Clinical Trials /

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

NCT03023904

Description:

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.

Related Conditions:
  • Non-Small Cell Lung Carcinoma
Recruiting Status:

Withdrawn

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Nivolumab in Treating Patients With Stage IV or Recurrent Lung Cancer With High Mutation Loads
  • Official Title: Nivolumab in Treating Patients With Stage IV or Recurrent Lung Cancer With High Mutation Loads

Clinical Trial IDs

  • ORG STUDY ID: VICC THO 16117
  • SECONDARY ID: NCI-2017-00047
  • NCT ID: NCT03023904

Conditions

  • Recurrent Non-Small Cell Lung Carcinoma
  • Stage IV Non-Small Cell Lung Cancer

Interventions

DrugSynonymsArms
NivolumabTreatment (nivolumab)

Purpose

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.

Detailed Description

      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.
    

Trial Arms

NameTypeDescriptionInterventions
Treatment (nivolumab)ExperimentalPatients 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.

    Eligibility Criteria

            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
          
    Maximum Eligible Age:N/A
    Minimum Eligible Age:18 Years
    Eligible Gender:All
    Healthy Volunteers:No

    Primary Outcome Measures

    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
    Safety Issue:
    Description:

    Secondary Outcome Measures

    Measure:Overall survival
    Time Frame:From date of enrollment to date of death due to any cause, assessed up to 2 years
    Safety Issue:
    Description:
    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
    Safety Issue:
    Description:
    Measure:Mutation load as determined by FoundationOne testing
    Time Frame:Up to 2 years
    Safety Issue:
    Description:
    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
    Safety Issue:
    Description:
    Measure:PD-L1 expression as determined by immunohistochemistry
    Time Frame:Up to 2 years
    Safety Issue:
    Description:

    Details

    Phase:Phase 2
    Primary Purpose:Interventional
    Overall Status:Withdrawn
    Lead Sponsor:Vanderbilt-Ingram Cancer Center

    Last Updated

    April 23, 2018