This phase III trial studies how well chemotherapy and radiation therapy (chemoradiation) with or without atezolizumab works in treating patients with limited stage small cell lung cancer. Drugs used in chemotherapy, such as etoposide, cisplatin, and carboplatin, 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. Radiation therapy uses high energy x-rays to kill tumor cells and shrink tumors. Immunotherapy with monoclonal antibodies, such as atezolizumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Giving chemoradiation with or without atezolizumab may work better in treating patients with limited stage small cell lung cancer.
PRIMARY OBJECTIVE: I. To compare overall survival (OS) for patients with LS-SCLC treated with chemoradiation +/- atezolizumab. SECONDARY OBJECTIVES: I. To compare progression free survival (PFS) for patients with limited stage small cell lung cancer (LS-SCLC) treated with chemoradiation +/- atezolizumab. II. To determine overall response rate (ORR), rates of local control, and distant metastases free survival with chemoradiation +/- atezolizumab. III. To characterize immune mediated and non-immune mediated toxicity from chemoradiotherapy plus atezolizumab. IV. To compare quality of life, as measured by the Functional Assessment of Cancer Therapy-Trial Outcome Index (FACT-TOI), for patients undergoing chemoradiation +/- atezolizumab. V. To evaluate the quality-adjusted survival, using scores from the 5-level EuroQol 5-dimensional questionnaire (EQ-5D-5L), of chemoradiation +/- atezolizumab for patients with LS-SCLC. VI. To characterize fatigue, as measured by the Patient-Reported Outcomes Measurement Information System (PROMIS), following chemoradiation +/- atezolizumab. VII. To determine the association of small cell lung cancer (SCLC) molecular subtypes with clinical outcomes. EXPLORATORY OBJECTIVES: I. To collect biospecimens at baseline, day 1 and 3 months after the end of chemoradiotherapy, to allow for future analyses. II. To characterize patient-reported symptomatic toxicities measured by the Patient-Reported Outcomes - Common Terminology Criteria for Adverse Events (PRO-CTCAE). III. To characterize the concordance between tumor and circulating cell-free deoxyribonucleic acid (cfDNA)-determined molecular subtypes. OUTLINE: Patients are randomized to 1 of 2 arms. ARM I: Patients receive etoposide intravenously (IV) on days 1-3 and cisplatin IV or carboplatin IV on day 1. Cycles repeat every 21 days for 3 cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo three-dimensional conformal radiation therapy (3D-CRT) or intensity-modulated radiation therapy (IMRT) twice daily (BID) for approximately 3 weeks or once daily (QD) for approximately 6-7 weeks in the absence of disease progression or unacceptable toxicity. Patients undergo blood specimen collection throughout the trial. ARM II: Patients receive treatment as in Arm I. Patients also receive atezolizumab IV over 30-60 minutes on day 1 or 2 of each chemotherapy cycle. Cycles repeat every 3 weeks for 17 cycles (1 year) in the absence of disease progression or unacceptable toxicity. Patients undergo blood specimen collection throughout the trial. After completion of study treatment, patients are followed up every 3 months for 2 years, then every 6 months for 3 years, then annually thereafter.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
544
Undergo 3D-CRT
Given IV
Correlative studies
Given IV
Given IV
Given IV
Undergo IMRT
Ancillary studies
Ancillary studies
University of Alabama at Birmingham Cancer Center
Birmingham, Alabama, United States
Fairbanks Memorial Hospital
Fairbanks, Alaska, United States
Banner MD Anderson Cancer Center
Gilbert, Arizona, United States
CTCA at Western Regional Medical Center
Goodyear, Arizona, United States
Banner University Medical Center - Tucson
Tucson, Arizona, United States
Overall Survival
Survival rates and median survival time are estimated using the Kaplan-Meier method, censoring participants alive at time of analysis.
Time frame: Randomization to date of death due or last follow-up. Median follow-up at the time of analysis was 23.8 months.
Progression Free Survival (PFS)
PFS failure event is defined as progressive disease (PD) determined by investigator per the Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 or death due to any cause. PD is defined as at least a 20% increase in the sum of longest diameters of target lesions, and an absolute increase of at least 5 mm. The appearance of any new lesions is also considered progression. PFS rates and median PFS time are estimated using the Kaplan-Meier method, censoring participants alive without progression at the date of their last evaluable radiographic tumor assessment.
Time frame: From randomization to progression or death due to any cause, whichever occurs first, or last tumor assessment if alive. MMedian follow-up at the time of analysis was 23.8 months.
Number of Participants by Highest Grade Adverse Event Reported
Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 grades adverse event severity as follows: 1 = mild, 2 = moderate, 3 = severe, 4 = life-threatening, 5 = death related to adverse event. Summary data is provided in this outcome measure; see Adverse Events Module for specific adverse event data.
Time frame: Randomization to last follow-up. Median follow-up at the time of analysis was 23.8 months.
Percentage of Participants With Confirmed Objective Response (Objective Response Rate (ORR))
Objective response rate (ORR) is defined as the proportion of subjects whose best overall response (BOR) is a confirmed complete or partial response as determined by the investigator according to Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 on two consecutive occasions ≥4 weeks apart.
Time frame: Randomization to last radiographic tumor assessment. Median follow-up at the time of analysis was 23.8 months.
Percentage of Participants With Local Progression
Local progression is defined as intrathoracic tumor progression (failure in the lobe of the primary tumor or mediastinal lymph nodes) by RECIST 1.1 criteria determined by the investigator. Local progression rates are estimated by the cumulative incidence method, treating non-local progression (i.e., distant metastasis or failure in a different lung) and death without local progression as competing risks, and otherwise censoring participants alive at last tumor assessment. Treatment effect comparisons will utilize a cause-specific hazard function in which competing risks are censored.
Time frame: From randomization to local progression, other progression, or death, whichever occurs first, or last tumor assessment if alive. Median follow-up at the time of analysis was 23.8 months. 1-, 2-, and 3-year rates are reported.
Distant Metastases-free Survival (DMFS)
DMFS failure event is defined as first date of documented distant metastases (or failures in a different lung lobe) or death due to any cause, whichever occurs first. Participants with local progression prior to such an event are censored on the date of local progression. Participants with no post-baseline tumor assessment and alive at last follow-up are censored on the date of randomization. Participants alive without distant metastasis, failures in a different lung lobe, or local progression are censored on the date of their last evaluable radiographic tumor assessment. DMFS rates and median DMFS time are estimated using the Kaplan-Meier method.
Time frame: Randomization to DMFS event or local progression, whichever occurs first, or last tumor assessment if alive. Median follow-up at the time of analysis was 23.8 months.
Percent of Participants With Deterioration in Functional Assessment of Cancer Therapy-Trial Outcome Index (FACT-TOI)
FACT-TOI is a measure of 21 items that sums the functional well-being (FWB), physical well-being (PWB), and the lung cancer subscale (LCS) of the Functional Assessment of Cancer Therapy - Lung (FACT-L) quality of life (QOL) instrument. The FACT-TOI total score ranges from 0 to 84 with higher scores indicating better quality of life and functioning. Clinically meaningful decline is defined as a decrease from baseline of at least 5 points.
Time frame: Baseline and 15 months after completion of chemoradiation (approximately 18 months after randomization)
Quality-adjusted Survival Months
Quality-adjusted survival is calculated as the sum of weighted time intervals. Weight is the EuroQol 5-dimensional 5-level (EQ-5d-5L) index score, which measures health-related quality of life and ranges from 0 (death) to 1 (full health).
Time frame: Baseline to death, last follow-up or two years, whichever occurs first.
Change From Baseline in the 7 Item Patient Reported Outcomes Measurement Information System (PROMIS) Fatigue Short Form Score
The PROMIS fatigue score measures self-reported fatigue symptoms over the past 7 days. Possible scores range from 29.4 to 83.2, with higher scores indicating more fatigue. Change score is calculated by subtracting baseline from later score, with a positive change score indicating increased fatigue.
Time frame: Baseline and 15 months after completion of chemoradiation (approximately 18 months after randomization)
Molecular Subtyping
Time frame: Up to 5 years
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University of Arizona Cancer Center-North Campus
Tucson, Arizona, United States
NEA Baptist Memorial Hospital and Fowler Family Cancer Center - Jonesboro
Jonesboro, Arkansas, United States
University of Arkansas for Medical Sciences
Little Rock, Arkansas, United States
Sutter Auburn Faith Hospital
Auburn, California, United States
Alta Bates Summit Medical Center-Herrick Campus
Berkeley, California, United States
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