xml: <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/NCT06003075</url>
    </required_header>
    <id_info>
      <org_study_id>85869</org_study_id>
      <nct_id>NCT06003075</nct_id>
    </id_info>
    <brief_title>Induction Chemo-Nivo in Unresectable Stage III NSCLC</brief_title>
    <official_title>Phase II Study of Induction Platinum Doublet in Combination With Nivolumab Followed by Surgery or Concurrent Chemoradiation in Unresectable Stage IIIA-C Non-small Cell Lung Cancer (NSCLC)</official_title>
    <sponsors>
      <lead_sponsor>
        <agency>Ralph G Zinner</agency>
        <agency_class>Other</agency_class>
      </lead_sponsor>
      <collaborator>
        <agency>Bristol-Myers Squibb</agency>
        <agency_class>Industry</agency_class>
      </collaborator>
    </sponsors>
    <source>University of Kentucky</source>
    <oversight_info>
      <has_dmc>Yes</has_dmc>
      <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
      <is_fda_regulated_device>No</is_fda_regulated_device>
    </oversight_info>
    <brief_summary>
      <textblock>
        The purpose of this study is to determine the response rate, safety, and effectiveness of a&#xD;
        combination therapy in patients with lung cancer.&#xD;
      </textblock>
    </brief_summary>
    <overall_status>Not yet recruiting</overall_status>
    <start_date type="Anticipated">September 2023</start_date>
    <completion_date type="Anticipated">August 2027</completion_date>
    <primary_completion_date type="Anticipated">June 2025</primary_completion_date>
    <phase>Phase 2</phase>
    <study_type>Interventional</study_type>
    <has_expanded_access>No</has_expanded_access>
    <study_design_info>
      <allocation>Non-Randomized</allocation>
      <intervention_model>Sequential Assignment</intervention_model>
      <intervention_model_description>Chemo, biopsy, surgery with option for post op chemo or no surgery with concurrent chemo</intervention_model_description>
      <primary_purpose>Treatment</primary_purpose>
      <masking>None (Open Label)</masking>
    </study_design_info>
    <primary_outcome>
      <measure>Response rate after induction</measure>
      <time_frame>9 weeks</time_frame>
      <description>post induction radiographic response by cat scan</description>
    </primary_outcome>
    <secondary_outcome>
      <measure>Change in Toxicity</measure>
      <time_frame>through study completion, up to 18 months</time_frame>
      <description>To assess safety, investigators will evaluate the rate of toxicity as defined by the Common Toxicity Criteria for Adverse Effects (CTCAE) scoring system.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Percent of participants receiving surgery</measure>
      <time_frame>date of surgery, approximately 10 weeks</time_frame>
      <description>Rate of converting non-surgical stage III(A-C) to surgically resectable disease</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Pathologic complete response (pCR)</measure>
      <time_frame>post surgery, approximately 10 weeks</time_frame>
      <description>Number of participants with Pathologic Complete Response. Pathologic complete response (pCR) is defined by a surgical pathology specimen</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Major pathological response (MPR)</measure>
      <time_frame>post surgery, approximately 10 weeks</time_frame>
      <description>MPR rate, defined as number of participants with ≤ 10% residual tumor in lung and lymph nodes</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Progression free survival</measure>
      <time_frame>2 years</time_frame>
      <description>PFS is defined as the duration of time from start of treatment to time of disease progression or death, whichever occurs first.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>overall survival (OS)</measure>
      <time_frame>2 years</time_frame>
      <description>defined as the duration of time from start of treatment to time of death</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Change in patient-reported Quality of Life as measured by FACT-TOI</measure>
      <time_frame>through study completion, up to 18 months</time_frame>
      <description>patient-reported Quality of Life as measured by FACT-TOI; defined as the sum of the scores of the Physical Well-Being (PWB), Functional Well-Being (FWB), and LCS. PWB, FWB, and LCS scores obtained from 7-item questionnaires from the FACT-L (Version 4.0). Questions are on a 5-point scale from 0-4, where 0 = &quot;not at all&quot; and 4 = &quot;very much.&quot; Scores range from 0 to 84; higher score indicates better physical aspects of quality of life (QoL).</description>
    </secondary_outcome>
    <number_of_arms>2</number_of_arms>
    <enrollment type="Anticipated">37</enrollment>
    <condition>Lung Cancer, Nonsmall Cell</condition>
    <condition>Lung Cancer Stage III</condition>
    <arm_group>
      <arm_group_label>Combination Chemotherapy and Nivolumab and Surgery</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>Patients with lung cancer receiving combination therapy with surgery</description>
    </arm_group>
    <arm_group>
      <arm_group_label>Combination Chemotherapy and Nivolumab and Radiation</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>Patients with lung cancer receiving combination therapy with radiation</description>
    </arm_group>
    <intervention>
      <intervention_type>Combination Product</intervention_type>
      <intervention_name>Nivolumab and Chemotherapy</intervention_name>
      <description>3 cycles of the proposed nivolumab + platinum doublet (either pemetrexed + carbo/cis or paclitaxel + carbo or docetaxel + carbo/cis for non squamos; or gemcitabine + carbo/cis or paclitaxel + carbo or docetaxel + carbo/cis for squamos) will be administered then CT and biopsy, followed by surgery with option for post-op NIVO-XRT, then 12 cycles NIVO at 480 mg IV every 4 weeks for 12 weeks</description>
      <arm_group_label>Combination Chemotherapy and Nivolumab and Radiation</arm_group_label>
      <arm_group_label>Combination Chemotherapy and Nivolumab and Surgery</arm_group_label>
    </intervention>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>Nivolumab</intervention_name>
      <description>Participants will receive NIVO at 480 mg IV every 4 weeks for 12 cycles after either surgery or treated with concurrent chemotherapy-nivolumab-radiation</description>
      <arm_group_label>Combination Chemotherapy and Nivolumab and Radiation</arm_group_label>
      <arm_group_label>Combination Chemotherapy and Nivolumab and Surgery</arm_group_label>
    </intervention>
    <intervention>
      <intervention_type>Procedure</intervention_type>
      <intervention_name>Post Induction Surgery</intervention_name>
      <description>Induction Chemo-NIVO x 3 cycles then CT and biopsy, followed by surgery in patients whose tumors were unresectable stage IIIA-C at baseline on the basis of lymphadenopathy and are determined to be resectable after responding to induction chemotherapy-nivolumab. The participants have an option for post op XRT, then will receive NIVO at 480 mg IV every 4 weeks for 12 cycles</description>
      <arm_group_label>Combination Chemotherapy and Nivolumab and Surgery</arm_group_label>
    </intervention>
    <intervention>
      <intervention_type>Radiation</intervention_type>
      <intervention_name>Post Induction XRT</intervention_name>
      <description>Induction Chemo-NIVO x 3 cycles then CT and biopsy, followed by concurrent Chemo and Nivo XRT (60Gy). Participants will receive concurrent thoracic radiation therapy using a standardized 3DCRT or IMRT technique on a linear accelerator operating at 2:6 MV beam energy. The target total dose of thoracic radiation therapy will be 60 Gy in 30 daily fractions of 2 Gy prescribed to the PTV. The participants then will receive NIVO at 480 mg IV every 4 weeks for 12 cycles.</description>
      <arm_group_label>Combination Chemotherapy and Nivolumab and Radiation</arm_group_label>
      <arm_group_label>Combination Chemotherapy and Nivolumab and Surgery</arm_group_label>
    </intervention>
    <eligibility>
      <criteria>
        <textblock>
          Inclusion Criteria:&#xD;
  &#xD;
            -  Squamous and non-squamous non-small cell lung cancer that is at baseline, unresectable&#xD;
               stage IIIA-IIIC (8th edition AJCC) and not previously treated&#xD;
  &#xD;
            -  PD-L1 level needs to be measured with values 0-100% eligible&#xD;
  &#xD;
            -  EGFR/ALK/ROS1 Wild Type or unknown genetic alterations in these genes&#xD;
  &#xD;
            -  ECOG Performance Status ≤ 1&#xD;
  &#xD;
            -  Adequate organ and marrow function&#xD;
  &#xD;
            -  Adequate pulmonary reserve (e.g., FVC, FEV1, TLC, FRC, and DLCO) capable of tolerating&#xD;
               the proposed lung resection&#xD;
  &#xD;
            -  Human immunodeficiency virus (HIV)-infected patients on effective anti-retroviral&#xD;
               therapy with undetectable viral load within 6 months&#xD;
  &#xD;
            -  For patients with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral&#xD;
               load must be undetectable on suppressive therapy, if indicated&#xD;
  &#xD;
            -  Patients with a history of hepatitis C virus (HCV) infection must have been treated&#xD;
               and cured. For patients with HCV infection who are currently on treatment, they are&#xD;
               eligible if they have an undetectable HCV viral load.&#xD;
  &#xD;
            -  Patients with a prior or concurrent malignancy whose natural history or treatment does&#xD;
               not have the potential to interfere with the safety or efficacy assessment of the&#xD;
               investigational regimen&#xD;
  &#xD;
            -  Clinical risk assessment of cardiac function using the New York Heart Association&#xD;
               Functional Classification class 2B or better&#xD;
  &#xD;
            -  Ability to understand and the willingness to sign a written informed consent document&#xD;
  &#xD;
          Exclusion Criteria:&#xD;
  &#xD;
            -  Patients who have participated in a study with an investigational agent or device&#xD;
               within 2 weeks of enrollment&#xD;
  &#xD;
            -  Any prior radiotherapy to the lung&#xD;
  &#xD;
            -  Any prior treatment for NSCLC&#xD;
  &#xD;
            -  Any prior therapy with anti-PD-1, anti-PD-L2, anti-CTLA-4 antibody, or any other&#xD;
               antibody or drug specifically targeting T-cell co-stimulation or immune checkpoint&#xD;
               pathways&#xD;
  &#xD;
            -  Any history of a severe hypersensitivity reaction to any monoclonal antibody&#xD;
  &#xD;
            -  Any history of allergy to the study drug components&#xD;
  &#xD;
            -  primary tumors involving the esophagus&#xD;
  &#xD;
            -  pancoast tumors&#xD;
  &#xD;
            -  Patients cannot have primary tumors which would remain unresectable&#xD;
  &#xD;
            -  History of allergic reactions attributed to compounds of similar chemical or biologic&#xD;
               composition to Nivolumab or other agents used in study&#xD;
  &#xD;
            -  Any active or history of autoimmune disease (including any history of inflammatory&#xD;
               bowel disease), or history of syndrome that required systemic steroids or&#xD;
               immunosuppressive medications&#xD;
  &#xD;
            -  Ongoing requirement for systemic corticosteroids greater than the equivalent of&#xD;
               prednisone 10mg&#xD;
  &#xD;
            -  previous malignancies&#xD;
  &#xD;
            -  history of interstitial lung disease&#xD;
  &#xD;
            -  Patients requiring continuous supplemental oxygen&#xD;
  &#xD;
            -  Use of any live vaccines against infectious diseases (e.g., influenza, varicella.&#xD;
               etc.) within 4 weeks (28 days) of initiation of study therapy&#xD;
  &#xD;
            -  Active systemic infection requiring therapy&#xD;
  &#xD;
            -  Patients with uncontrolled intercurrent illness&#xD;
  &#xD;
            -  Patients with psychiatric illness/social situations that would limit compliance with&#xD;
               study requirements&#xD;
  &#xD;
            -  Pregnant or lactating women&#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>Ralph Zinner, MD</last_name>
      <role>Principal Investigator</role>
      <affiliation>University of Kentucky</affiliation>
    </overall_official>
    <overall_contact>
      <last_name>Yvonne Taul, RN</last_name>
      <phone>859-323-2354</phone>
      <email>yvonne.taul@uky.edu</email>
    </overall_contact>
    <verification_date>August 2023</verification_date>
    <study_first_submitted>August 15, 2023</study_first_submitted>
    <study_first_submitted_qc>August 15, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">August 21, 2023</study_first_posted>
    <last_update_submitted>August 15, 2023</last_update_submitted>
    <last_update_submitted_qc>August 15, 2023</last_update_submitted_qc>
    <last_update_posted type="Actual">August 21, 2023</last_update_posted>
    <responsible_party>
      <responsible_party_type>Sponsor-Investigator</responsible_party_type>
      <investigator_affiliation>University of Kentucky</investigator_affiliation>
      <investigator_full_name>Ralph G Zinner</investigator_full_name>
      <investigator_title>Professor</investigator_title>
    </responsible_party>
    <keyword>Nivolumab</keyword>
    <keyword>unresectable</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>
    </intervention_browse>
    <!-- Results have not yet been posted for this study                                          -->
  </clinical_study>
  
  
text: 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/NCT06003075
  org study id: 85869
  nct id: NCT06003075
  lead sponsor: 
  collaborator: 
  has dmc: Yes
  is fda regulated drug: Yes
  is fda regulated device: No
  The purpose of this study is to determine the response rate, safety, and effectiveness of a
        combination therapy in patients with lung cancer.
  allocation: Non-Randomized
  intervention model: Sequential Assignment
  intervention model description: Chemo, biopsy, surgery with option for post op chemo or no surgery with concurrent chemo
  primary purpose: Treatment
  masking: None (Open Label)
  measure: Response rate after induction
  time frame: 9 weeks
  description: post induction radiographic response by cat scan
  measure: Change in Toxicity
  time frame: through study completion, up to 18 months
  description: To assess safety, investigators will evaluate the rate of toxicity as defined by the Common Toxicity Criteria for Adverse Effects (CTCAE) scoring system.
  measure: Percent of participants receiving surgery
  time frame: date of surgery, approximately 10 weeks
  description: Rate of converting non-surgical stage III(A-C) to surgically resectable disease
  measure: Pathologic complete response (pCR)
  time frame: post surgery, approximately 10 weeks
  description: Number of participants with Pathologic Complete Response. Pathologic complete response (pCR) is defined by a surgical pathology specimen
  measure: Major pathological response (MPR)
  time frame: post surgery, approximately 10 weeks
  description: MPR rate, defined as number of participants with ≤ 10% residual tumor in lung and lymph nodes
  measure: Progression free survival
  time frame: 2 years
  description: PFS is defined as the duration of time from start of treatment to time of disease progression or death, whichever occurs first.
  measure: overall survival (OS)
  time frame: 2 years
  description: defined as the duration of time from start of treatment to time of death
  measure: Change in patient-reported Quality of Life as measured by FACT-TOI
  time frame: through study completion, up to 18 months
  description: patient-reported Quality of Life as measured by FACT-TOI; defined as the sum of the scores of the Physical Well-Being (PWB), Functional Well-Being (FWB), and LCS. PWB, FWB, and LCS scores obtained from 7-item questionnaires from the FACT-L (Version 4.0). Questions are on a 5-point scale from 0-4, where 0 = "not at all" and 4 = "very much." Scores range from 0 to 84; higher score indicates better physical aspects of quality of life (QoL).
  arm group label: Combination Chemotherapy and Nivolumab and Surgery
  arm group type: Experimental
  description: Patients with lung cancer receiving combination therapy with surgery
  arm group label: Combination Chemotherapy and Nivolumab and Radiation
  arm group type: Experimental
  description: Patients with lung cancer receiving combination therapy with radiation
  intervention type: Combination Product
  intervention name: Nivolumab and Chemotherapy
  description: 3 cycles of the proposed nivolumab + platinum doublet (either pemetrexed + carbo/cis or paclitaxel + carbo or docetaxel + carbo/cis for non squamos; or gemcitabine + carbo/cis or paclitaxel + carbo or docetaxel + carbo/cis for squamos) will be administered then CT and biopsy, followed by surgery with option for post-op NIVO-XRT, then 12 cycles NIVO at 480 mg IV every 4 weeks for 12 weeks
  arm group label: Combination Chemotherapy and Nivolumab and Radiation
  arm group label: Combination Chemotherapy and Nivolumab and Surgery
  intervention type: Drug
  intervention name: Nivolumab
  description: Participants will receive NIVO at 480 mg IV every 4 weeks for 12 cycles after either surgery or treated with concurrent chemotherapy-nivolumab-radiation
  arm group label: Combination Chemotherapy and Nivolumab and Radiation
  arm group label: Combination Chemotherapy and Nivolumab and Surgery
  intervention type: Procedure
  intervention name: Post Induction Surgery
  description: Induction Chemo-NIVO x 3 cycles then CT and biopsy, followed by surgery in patients whose tumors were unresectable stage IIIA-C at baseline on the basis of lymphadenopathy and are determined to be resectable after responding to induction chemotherapy-nivolumab. The participants have an option for post op XRT, then will receive NIVO at 480 mg IV every 4 weeks for 12 cycles
  arm group label: Combination Chemotherapy and Nivolumab and Surgery
  intervention type: Radiation
  intervention name: Post Induction XRT
  description: Induction Chemo-NIVO x 3 cycles then CT and biopsy, followed by concurrent Chemo and Nivo XRT (60Gy). Participants will receive concurrent thoracic radiation therapy using a standardized 3DCRT or IMRT technique on a linear accelerator operating at 2:6 MV beam energy. The target total dose of thoracic radiation therapy will be 60 Gy in 30 daily fractions of 2 Gy prescribed to the PTV. The participants then will receive NIVO at 480 mg IV every 4 weeks for 12 cycles.
  arm group label: Combination Chemotherapy and Nivolumab and Radiation
  arm group label: Combination Chemotherapy and Nivolumab and Surgery
  criteria: 
  gender: All
  minimum age: 18 Years
  maximum age: N/A
  healthy volunteers: No
  last name: Ralph Zinner, MD
  role: Principal Investigator
  affiliation: University of Kentucky
  last name: Yvonne Taul, RN
  phone: 859-323-2354
  email: yvonne.taul@uky.edu
  responsible party type: Sponsor-Investigator
  investigator affiliation: University of Kentucky
  investigator full name: Ralph G Zinner
  investigator title: Professor
  mesh term: Lung Neoplasms
  mesh term: Carcinoma, Non-Small-Cell Lung
  mesh term: Nivolumab