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.

Conditions

Eligibility

Eligible Ages
Over 18 Years
Eligible Genders
All
Accepts Healthy Volunteers
No

Criteria


Inclusion Criteria:

- Age >= 18 years

- 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 CT must be performed within 1 month (30 days) prior to 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 EGFR exon 19 deletion or exon 21 L858R
mutation (centrally as part of the ALCHEMIST-SCREEN protocol) and 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-PD-1, anti-PD-L1,
anti-CTLA4 monoclonal antibody)

- Patients must have adequately recovered from thoracic 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

Study Design

Phase
Phase 3
Study Type
Interventional
Allocation
Randomized
Intervention Model
Parallel Assignment
Primary Purpose
Treatment
Masking
None (Open Label)

Arm Groups

ArmDescriptionAssigned Intervention
Experimental
Arm I (nivolumab)
Patients receive nivolumab IV over 30 minutes on day 1 of each cycle. Cycles repeat every 4 weeks for up to 1 year in the absence of disease progression or unacceptable toxicity. Patients also undergo CT and/or PET/CT throughout the trial and blood sample collection during screening and follow-up. Patients may undergo an ECHO as clinically indicated on study.
  • Procedure: Biospecimen Collection
    Undergo blood sample collection
    Other names:
    • Biological Sample Collection
    • Biospecimen Collected
    • Specimen Collection
  • Procedure: Computed Tomography
    Undergo CT
    Other names:
    • CAT
    • CAT Scan
    • Computed Axial Tomography
    • Computerized Axial Tomography
    • Computerized axial tomography (procedure)
    • Computerized Tomography
    • Computerized Tomography (CT) scan
    • CT
    • CT Scan
    • tomography
  • Procedure: Echocardiography
    Undergo ECHO
    Other names:
    • EC
  • Biological: Nivolumab
    Given IV
    Other names:
    • ABP 206
    • BCD-263
    • BMS-936558
    • CMAB819
    • MDX-1106
    • NIVO
    • Nivolumab Biosimilar ABP 206
    • Nivolumab Biosimilar BCD-263
    • Nivolumab Biosimilar CMAB819
    • ONO-4538
    • Opdivo
  • Procedure: Positron Emission Tomography
    Undergo PET-CT
    Other names:
    • Medical Imaging, Positron Emission Tomography
    • PET
    • PET Scan
    • Positron emission tomography (procedure)
    • Positron Emission Tomography Scan
    • Positron-Emission Tomography
    • proton magnetic resonance spectroscopic imaging
    • PT
Active Comparator
Arm II (observation)
Patients are followed serially with CT and/or PET/CT imaging for up to 1 year and then during follow-up. Patients also undergo blood sample collection during screening and follow-up. Patients may undergo an ECHO as clinically indicated on study.
  • Procedure: Biospecimen Collection
    Undergo blood sample collection
    Other names:
    • Biological Sample Collection
    • Biospecimen Collected
    • Specimen Collection
  • Procedure: Computed Tomography
    Undergo CT
    Other names:
    • CAT
    • CAT Scan
    • Computed Axial Tomography
    • Computerized Axial Tomography
    • Computerized axial tomography (procedure)
    • Computerized Tomography
    • Computerized Tomography (CT) scan
    • CT
    • CT Scan
    • tomography
  • Procedure: Echocardiography
    Undergo ECHO
    Other names:
    • EC
  • Other: Observation
    Undergo observation
    Other names:
    • Inspection
    • Visual Inspection
  • Procedure: Positron Emission Tomography
    Undergo PET-CT
    Other names:
    • Medical Imaging, Positron Emission Tomography
    • PET
    • PET Scan
    • Positron emission tomography (procedure)
    • Positron Emission Tomography Scan
    • Positron-Emission Tomography
    • proton magnetic resonance spectroscopic imaging
    • PT

More Details

Status
Active, not recruiting
Sponsor
National Cancer Institute (NCI)

Study Contact

Detailed Description

PRIMARY OBJECTIVES: I. To evaluate whether adjuvant therapy with nivolumab will result in improved 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 PD-L1 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 arms. ARM I: Patients receive nivolumab intravenously (IV) over 30 minutes on day 1 of each cycle. Cycles repeat every 4 weeks for up to 1 year in the absence of disease progression or unacceptable toxicity. Patients also undergo computed tomography (CT) and/or positron emission tomography (PET)/CT throughout the trial and blood sample collection during screening and follow-up. Patients may undergo an echocardiography (ECHO) as clinically indicated on study. ARM II: Patients are followed serially with CT and/or PET/CT imaging for up to 1 year and then during follow-up. Patients also undergo blood sample collection during screening and follow-up. Patients may undergo an ECHO as clinically indicated on study. 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.

Notice

Study information shown on this site is derived from ClinicalTrials.gov (a public registry operated by the National Institutes of Health). The listing of studies provided is not certain to be all studies for which you might be eligible. Furthermore, study eligibility requirements can be difficult to understand and may change over time, so it is wise to speak with your medical care provider and individual research study teams when making decisions related to participation.