<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/NCT03285321</url>
  </required_header>
  <id_info>
    <org_study_id>BTCRC-LUN16-081</org_study_id>
    <nct_id>NCT03285321</nct_id>
  </id_info>
  <brief_title>Unresectable Stage IIIA/IIIB Non-small Cell Lung Cancer (NSCLC)</brief_title>
  <official_title>Phase II Study of Consolidation Immunotherapy With Nivolumab and Ipilimumab or Nivolumab Alone Following Concurrent Chemoradiotherapy for Unresectable Stage IIIA/IIIB Non-small Cell Lung Cancer (NSCLC): BTCRC-LUN16-081</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Greg Durm, MD</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Bristol-Myers Squibb</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
    <collaborator>
      <agency>Big Ten Cancer Research Consortium</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Big Ten Cancer Research Consortium</source>
  <oversight_info>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      This study is an open label, multicenter, randomized phase II trial of consolidation&#xD;
      immunotherapy with either nivolumab alone or the combination of nivolumab and ipilimumab&#xD;
      following concurrent chemoradiation in patients with unresectable stage III NSCLC.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Patients with unresectable stage IIIA or IIIB NSCLC (unresectable as defined by treating&#xD;
      physician) will be treated outside this study with concurrent chemoradiation with one of&#xD;
      three chemotherapy regimens (cisplatin/etoposide, cisplatin/pemetrexed, or weekly&#xD;
      carboplatin/paclitaxel) in addition to standard dose radiation (dosing can range from 59.4 Gy&#xD;
      to 66.6 Gy). If repeat imaging between 28-56 days following completion of chemoradiation&#xD;
      shows no progressive or metastatic disease, the patients will be eligible for enrollment on&#xD;
      the study.&#xD;
&#xD;
      Randomization and Stratification:&#xD;
&#xD;
      At the time of enrollment, patients will be randomized in a 1:1 fashion to receive either&#xD;
      nivolumab 480mg IV every 4 weeks or the combination of nivolumab 3mg/kg IV every 2 weeks with&#xD;
      ipilimumab 1mg/kg IV every 6 weeks. Consolidation immunotherapy will be continued until&#xD;
      progression or unacceptable toxicity for up to a total of 24 weeks.&#xD;
&#xD;
      Subjects will be stratified by stage (IIIA vs. IIIB) and histology (squamous vs.&#xD;
      non-squamous).&#xD;
&#xD;
      Dose Calculations:&#xD;
&#xD;
      Arm 1: The dose of nivolumab will be a fixed dose (not based on subject's weight) at 480mg.&#xD;
&#xD;
      Arm 2: The dose of nivolumab will be weight-based at 3mg/kg. The dose of ipilimumab will be&#xD;
      weight-based at 1mg/kg.&#xD;
&#xD;
      Nivolumab Alone (Arm 1):&#xD;
&#xD;
      Arm 1: Nivolumab Administration:&#xD;
&#xD;
      Nivolumab 480 mg will be administered as a 60 minute IV infusion on Day 1 of each 28 day&#xD;
      cycle. Sites should make every effort to target infusion timing to be as close to 60 minutes&#xD;
      as possible. However, given the variability of infusion pumps from site to site, a window of&#xD;
      -five minutes and +10 minutes is permitted (i.e., infusion time is 60 minutes: -5 min/+10&#xD;
      min). Treatment will continue for up to 6 cycles, in the absence of prohibitive toxicities or&#xD;
      disease progression.&#xD;
&#xD;
      Nivolumab Plus Ipilimumab (Arm 2):&#xD;
&#xD;
      Arm 2: Nivolumb Administration:&#xD;
&#xD;
      Nivolumab 3mg/kg will be administered as a 60 minute IV infusion on Day 1, 15, and 29 of each&#xD;
      42 day cycle. Nivolumab should not be given any earlier than 12 days from the previous dose.&#xD;
      Sites should make every effort to target infusion timing to be as close to 60 minutes as&#xD;
      possible. However, given the variability of infusion pumps from site to site, a window of&#xD;
      -five minutes and +10 minutes is permitted (i.e., infusion time is 60 minutes: -5 min/+10&#xD;
      min). Treatment will continue for up to 4 cycles, in the absence of prohibitive toxicities or&#xD;
      disease progression.&#xD;
&#xD;
      Arm 2: Ipilimumab Administration:&#xD;
&#xD;
      Ipilimumab 1mg/kg will be administered as a 90 minute IV infusion on Day 1 of each 42 day&#xD;
      cycle. Sites should make every effort to target infusion timing to be as close to 90 minutes&#xD;
      as possible. However, given the variability of infusion pumps from site to site, a window of&#xD;
      -five minutes and +10 minutes is permitted (i.e., infusion time is 60 minutes: -5 min/+10&#xD;
      min). Treatment will continue for up to 4 cycles, in the absence of prohibitive toxicities or&#xD;
      disease progression.&#xD;
&#xD;
      On day 1 of cycle 1, nivolumab will be given first, followed by 30 minutes of monitoring, and&#xD;
      then ipilimumab given second, followed by 30 minutes of monitoring. If the subject does not&#xD;
      have an infusion reaction during the first cycle, the post-ipilimumab monitoring may be&#xD;
      discontinued for subsequent cycles at the discretion of the treating physician. Day 1&#xD;
      monitoring between the nivolumab/ipilimumab infusions will continue throughout all 4 cycles.&#xD;
      Post nivolumab monitoring on days 15 and 29 is not mandatory and should follow the guidelines&#xD;
      of the local infusion center.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Active, not recruiting</overall_status>
  <start_date type="Actual">September 15, 2017</start_date>
  <completion_date type="Anticipated">December 2023</completion_date>
  <primary_completion_date type="Anticipated">August 2023</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)</measure>
    <time_frame>18 months</time_frame>
    <description>PFS is defined as the time from randomization until the criteria for disease progression is met as defined by RECIST 1.1 or death as a result of any cause.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Overall Survival (OS)</measure>
    <time_frame>4 years</time_frame>
    <description>The time from randomization until death from any cause. Will be assessed with RECIST 1.1</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time to Metastatic Disease</measure>
    <time_frame>4 years</time_frame>
    <description>the time from randomization until evidence of disease outside of the radiated field. Will be assessed with RECIST 1.1</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Assess Adverse Events</measure>
    <time_frame>4 years</time_frame>
    <description>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">105</enrollment>
  <condition>Non-small Cell Lung Cancer</condition>
  <arm_group>
    <arm_group_label>Arm 1</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Nivolumab 480mg IV every 4 weeks for up to 6 cycles</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Arm 2</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Nivolumab 240mg IV every 2 weeks PLUS Ipilimumab 1mg/kg IV every 6 weeks for up to 4 cycles (12 doses Nivolumab and 4 doses of Ipilimumab)</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Nivolumab</intervention_name>
    <description>480mg</description>
    <arm_group_label>Arm 1</arm_group_label>
    <other_name>OPDIVO</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Nivolumab</intervention_name>
    <description>240mg</description>
    <arm_group_label>Arm 2</arm_group_label>
    <other_name>OPDIVO</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Ipilimumab</intervention_name>
    <description>1mg/kg</description>
    <arm_group_label>Arm 2</arm_group_label>
    <other_name>Yervoy</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;
          -  Written informed consent and HIPAA authorization for release of personal health&#xD;
             information.&#xD;
&#xD;
          -  Age ≥ 18 years at the time of consent.&#xD;
&#xD;
          -  ECOG Performance Status of 0 or 1 within 14 days prior to registration.&#xD;
&#xD;
          -  Histological or cytological confirmation of NSCLC. A pathology report confirming the&#xD;
             diagnosis of NSCLC must be obtained and reviewed by the treating physician prior to&#xD;
             registration to study.&#xD;
&#xD;
          -  Must have unresectable or inoperable stage IIIA or IIIB disease according to the 7th&#xD;
             edition IASLC stage classification for lung cancer. Subjects must be considered&#xD;
             unresectable or inoperable based on the judgment of the treating physician.&#xD;
&#xD;
          -  Subjects must have completed concurrent chemoradiation with a platinum doublet and a&#xD;
             dose of radiation ranging from 59.4-66.6 Gy. Subjects must have stable disease or&#xD;
             disease response as evidenced on CT or PET scan evaluation. For those eligible,&#xD;
             protocol therapy should begin within 56 days of completing chemoradiation OR Subjects&#xD;
             must have completed up to 2 cycles of consolidation therapy started within 56 days of&#xD;
             completion of radiation. After completion of consolidation chemotherapy, subjects must&#xD;
             have stable disease or disease response as evidenced by CT or PET scan evaluation. For&#xD;
             those eligible, protocol therapy should begin within 56 days after the last cycle of&#xD;
             chemotherapy.&#xD;
&#xD;
          -  Prior cancer treatment must be completed between 1-56 days prior to registration and&#xD;
             the subject must have recovered from all reversible acute toxic effects of the regimen&#xD;
             (other than alopecia) to ≤Grade 1 or baseline.&#xD;
&#xD;
          -  Demonstrate adequate organ function, all screening labs to be obtained within 14 days&#xD;
             prior to registration:&#xD;
&#xD;
        Hematological:&#xD;
&#xD;
          -  Absolute Neutrophil Count (ANC) ≥ 1.5 K/mm^3&#xD;
&#xD;
          -  Hemoglobin (Hgb) ≥ 9 g/dL&#xD;
&#xD;
          -  Platelets ≥100,000/mcl&#xD;
&#xD;
        Renal:&#xD;
&#xD;
          -  Serum creatinine OR Measured or calculated creatinine clearance (GFR can also be used&#xD;
             in place of creatinine or CrCl) ≤ 1.5 x upper limit of normal (ULN) OR ≥ 60 mL/min for&#xD;
             subjects with creatinine levels &gt;1.5 x institutional ULN&#xD;
&#xD;
        Hepatic:&#xD;
&#xD;
          -  Bilirubin ≤ 1.5 × ULN OR Direct bilirubin of ≤ ULN for subjects with total bilirubin&#xD;
             levels of &gt;1.5x ULN&#xD;
&#xD;
          -  Aspartate aminotransferase (AST) ≤ 2.5 × ULN&#xD;
&#xD;
          -  Alanine aminotransferase (ALT) ≤ 2.5 × ULN&#xD;
&#xD;
        Coagulation:&#xD;
&#xD;
          -  International Normalized Ratio (INR) or Prothrombin Time (PT) Activated Partial&#xD;
             Thromboplastin Time (aPTT) ≤1.5 X ULN unless subject is receiving anticoagulant&#xD;
             therapy as long as PT/INR/PTT is within therapeutic range of intended use of&#xD;
             anticoagulants&#xD;
&#xD;
               -  Women of childbearing potential (WOCBP) must have a negative serum or urine&#xD;
                  pregnancy test (minimum sensitivity 25 IU/L or equivalent units of HCG) within 7&#xD;
                  days prior to registration. NOTE: Women are considered of childbearing potential&#xD;
                  unless they are surgically sterile (have undergone a hysterectomy, bilateral&#xD;
                  tubal ligation, or bilateral oophorectomy) or are post-menopausal. Menopause is&#xD;
                  defined clinically as 12 months of amenorrhea in a woman over 45 in the absence&#xD;
                  of other biological or physiological causes. In addition, women under the age of&#xD;
                  62 must have a documented serum follicle stimulating hormone (FSH) level less&#xD;
                  than 40 mIU/mL to be considered post-menopausal.&#xD;
&#xD;
               -  Women of childbearing potential must be willing to abstain from heterosexual&#xD;
                  activity or use an effective method of contraception from the time of informed&#xD;
                  consent until 23 weeks after treatment discontinuation.&#xD;
&#xD;
               -  Men who are sexually active with women of childbearing potential (WOCBP) must use&#xD;
                  any contraceptive method with a failure rate of less than 1% per year. Men&#xD;
                  receiving study drug and who are sexually active with WOCBP will be instructed to&#xD;
                  adhere to contraception for a period of 31 weeks after the last dose of&#xD;
                  investigational product.&#xD;
&#xD;
               -  As determined by the enrolling physician or protocol designee, ability of the&#xD;
                  subject to understand and comply with study procedures for the entire length of&#xD;
                  the study.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
        Subjects meeting any of the criteria below may not participate in the study:&#xD;
&#xD;
          -  Pregnant or breastfeeding, or expecting to conceive or father children within the&#xD;
             projected duration of the trial, starting with the pre-screening or screening visit&#xD;
             through 23 weeks (female) or 31 weeks (male) after the last dose of trial treatment.&#xD;
&#xD;
          -  Active central nervous system (CNS) metastases. Subjects must undergo a head computed&#xD;
             tomography (CT) scan or brain MRI within 28 days prior to registration for protocol&#xD;
             therapy to exclude brain metastases if symptomatic or without prior brain imaging.&#xD;
&#xD;
          -  Treatment with any investigational agent within 28 days prior to registration for&#xD;
             protocol therapy.&#xD;
&#xD;
          -  Prior chemotherapy, adjuvant therapy, or radiotherapy for lung cancer other than&#xD;
             standard concurrent chemoradiation or up to 2 cycles of consolidation.&#xD;
&#xD;
          -  Prior therapy with a PD-1, PD-L1, PD-L2 or CTLA-4 inhibitor or a lung cancer-specific&#xD;
             vaccine therapy.&#xD;
&#xD;
          -  Presence of metastatic disease (stage IV NSCLC) is not allowed. Subjects must be&#xD;
             evaluated with a CT or PET scan prior to registration for protocol therapy to exclude&#xD;
             metastatic disease.&#xD;
&#xD;
          -  Active second cancers.&#xD;
&#xD;
          -  Evidence of active autoimmune disease requiring systemic treatment within the past 90&#xD;
             days or a documented history of clinically severe autoimmune disease, or a syndrome&#xD;
             that requires systemic steroids or immunosuppressive agents. Subjects with vitiligo or&#xD;
             resolved childhood asthma/atopy would be an exception to this rule. Subjects that&#xD;
             require intermittent use of bronchodilators or local steroid injections would not be&#xD;
             excluded from the study. Subjects with hypothyroidism stable on hormone replacement or&#xD;
             Sjogren's syndrome will not be excluded from the study.&#xD;
&#xD;
          -  Interstitial lung disease or history of pneumonitis requiring treatment with&#xD;
             corticosteroids.&#xD;
&#xD;
          -  Diagnosis of immunodeficiency or is receiving chronic systemic corticosteroid therapy&#xD;
             or other immunosuppressive therapy (excludes inhaled corticosteroids) within 7 days of&#xD;
             first dose of study drug.&#xD;
&#xD;
          -  History of psychiatric illness or social situations that would limit compliance with&#xD;
             study requirements.&#xD;
&#xD;
          -  Clinically active infection as judged by the site investigator (≥ Grade 2 by CTCAE&#xD;
             v4).&#xD;
&#xD;
          -  History of human immunodeficiency virus (HIV) infection or chronic hepatitis B or C.&#xD;
&#xD;
          -  Has a history or current evidence of any condition, therapy, or laboratory abnormality&#xD;
             that might confound the results of the trial, interfere with the subject's&#xD;
             participation for the full duration of the trial, or is not in the best interest of&#xD;
             the subject to participate, in the opinion of the site investigator.&#xD;
&#xD;
          -  Has a known history of active TB (Bacillus Tuberculosis).&#xD;
&#xD;
          -  Hypersensitivity to nivolumab, ipilimumab, or any of their excipients.&#xD;
&#xD;
          -  Has received a live vaccine within 30 days prior to planned start of study therapy.&#xD;
             Note: Seasonal influenza vaccines for injection are generally inactivated flu vaccines&#xD;
             and are allowed; however, intranasal influenza vaccines (e.g., Flu-Mist®) are live&#xD;
             attenuated vaccines, and are not allowed.&#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>Greg Durm, M.D.</last_name>
    <role>Study Chair</role>
    <affiliation>Indiana University Health Simon Cancer Center</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Rush University Medical Center</name>
      <address>
        <city>Chicago</city>
        <state>Illinois</state>
        <zip>60612</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Illinois Cancer Center</name>
      <address>
        <city>Chicago</city>
        <state>Illinois</state>
        <zip>60612</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Indiana University</name>
      <address>
        <city>Indianapolis</city>
        <state>Indiana</state>
        <zip>46202</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Louisville James Graham Brown Cancer Center</name>
      <address>
        <city>Louisville</city>
        <state>Kentucky</state>
        <zip>40202</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Johns Hopkins Sidney Kimmel Comprehensive</name>
      <address>
        <city>Baltimore</city>
        <state>Maryland</state>
        <zip>21287</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Karmanos Cancer Center (Wayne State University)</name>
      <address>
        <city>Detroit</city>
        <state>Michigan</state>
        <zip>48201</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Michigan State University</name>
      <address>
        <city>Lansing</city>
        <state>Michigan</state>
        <zip>48910</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Minnesota</name>
      <address>
        <city>Minneapolis</city>
        <state>Minnesota</state>
        <zip>55455</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Nebraska Medical Center</name>
      <address>
        <city>Omaha</city>
        <state>Nebraska</state>
        <zip>68198</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Rutgers Cancer Institute of New Jersey</name>
      <address>
        <city>New Brunswick</city>
        <state>New Jersey</state>
        <zip>08903</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Penn State Cancer Institute</name>
      <address>
        <city>Hershey</city>
        <state>Pennsylvania</state>
        <zip>17033</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Wisconsin</name>
      <address>
        <city>Madison</city>
        <state>Wisconsin</state>
        <zip>53705</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <link>
    <url>http://www.bigtencrc.org</url>
    <description>Big Ten Cancer Research Consortium Website</description>
  </link>
  <verification_date>August 2022</verification_date>
  <study_first_submitted>September 14, 2017</study_first_submitted>
  <study_first_submitted_qc>September 14, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">September 18, 2017</study_first_posted>
  <last_update_submitted>August 31, 2022</last_update_submitted>
  <last_update_submitted_qc>August 31, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">September 2, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor-Investigator</responsible_party_type>
    <investigator_affiliation>Big Ten Cancer Research Consortium</investigator_affiliation>
    <investigator_full_name>Greg Durm, MD</investigator_full_name>
    <investigator_title>Sponsor-Investigator</investigator_title>
  </responsible_party>
  <keyword>Nivolumab</keyword>
  <keyword>Ipilimumab</keyword>
  <keyword>immunotherapy</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>
  </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>
  <!-- Results have not yet been posted for this study                                          -->
</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/NCT03285321
org study id: BTCRC-LUN16-081
nct id: NCT03285321
lead sponsor: 
collaborator: 
collaborator: 
is fda regulated drug: Yes
is fda regulated device: No
This study is an open label, multicenter, randomized phase II trial of consolidation
      immunotherapy with either nivolumab alone or the combination of nivolumab and ipilimumab
      following concurrent chemoradiation in patients with unresectable stage III NSCLC.
Patients with unresectable stage IIIA or IIIB NSCLC (unresectable as defined by treating
      physician) will be treated outside this study with concurrent chemoradiation with one of
      three chemotherapy regimens (cisplatin/etoposide, cisplatin/pemetrexed, or weekly
      carboplatin/paclitaxel) in addition to standard dose radiation (dosing can range from 59.4 Gy
      to 66.6 Gy). If repeat imaging between 28-56 days following completion of chemoradiation
      shows no progressive or metastatic disease, the patients will be eligible for enrollment on
      the study.

      Randomization and Stratification:

      At the time of enrollment, patients will be randomized in a 1:1 fashion to receive either
      nivolumab 480mg IV every 4 weeks or the combination of nivolumab 3mg/kg IV every 2 weeks with
      ipilimumab 1mg/kg IV every 6 weeks. Consolidation immunotherapy will be continued until
      progression or unacceptable toxicity for up to a total of 24 weeks.

      Subjects will be stratified by stage (IIIA vs. IIIB) and histology (squamous vs.
      non-squamous).

      Dose Calculations:

      Arm 1: The dose of nivolumab will be a fixed dose (not based on subject's weight) at 480mg.

      Arm 2: The dose of nivolumab will be weight-based at 3mg/kg. The dose of ipilimumab will be
      weight-based at 1mg/kg.

      Nivolumab Alone (Arm 1):

      Arm 1: Nivolumab Administration:

      Nivolumab 480 mg will be administered as a 60 minute IV infusion on Day 1 of each 28 day
      cycle. Sites should make every effort to target infusion timing to be as close to 60 minutes
      as possible. However, given the variability of infusion pumps from site to site, a window of
      -five minutes and +10 minutes is permitted (i.e., infusion time is 60 minutes: -5 min/+10
      min). Treatment will continue for up to 6 cycles, in the absence of prohibitive toxicities or
      disease progression.

      Nivolumab Plus Ipilimumab (Arm 2):

      Arm 2: Nivolumb Administration:

      Nivolumab 3mg/kg will be administered as a 60 minute IV infusion on Day 1, 15, and 29 of each
      42 day cycle. Nivolumab should not be given any earlier than 12 days from the previous dose.
      Sites should make every effort to target infusion timing to be as close to 60 minutes as
      possible. However, given the variability of infusion pumps from site to site, a window of
      -five minutes and +10 minutes is permitted (i.e., infusion time is 60 minutes: -5 min/+10
      min). Treatment will continue for up to 4 cycles, in the absence of prohibitive toxicities or
      disease progression.

      Arm 2: Ipilimumab Administration:

      Ipilimumab 1mg/kg will be administered as a 90 minute IV infusion on Day 1 of each 42 day
      cycle. Sites should make every effort to target infusion timing to be as close to 90 minutes
      as possible. However, given the variability of infusion pumps from site to site, a window of
      -five minutes and +10 minutes is permitted (i.e., infusion time is 60 minutes: -5 min/+10
      min). Treatment will continue for up to 4 cycles, in the absence of prohibitive toxicities or
      disease progression.

      On day 1 of cycle 1, nivolumab will be given first, followed by 30 minutes of monitoring, and
      then ipilimumab given second, followed by 30 minutes of monitoring. If the subject does not
      have an infusion reaction during the first cycle, the post-ipilimumab monitoring may be
      discontinued for subsequent cycles at the discretion of the treating physician. Day 1
      monitoring between the nivolumab/ipilimumab infusions will continue throughout all 4 cycles.
      Post nivolumab monitoring on days 15 and 29 is not mandatory and should follow the guidelines
      of the local infusion center.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
masking description: Open label
measure: Progression Free Survival (PFS)
time frame: 18 months
description: PFS is defined as the time from randomization until the criteria for disease progression is met as defined by RECIST 1.1 or death as a result of any cause.
measure: Overall Survival (OS)
time frame: 4 years
description: The time from randomization until death from any cause. Will be assessed with RECIST 1.1
measure: Time to Metastatic Disease
time frame: 4 years
description: the time from randomization until evidence of disease outside of the radiated field. Will be assessed with RECIST 1.1
measure: Assess Adverse Events
time frame: 4 years
description: By the NCI Common Terminology Criteria for Adverse Events (NCI CTCAE) v4.
arm group label: Arm 1
arm group type: Experimental
description: Nivolumab 480mg IV every 4 weeks for up to 6 cycles
arm group label: Arm 2
arm group type: Experimental
description: Nivolumab 240mg IV every 2 weeks PLUS Ipilimumab 1mg/kg IV every 6 weeks for up to 4 cycles (12 doses Nivolumab and 4 doses of Ipilimumab)
intervention type: Drug
intervention name: Nivolumab
description: 480mg
arm group label: Arm 1
other name: OPDIVO
intervention type: Drug
intervention name: Nivolumab
description: 240mg
arm group label: Arm 2
other name: OPDIVO
intervention type: Drug
intervention name: Ipilimumab
description: 1mg/kg
arm group label: Arm 2
other name: Yervoy
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Greg Durm, M.D.
role: Study Chair
affiliation: Indiana University Health Simon Cancer Center
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country: United States
url: http://www.bigtencrc.org
description: Big Ten Cancer Research Consortium Website
responsible party type: Sponsor-Investigator
investigator affiliation: Big Ten Cancer Research Consortium
investigator full name: Greg Durm, MD
investigator title: Sponsor-Investigator
mesh term: Lung Neoplasms
mesh term: Carcinoma, Non-Small-Cell Lung
mesh term: Nivolumab
mesh term: Ipilimumab