This phase I trial studies the side effects and best dose of atezolizumab that can be given together with stereotactic body radiation therapy (SBRT) in treating patients with stage I non-small cell lung cancer that cannot be removed by surgery. Monoclonal antibodies, such as atezolizumab, may interfere with the ability of tumor cells to grow and spread. Radiation therapy uses high energy x-rays to kill tumor cells and shrink tumors. Stereotactic body radiation therapy is a specialized radiation therapy that delivers a single, high dose of radiation directly to the tumor and may kill more tumor cells and cause less damage to normal tissue. Giving atezolizumab together with stereotactic body radiation therapy may kill more tumor cells and be a better treatment for non-small cell lung cancer that cannot be removed by surgery.
PRIMARY OBJECTIVES: I. To determine the maximum tolerated dose (MTD) of MPDL3280A (atezolizumab) that can be given with stereotactic ablative radiotherapy (SAR) (stereotactic body radiation therapy) in patients with inoperable stage I non-small cell lung cancer (NSCLC). SECONDARY OBJECTIVES: I. To characterize the safety profile of this regimen using CTCAE v4 (Common Toxicity Criteria for Adverse Events version 4). II. To provide preliminary efficacy data of the combination as determine by objective response rate and disease free survival using RECIST 1.1 (Response Evaluation Criteria for Solid Tumors) and Immune Related RECIST (irRECIST). TERTIARY OBJECTIVES: I. To analyze serial blood for change in cytokine signatures, fluorescence activated cell sorting (FACS) and immunophenotyping of peripheral blood mononuclear cells (PBMCs) and tumor infiltrating immune cells. II. To evaluate pre and post treatment tumor tissue (if available) for programmed cell death-ligand 1 (PD-L1) and other immune proteins in the tumor and tumor microenvironment and for molecular profiling in a subset of patient samples. III. To discover biomarkers of response from the data obtained. OUTLINE: This is a dose-escalation study of atezolizumab. DOSE ESCALATION PHASE: Patients receive atezolizumab intravenously (IV) over 30-60 minutes on day 1. Treatment repeats every 3 weeks for 6 courses in the absence of disease progression or unacceptable toxicity. Within 24-48 hours after receiving atezolizumab, patients also undergo 4-5 fractions of stereotactic body radiation therapy over days 1-5 of course 3. EXPANSION PHASE: Patients receive atezolizumab IV over 30-60 minutes on day 1. Courses repeat every 3 weeks in the absence of disease progression or unacceptable toxicity. Within 24-48 hours after receiving atezolizumab, patients also undergo 4-5 fractions of stereotactic body radiation therapy over days 1-5 of course 3. After completion of study treatment, patients are followed up at 30 days, every 3 months for 2 years, and then every 6 months for 3 years.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
20
Into the vein Day 1 every 3 weeks for 6 cycles
Radiation therapy will be performed to 50 Gy over 4 fractions of 12/5 Gy each for peripherally located tumors and 50 Gy over 5 fractions of 10 Gy each for centrally located tumors
University of California Davis Comprehensive Cancer Center
Sacramento, California, United States
David Grant United States Air Force Medical Center
Travis AFB, California, United States
Maximum Tolerated Dose
The adverse events will be summarized as frequency, proportion of patients MTD. The exact 95% confidence interval for proportion will be categorized by type, severity, nadir or maximum values for the laboratory measures, time of onset, duration, and reversibility or outcome. Tables will be created to summarize these toxicities by dose and course.
Time frame: 9 weeks
Disease free survival (DFS), assessed by RECIST 1.1 and irRECIST
DFS will be summarized with Kaplan-Meier plots. The median DFS time will be estimated using standard life table methods.
Time frame: Up to 5 years
Overall response rate (ORR), assessed by RECIST 1.1
ORR will be summarized by exact binomial confidence intervals.
Time frame: Time from the start of the treatment until disease progression/recurrence, assessed up to 5 years
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