<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/NCT03043599</url>
  </required_header>
  <id_info>
    <org_study_id>MCC-18914</org_study_id>
    <secondary_id>CA209-840</secondary_id>
    <nct_id>NCT03043599</nct_id>
  </id_info>
  <brief_title>Ipilimumab + Nivolumab w/Thoracic Radiotherapy for Extensive-Stage Small Cell Lung Cancer</brief_title>
  <official_title>Consolidative Ipilimumab and Nivolumab With Thoracic Radiotherapy After Platinum Based Chemotherapy for Patients With Extensive-Stage Small Cell Lung Cancer</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>H. Lee Moffitt Cancer Center and Research Institute</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Bristol-Myers Squibb</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>H. Lee Moffitt Cancer Center and Research Institute</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
    <is_us_export>No</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      The purpose of the safety run in Phase I portion of this study is to confirm the recommended&#xD;
      Phase II dose of ipilimumab and nivolumab among participants treated with combined thoracic&#xD;
      radiation therapy (30 Gy in 10 fractions) and nivolumab/ipilimumab following standard&#xD;
      treatment with 4-6 cycles of platinum-based chemotherapy.&#xD;
&#xD;
      The purpose of the Phase II portion of this study is to estimate the 6-month Progression Free&#xD;
      Survival (PFS) rate among participants treated with ipilimumab and nivolumab with thoracic&#xD;
      radiation therapy (30 Gy in 10 fractions) after standard treatment with 4 to 6 cycles of&#xD;
      platinum based chemotherapy.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This study is a nonrandomized, phase II, single arm, multicenter trial evaluating safety and&#xD;
      efficacy of thoracic radiation therapy followed by nivolumab and ipilimumab in participants&#xD;
      with Extensive-Stage Disease Small Cell Lung Cancer (ED-SCLC) who have completed a first-line&#xD;
      platinum-based chemotherapy regimen and achieved ongoing complete response (CR), partial&#xD;
      response (PR), or stable disease (SD). This study will determine whether nivolumab and&#xD;
      ipilimumab delivered 2 weeks following consolidative thoracic radiation therapy demonstrates&#xD;
      acceptable toxicity and whether the treatment regimen will improve 6-month progression-free&#xD;
      survival (PFS) compared with a similar historical control cohort in this participant&#xD;
      population. Additional objectives include further characterization of overall survival,&#xD;
      adverse event profile, patterns of failure analysis, and potential predictive biomarkers of&#xD;
      response to nivolumab in combination with ipilimumab and thoracic radiation therapy in&#xD;
      patients with ED-SCLC.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Active, not recruiting</overall_status>
  <start_date type="Actual">February 13, 2017</start_date>
  <completion_date type="Anticipated">December 2023</completion_date>
  <primary_completion_date type="Actual">October 26, 2018</primary_completion_date>
  <phase>Phase 1/Phase 2</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>N/A</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Phase I: Confirmation of Recommended Phase II Dose</measure>
    <time_frame>13 weeks</time_frame>
    <description>Recommended Phase II dose of ipilimumab and nivolumab among participants treated with combined thoracic radiation therapy (30 Gy in 10 fractions) and nivolumab/ipilimumab following standard treatment with 4-6 cycles of platinum-based chemotherapy. Investigators will initially enroll 6 patients and wait until completion of the 13-week safety observation period following initiation of ipilimumab + nivolumab combination treatment.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Phase II: Progression Free Survival (PFS)</measure>
    <time_frame>6 months</time_frame>
    <description>PFS is defined as the duration from date of registration to date of first documentation of progression assessed by local investigator or symptomatic deterioration (as defined above) or death due to any cause.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Overall Survival (OS)</measure>
    <time_frame>1 year</time_frame>
    <description>OS is defined as the duration from date of registration to date of death due to any cause. Participants last known to be alive are censored at date of last contact.</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">21</enrollment>
  <condition>Small Cell Lung Cancer</condition>
  <condition>Extensive-stage Small Cell Lung Cancer</condition>
  <arm_group>
    <arm_group_label>Combination Therapy</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Consolidative Ipilimumab and Nivolumab with Thoracic Radiotherapy after Platinum Based Chemotherapy. Radiotherapy, followed by a 14 to 21 day break between radiotherapy and the beginning of study drug treatment.</description>
  </arm_group>
  <intervention>
    <intervention_type>Radiation</intervention_type>
    <intervention_name>Thoracic Radiation Therapy</intervention_name>
    <description>All participants will receive radiation therapy (3Gy x 10 fractions) to the chest for 10 days (Monday through Friday for 2 weeks).</description>
    <arm_group_label>Combination Therapy</arm_group_label>
    <other_name>radiotherapy</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Ipilimumab</intervention_name>
    <description>Ipilimumab 3 mg/kg (90 minute IV infusion) will be administered every 3 weeks for 4 doses.</description>
    <arm_group_label>Combination Therapy</arm_group_label>
    <other_name>YERVOY</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Nivolumab</intervention_name>
    <description>Nivolumab 1 mg/kg (30 minute IV infusion) will be administered every 3 weeks for 4 doses, followed by nivolumab 480 mg every 4 weeks.</description>
    <arm_group_label>Combination Therapy</arm_group_label>
    <other_name>OPDIVO</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Signed Written Informed Consent&#xD;
&#xD;
          -  Willing and able to comply with scheduled visits, treatment schedule, laboratory tests&#xD;
             and other requirements of the study.&#xD;
&#xD;
          -  Patients with Small Cell Lung Cancer (SCLC) documented by histology or cytology from&#xD;
             brushing, washing, or needle aspiration of a defined lesion, but not from sputum&#xD;
             cytology alone&#xD;
&#xD;
          -  Have presented at initial diagnosis with extensive-stage disease&#xD;
&#xD;
          -  Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) 0 or 1&#xD;
&#xD;
          -  Have received 4-6 cycles of platinum-based first-line chemotherapy and have an ongoing&#xD;
             response of complete response (CR), partial response (PR), or stable disease (SD)&#xD;
             after completion of chemotherapy. Acceptable combinations, as recommended per National&#xD;
             Comprehensive Cancer Network (NCCN) guidelines, include cisplatin or carboplatin&#xD;
             combined with either etoposide or irinotecan; As an exception to the above criterion,&#xD;
             participants receiving only 3 cycles of chemotherapy due to toxicity are eligible, if&#xD;
             they have an ongoing PR or CR after the 3rd cycle; Participants who have received &gt; 6&#xD;
             cycles of platinum-based first-line chemotherapy are not eligible.&#xD;
&#xD;
          -  Participants must initiate study treatment with thoracic radiation therapy less than&#xD;
             or equal to 8 weeks (56 days) from the last dose of platinum-based first line&#xD;
             chemotherapy.&#xD;
&#xD;
          -  Whenever possible, a formalin-fixed, paraffin-embedded (FFPE) tumor tissue block or 10&#xD;
             unstained slides of tumor sample (archival or recent) for biomarker evaluation should&#xD;
             be made available and submitted to the central lab for correlative studies.&#xD;
&#xD;
          -  Participant re-enrollment: This study permits the re-enrollment of a participant who&#xD;
             has discontinued the study due to pre-treatment failure (i.e., participant has not&#xD;
             been treated). If re-enrolled, the participant must be re-consented.&#xD;
&#xD;
          -  Men and women at least 18 years of age&#xD;
&#xD;
          -  Women of childbearing potential (WOCBP) must have a negative serum or urine pregnancy&#xD;
             test within 24 hours prior to the start of thoracic radiation therapy&#xD;
&#xD;
          -  Women must not be breastfeeding.&#xD;
&#xD;
          -  WOCBP must agree to follow instructions for method(s) of contraception for the&#xD;
             duration of treatment with study drug(s) plus 5 half-lives of study drug (half-life up&#xD;
             to 25 days) plus 30 days (duration of ovulatory cycle) for a total of 5 months&#xD;
             post-treatment completion.&#xD;
&#xD;
          -  Males who are sexually active with WOCBP must agree to follow instructions for&#xD;
             method(s) of contraception for the duration of treatment with study drug (s) plus 5&#xD;
             half-lives of the study drug (half-life up to 25 days) plus 90 days (duration of sperm&#xD;
             turnover) for a total of 7 months post-treatment completion.&#xD;
&#xD;
          -  Additional criteria may apply&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Participants with previous brain metastases are eligible provided that they are&#xD;
             treated and asymptomatic not requiring steroids or anticonvulsants, and have stable&#xD;
             disease at the screening tumor assessment. A 4 week disease stable interval as&#xD;
             confirmed by MRI or CT brain with contrast is required after treatment of brain&#xD;
             metastases before initiation of thoracic radiation therapy. In addition, participants&#xD;
             must have been either off corticosteroids, or on a stable or decreasing dose of 10 mg&#xD;
             daily prednisone (or equivalent).&#xD;
&#xD;
          -  Participants who have received prior chest radiation which at the discretion of the&#xD;
             treating radiation oncologist precludes delivery of protocol radiation therapy&#xD;
&#xD;
          -  Carcinomatous meningitis&#xD;
&#xD;
          -  Pleural effusion that cannot be controlled with appropriate interventions&#xD;
&#xD;
          -  All toxicities attributed to prior anti-cancer therapy must have been resolved to&#xD;
             Grade 1 (NCI CTCAE Version 4) or baseline before administration of study drug(s) other&#xD;
             than: Patients with toxicities attributed to prior anti-cancer therapy that either are&#xD;
             not expected to resolve and/or result in long-lasting sequelae, such as neuropathy&#xD;
             after platinum-based therapy, or are not expected to interfere with treatment on&#xD;
             study, such as fatigue,alopecia, or grade 2 hematologic toxicity are eligible.&#xD;
&#xD;
          -  Women who are pregnant or breastfeeding&#xD;
&#xD;
          -  Active, known, or suspected autoimmune disease. Patients with an autoimmune&#xD;
             paraneoplastic syndrome requiring concurrent immunosuppressive treatment are excluded.&#xD;
             Patients with type I diabetes mellitus, hypothyroidism only requiring hormone&#xD;
             replacement, skin disorders (such as vitiligo, psoriasis, or alopecia) not requiring&#xD;
             systemic treatment, or conditions not expected to recur in the absence of an external&#xD;
             trigger are permitted to enroll.&#xD;
&#xD;
          -  A condition requiring systemic treatment with either corticosteroids (&gt; 10 mg daily&#xD;
             prednisone equivalent) or other immunosuppressive medications within 14 days of&#xD;
             randomization. Corticosteroids with minimal systemic absorption (inhaled or topical&#xD;
             steroids) and adrenal replacement steroid doses &gt; 10 mg daily prednisone equivalent&#xD;
             are permitted in the absence of active autoimmune disease.&#xD;
&#xD;
          -  Prior therapy with anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CD137, or anti-CTLA-4&#xD;
             antibody (including ipilimumab or any other antibody or drug specifically targeting T&#xD;
             cell co-stimulation or checkpoint pathways)&#xD;
&#xD;
          -  Interstitial lung disease that is symptomatic or may interfere with the detection or&#xD;
             management of suspected drug-related pulmonary toxicity&#xD;
&#xD;
          -  Any patient requiring supplemental oxygen therapy&#xD;
&#xD;
          -  Previous malignancies (except non-melanoma skin cancers, and the following in situ&#xD;
             cancers: bladder, gastric, colon, endometrial, cervical/dysplasia, melanoma, or&#xD;
             breast) unless a complete remission was achieved at least 2 years prior to study entry&#xD;
             AND no additional therapy is required during the study period&#xD;
&#xD;
          -  Known medical condition that, in the investigator's opinion, would increase the risk&#xD;
             associated with study participation or study drug(s) administration or interfere with&#xD;
             the interpretation of safety results&#xD;
&#xD;
          -  Major surgery or significant traumatic injury that is not recovered at least 14 days&#xD;
             before the initiation of thoracic radiation therapy.&#xD;
&#xD;
          -  Positive test for hepatitis B virus (HBV) using HBV surface antigen (HBVsAg) test or&#xD;
             positive test for hepatitis C virus (HCV) using HCV ribonucleic acid (RNA) or HCV&#xD;
             antibody test indicating acute or chronic infection&#xD;
&#xD;
          -  Individuals with a positive test for HCV antibody but no detection of HCV RNA&#xD;
             indicating no current infection are eligible&#xD;
&#xD;
          -  Known medical history of testing positive for human immunodeficiency virus (HIV) or&#xD;
             known medical history of acquired immunodeficiency syndrome (AIDS)&#xD;
&#xD;
          -  Inadequate hematologic function according to study guidelines&#xD;
&#xD;
          -  Inadequate hepatic function according to study guidelines&#xD;
&#xD;
          -  History of allergy or hypersensitivity to any of the study drugs or study drug&#xD;
             components&#xD;
&#xD;
          -  Additional criteria may apply&#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>Bradford A. Perez, M.D.</last_name>
    <role>Principal Investigator</role>
    <affiliation>H. Lee Moffitt Cancer Center and Research Institute</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>H. Lee Moffitt Cancer Center and Research Institute</name>
      <address>
        <city>Tampa</city>
        <state>Florida</state>
        <zip>33612</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>May 2023</verification_date>
  <study_first_submitted>February 2, 2017</study_first_submitted>
  <study_first_submitted_qc>February 2, 2017</study_first_submitted_qc>
  <study_first_posted type="Estimate">February 6, 2017</study_first_posted>
  <results_first_submitted>September 19, 2019</results_first_submitted>
  <results_first_submitted_qc>September 19, 2019</results_first_submitted_qc>
  <results_first_posted type="Actual">October 11, 2019</results_first_posted>
  <last_update_submitted>May 3, 2023</last_update_submitted>
  <last_update_submitted_qc>May 3, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">May 6, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Thoracic</keyword>
  <keyword>Radiotherapy</keyword>
  <keyword>Platinum Based Chemotherapy</keyword>
  <keyword>Immunotherapy</keyword>
  <keyword>Ipilimumab</keyword>
  <keyword>Nivolumab</keyword>
  <keyword>Extensive-Stage Disease Small Cell Lung Cancer (ED-SCLC)</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Lung Neoplasms</mesh_term>
    <mesh_term>Small Cell Lung Carcinoma</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Nivolumab</mesh_term>
    <mesh_term>Ipilimumab</mesh_term>
  </intervention_browse>
  <provided_document_section>
    <provided_document>
      <document_type>Study Protocol and Statistical Analysis Plan</document_type>
      <document_has_protocol>Yes</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>Yes</document_has_sap>
      <document_date>June 21, 2019</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/99/NCT03043599/Prot_SAP_000.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <group_list>
        <group group_id="P1">
          <title>Combination Therapy</title>
          <description>Consolidative Ipilimumab and Nivolumab with Thoracic Radiotherapy after Platinum Based Chemotherapy. Radiotherapy, followed by a 14 to 21 day break between radiotherapy and the beginning of study drug treatment.&#xD;
Thoracic Radiation Therapy: All participants will receive radiation therapy (3Gy x 10 fractions) to the chest for 10 days (Monday through Friday for 2 weeks).&#xD;
Ipilimumab: Ipilimumab 3 mg/kg (90 minute IV infusion) will be administered every 3 weeks for 4 doses.&#xD;
Nivolumab: Nivolumab 1 mg/kg (30 minute IV infusion) will be administered every 3 weeks for 4 doses, followed by nivolumab 480 mg every 4 weeks.</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="21"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="21"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
              </participants_list>
            </milestone>
          </milestone_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>Combination Therapy</title>
          <description>Consolidative Ipilimumab and Nivolumab with Thoracic Radiotherapy after Platinum Based Chemotherapy. Radiotherapy, followed by a 14 to 21 day break between radiotherapy and the beginning of study drug treatment.&#xD;
Thoracic Radiation Therapy: All participants will receive radiation therapy (3Gy x 10 fractions) to the chest for 10 days (Monday through Friday for 2 weeks).&#xD;
Ipilimumab: Ipilimumab 3 mg/kg (90 minute IV infusion) will be administered every 3 weeks for 4 doses.&#xD;
Nivolumab: Nivolumab 1 mg/kg (30 minute IV infusion) will be administered every 3 weeks for 4 doses, followed by nivolumab 480 mg every 4 weeks.</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="21"/>
          </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_list>
                </category>
                <category>
                  <title>Between 18 and 65 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="10"/>
                  </measurement_list>
                </category>
                <category>
                  <title>&gt;=65 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="11"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Age</title>
          <units>years</units>
          <param>Median</param>
          <dispersion>Full Range</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="66" lower_limit="45" upper_limit="77"/>
                  </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="8"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="13"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Ethnicity (NIH/OMB)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Not Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="20"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Race (NIH/OMB)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>American Indian or Alaska Native</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Asian</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Native Hawaiian or Other Pacific Islander</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Black or African American</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>White</title>
                  <measurement_list>
                    <measurement group_id="B1" value="19"/>
                  </measurement_list>
                </category>
                <category>
                  <title>More than one race</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                  </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="21"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Phase I: Confirmation of Recommended Phase II Dose</title>
        <description>Recommended Phase II dose of ipilimumab and nivolumab among participants treated with combined thoracic radiation therapy (30 Gy in 10 fractions) and nivolumab/ipilimumab following standard treatment with 4-6 cycles of platinum-based chemotherapy. Investigators will initially enroll 6 patients and wait until completion of the 13-week safety observation period following initiation of ipilimumab + nivolumab combination treatment.</description>
        <time_frame>13 weeks</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Combination Therapy</title>
            <description>Consolidative Ipilimumab and Nivolumab with Thoracic Radiotherapy after Platinum Based Chemotherapy. Radiotherapy, followed by a 14 to 21 day break between radiotherapy and the beginning of study drug treatment.&#xD;
Thoracic Radiation Therapy: All participants will receive radiation therapy (3Gy x 10 fractions) to the chest for 10 days (Monday through Friday for 2 weeks).&#xD;
Ipilimumab: Ipilimumab 3 mg/kg (90 minute IV infusion) will be administered every 3 weeks for 4 doses.&#xD;
Nivolumab: Nivolumab 1 mg/kg (30 minute IV infusion) will be administered every 3 weeks for 4 doses, followed by nivolumab 480 mg every 4 weeks.</description>
          </group>
        </group_list>
        <measure>
          <title>Phase I: Confirmation of Recommended Phase II Dose</title>
          <description>Recommended Phase II dose of ipilimumab and nivolumab among participants treated with combined thoracic radiation therapy (30 Gy in 10 fractions) and nivolumab/ipilimumab following standard treatment with 4-6 cycles of platinum-based chemotherapy. Investigators will initially enroll 6 patients and wait until completion of the 13-week safety observation period following initiation of ipilimumab + nivolumab combination treatment.</description>
          <units>mg/kg dose</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="21"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Ipilimumab</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Nivoumab</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Phase II: Progression Free Survival (PFS)</title>
        <description>PFS is defined as the duration from date of registration to date of first documentation of progression assessed by local investigator or symptomatic deterioration (as defined above) or death due to any cause.</description>
        <time_frame>6 months</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Combination Therapy</title>
            <description>Consolidative Ipilimumab and Nivolumab with Thoracic Radiotherapy after Platinum Based Chemotherapy. Radiotherapy, followed by a 14 to 21 day break between radiotherapy and the beginning of study drug treatment.&#xD;
Thoracic Radiation Therapy: All participants will receive radiation therapy (3Gy x 10 fractions) to the chest for 10 days (Monday through Friday for 2 weeks).&#xD;
Ipilimumab: Ipilimumab 3 mg/kg (90 minute IV infusion) will be administered every 3 weeks for 4 doses.&#xD;
Nivolumab: Nivolumab 1 mg/kg (30 minute IV infusion) will be administered every 3 weeks for 4 doses, followed by nivolumab 480 mg every 4 weeks.</description>
          </group>
        </group_list>
        <measure>
          <title>Phase II: Progression Free Survival (PFS)</title>
          <description>PFS is defined as the duration from date of registration to date of first documentation of progression assessed by local investigator or symptomatic deterioration (as defined above) or death due to any cause.</description>
          <units>months</units>
          <param>Median</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="21"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="4.5" lower_limit="2.7" upper_limit="4.6"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Overall Survival (OS)</title>
        <description>OS is defined as the duration from date of registration to date of death due to any cause. Participants last known to be alive are censored at date of last contact.</description>
        <time_frame>1 year</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Combination Therapy</title>
            <description>Consolidative Ipilimumab and Nivolumab with Thoracic Radiotherapy after Platinum Based Chemotherapy. Radiotherapy, followed by a 14 to 21 day break between radiotherapy and the beginning of study drug treatment.&#xD;
Thoracic Radiation Therapy: All participants will receive radiation therapy (3Gy x 10 fractions) to the chest for 10 days (Monday through Friday for 2 weeks).&#xD;
Ipilimumab: Ipilimumab 3 mg/kg (90 minute IV infusion) will be administered every 3 weeks for 4 doses.&#xD;
Nivolumab: Nivolumab 1 mg/kg (30 minute IV infusion) will be administered every 3 weeks for 4 doses, followed by nivolumab 480 mg every 4 weeks.</description>
          </group>
        </group_list>
        <measure>
          <title>Overall Survival (OS)</title>
          <description>OS is defined as the duration from date of registration to date of death due to any cause. Participants last known to be alive are censored at date of last contact.</description>
          <units>months</units>
          <param>Median</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="21"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="11.7" lower_limit="4.7" upper_limit="16.0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>2 years</time_frame>
      <desc>All Serious Adverse Events are reported, regardless of causality. Serious Adverse Events were reported during screening period and within 100 days of discontinuation of dosing.</desc>
      <group_list>
        <group group_id="E1">
          <title>Combination Therapy</title>
          <description>Consolidative Ipilimumab and Nivolumab with Thoracic Radiotherapy after Platinum Based Chemotherapy. Radiotherapy, followed by a 14 to 21 day break between radiotherapy and the beginning of study drug treatment.&#xD;
Thoracic Radiation Therapy: All participants will receive radiation therapy (3Gy x 10 fractions) to the chest for 10 days (Monday through Friday for 2 weeks).&#xD;
Ipilimumab: Ipilimumab 3 mg/kg (90 minute IV infusion) will be administered every 3 weeks for 4 doses.&#xD;
Nivolumab: Nivolumab 1 mg/kg (30 minute IV infusion) will be administered every 3 weeks for 4 doses, followed by nivolumab 480 mg every 4 weeks.</description>
        </group>
      </group_list>
      <serious_events>
        <default_vocab>CTCAE (4.0)</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="6" subjects_at_risk="21"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="13" subjects_at_risk="21"/>
              </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="1" subjects_affected="1" subjects_at_risk="21"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Cardiac disorders</title>
            <event_list>
              <event>
                <sub_title>Pericardial effusion</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="21"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Diarrhea</sub_title>
                <counts group_id="E1" events="7" subjects_affected="4" subjects_at_risk="21"/>
              </event>
              <event>
                <sub_title>Colitis</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="21"/>
              </event>
              <event>
                <sub_title>Constipation</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="21"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Fever</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="21"/>
              </event>
              <event>
                <sub_title>Neck Pain</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="21"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Urosepsis</sub_title>
                <description>Urosepsis presumed related to kiebsiella pneumoniae</description>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="21"/>
              </event>
              <event>
                <sub_title>Lung Infection</sub_title>
                <counts group_id="E1" events="7" subjects_affected="6" subjects_at_risk="21"/>
              </event>
              <event>
                <sub_title>Sepsis</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="21"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Investigations</title>
            <event_list>
              <event>
                <sub_title>Alanine aminotransferase increased</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="21"/>
              </event>
              <event>
                <sub_title>Aspartate aminotransferase</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="21"/>
              </event>
              <event>
                <sub_title>Blood bilirubin increased</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="21"/>
              </event>
              <event>
                <sub_title>Platelet count decreased</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="21"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Metabolism and nutrition disorders</title>
            <event_list>
              <event>
                <sub_title>Hyponatremia</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="21"/>
              </event>
              <event>
                <sub_title>Anorexia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="21"/>
              </event>
              <event>
                <sub_title>Dehydration</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="21"/>
              </event>
              <event>
                <sub_title>Hypokalemia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="21"/>
              </event>
              <event>
                <sub_title>Metabolism and nutrition disorders -Other</sub_title>
                <description>SIADH</description>
                <counts group_id="E1" events="2" subjects_affected="1" subjects_at_risk="21"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Musculoskeletal and connective tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Back Pain</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="21"/>
              </event>
              <event>
                <sub_title>Generalized muscle weakness</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="21"/>
              </event>
              <event>
                <sub_title>Muscle weakness - lower limb</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="21"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Neoplasms benign, malignant and unspecified (incl cysts and polyps)</title>
            <event_list>
              <event>
                <sub_title>Neoplasms benign, malignant and unspecified -Other</sub_title>
                <counts group_id="E1" events="7" subjects_affected="7" subjects_at_risk="21"/>
              </event>
              <event>
                <sub_title>Death</sub_title>
                <description>Death due to disease progression</description>
                <counts group_id="E1" events="5" subjects_affected="5" subjects_at_risk="21"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Cognitive disturbance</sub_title>
                <counts group_id="E1" events="3" subjects_affected="2" subjects_at_risk="21"/>
              </event>
              <event>
                <sub_title>Headache</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="21"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Renal and urinary disorders</title>
            <event_list>
              <event>
                <sub_title>Acute kidney injury</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="21"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>COPD Exacerbation</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="21"/>
              </event>
              <event>
                <sub_title>Hypoxia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="21"/>
              </event>
              <event>
                <sub_title>Pneumonitis</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="21"/>
              </event>
              <event>
                <sub_title>Death</sub_title>
                <description>Death due to lung infection</description>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="21"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Vascular disorders</title>
            <event_list>
              <event>
                <sub_title>Hypertension</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="21"/>
              </event>
              <event>
                <sub_title>Hypotension</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="21"/>
              </event>
              <event>
                <sub_title>Thromboembolic event</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="21"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>0</frequency_threshold>
        <default_vocab>CTCAE (4.0)</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="21" subjects_at_risk="21"/>
              </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="3" subjects_affected="3" subjects_at_risk="21"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Cardiac disorders</title>
            <event_list>
              <event>
                <sub_title>Sinus tachycardia</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="21"/>
              </event>
              <event>
                <sub_title>Sinus bradycardia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="21"/>
              </event>
              <event>
                <sub_title>Pericardial effusion</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="21"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Ear and labyrinth disorders</title>
            <event_list>
              <event>
                <sub_title>Hearing impaired</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="21"/>
              </event>
              <event>
                <sub_title>Vertigo</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="21"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Endocrine disorders</title>
            <event_list>
              <event>
                <sub_title>Hypothyroidism</sub_title>
                <counts group_id="E1" events="7" subjects_affected="3" subjects_at_risk="21"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Eye disorders</title>
            <event_list>
              <event>
                <sub_title>Eye Disorders - Other</sub_title>
                <counts group_id="E1" events="2" subjects_affected="1" subjects_at_risk="21"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Diarrhea</sub_title>
                <counts group_id="E1" events="20" subjects_affected="7" subjects_at_risk="21"/>
              </event>
              <event>
                <sub_title>Nausea</sub_title>
                <counts group_id="E1" events="8" subjects_affected="7" subjects_at_risk="21"/>
              </event>
              <event>
                <sub_title>Dry Mouth</sub_title>
                <counts group_id="E1" events="6" subjects_affected="6" subjects_at_risk="21"/>
              </event>
              <event>
                <sub_title>Abdominal Pain</sub_title>
                <counts group_id="E1" events="6" subjects_affected="5" subjects_at_risk="21"/>
              </event>
              <event>
                <sub_title>Constipation</sub_title>
                <counts group_id="E1" events="4" subjects_affected="4" subjects_at_risk="21"/>
              </event>
              <event>
                <sub_title>Vomiting</sub_title>
                <counts group_id="E1" events="8" subjects_affected="6" subjects_at_risk="21"/>
              </event>
              <event>
                <sub_title>Esophagitis</sub_title>
                <counts group_id="E1" events="11" subjects_affected="10" subjects_at_risk="21"/>
              </event>
              <event>
                <sub_title>Gastroesophageal reflux disease</sub_title>
                <counts group_id="E1" events="3" subjects_affected="2" subjects_at_risk="21"/>
              </event>
              <event>
                <sub_title>Toothache</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="21"/>
              </event>
              <event>
                <sub_title>Gastrointestinal disorders - Other</sub_title>
                <description>mouth sores</description>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="21"/>
              </event>
              <event>
                <sub_title>Colitis</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="21"/>
              </event>
              <event>
                <sub_title>Dysphagia</sub_title>
                <counts group_id="E1" events="5" subjects_affected="5" subjects_at_risk="21"/>
              </event>
              <event>
                <sub_title>Abdominal distension</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="21"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Fatigue</sub_title>
                <counts group_id="E1" events="8" subjects_affected="6" subjects_at_risk="21"/>
              </event>
              <event>
                <sub_title>Fever</sub_title>
                <counts group_id="E1" events="11" subjects_affected="8" subjects_at_risk="21"/>
              </event>
              <event>
                <sub_title>Pain</sub_title>
                <counts group_id="E1" events="8" subjects_affected="5" subjects_at_risk="21"/>
              </event>
              <event>
                <sub_title>Gait Disturbance</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="21"/>
              </event>
              <event>
                <sub_title>Edema Limbs</sub_title>
                <counts group_id="E1" events="5" subjects_affected="4" subjects_at_risk="21"/>
              </event>
              <event>
                <sub_title>Infusion related reaction</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="21"/>
              </event>
              <event>
                <sub_title>Chills</sub_title>
                <counts group_id="E1" events="3" subjects_affected="2" subjects_at_risk="21"/>
              </event>
              <event>
                <sub_title>Flu like symptoms</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="21"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Immune system disorders</title>
            <event_list>
              <event>
                <sub_title>Allergic Reaction</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="21"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Urinary Tract Infection</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="21"/>
              </event>
              <event>
                <sub_title>Infections and Investigations- Other</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="21"/>
              </event>
              <event>
                <sub_title>Lung Infection</sub_title>
                <counts group_id="E1" events="9" subjects_affected="6" subjects_at_risk="21"/>
              </event>
              <event>
                <sub_title>Esophageal infection</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="21"/>
              </event>
              <event>
                <sub_title>Bronchial infection</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="21"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Injury, poisoning and procedural complications</title>
            <event_list>
              <event>
                <sub_title>Dermatitis Radiation</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="21"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Investigations</title>
            <event_list>
              <event>
                <sub_title>Weight Loss</sub_title>
                <counts group_id="E1" events="2" subjects_affected="1" subjects_at_risk="21"/>
              </event>
              <event>
                <sub_title>Blood bilirubin increased</sub_title>
                <counts group_id="E1" events="4" subjects_affected="2" subjects_at_risk="21"/>
              </event>
              <event>
                <sub_title>Alanine aminotransferase increased</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="21"/>
              </event>
              <event>
                <sub_title>Aspartate aminotransferase increased</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="21"/>
              </event>
              <event>
                <sub_title>Platelet count decreased</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="21"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Metabolism and nutrition disorders</title>
            <event_list>
              <event>
                <sub_title>Hyponatremia</sub_title>
                <counts group_id="E1" events="4" subjects_affected="4" subjects_at_risk="21"/>
              </event>
              <event>
                <sub_title>SIADH</sub_title>
                <counts group_id="E1" events="2" subjects_affected="1" subjects_at_risk="21"/>
              </event>
              <event>
                <sub_title>Anorexia</sub_title>
                <counts group_id="E1" events="8" subjects_affected="7" subjects_at_risk="21"/>
              </event>
              <event>
                <sub_title>Dehydration</sub_title>
                <counts group_id="E1" events="5" subjects_affected="5" subjects_at_risk="21"/>
              </event>
              <event>
                <sub_title>Hypomagnesemia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="21"/>
              </event>
              <event>
                <sub_title>Hypokalemia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="21"/>
              </event>
              <event>
                <sub_title>Metabolism and Nutrition disorders - Other</sub_title>
                <description>Alkalosis and hypokalemia attributed to cushings syndrome secondary to ectopic ACTH from SCLC</description>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="21"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Musculoskeletal and connective tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Back Pain</sub_title>
                <counts group_id="E1" events="5" subjects_affected="4" subjects_at_risk="21"/>
              </event>
              <event>
                <sub_title>Chest Wall Pain</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="21"/>
              </event>
              <event>
                <sub_title>Neck Pain</sub_title>
                <counts group_id="E1" events="2" subjects_affected="1" subjects_at_risk="21"/>
              </event>
              <event>
                <sub_title>Arthralgia</sub_title>
                <counts group_id="E1" events="5" subjects_affected="5" subjects_at_risk="21"/>
              </event>
              <event>
                <sub_title>Generalized Muscle Weakness</sub_title>
                <counts group_id="E1" events="8" subjects_affected="6" subjects_at_risk="21"/>
              </event>
              <event>
                <sub_title>Myalgia</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="21"/>
              </event>
              <event>
                <sub_title>Arthritis</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="21"/>
              </event>
              <event>
                <sub_title>Muscle weakness lower limb</sub_title>
                <counts group_id="E1" events="2" subjects_affected="1" subjects_at_risk="21"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Neoplasms benign, malignant and unspecified (incl cysts and polyps)</title>
            <event_list>
              <event>
                <sub_title>Neoplasms benign, malignant and unspecified -Other</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="21"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Dizziness</sub_title>
                <counts group_id="E1" events="8" subjects_affected="7" subjects_at_risk="21"/>
              </event>
              <event>
                <sub_title>Cognitive Disturbance</sub_title>
                <counts group_id="E1" events="4" subjects_affected="3" subjects_at_risk="21"/>
              </event>
              <event>
                <sub_title>Headache</sub_title>
                <counts group_id="E1" events="4" subjects_affected="4" subjects_at_risk="21"/>
              </event>
              <event>
                <sub_title>Dysgeusia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="21"/>
              </event>
              <event>
                <sub_title>Paresthesia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="21"/>
              </event>
              <event>
                <sub_title>Peripheral sensory neuropathy</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="21"/>
              </event>
              <event>
                <sub_title>Memory impairment</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="21"/>
              </event>
              <event>
                <sub_title>Stroke</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="21"/>
              </event>
              <event>
                <sub_title>Dysarthria</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="21"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Psychiatric disorders</title>
            <event_list>
              <event>
                <sub_title>Insomnia</sub_title>
                <counts group_id="E1" events="5" subjects_affected="5" subjects_at_risk="21"/>
              </event>
              <event>
                <sub_title>Confusion</sub_title>
                <counts group_id="E1" events="6" subjects_affected="2" subjects_at_risk="21"/>
              </event>
              <event>
                <sub_title>Anxiety</sub_title>
                <counts group_id="E1" events="5" subjects_affected="4" subjects_at_risk="21"/>
              </event>
              <event>
                <sub_title>Depression</sub_title>
                <counts group_id="E1" events="5" subjects_affected="4" subjects_at_risk="21"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Renal and urinary disorders</title>
            <event_list>
              <event>
                <sub_title>Acute kidney injury</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="21"/>
              </event>
              <event>
                <sub_title>Urinary retention</sub_title>
                <counts group_id="E1" events="4" subjects_affected="2" subjects_at_risk="21"/>
              </event>
              <event>
                <sub_title>Urinary frequency</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="21"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Reproductive system and breast disorders</title>
            <event_list>
              <event>
                <sub_title>Breast Pain</sub_title>
                <counts group_id="E1" events="3" subjects_affected="1" subjects_at_risk="21"/>
              </event>
              <event>
                <sub_title>Gynecomastia</sub_title>
                <counts group_id="E1" events="3" subjects_affected="1" subjects_at_risk="21"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Cough</sub_title>
                <counts group_id="E1" events="12" subjects_affected="10" subjects_at_risk="21"/>
              </event>
              <event>
                <sub_title>Productive Cough</sub_title>
                <counts group_id="E1" events="3" subjects_affected="3" subjects_at_risk="21"/>
              </event>
              <event>
                <sub_title>Dyspnea</sub_title>
                <counts group_id="E1" events="8" subjects_affected="6" subjects_at_risk="21"/>
              </event>
              <event>
                <sub_title>Pneumonitis</sub_title>
                <counts group_id="E1" events="6" subjects_affected="5" subjects_at_risk="21"/>
              </event>
              <event>
                <sub_title>Hypoxia</sub_title>
                <counts group_id="E1" events="5" subjects_affected="4" subjects_at_risk="21"/>
              </event>
              <event>
                <sub_title>Nasal congestion</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="21"/>
              </event>
              <event>
                <sub_title>Pleural effusion</sub_title>
                <counts group_id="E1" events="4" subjects_affected="1" subjects_at_risk="21"/>
              </event>
              <event>
                <sub_title>Hoarseness</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="21"/>
              </event>
              <event>
                <sub_title>COPD Exacerbation</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="21"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Skin and subcutaneous tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Pruritus</sub_title>
                <counts group_id="E1" events="5" subjects_affected="5" subjects_at_risk="21"/>
              </event>
              <event>
                <sub_title>Erythema</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="21"/>
              </event>
              <event>
                <sub_title>Rash, erythematous</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="21"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Vascular disorders</title>
            <event_list>
              <event>
                <sub_title>Hypertension</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="21"/>
              </event>
              <event>
                <sub_title>Thromboembolic event</sub_title>
                <counts group_id="E1" events="5" subjects_affected="5" subjects_at_risk="21"/>
              </event>
              <event>
                <sub_title>Hypotension</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="21"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </other_events>
    </reported_events>

    <certain_agreements>
      <pi_employee>All Principal Investigators ARE employed by the organization sponsoring the study.</pi_employee>
      <restrictive_agreement>There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed. </restrictive_agreement>
    </certain_agreements>
    <point_of_contact>
      <name_or_title>Bradford Perez, MD</name_or_title>
      <organization>H Lee Moffitt Cancer Center &amp; Research Institute</organization>
      <phone>813-745-8234</phone>
      <email>Bradford.Perez@moffitt.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/NCT03043599
org study id: MCC-18914
secondary id: CA209-840
nct id: NCT03043599
lead sponsor: 
collaborator: 
has dmc: No
is fda regulated drug: Yes
is fda regulated device: No
is us export: No
The purpose of the safety run in Phase I portion of this study is to confirm the recommended
      Phase II dose of ipilimumab and nivolumab among participants treated with combined thoracic
      radiation therapy (30 Gy in 10 fractions) and nivolumab/ipilimumab following standard
      treatment with 4-6 cycles of platinum-based chemotherapy.

      The purpose of the Phase II portion of this study is to estimate the 6-month Progression Free
      Survival (PFS) rate among participants treated with ipilimumab and nivolumab with thoracic
      radiation therapy (30 Gy in 10 fractions) after standard treatment with 4 to 6 cycles of
      platinum based chemotherapy.
This study is a nonrandomized, phase II, single arm, multicenter trial evaluating safety and
      efficacy of thoracic radiation therapy followed by nivolumab and ipilimumab in participants
      with Extensive-Stage Disease Small Cell Lung Cancer (ED-SCLC) who have completed a first-line
      platinum-based chemotherapy regimen and achieved ongoing complete response (CR), partial
      response (PR), or stable disease (SD). This study will determine whether nivolumab and
      ipilimumab delivered 2 weeks following consolidative thoracic radiation therapy demonstrates
      acceptable toxicity and whether the treatment regimen will improve 6-month progression-free
      survival (PFS) compared with a similar historical control cohort in this participant
      population. Additional objectives include further characterization of overall survival,
      adverse event profile, patterns of failure analysis, and potential predictive biomarkers of
      response to nivolumab in combination with ipilimumab and thoracic radiation therapy in
      patients with ED-SCLC.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Phase I: Confirmation of Recommended Phase II Dose
time frame: 13 weeks
description: Recommended Phase II dose of ipilimumab and nivolumab among participants treated with combined thoracic radiation therapy (30 Gy in 10 fractions) and nivolumab/ipilimumab following standard treatment with 4-6 cycles of platinum-based chemotherapy. Investigators will initially enroll 6 patients and wait until completion of the 13-week safety observation period following initiation of ipilimumab + nivolumab combination treatment.
measure: Phase II: Progression Free Survival (PFS)
time frame: 6 months
description: PFS is defined as the duration from date of registration to date of first documentation of progression assessed by local investigator or symptomatic deterioration (as defined above) or death due to any cause.
measure: Overall Survival (OS)
time frame: 1 year
description: OS is defined as the duration from date of registration to date of death due to any cause. Participants last known to be alive are censored at date of last contact.
arm group label: Combination Therapy
arm group type: Experimental
description: Consolidative Ipilimumab and Nivolumab with Thoracic Radiotherapy after Platinum Based Chemotherapy. Radiotherapy, followed by a 14 to 21 day break between radiotherapy and the beginning of study drug treatment.
intervention type: Radiation
intervention name: Thoracic Radiation Therapy
description: All participants will receive radiation therapy (3Gy x 10 fractions) to the chest for 10 days (Monday through Friday for 2 weeks).
arm group label: Combination Therapy
other name: radiotherapy
intervention type: Drug
intervention name: Ipilimumab
description: Ipilimumab 3 mg/kg (90 minute IV infusion) will be administered every 3 weeks for 4 doses.
arm group label: Combination Therapy
other name: YERVOY
intervention type: Drug
intervention name: Nivolumab
description: Nivolumab 1 mg/kg (30 minute IV infusion) will be administered every 3 weeks for 4 doses, followed by nivolumab 480 mg every 4 weeks.
arm group label: Combination Therapy
other name: OPDIVO
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Bradford A. Perez, M.D.
role: Principal Investigator
affiliation: H. Lee Moffitt Cancer Center and Research Institute
facility: 
country: United States
responsible party type: Sponsor
mesh term: Lung Neoplasms
mesh term: Small Cell Lung Carcinoma
mesh term: Nivolumab
mesh term: Ipilimumab
provided document: 
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 