Clinical Trials /

Nivolumab After Surgery and Chemotherapy in Treating Patients With Stage IB-IIIA Non-small Cell Lung Cancer (An ALCHEMIST Treatment Trial)

NCT02595944

Description:

This phase III ALCHEMIST trial studies how well nivolumab after surgery and chemotherapy work in treating patients with stage IB-IIIA non-small cell lung cancer. Immunotherapy with monoclonal antibodies, such as nivolumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread.

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

Recruiting

Phase:

Phase 3

Trial Eligibility

Document

Title

  • Brief Title: Nivolumab After Surgery and Chemotherapy in Treating Patients With Stage IB-IIIA Non-small Cell Lung Cancer
  • Official Title: Adjuvant Nivolumab in Resected Lung Cancers (ANVIL)-A Randomized Phase III Study of Nivolumab After Surgical Resection and Adjuvant Chemotherapy in Non-small Cell Lung Cancers

Clinical Trial IDs

  • ORG STUDY ID: NCI-2015-01916
  • SECONDARY ID: NCI-2015-01916
  • SECONDARY ID: EA5142
  • SECONDARY ID: s16-02074
  • SECONDARY ID: EA5142
  • SECONDARY ID: EA5142
  • SECONDARY ID: U10CA180820
  • NCT ID: NCT02595944

Conditions

  • Stage IB Non-Small Cell Lung Carcinoma AJCC v7
  • Stage II Non-Small Cell Lung Cancer AJCC v7
  • Stage IIA Non-Small Cell Lung Carcinoma AJCC v7
  • Stage IIB Non-Small Cell Lung Carcinoma AJCC v7
  • Stage IIIA Non-Small Cell Lung Cancer AJCC v7

Interventions

DrugSynonymsArms
NivolumabBMS-936558, MDX-1106, NIVO, ONO-4538, OpdivoArm I (nivolumab)

Purpose

This randomized phase III trial studies how well nivolumab after surgery and chemotherapy work in treating patients with stage IB-IIIA non-small cell lung cancer. Monoclonal antibodies, such as nivolumab, may stimulate the immune system in different ways and kill tumor cells remaining after surgery and standard of care chemotherapy.

Detailed Description

      PRIMARY OBJECTIVES:

      I. To evaluate whether adjuvant therapy with nivolumab will result in improved overall
      survival (OS) and/or disease-free survival (DFS) over standard observation in patients with
      stage IB >= 4 cm, II and IIIA, non-small cell lung cancer (NSCLC) following surgical
      resection and standard adjuvant therapy.

      SECONDARY OBJECTIVES:

      I. To evaluate the safety profile of nivolumab when given as an adjuvant therapy.

      II. To evaluate and compare disease free and overall survival in patients with tumors that
      express programmed cell death ligand (PD-L)1 in various patterns associated with nivolumab
      and standard observation.

      III. To evaluate and compare disease free and overall survival in patients with tumors that
      have high mutational load associated with nivolumab and standard observation.

      IV. To evaluate OS and DFS by stage. V. To evaluate OS and DFS by each stratification factor.
      VI. To evaluate the proportion of patients alive and progression free at 1 year, 2 years, and
      5 years (OS and DFS rate).

      OUTLINE: Patients are randomized to 1 of 2 treatment arms.

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

      ARM II: Patients are followed serially with imaging.

      After completion of study treatment, patients are followed up at 6 weeks, every 3 months for
      2 years, every 6 months for 2 years, and then every 12 months for 6 years.
    

Trial Arms

NameTypeDescriptionInterventions
Arm I (nivolumab)ExperimentalPatients receive nivolumab IV over 30 minutes on day 1. Courses repeat every 2 weeks for up to 1 year in the absence of disease progression or unacceptable toxicity.
    Arm II (observation)No InterventionPatients are followed serially with imaging.

      Eligibility Criteria

              Inclusion Criteria:
      
                -  Patients must have undergone complete surgical resection of their stage IB (>= 4 cm),
                   II or IIIA NSCLC according to the American Joint Committee on Cancer (AJCC) 7th
                   edition and have had negative surgical margins
      
                -  Baseline chest computed tomography (CT) must be performed within 1 month (30 days) of
                   randomization to ensure no evidence of disease; if clinically indicated, additional
                   imaging studies must be performed to rule out metastatic disease
      
                -  Eastern Cooperative Oncology Group (ECOG) performance status 0-1
      
                -  Patients must be registered to the ALCHEMIST-SCREEN (ALLIANCE A151216) trial prior to
                   randomization
      
                -  Non-squamous tumors must be epidermal growth factor receptor (EGFR) and anaplastic
                   lymphoma receptor tyrosine kinase (ALK) wild-type (results ascertained in centrally as
                   part of ALCHEMIST-SCREEN protocol)
      
                -  Tumors must have PD-L1 status tested centrally as part of the ALCHEMIST-SCREEN
                   protocol
      
                -  Women must not be pregnant or breast-feeding
      
                -  All females of childbearing potential must have a blood test or urine study within 2
                   weeks prior to registration to rule out pregnancy; a female of childbearing potential
                   is any woman, regardless of sexual orientation or whether they have undergone tubal
                   ligation, who meets the following criteria: 1) has not undergone a hysterectomy or
                   bilateral oophorectomy; or 2) has not been naturally postmenopausal for at least 24
                   consecutive months (i.e., has had menses at any time in the preceding 24 consecutive
                   months)
      
                -  Women of childbearing potential and sexually active males must be strongly advised to
                   use an accepted and effective method of contraception or to abstain from sexual
                   intercourse during the treatment period and for 31 weeks after the last nivolumab
                   infusion
      
                -  Patients must NOT have uncontrolled intercurrent illness including, but not limited
                   to, serious ongoing or active infection, symptomatic congestive heart failure,
                   unstable angina pectoris, uncontrolled cardiac arrhythmia, or psychiatric
                   illness/social situation that would limit compliance with study requirements
      
                -  No prior treatment with an immune checkpoint inhibitor (anti-programmed cell death
                   [PD]-1, anti-PD-L1, anti-cytotoxic T-lymphocyte-associated protein 4 [CTLA4]
                   monoclonal antibody)
      
                -  Patients must have adequately recovered from surgery and chemotherapy at the time of
                   randomization
      
                     -  Minimum time between date of surgery and randomization is 4 weeks (28 days)
      
                     -  Maximum time allowed between surgery and randomization:
      
                          -  3 months (90 days) if no chemotherapy is administered
      
                          -  8 months (240 days) if adjuvant chemotherapy was administered
      
                          -  10 months (300 days) if adjuvant chemotherapy and radiation therapy was
                             administered
      
                -  Patients must have completed and recovered from any adjuvant chemotherapy 2 or more
                   weeks prior to randomization (6 weeks for mitomycin and nitrosoureas; 4 weeks for
                   post-operative radiation therapy)
      
                -  Serum aspartate transaminase (aspartate aminotransferase [AST]) and serum alanine
                   transaminase (alanine aminotransferase [ALT]) =< 2.5 x upper limit normal
      
                -  Total bilirubin =< 1.5 x upper limit of normal (ULN) (except in subjects with Gilbert
                   syndrome who must have a total bilirubin < 3.0 x ULN)
      
                -  White blood cell (WBC) >= 2000/uL
      
                -  Neutrophils >= 1000/uL
      
                -  Platelets >= 100 x 10^3/uL
      
                -  Hemoglobin >= 8 g/dL
      
                -  Serum creatinine =< 2 x ULN
      
                -  Prior to randomization patients with any non-hematologic toxicity from surgery,
                   chemotherapy and radiation therapy must have recovered to grade =< 1 with the
                   exception of alopecia, ototoxicity and neuropathy
      
                -  Patients must not be receiving any other investigational anti-cancer agents while on
                   study
      
                -  Patients must not have known or suspected autoimmune disease; subjects with type I
                   diabetes mellitus, hypothyroidism requiring hormone replacement, or skin disorders not
                   requiring systemic treatment are permitted to enroll
      
                -  Patients must not have a condition requiring systemic corticosteroids equivalent to >
                   10 mg prednisone per day or other immunosuppressive medications within 2 weeks of
                   randomization
      
                -  Patients must not have known interstitial lung disease that is symptomatic or may
                   interfere with the detection or management of suspected drug-related pulmonary
                   toxicity
      
                -  Patients must not have a known history of human immunodeficiency virus (HIV),
                   hepatitis B, or hepatitis C infection that is untreated and/or with a detectable viral
                   load
      
                -  Patients must not have a history of allergic reactions attributed to compounds of
                   similar chemical or biologic composition to nivolumab
            
      Maximum Eligible Age:N/A
      Minimum Eligible Age:18 Years
      Eligible Gender:All
      Healthy Volunteers:No

      Primary Outcome Measures

      Measure:Overall survival
      Time Frame:Time from randomization to death from any cause, assessed up to 10 years
      Safety Issue:
      Description:OS distributions will be estimated using the Kaplan-Meier method, and Cox proportional hazards models will be used to estimate the treatment hazard ratios. The primary comparisons of OS will use a logrank tests stratified on the randomization stratification factors with a one-sided type I error rate of 2.0% for OS. Other comparisons of groups will be made using the logrank test and Cox modeling. Point estimates of all endpoints will be accompanied by the corresponding confidence intervals adjusted for the type I error rates associated with the endpoint. Subset analyses are planned for all stratification factors and all known prognostic factors such as performance status, age, gender, etc.

      Secondary Outcome Measures

      Measure:Incidence of toxicity graded according to Common Terminology Criteria for Adverse Events version 4.0
      Time Frame:Up to 10 years
      Safety Issue:
      Description:Toxicity rates will be compared using Fisher's exact tests with a one-sided type I error rate of 2.5%; multivariable logistic regression modeling will be used to adjust for the effect of any covariates that are associated with these categorical outcomes. Point estimates of all endpoints will be accompanied by the corresponding confidence intervals adjusted for the type I error rates associated with the endpoint. Subset analyses are planned for all stratification factors and all known prognostic factors such as performance status, age, gender, etc.

      Details

      Phase:Phase 3
      Primary Purpose:Interventional
      Overall Status:Recruiting
      Lead Sponsor:National Cancer Institute (NCI)

      Last Updated

      March 2, 2018