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Nivolumab in Treating Patients With Stage IV or Recurrent Lung Cancer With High Mutation Loads

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT03023904
Recruitment Status : Withdrawn (Research cancelled)
First Posted : January 18, 2017
Last Update Posted : April 25, 2018
Information provided by (Responsible Party):
Douglas Johnson, Vanderbilt-Ingram Cancer Center

Brief Summary:
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.

Condition or disease Intervention/treatment Phase
Recurrent Non-Small Cell Lung Carcinoma Stage IV Non-Small Cell Lung Cancer Biological: Nivolumab Other: Laboratory Biomarker Analysis Phase 2

Detailed Description:


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


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.


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.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 0 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Nivolumab in Treating Patients With Stage IV or Recurrent Lung Cancer With High Mutation Loads
Actual Study Start Date : December 29, 2017
Estimated Primary Completion Date : July 30, 2019
Estimated Study Completion Date : July 30, 2020

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Lung Cancer
Drug Information available for: Nivolumab

Arm Intervention/treatment
Experimental: Treatment (nivolumab)
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.
Biological: Nivolumab
Given IV

Other: Laboratory Biomarker Analysis
Correlative studies

Primary Outcome Measures :
  1. 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 ]

Secondary Outcome Measures :
  1. Overall survival [ Time Frame: From date of enrollment to date of death due to any cause, assessed up to 2 years ]
  2. 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 ]
  3. Mutation load as determined by FoundationOne testing [ Time Frame: Up to 2 years ]
  4. 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 ]
  5. PD-L1 expression as determined by immunohistochemistry [ Time Frame: Up to 2 years ]

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • • Signed written informed consent

    • Subjects must have signed and dated an Institutional Review Board (IRB)/Independent Ethics Committee (IEC) approved written informed consent form in accordance with regulatory and institutional guidelines; this must be obtained before the performance of any protocol related procedures that are not part of normal subject care
    • Subjects must be willing and able to comply with scheduled visits, treatment schedule, and laboratory testing

      • Eastern Cooperative Oncology Group (ECOG) performance status of =< 1
      • Subjects with histologically confirmed stage IV or recurrent NSCLC (per the 7th International Association for the Study of Lung Cancer classification squamous or nonsquamous histology, with no prior systemic anticancer therapy (including EGFR and ALK inhibitors) given as primary therapy for advanced or metastatic disease
    • Prior adjuvant or neoadjuvant chemotherapy is permitted as long as the last administration is at least 2 months prior to enrollment
    • Prior definitive chemoradiation for locally advanced disease is also permitted as long as the last administration of chemotherapy or radiotherapy (whichever was given last) occurred at least 2 months prior to enrollment

      • Mutation load determined by FoundationOne of >= 20 mutations/MB tested on archival tumor sample; the mutation load metric will be displayed on the FoundationOne report for all participating sites as "tumor mutation burden (TMB) - high" or may be obtained from Foundation Medicine from older reports using the Insights Portal, which will be available to all participating sites, or by emailing Foundation Medicine
      • Measurable disease by computed tomography (CT) or magnetic resonance imaging (MRI) per RECIST 1.1 criteria
    • Target lesions may be located in a previously irradiated field if there is documented (radiographic) disease progression in that site after the completion of radiation therapy

      • Prior palliative radiotherapy to non-central nervous system (CNS) lesions must have been completed at least 2 weeks prior to enrollment; subjects with symptomatic tumor lesions at baseline that may require palliative radiotherapy within 4 weeks of enrollment are strongly encouraged to receive palliative radiotherapy prior to enrollment
      • White blood cell (WBC) > 2000/uL
      • Neutrophils > 1500/uL
      • Platelets > 100 x 10^9/uL
      • Hemoglobin > 9.0 g/dL
      • Serum creatinine =< 2 x upper limit normal (ULN) or creatinine clearance (CrCl) >= 30 mL/min using the Cockcroft-Gault formula
      • Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) =< 3 x ULN (unless liver metastases, who can have AST/ALT =< 5 x ULN)
      • Total bilirubin =< 3 x ULN (except subjects with Gilbert syndrome, who can have total bilirubin < 3.0 mg/dL)
      • Women must not be breastfeeding
      • Women of childbearing potential must have a negative serum or urine pregnancy test within 24 hours prior to the start of nivolumab
    • "Women of childbearing potential" is defined as any female who has experienced menarche and who has not undergone surgical sterilization (hysterectomy or bilateral oophorectomy) or who is not postmenopausal
    • Menopause is defined as 12 months of amenorrhea in a woman over 45 in the absence of other biological or physiological causes; if menopausal status is considered for the purpose of evaluating childbearing potential, women under the age of 62 must have a documented serum follicle stimulating hormone (FSH) level > 40 mIU/mL, in order to be considered postmenopausal and not of childbearing potential

      • Women of child bearing potential (WOCBP) and men able to father children who are sexually active with WOCBP must agree to use acceptable contraception

    • Women who are not of childbearing potential (i.e., who are postmenopausal or surgically sterile) and azoospermic men do not require contraception
    • Women of childbearing potential receiving nivolumab will be instructed to use and must be willing to use appropriate method(s) of contraception for a period of 23 weeks after the last dose of investigational product
    • Men receiving nivolumab who are sexually active with WOCBP will be instructed to use and must be willing to use acceptable contraception for a period of 31 weeks after the last dose of investigational product

Exclusion Criteria:

  • Subjects with known EGFR mutations which are sensitive to available targeted inhibitor therapy (including, but not limited to, deletions in exon 19 and exon 21 [L858R] substitution mutations) are excluded; all subjects with non-squamous histology must have been tested for EGFR mutation status; use of a Food and Drug Administration (FDA)-approved test is strongly encouraged
  • Subjects with known ALK translocations which are sensitive to available targeted inhibitor therapy are excluded; if tested, use of an FDA-approved test is strongly encouraged; subjects with unknown or indeterminate ALK status may be enrolled
  • Active brain metastases or leptomeningeal metastases (carcinomatous meningitis); subjects with brain metastases are eligible if these have been treated and there is no evidence of progression for at least 2 weeks after treatment is complete and corticosteroid dose is stable (and equivalent dose of < 10 mg prednisone) for at least 2 weeks
  • Subjects must have recovered from the effects of major surgery or significant traumatic injury at least 14 days before enrollment
  • Subjects with an active, known or suspected autoimmune disease; subjects with type I diabetes mellitus, hypothyroidism only requiring hormone replacement, skin disorders (such as vitiligo, psoriasis, or alopecia) not requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger are permitted to enroll
  • Subjects with a condition requiring systemic treatment with either corticosteroids (> 10 mg daily prednisone equivalent) or other immunosuppressive medications within 14 days of first study treatment with nivolumab; inhaled or topical steroids, and adrenal replacement steroid > 10 mg daily prednisone equivalent, are permitted in the absence of active autoimmune disease
  • Patients with concurrent severe and/or uncontrolled concurrent medical conditions that could compromise participation in the study (e.g., uncontrolled hypertension and/or diabetes mellitus, clinically significant pulmonary disease, clinically significant neurological disorder, active or uncontrolled infection)
  • Subjects with interstitial lung disease that is symptomatic or may interfere with the detection or management of suspected drug-related pulmonary toxicity
  • Known history of testing positive for human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome (AIDS)
  • Any serious or uncontrolled medical disorder that, in the opinion of the investigator, may increase the risk associated with study participation or study drug administration
  • Subjects with previous or active malignancies (except non-melanoma skin cancers, and in situ cancers such as the following: bladder, gastric, colon, cervical/dysplasia, melanoma, or breast) are excluded unless a complete remission was achieved at least 2 years prior to enrollment and no additional therapy is required or anticipated to be required during the study period
  • History of allergy to study drug components or of severe hypersensitivity reaction to any monoclonal antibody
  • Prisoners or subjects who are involuntarily incarcerated
  • Subjects who are compulsorily detained for treatment of either a psychiatric or physical (e.g., infectious disease) illness

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT03023904

Sponsors and Collaborators
Vanderbilt-Ingram Cancer Center
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Principal Investigator: Douglas Johnson, M.D. Vanderbilt-Ingram Cancer Center
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Responsible Party: Douglas Johnson, Principal Investigator, Vanderbilt-Ingram Cancer Center Identifier: NCT03023904    
Other Study ID Numbers: VICC THO 16117
NCI-2017-00047 ( Registry Identifier: NCI, Clinical Trials Reporting Program )
First Posted: January 18, 2017    Key Record Dates
Last Update Posted: April 25, 2018
Last Verified: April 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Lung Neoplasms
Carcinoma, Non-Small-Cell Lung
Disease Attributes
Pathologic Processes
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Lung Diseases
Respiratory Tract Diseases
Carcinoma, Bronchogenic
Bronchial Neoplasms
Antineoplastic Agents, Immunological
Antineoplastic Agents
Immune Checkpoint Inhibitors
Molecular Mechanisms of Pharmacological Action