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

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ClinicalTrials.gov Identifier: NCT03023904
Recruitment Status : Withdrawn (Research cancelled)
First Posted : January 18, 2017
Last Update Posted : April 25, 2018
Sponsor:
Information provided by (Responsible Party):
Douglas Johnson, Vanderbilt-Ingram Cancer Center

Tracking Information
First Submitted Date  ICMJE January 10, 2017
First Posted Date  ICMJE January 18, 2017
Last Update Posted Date April 25, 2018
Actual Study Start Date  ICMJE December 29, 2017
Estimated Primary Completion Date July 30, 2019   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: January 13, 2017)
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 ]
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: January 13, 2017)
  • Overall survival [ Time Frame: From date of enrollment to date of death due to any cause, assessed up to 2 years ]
  • 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 ]
  • Mutation load as determined by FoundationOne testing [ Time Frame: Up to 2 years ]
  • 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 ]
  • PD-L1 expression as determined by immunohistochemistry [ Time Frame: Up to 2 years ]
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Nivolumab in Treating Patients With Stage IV or Recurrent Lung Cancer With High Mutation Loads
Official Title  ICMJE Nivolumab in Treating Patients With Stage IV or Recurrent Lung Cancer With High Mutation Loads
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.
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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Recurrent Non-Small Cell Lung Carcinoma
  • Stage IV Non-Small Cell Lung Cancer
Intervention  ICMJE
  • Biological: Nivolumab
    Given IV
  • Other: Laboratory Biomarker Analysis
    Correlative studies
Study Arms  ICMJE 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.
Interventions:
  • Biological: Nivolumab
  • Other: Laboratory Biomarker Analysis
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Withdrawn
Actual Enrollment  ICMJE
 (submitted: April 23, 2018)
0
Original Estimated Enrollment  ICMJE
 (submitted: January 13, 2017)
47
Estimated Study Completion Date  ICMJE July 30, 2020
Estimated Primary Completion Date July 30, 2019   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Not Provided
Removed Location Countries United States
 
Administrative Information
NCT Number  ICMJE NCT03023904
Other Study ID Numbers  ICMJE VICC THO 16117
NCI-2017-00047 ( Registry Identifier: NCI, Clinical Trials Reporting Program )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: Undecided
Responsible Party Douglas Johnson, Vanderbilt-Ingram Cancer Center
Study Sponsor  ICMJE Vanderbilt-Ingram Cancer Center
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Douglas Johnson, M.D. Vanderbilt-Ingram Cancer Center
PRS Account Vanderbilt-Ingram Cancer Center
Verification Date April 2018

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP