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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) (ANVIL)

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ClinicalTrials.gov Identifier: NCT02595944
Recruitment Status : Active, not recruiting
First Posted : November 4, 2015
Last Update Posted : October 7, 2019
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)

Tracking Information
First Submitted Date  ICMJE November 3, 2015
First Posted Date  ICMJE November 4, 2015
Last Update Posted Date October 7, 2019
Actual Study Start Date  ICMJE May 6, 2016
Estimated Primary Completion Date July 1, 2024   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: March 11, 2019)
  • 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 ]
    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.
  • Overall survival (OS) [ Time Frame: Time from randomization to death from any cause, assessed up to 10 years ]
    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 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.
Original Primary Outcome Measures  ICMJE
 (submitted: November 3, 2015)
  • Disease-free survival [ Time Frame: Time from randomization to the earliest event defined as disease any new lung cancer confirmed by biopsy, or death from any cause at any known point in time, assessed up to 10 years ]
    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 of 0.5% for DFS. 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 s
  • Overall survival [ Time Frame: Time from randomization to death from any cause, assessed up to 10 years ]
    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 stra
Change History Complete list of historical versions of study NCT02595944 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: May 31, 2018)
Incidence of toxicity graded according to Common Terminology Criteria for Adverse Events version 5.0 [ Time Frame: Up to 10 years ]
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.
Original Secondary Outcome Measures  ICMJE
 (submitted: November 3, 2015)
Incidence of toxicity graded according to Common Terminology Criteria for Adverse Events version 4.0 [ Time Frame: Up to 10 years ]
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.
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Nivolumab After Surgery and Chemotherapy in Treating Patients With Stage IB-IIIA Non-small Cell Lung Cancer (An ALCHEMIST Treatment Trial)
Official Title  ICMJE 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
Brief Summary 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.
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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • 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
Intervention  ICMJE Biological: Nivolumab
Given IV
Other Names:
  • BMS-936558
  • MDX-1106
  • NIVO
  • ONO-4538
  • Opdivo
Study Arms  ICMJE
  • Experimental: Arm I (nivolumab)
    Patients 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.
    Intervention: Biological: Nivolumab
  • No Intervention: Arm II (observation)
    Patients are followed serially with imaging for 1 year.
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 Active, not recruiting
Estimated Enrollment  ICMJE
 (submitted: March 11, 2019)
903
Original Estimated Enrollment  ICMJE
 (submitted: November 3, 2015)
714
Study Completion Date  ICMJE Not Provided
Estimated Primary Completion Date July 1, 2024   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
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 United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02595944
Other Study ID Numbers  ICMJE NCI-2015-01916
NCI-2015-01916 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
EA5142
s16-02074
EA5142 ( Other Identifier: ECOG-ACRIN Cancer Research Group )
EA5142 ( Other Identifier: CTEP )
U10CA180820 ( U.S. NIH Grant/Contract )
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party National Cancer Institute (NCI)
Study Sponsor  ICMJE National Cancer Institute (NCI)
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Jamie E Chaft ECOG-ACRIN Cancer Research Group
PRS Account National Cancer Institute (NCI)
Verification Date October 2019

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