This phase II trial studies how well platinum-based chemotherapy works when given together with durvalumab in treating patients with stage IIIB or stage IV non-small cell lung cancer. Drugs used in chemotherapy, such as carboplatin, paclitaxel, and pemetrexed, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. 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 purpose of this study is to find out if the combination of chemotherapy in combination with the immune therapy drug durvalumab would be efficacious and have an acceptable toxicity profile in patients with advanced non-small cell lung cancer.
PRIMARY OBJECTIVE: I. To determine the 6-months progression-free survival (PFS) rate with the combination of dose attenuated doublet chemotherapy with durvalumab in advanced non-small cell lung cancer (NSCLC) patients with Eastern Cooperative Oncology Group (ECOG) performance status (PS) 2 status or age \>= 70. SECONDARY OBJECTIVES: I. To investigate overall response rate. II. To determine the safety profile of the regimen. III. To determine the median PFS and overall survival. EXPLORATORY OBJECTIVE: I. Exploratory investigation of biomarkers that could potentially serve as predictive indicators: characterize immunoprofile in peripheral blood by flow cytometry. OUTLINE: Patients are assigned to 1 of 2 arms. ARM I (SQUAMOUS NSCLC): Patients receive carboplatin intravenously (IV) over 15-60 minutes, paclitaxel IV over 3 hours and durvalumab IV over 1 hour on day 1. Treatment repeats every 3 weeks for up to 4 cycles in the absence of disease progression or unacceptable toxicity. Patients who do not progress receive durvalumab IV every 4 weeks for up to 35 cycles in the absence of disease progression or unacceptable toxicity. ARM II (NON-SQUAMOUS NSCLC): Patients receive carboplatin IV over 15-60 minutes, pemetrexed IV over 10 minutes and durvalumab IV over 1 hour on day 1. Treatment repeats every 3 weeks for up to 4 cycles in the absence of disease progression or unacceptable toxicity. Patients who do not progress receive durvalumab IV and pemetrexed IV every 3 weeks for up to 35 cycles in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up every 3 months.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
6-months progression-free survival (PFS) rate
Will be calculated as proportion along with 95% confidence intervals (CI) using the Clopper-Pearson method. Chi-square test or Fisher's exact test will be used to compare the 6-months PFS rate between the different groups stratified by different factors, respectively. Logistics regression model will be further employed to test the adjusted effect of each factor on 6-month PFS rate after adjusting for other clinical factors and demographic factors.
Time frame: 6 months
Overall survival (OS)
Will be estimated with the Kaplan-Meier method and compared between different groups using the log-rank test, respectively. The OS of each patient group at specific time points, such as 6 months, 1 year, 3 year, and 5 year, etc. will be also estimated alone with 95% CI. Cox proportional hazards models will be further used in the multivariable analyses to assess adjusted effect of dose levels on the patients' OS after adjusting for other factors. Interaction terms between these factors will also be tested for statistical significance. The proportional hazards assumption will be evaluated graphically and analytically with regression diagnostics. Violations of the proportional hazards assumptions will be addressed by use of time-dependent covariates or extended Cox regression models.
Time frame: Up to 5 years
PFS
Will be estimated with the Kaplan-Meier method and compared between different groups using the log-rank test, respectively. The PFS of each patient group at specific time points, such as 6 months, 1 year, 3 year, and 5 year, etc. will be also estimated alone with 95% CI. Cox proportional hazards models will be further used in the multivariable analyses to assess adjusted effect of dose levels on the patients' PFS after adjusting for other factors. Interaction terms between these factors will also be tested for statistical significance. The proportional hazards assumption will be evaluated graphically and analytically with regression diagnostics. Violations of the proportional hazards assumptions will be addressed by use of time-dependent covariates or extended Cox regression models.
Time frame: Up to 5 years
Incidence of adverse events (AEs)
Safety profile of the regimen will be listed and summarized overall and by prognostic factor. Adverse events will also be listed by severity, seriousness, and by system organ class. The number and percentage of subjects who experience AEs will be presented in tabular and/or graphical format and summarized descriptively, where appropriate. No formal statistical comparison between the different factors will be performed. AEs will be presented with and without regard to causality based on the investigator's judgment. The frequency of overall toxicity, categorized by toxicity grades 1 through 5, will be described. Additional summaries will be provided for AEs that are observed with higher frequency.
Time frame: Up to 90 days post treatment
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