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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 treatment 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:

Active, not 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 (An ALCHEMIST Treatment Trial)
  • 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 Lung Non-Small Cell Carcinoma AJCC v7
  • Stage II Lung Non-Small Cell Cancer AJCC v7
  • Stage IIA Lung Non-Small Cell Carcinoma AJCC v7
  • Stage IIB Lung Non-Small Cell Carcinoma AJCC v7
  • Stage IIIA Lung Non-Small Cell Cancer AJCC v7

Interventions

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

Purpose

This phase III ALCHEMIST treatment 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.

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.

      II. To evaluate whether adjuvant therapy with nivolumab will result in improved disease-free
      survival (DFS) over standard observation in patients with stage IB >= 4cm, II and IIIA, NSCLC
      with high PD-L1 expression (>= 50% staining) following surgical resection and standard
      adjuvant therapy.

      III. To evaluate whether adjuvant therapy with nivolumab will result in improved overall
      survival (OS) over standard observation in patients with stage IB >= 4cm, II and IIIA, 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.

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

      ARM I: Patients receive nivolumab intravenously (IV) over 30 minutes on day 1. Cycles repeat
      every 4 weeks for up to 1 year in the absence of disease progression or unacceptable
      toxicity.

      ARM II: Patients are followed serially with imaging for 1 year.

      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. Cycles repeat every 4 weeks for up to 1 year in the absence of disease progression or unacceptable toxicity.
  • Nivolumab
Arm II (observation)No InterventionPatients are followed serially with imaging for 1 year.

    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 not be positive for epidermal growth factor receptor (EGFR)
                 exon 19 deletion or exon 21 L858R mutation (centrally as part of the ALCHEMIST-SCREEN
                 protocol) and anaplastic lymphoma receptor tyrosine kinase (ALK) rearrangement
                 (centrally as part of ALCHEMIST-SCREEN and/or locally)
    
                   -  NOTE: if the results of the central EGFR testing are negative, but the ALK
                      testing was not able to be completed by the ALCHEMIST central lab, the ALK status
                      will be considered negative (unless locally positive for ALK rearrangement) and
                      the patient may be considered for enrollment onto EA5142, once PD-L1 results are
                      received and all other eligibility requirements are met
    
              -  Tumors must have PD-L1 status tested centrally as part of the ALCHEMIST-SCREEN
                 protocol
    
              -  Women must not be pregnant or breast-feeding due to unknown and potentially harmful
                 effects of nivolumab on the developing fetus or child
    
              -  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 any administered
                 chemotherapy/radiotherapy at the time of randomization (NOTE: adjuvant chemotherapy
                 and/or radiation is not required)
    
                   -  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) (NOTE: adjuvant chemotherapy and/or radiation is not
                 required)
    
              -  Serum aspartate transaminase (aspartate aminotransferase [AST]) and serum alanine
                 transaminase (alanine aminotransferase [ALT]) =< 2.5 x upper limit normal (within 2
                 weeks prior to randomization)
    
              -  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) (within 2 weeks prior to
                 randomization)
    
              -  White blood cell (WBC) >= 2000/uL (within 2 weeks prior to randomization)
    
              -  Neutrophils >= 1000/uL (within 2 weeks prior to randomization)
    
              -  Platelets >= 100 x 10^3/uL (within 2 weeks prior to randomization)
    
              -  Hemoglobin >= 8 g/dL (within 2 weeks prior to randomization)
    
              -  Serum creatinine =< 2 x ULN (within 2 weeks prior to randomization)
    
              -  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; inhaled, intra-articular, and epidural steroids are permissible
    
              -  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:Disease-free survival (DFS)
    Time Frame:Time from randomization to the earliest event defined as disease recurrence, any new lung cancer (even in the opposite lung), or death from any cause at any known point in time, assessed up to 10 years
    Safety Issue:
    Description:DFS 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 DFS will use a logrank tests stratified on the randomization stratification factors with a one-sided type I error rate corresponding to the significance level associated with population being analyzed; that is, 1.5% for the overall population and 1% for the >= 50% population. The latter test will only be performed in the event that the primary test in all-comers is not statistically significant. 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 5.0
    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:Active, not recruiting
    Lead Sponsor:National Cancer Institute (NCI)

    Last Updated

    March 19, 2021