;
Docetaxel: Docetaxel 75 mg/m2 IV Day 1 of each cycle (21 days = 1 cycle)&#xD;
Nivolumab: Nivolumab 360 mg IV Day 1 of each cycle (21 days = 1 cycle)&#xD;
Gemcitabine: Gemcitabine 1000 mg/m2 IV Day 1 and Day 8 of each cycle (21 days = 1 cycle)&#xD;
Pemetrexed: Pemetrexed 500 mg/m2 IV Day 1 of each cycle (21 days = 1 cycle)</description>
          </group>
          <group group_id="O2">
            <title>Arm B</title>
            <description>Single Agent Chemotherapy of choice Taxotere Pemetrexed Gemcitabine&#xD;
Docetaxel: Docetaxel 75 mg/m2 IV Day 1 of each cycle (21 days = 1 cycle)&#xD;
Gemcitabine: Gemcitabine 1000 mg/m2 IV Day 1 and Day 8 of each cycle (21 days = 1 cycle)&#xD;
Pemetrexed: Pemetrexed 500 mg/m2 IV Day 1 of each cycle (21 days = 1 cycle)</description>
          </group>
        </group_list>
        <measure>
          <title>Clinical Benefit Rate (CBR) for Subjects on Each Treatment Arm, as Defined by RECIST 1.1 and irRECIST</title>
          <description>Proportion of subjects on each arm with complete response, partial response or stable disease for at least 3 months, per RECIST 1.1 and irRECIST</description>
          <population>Data for this objective was neither collected or analyzed due to the early termination of the study.</population>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="0"/>
                <count group_id="O2" value="0"/>
              </count_list>
            </analyzed>
          </analyzed_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Progression Free Survival (PFS), as Defined by irRECIST</title>
        <description>Compare PFS rates for subjects on each treatment arm, per irRECIST. From date of randomization until the criteria for disease progression is met or death as a result of any cause, assessed up to 24 months</description>
        <time_frame>24 months</time_frame>
        <population>Data for this objective was neither collected or analyzed due to the early termination of the study.</population>
        <group_list>
          <group group_id="O1">
            <title>Arm A</title>
            <description>Single Agent Chemotherapy of choice plus nivolumab:&#xD;
Taxotere Pemetrexed Gemcitabine&#xD;
Docetaxel: Docetaxel 75 mg/m2 IV Day 1 of each cycle (21 days = 1 cycle)&#xD;
Nivolumab: Nivolumab 360 mg IV Day 1 of each cycle (21 days = 1 cycle)&#xD;
Gemcitabine: Gemcitabine 1000 mg/m2 IV Day 1 and Day 8 of each cycle (21 days = 1 cycle)&#xD;
Pemetrexed: Pemetrexed 500 mg/m2 IV Day 1 of each cycle (21 days = 1 cycle)</description>
          </group>
          <group group_id="O2">
            <title>Arm B</title>
            <description>Single Agent Chemotherapy of choice Taxotere Pemetrexed Gemcitabine&#xD;
Docetaxel: Docetaxel 75 mg/m2 IV Day 1 of each cycle (21 days = 1 cycle)&#xD;
Gemcitabine: Gemcitabine 1000 mg/m2 IV Day 1 and Day 8 of each cycle (21 days = 1 cycle)&#xD;
Pemetrexed: Pemetrexed 500 mg/m2 IV Day 1 of each cycle (21 days = 1 cycle)</description>
          </group>
        </group_list>
        <measure>
          <title>Progression Free Survival (PFS), as Defined by irRECIST</title>
          <description>Compare PFS rates for subjects on each treatment arm, per irRECIST. From date of randomization until the criteria for disease progression is met or death as a result of any cause, assessed up to 24 months</description>
          <population>Data for this objective was neither collected or analyzed due to the early termination of the study.</population>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="0"/>
                <count group_id="O2" value="0"/>
              </count_list>
            </analyzed>
          </analyzed_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Number of Participants With Grade 3 or Grade 4 Adverse Events</title>
        <description>Assess toxicity of Nivolumab plus single agent chemotherapy compared with single agent chemotherapy alone. Number of grade 3 and 4 toxicities as defined by the NCI Common Terminology Criteria for Adverse Events (NCI CTCAE) v4.</description>
        <time_frame>6 months</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Arm A</title>
            <description>Single Agent Chemotherapy of choice plus nivolumab:&#xD;
Taxotere Pemetrexed Gemcitabine&#xD;
Docetaxel: Docetaxel 75 mg/m2 IV Day 1 of each cycle (21 days = 1 cycle)&#xD;
Nivolumab: Nivolumab 360 mg IV Day 1 of each cycle (21 days = 1 cycle)&#xD;
Gemcitabine: Gemcitabine 1000 mg/m2 IV Day 1 and Day 8 of each cycle (21 days = 1 cycle)&#xD;
Pemetrexed: Pemetrexed 500 mg/m2 IV Day 1 of each cycle (21 days = 1 cycle)</description>
          </group>
          <group group_id="O2">
            <title>Arm B</title>
            <description>Single Agent Chemotherapy of choice Taxotere Pemetrexed Gemcitabine&#xD;
Docetaxel: Docetaxel 75 mg/m2 IV Day 1 of each cycle (21 days = 1 cycle)&#xD;
Gemcitabine: Gemcitabine 1000 mg/m2 IV Day 1 and Day 8 of each cycle (21 days = 1 cycle)&#xD;
Pemetrexed: Pemetrexed 500 mg/m2 IV Day 1 of each cycle (21 days = 1 cycle)</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Participants With Grade 3 or Grade 4 Adverse Events</title>
          <description>Assess toxicity of Nivolumab plus single agent chemotherapy compared with single agent chemotherapy alone. Number of grade 3 and 4 toxicities as defined by the NCI Common Terminology Criteria for Adverse Events (NCI CTCAE) v4.</description>
          <units>participants</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="1"/>
                <count group_id="O2" value="2"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>GR4 Thromboembolic Event</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>GR3 Adverse Events</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>Adverse events are to be collected for the duration of the subject's participation on study, up to a maximum of six months.</time_frame>
      <group_list>
        <group group_id="E1">
          <title>Arm A</title>
          <description>Single Agent Chemotherapy of choice plus nivolumab:&#xD;
Taxotere Pemetrexed Gemcitabine&#xD;
Docetaxel: Docetaxel 75 mg/m2 IV Day 1 of each cycle (21 days = 1 cycle)&#xD;
Nivolumab: Nivolumab 360 mg IV Day 1 of each cycle (21 days = 1 cycle)&#xD;
Gemcitabine: Gemcitabine 1000 mg/m2 IV Day 1 and Day 8 of each cycle (21 days = 1 cycle)&#xD;
Pemetrexed: Pemetrexed 500 mg/m2 IV Day 1 of each cycle (21 days = 1 cycle)</description>
        </group>
        <group group_id="E2">
          <title>Arm B</title>
          <description>Single Agent Chemotherapy of choice Taxotere Pemetrexed Gemcitabine&#xD;
Docetaxel: Docetaxel 75 mg/m2 IV Day 1 of each cycle (21 days = 1 cycle)&#xD;
Gemcitabine: Gemcitabine 1000 mg/m2 IV Day 1 and Day 8 of each cycle (21 days = 1 cycle)&#xD;
Pemetrexed: Pemetrexed 500 mg/m2 IV Day 1 of each cycle (21 days = 1 cycle)</description>
        </group>
      </group_list>
      <serious_events>
        <default_vocab>CTCAEv4</default_vocab>
        <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="1"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="2"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="2"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Vascular disorders</title>
            <event_list>
              <event>
                <sub_title>THROMBOEMBOLIC EVENT</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="2"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>0</frequency_threshold>
        <default_vocab>CTCAEv4</default_vocab>
        <default_assessment>Non-systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, other adverse events</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="1"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="2"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Blood and lymphatic system disorders</title>
            <event_list>
              <event>
                <sub_title>ANEMIA</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="2"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>CONSTIPATION</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="1"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="2"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>NON-CARDIAC CHEST PAIN</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E2" events="2" subjects_affected="1" subjects_at_risk="2"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>LUNG INFECTION</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="1"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="2"/>
              </event>
              <event>
                <sub_title>SINUSITIS</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="1"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="2"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Investigations</title>
            <event_list>
              <event>
                <sub_title>INVESTIGATIONS - OTHER, SPECIFY</sub_title>
                <counts group_id="E1" events="2" subjects_affected="1" subjects_at_risk="1"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="2"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Musculoskeletal and connective tissue disorders</title>
            <event_list>
              <event>
                <sub_title>MUSCULOSKELETAL AND CONNECTIVE TISSUE DISORDER - OTHER, SPECIFY</sub_title>
                <counts group_id="E1" events="2" subjects_affected="1" subjects_at_risk="1"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="2"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>HEADACHE</sub_title>
                <counts group_id="E1" events="2" subjects_affected="1" subjects_at_risk="1"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="2"/>
              </event>
              <event>
                <sub_title>PERIPHERAL SENSORY NEUROPATHY</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="2"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Psychiatric disorders</title>
            <event_list>
              <event>
                <sub_title>ANXIETY</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="2"/>
              </event>
              <event>
                <sub_title>DEPRESSION</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="2"/>
              </event>
              <event>
                <sub_title>INSOMNIA</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="2"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>ALLERGIC RHINITIS</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="1"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="2"/>
              </event>
              <event>
                <sub_title>PRODUCTIVE COUGH</sub_title>
                <counts group_id="E1" events="2" subjects_affected="1" subjects_at_risk="1"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="2"/>
              </event>
              <event>
                <sub_title>COUGH</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="2"/>
              </event>
              <event>
                <sub_title>DYSPNEA</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="2"/>
              </event>
              <event>
                <sub_title>NASAL CONGESTION</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="2"/>
              </event>
              <event>
                <sub_title>PNEUMOTHORAX</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="2"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Vascular disorders</title>
            <event_list>
              <event>
                <sub_title>HOT FLASHES</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="1"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="2"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </other_events>
    </reported_events>

    <certain_agreements>
      <pi_employee>Principal Investigators are NOT employed by the organization sponsoring the study.</pi_employee>
      <restrictive_agreement>There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed. </restrictive_agreement>
    </certain_agreements>
    <limitations_and_caveats>Study was terminated early due to lack of accrual. Sufficient data was not collected to analyze any pre-specified endpoint.</limitations_and_caveats>
    <point_of_contact>
      <name_or_title>Clinicaltrials.gov Results Coordinator</name_or_title>
      <organization>Hoosier Cancer Research Network</organization>
      <phone>317-643-5842 ext 41</phone>
      <email>jsmith@hoosiercancer.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/NCT03041181
org study id: HCRN LUN15-233
nct id: NCT03041181
lead sponsor: 
collaborator: 
collaborator: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
is us export: Yes
This is a randomized phase II study assessing the activity of single agent chemotherapy
      combined with nivolumab (Arm A) compared to single agent chemotherapy alone (Arm B) in
      squamous or non-squamous NSCLC subjects with primary resistance to prior PD-1 or PDL-1
      inhibitor. The single agent chemotherapy chosen is at the discretion of the site investigator
      and may include pemetrexed, gemcitabine or taxotere. Institutional standards should be used
      for administration of the single agent chemotherapy. For both treatment arms, 21 days equals
      1 cycle of therapy and subjects will be eligible to continue treatment until progressive
      disease by RECIST v1.1 or unacceptable toxicity.

      Upon registration, subjects will be randomized in a 1:1 ratio to either treatment with single
      agent chemotherapy or single agent chemotherapy in combination with nivolumab. Randomization
      is un-blinded and open-label; therefore there will be no placebo treatment for subjects
      randomized to single agent chemotherapy
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
masking description: Open-Label
measure: Progression Free Survival (PFS), as Defined by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1.
time frame: 24 months
description: Compare PFS rates for subjects on each treatment arm, per RECIST 1.1. Subjects who have not progressed will be right-censored at the date of the last follow up.
measure: Overall Response Rate (ORR) for Subjects on Each Treatment Arm, as Defined by RECIST 1.1 and Immune-related Response Criteria (irRECIST)
time frame: Every 6 weeks beginning with C3D1 and every odd numbered cycle thereafter, assessed for up to 24 months
description: Proportion of subjects on each arm with complete response or partial response, per RECIST 1.1 and irRECIST
measure: Clinical Benefit Rate (CBR) for Subjects on Each Treatment Arm, as Defined by RECIST 1.1 and irRECIST
time frame: From D1 of treatment until documented disease progression/recurrence, assessed for up to 24 months
description: Proportion of subjects on each arm with complete response, partial response or stable disease for at least 3 months, per RECIST 1.1 and irRECIST
measure: Progression Free Survival (PFS), as Defined by irRECIST
time frame: 24 months
description: Compare PFS rates for subjects on each treatment arm, per irRECIST. From date of randomization until the criteria for disease progression is met or death as a result of any cause, assessed up to 24 months
measure: Number of Participants With Grade 3 or Grade 4 Adverse Events
time frame: 6 months
description: Assess toxicity of Nivolumab plus single agent chemotherapy compared with single agent chemotherapy alone. Number of grade 3 and 4 toxicities as defined by the NCI Common Terminology Criteria for Adverse Events (NCI CTCAE) v4.
arm group label: Arm A - Single Agent Chemotherapy + Nivolumab
arm group type: Experimental
description: Single Agent Chemotherapy of choice plus nivolumab:
Taxotere Pemetrexed Gemcitabine
arm group label: Arm B - Single Agent Chemotherapy
arm group type: Active Comparator
description: Single Agent Chemotherapy of choice Taxotere Pemetrexed Gemcitabine
intervention type: Drug
intervention name: Docetaxel
description: Docetaxel 75 mg/m2 IV Day 1 of each cycle (21 days = 1 cycle)
arm group label: Arm A - Single Agent Chemotherapy + Nivolumab
arm group label: Arm B - Single Agent Chemotherapy
other name: Taxotere
intervention type: Drug
intervention name: Nivolumab
description: Nivolumab 360 mg IV Day 1 of each cycle (21 days = 1 cycle)
arm group label: Arm A - Single Agent Chemotherapy + Nivolumab
other name: BMS-936558-01
other name: Opdivo
intervention type: Drug
intervention name: Gemcitabine
description: Gemcitabine 1000 mg/m2 IV Day 1 and Day 8 of each cycle (21 days = 1 cycle)
arm group label: Arm A - Single Agent Chemotherapy + Nivolumab
arm group label: Arm B - Single Agent Chemotherapy
other name: Gemzar
intervention type: Drug
intervention name: Pemetrexed
description: Pemetrexed 500 mg/m2 IV Day 1 of each cycle (21 days = 1 cycle)
arm group label: Arm A - Single Agent Chemotherapy + Nivolumab
arm group label: Arm B - Single Agent Chemotherapy
other name: Alimta
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Nasser Hanna, M.D.
role: Principal Investigator
affiliation: Hoosier Cancer Research Network
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
country: United States
url: https://hoosiercancer.org/
description: Hoosier Cancer Research Network Website
responsible party type: Sponsor-Investigator
investigator affiliation: Hoosier Cancer Research Network
investigator full name: Nasser Hanna, M.D.
investigator title: Sponsor-Investigator
mesh term: Lung Neoplasms
mesh term: Carcinoma, Non-Small-Cell Lung
mesh term: Adenocarcinoma of Lung
mesh term: Gemcitabine
mesh term: Docetaxel
mesh term: Nivolumab
mesh term: Pemetrexed
sharing ipd: No
provided document: 
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
limitations and caveats: Study was terminated early due to lack of accrual. Sufficient data was not collected to analyze any pre-specified endpoint.
point of contact: 