This phase III trial compares durvalumab to the usual approach (patient observation) after surgery for the treatment of patients with early-stage non-small cell lung cancer. Immunotherapy with monoclonal antibodies, such as durvalumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. The usual approach for patients who are not in a study is to closely watch a patient's condition after surgery and to have regular visits with their doctor to watch for signs of the cancer coming back. Usually, patients do not receive further treatment unless the cancer returns. This study will help determine whether this different approach with durvalumab is better, the same, or worse than the usual approach of observation. Giving durvalumab may help patients live longer and prevent early-stage non-small cell lung cancer from coming back as compared to the usual approach.
PRIMARY OBJECTIVE: I. To compare disease free survival (DFS) in stage II-IIIB non-small cell lung cancer participants who achieved a pathologic complete response (pCR) following standard of care neoadjuvant chemo-immunotherapy and are randomized to adjuvant durvalumab (MEDI4736) versus surveillance. SECONDARY OBJECTIVES: I. To compare the overall survival (OS) between the arms. II. To evaluate the frequency and severity of toxicities of adjuvant durvalumab (MEDI4736). III. To compare the event free survival (EFS) between the arms. TRANSLATIONAL MEDICINE OBJECTIVE: I. To bank specimens and images for additional future translational medicine studies. QUALITY OF LIFE (QOL) PRIMARY OBJECTIVE: I. To compare patient-reported quality of life (QOL) status between treatment arms at 6 months from randomization using the Functional Assessment of Cancer Therapy-Lung (FACT-L) Trial Outcome Index (TOI). QOL SECONDARY OBJECTIVES: I. To compare patient-reported QOL between treatment arms at 24 weeks (6 months) from randomization using the Functional Assessment of Cancer Therapy-Biologic Response Modifier (FACT-BRM) physical and mental subscale scores. II. To compare longitudinal changes in global health status between treatment arms from randomization to 48 week (12 months) using the FACT-L TOI. PATIENT REPORTED OUTCOMES-COMMON TERMINOLOGY CRITERIA FOR ADVERSE EVENTS (PRO-CTCAE) OBJECTIVE: I. To compare participant-reported symptoms using selected PRO-CTCAE items between treatment arms such as rash, itching, skin dryness, numbness, and tingling. OUTLINE: Patients are randomized to 1 of 2 arms. ARM I: Patients receive durvalumab intravenously (IV) over 60 minutes on day 1 of each cycle. Treatment repeats every 28 days for up to 12 cycles in the absence of disease progression or unacceptable toxicity. Patients undergo computed tomography (CT) and blood sample collection throughout the trial. ARM II: Patients undergo active surveillance for 12 months on study. Patients undergo CT and blood sample collection throughout the trial. After completion of study treatment, patients are followed up annually until 10 years from randomization.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
306
Undergo blood sample collection
Undergo CT
Given IV
Undergo active surveillance
Ancillary studies
NEA Baptist Memorial Hospital and Fowler Family Cancer Center - Jonesboro
Jonesboro, Arkansas, United States
RECRUITINGTower Cancer Research Foundation
Beverly Hills, California, United States
RECRUITINGVeterans Affairs Loma Linda Healthcare System
Loma Linda, California, United States
RECRUITINGCedars Sinai Medical Center
Los Angeles, California, United States
Disease-free survival (DFS)
Will be assessed using a 1-sided 5% level log-rank test accounting for interim testing, stratified on the randomization stratification factors.
Time frame: From date of randomization to the earliest event defined as date of first documentation of recurrence, any new lung cancer (even in the contralateral lung), or death due to any cause, assessed up to 10 years
Event-free survival (EFS)
EFS events are defined as: Discontinuation of durvalumab (MEDI4736) due to toxicity, either immune or non-immune related, any new lung cancer (even in the contralateral lung), the use of glucocorticoids for \> 14 days for the treatment of toxicity secondary to durvalumab (MEDI4736), hospitalization due to toxicity from durvalumab (MEDI4736), disease recurrence, or death due to any cause. Will be estimated using the method of Kaplan-Meier. 95% confidence for the medians will be constructed using the method of Brookmeyer-Crowley. Hazard ratios (HRs) and corresponding 90% confidence intervals (CI) will be estimated using a Cox proportional hazards model with treatment arm as a single covariate. EFS will be compared between treatment arms using log-rank test, stratified on the randomization stratification factors.
Time frame: From date of randomization to date of first occurrence of EFS event, assessed up to 10 years
Overall survival (OS)
Will be estimated using the method of Kaplan-Meier. 95% confidence for the medians will be constructed using the method of Brookmeyer-Crowley. HRs and corresponding 90% CI will be estimated using a Cox proportional hazards model with treatment arm as a single covariate. OS will be compared between treatment arms using log-rank test, stratified on the randomization stratification factors.
Time frame: From date of randomization to date of death due to any cause, assessed up to 10 years
Incidence of adverse events
Will be evaluated using the Common Terminology Criteria for Adverse Events version 5 items. Binary proportions and associated confidence intervals will be calculated.
Time frame: Up to 10 years
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University of California Davis Comprehensive Cancer Center
Sacramento, California, United States
RECRUITINGTorrance Memorial Physician Network - Cancer Care
Torrance, California, United States
RECRUITINGSaint Mary's Hospital and Regional Medical Center
Grand Junction, Colorado, United States
RECRUITINGHartford HealthCare - Avon
Avon, Connecticut, United States
RECRUITINGHartford Hospital
Hartford, Connecticut, United States
RECRUITINGHartford HealthCare - Manchester
Manchester, Connecticut, United States
RECRUITING...and 199 more locations