<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/NCT03023904</url>
  </required_header>
  <id_info>
    <org_study_id>VICC THO 16117</org_study_id>
    <secondary_id>NCI-2017-00047</secondary_id>
    <nct_id>NCT03023904</nct_id>
  </id_info>
  <brief_title>Nivolumab in Treating Patients With Stage IV or Recurrent Lung Cancer With High Mutation Loads</brief_title>
  <official_title>Nivolumab in Treating Patients With Stage IV or Recurrent Lung Cancer With High Mutation Loads</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Vanderbilt-Ingram Cancer Center</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Vanderbilt-Ingram Cancer Center</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>
      This phase II trial studies how well nivolumab works in treating patients with stage IV lung&#xD;
      cancer or that has come back after initial treatment who has high mutation loads. Monoclonal&#xD;
      antibodies, such as nivolumab, may block tumor growth in different ways by targeting certain&#xD;
      cells.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      PRIMARY OBJECTIVES:&#xD;
&#xD;
      I. To assess the objective response rate using Response Evaluation Criteria in Solid Tumors&#xD;
      (RECIST) 1.1 criteria.&#xD;
&#xD;
      SECONDARY OBJECTIVES:&#xD;
&#xD;
      I. To assess the progression-free survival (PFS). II. To assess the overall survival (OS).&#xD;
      III. To correlate response and mutation load with PD-L1 status (5% and 1% cutoffs).&#xD;
&#xD;
      IV. To assess clinical benefit (responses and stable disease lasting &gt;= 6 months).&#xD;
&#xD;
      V. To assess the response rate in mutation-defined subgroups, including subjects with &gt;= 25&#xD;
      mutations/mutational burden (MB) and &gt;= 30 mutations/MB.&#xD;
&#xD;
      VI. To correlate the type of mutations with response.&#xD;
&#xD;
      OUTLINE:&#xD;
&#xD;
      Patients receive nivolumab intravenously (IV) over 30 minutes on day 1. Courses repeat every&#xD;
      2 weeks for up to 2 years (104 weeks) in the absence of disease progression or unacceptable&#xD;
      toxicity.&#xD;
&#xD;
      After completion of study treatment, patients are followed up at 35 days and then every 3&#xD;
      months for 2 years.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Withdrawn</overall_status>
  <why_stopped>
    Research cancelled&#xD;
  </why_stopped>
  <start_date type="Actual">December 29, 2017</start_date>
  <completion_date type="Anticipated">July 30, 2020</completion_date>
  <primary_completion_date type="Anticipated">July 30, 2019</primary_completion_date>
  <phase>Phase 2</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>N/A</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Objective Response Rate defined as the number of subjects with a best overall response of complete response or partial response divided by the number of subjects that receive nivolumab as assessed by RECIST 1.1</measure>
    <time_frame>Up to 6 months</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>Overall survival</measure>
    <time_frame>From date of enrollment to date of death due to any cause, assessed up to 2 years</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Progression Free Survival as determined by RECIST 1.1</measure>
    <time_frame>From date of enrollment until first date of documented progression or death due to any cause, assessed up to 2 years</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Mutation load as determined by FoundationOne testing</measure>
    <time_frame>Up to 2 years</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Incidence of adverse events (AEs) graded using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.03</measure>
    <time_frame>Up to 100 days after the last dose of study drug</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>PD-L1 expression as determined by immunohistochemistry</measure>
    <time_frame>Up to 2 years</time_frame>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">0</enrollment>
  <condition>Recurrent Non-Small Cell Lung Carcinoma</condition>
  <condition>Stage IV Non-Small Cell Lung Cancer</condition>
  <arm_group>
    <arm_group_label>Treatment (nivolumab)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Patients receive nivolumab IV over 30 minutes on day 1. Courses repeat every 2 weeks for up to 2 years (104 weeks) in the absence of disease progression or unacceptable toxicity.</description>
  </arm_group>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>Nivolumab</intervention_name>
    <description>Given IV</description>
    <arm_group_label>Treatment (nivolumab)</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Laboratory Biomarker Analysis</intervention_name>
    <description>Correlative studies</description>
    <arm_group_label>Treatment (nivolumab)</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  • Signed written informed consent&#xD;
&#xD;
               -  Subjects must have signed and dated an Institutional Review Board&#xD;
                  (IRB)/Independent Ethics Committee (IEC) approved written informed consent form&#xD;
                  in accordance with regulatory and institutional guidelines; this must be obtained&#xD;
                  before the performance of any protocol related procedures that are not part of&#xD;
                  normal subject care&#xD;
&#xD;
               -  Subjects must be willing and able to comply with scheduled visits, treatment&#xD;
                  schedule, and laboratory testing&#xD;
&#xD;
                    -  Eastern Cooperative Oncology Group (ECOG) performance status of =&lt; 1&#xD;
&#xD;
                    -  Subjects with histologically confirmed stage IV or recurrent NSCLC (per the&#xD;
                       7th International Association for the Study of Lung Cancer classification&#xD;
                       squamous or nonsquamous histology, with no prior systemic anticancer therapy&#xD;
                       (including EGFR and ALK inhibitors) given as primary therapy for advanced or&#xD;
                       metastatic disease&#xD;
&#xD;
               -  Prior adjuvant or neoadjuvant chemotherapy is permitted as long as the last&#xD;
                  administration is at least 2 months prior to enrollment&#xD;
&#xD;
               -  Prior definitive chemoradiation for locally advanced disease is also permitted as&#xD;
                  long as the last administration of chemotherapy or radiotherapy (whichever was&#xD;
                  given last) occurred at least 2 months prior to enrollment&#xD;
&#xD;
                    -  Mutation load determined by FoundationOne of &gt;= 20 mutations/MB tested on&#xD;
                       archival tumor sample; the mutation load metric will be displayed on the&#xD;
                       FoundationOne report for all participating sites as &quot;tumor mutation burden&#xD;
                       (TMB) - high&quot; or may be obtained from Foundation Medicine from older reports&#xD;
                       using the Insights Portal, which will be available to all participating&#xD;
                       sites, or by emailing Foundation Medicine&#xD;
&#xD;
                    -  Measurable disease by computed tomography (CT) or magnetic resonance imaging&#xD;
                       (MRI) per RECIST 1.1 criteria&#xD;
&#xD;
               -  Target lesions may be located in a previously irradiated field if there is&#xD;
                  documented (radiographic) disease progression in that site after the completion&#xD;
                  of radiation therapy&#xD;
&#xD;
                    -  Prior palliative radiotherapy to non-central nervous system (CNS) lesions&#xD;
                       must have been completed at least 2 weeks prior to enrollment; subjects with&#xD;
                       symptomatic tumor lesions at baseline that may require palliative&#xD;
                       radiotherapy within 4 weeks of enrollment are strongly encouraged to receive&#xD;
                       palliative radiotherapy prior to enrollment&#xD;
&#xD;
                    -  White blood cell (WBC) &gt; 2000/uL&#xD;
&#xD;
                    -  Neutrophils &gt; 1500/uL&#xD;
&#xD;
                    -  Platelets &gt; 100 x 10^9/uL&#xD;
&#xD;
                    -  Hemoglobin &gt; 9.0 g/dL&#xD;
&#xD;
                    -  Serum creatinine =&lt; 2 x upper limit normal (ULN) or creatinine clearance&#xD;
                       (CrCl) &gt;= 30 mL/min using the Cockcroft-Gault formula&#xD;
&#xD;
                    -  Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) =&lt; 3 x ULN&#xD;
                       (unless liver metastases, who can have AST/ALT =&lt; 5 x ULN)&#xD;
&#xD;
                    -  Total bilirubin =&lt; 3 x ULN (except subjects with Gilbert syndrome, who can&#xD;
                       have total bilirubin &lt; 3.0 mg/dL)&#xD;
&#xD;
                    -  Women must not be breastfeeding&#xD;
&#xD;
                    -  Women of childbearing potential must have a negative serum or urine&#xD;
                       pregnancy test within 24 hours prior to the start of nivolumab&#xD;
&#xD;
               -  &quot;Women of childbearing potential&quot; is defined as any female who has experienced&#xD;
                  menarche and who has not undergone surgical sterilization (hysterectomy or&#xD;
                  bilateral oophorectomy) or who is not postmenopausal&#xD;
&#xD;
               -  Menopause is defined as 12 months of amenorrhea in a woman over 45 in the absence&#xD;
                  of other biological or physiological causes; if menopausal status is considered&#xD;
                  for the purpose of evaluating childbearing potential, women under the age of 62&#xD;
                  must have a documented serum follicle stimulating hormone (FSH) level &gt; 40&#xD;
                  mIU/mL, in order to be considered postmenopausal and not of childbearing&#xD;
                  potential&#xD;
&#xD;
                  • Women of child bearing potential (WOCBP) and men able to father children who&#xD;
                  are sexually active with WOCBP must agree to use acceptable contraception&#xD;
&#xD;
               -  Women who are not of childbearing potential (i.e., who are postmenopausal or&#xD;
                  surgically sterile) and azoospermic men do not require contraception&#xD;
&#xD;
               -  Women of childbearing potential receiving nivolumab will be instructed to use and&#xD;
                  must be willing to use appropriate method(s) of contraception for a period of 23&#xD;
                  weeks after the last dose of investigational product&#xD;
&#xD;
               -  Men receiving nivolumab who are sexually active with WOCBP will be instructed to&#xD;
                  use and must be willing to use acceptable contraception for a period of 31 weeks&#xD;
                  after the last dose of investigational product&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Subjects with known EGFR mutations which are sensitive to available targeted inhibitor&#xD;
             therapy (including, but not limited to, deletions in exon 19 and exon 21 [L858R]&#xD;
             substitution mutations) are excluded; all subjects with non-squamous histology must&#xD;
             have been tested for EGFR mutation status; use of a Food and Drug Administration&#xD;
             (FDA)-approved test is strongly encouraged&#xD;
&#xD;
          -  Subjects with known ALK translocations which are sensitive to available targeted&#xD;
             inhibitor therapy are excluded; if tested, use of an FDA-approved test is strongly&#xD;
             encouraged; subjects with unknown or indeterminate ALK status may be enrolled&#xD;
&#xD;
          -  Active brain metastases or leptomeningeal metastases (carcinomatous meningitis);&#xD;
             subjects with brain metastases are eligible if these have been treated and there is no&#xD;
             evidence of progression for at least 2 weeks after treatment is complete and&#xD;
             corticosteroid dose is stable (and equivalent dose of &lt; 10 mg prednisone) for at least&#xD;
             2 weeks&#xD;
&#xD;
          -  Subjects must have recovered from the effects of major surgery or significant&#xD;
             traumatic injury at least 14 days before enrollment&#xD;
&#xD;
          -  Subjects with an active, known or suspected autoimmune disease; subjects with type I&#xD;
             diabetes mellitus, hypothyroidism only requiring hormone replacement, skin disorders&#xD;
             (such as vitiligo, psoriasis, or alopecia) not requiring systemic treatment, or&#xD;
             conditions not expected to recur in the absence of an external trigger are permitted&#xD;
             to enroll&#xD;
&#xD;
          -  Subjects with a condition requiring systemic treatment with either corticosteroids (&gt;&#xD;
             10 mg daily prednisone equivalent) or other immunosuppressive medications within 14&#xD;
             days of first study treatment with nivolumab; inhaled or topical steroids, and adrenal&#xD;
             replacement steroid &gt; 10 mg daily prednisone equivalent, are permitted in the absence&#xD;
             of active autoimmune disease&#xD;
&#xD;
          -  Patients with concurrent severe and/or uncontrolled concurrent medical conditions that&#xD;
             could compromise participation in the study (e.g., uncontrolled hypertension and/or&#xD;
             diabetes mellitus, clinically significant pulmonary disease, clinically significant&#xD;
             neurological disorder, active or uncontrolled infection)&#xD;
&#xD;
          -  Subjects with interstitial lung disease that is symptomatic or may interfere with the&#xD;
             detection or management of suspected drug-related pulmonary toxicity&#xD;
&#xD;
          -  Known history of testing positive for human immunodeficiency virus (HIV) or known&#xD;
             acquired immunodeficiency syndrome (AIDS)&#xD;
&#xD;
          -  Any serious or uncontrolled medical disorder that, in the opinion of the investigator,&#xD;
             may increase the risk associated with study participation or study drug administration&#xD;
&#xD;
          -  Subjects with previous or active malignancies (except non-melanoma skin cancers, and&#xD;
             in situ cancers such as the following: bladder, gastric, colon, cervical/dysplasia,&#xD;
             melanoma, or breast) are excluded unless a complete remission was achieved at least 2&#xD;
             years prior to enrollment and no additional therapy is required or anticipated to be&#xD;
             required during the study period&#xD;
&#xD;
          -  History of allergy to study drug components or of severe hypersensitivity reaction to&#xD;
             any monoclonal antibody&#xD;
&#xD;
          -  Prisoners or subjects who are involuntarily incarcerated&#xD;
&#xD;
          -  Subjects who are compulsorily detained for treatment of either a psychiatric or&#xD;
             physical (e.g., infectious disease) illness&#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>Douglas Johnson, M.D.</last_name>
    <role>Principal Investigator</role>
    <affiliation>Vanderbilt-Ingram Cancer Center</affiliation>
  </overall_official>
  <removed_countries>
    <country>United States</country>
  </removed_countries>
  <verification_date>April 2018</verification_date>
  <study_first_submitted>January 10, 2017</study_first_submitted>
  <study_first_submitted_qc>January 13, 2017</study_first_submitted_qc>
  <study_first_posted type="Estimate">January 18, 2017</study_first_posted>
  <last_update_submitted>April 23, 2018</last_update_submitted>
  <last_update_submitted_qc>April 23, 2018</last_update_submitted_qc>
  <last_update_posted type="Actual">April 25, 2018</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Vanderbilt-Ingram Cancer Center</investigator_affiliation>
    <investigator_full_name>Douglas Johnson</investigator_full_name>
    <investigator_title>Principal Investigator</investigator_title>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Lung Neoplasms</mesh_term>
    <mesh_term>Carcinoma, Non-Small-Cell Lung</mesh_term>
    <mesh_term>Recurrence</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Nivolumab</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>Undecided</sharing_ipd>
  </patient_data>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT03023904
org study id: VICC THO 16117
secondary id: NCI-2017-00047
nct id: NCT03023904
lead sponsor: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
This phase II trial studies how well nivolumab works in treating patients with stage IV lung
      cancer or that has come back after initial treatment who has high mutation loads. Monoclonal
      antibodies, such as nivolumab, may block tumor growth in different ways by targeting certain
      cells.
PRIMARY OBJECTIVES:

      I. To assess the objective response rate using Response Evaluation Criteria in Solid Tumors
      (RECIST) 1.1 criteria.

      SECONDARY OBJECTIVES:

      I. To assess the progression-free survival (PFS). II. To assess the overall survival (OS).
      III. To correlate response and mutation load with PD-L1 status (5% and 1% cutoffs).

      IV. To assess clinical benefit (responses and stable disease lasting >= 6 months).

      V. To assess the response rate in mutation-defined subgroups, including subjects with >= 25
      mutations/mutational burden (MB) and >= 30 mutations/MB.

      VI. To correlate the type of mutations with response.

      OUTLINE:

      Patients receive nivolumab intravenously (IV) over 30 minutes on day 1. Courses repeat every
      2 weeks for up to 2 years (104 weeks) in the absence of disease progression or unacceptable
      toxicity.

      After completion of study treatment, patients are followed up at 35 days and then every 3
      months for 2 years.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Objective Response Rate defined as the number of subjects with a best overall response of complete response or partial response divided by the number of subjects that receive nivolumab as assessed by RECIST 1.1
time frame: Up to 6 months
measure: Overall survival
time frame: From date of enrollment to date of death due to any cause, assessed up to 2 years
measure: Progression Free Survival as determined by RECIST 1.1
time frame: From date of enrollment until first date of documented progression or death due to any cause, assessed up to 2 years
measure: Mutation load as determined by FoundationOne testing
time frame: Up to 2 years
measure: Incidence of adverse events (AEs) graded using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.03
time frame: Up to 100 days after the last dose of study drug
measure: PD-L1 expression as determined by immunohistochemistry
time frame: Up to 2 years
arm group label: Treatment (nivolumab)
arm group type: Experimental
description: Patients receive nivolumab IV over 30 minutes on day 1. Courses repeat every 2 weeks for up to 2 years (104 weeks) in the absence of disease progression or unacceptable toxicity.
intervention type: Biological
intervention name: Nivolumab
description: Given IV
arm group label: Treatment (nivolumab)
intervention type: Other
intervention name: Laboratory Biomarker Analysis
description: Correlative studies
arm group label: Treatment (nivolumab)
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Douglas Johnson, M.D.
role: Principal Investigator
affiliation: Vanderbilt-Ingram Cancer Center
country: United States
responsible party type: Principal Investigator
investigator affiliation: Vanderbilt-Ingram Cancer Center
investigator full name: Douglas Johnson
investigator title: Principal Investigator
mesh term: Lung Neoplasms
mesh term: Carcinoma, Non-Small-Cell Lung
mesh term: Recurrence
mesh term: Nivolumab
sharing ipd: Undecided