This phase II trial studies how well radical-dose image guided radiation therapy works in treating patients with non-small cell lung cancer that has spread to other places in the body who are undergoing immunotherapy. Radiation therapy uses high energy x-rays to kill tumor cells and shrink tumors. Giving radical-dose image guided radiation therapy to patients with non-small cell lung cancer may help to improve response to immunotherapy anti-cancer treatment.
PRIMARY OBJECTIVES: I. Determine if progression-free survival at 24 weeks with this treatment combination is improved compared to historical controls who received immunotherapy without radiation therapy. SECONDARY OBJECTIVES: I. Assess acute (0-6 months) and late (\> 6 months) grade 3-5 toxicity. II. Assess overall survival. III. Correlate circulating tumor deoxyribonucleic acid (DNA) (ratio of post-radiation therapy \[RT\] to pre-RT level) with radiographic response. IV. Correlate immune markers in peripheral blood with radiographic response. TERTIARY OBJECTIVES: I. Analyze progression-free survival with immune-related response criteria. II. Measure time to discontinuation of study immunotherapy agent. III. Assess patterns of progression. OUTLINE: Patients are assigned to 1 of 2 arms. ARM I: Patients undergo radical-dose image guided radiation therapy daily for up to 10 days (within 2 weeks) while undergoing standard of care immunotherapy. Arm II: Patients who decline to undergo radiation therapy receive standard of care immunotherapy. After completion of study treatment, patients are followed up at 30 days and every 6 months thereafter.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
45
Ablative treatment as 50 Gy in 5 or 10 fractions. Non-ablative treatment as 27 Gy in 3 fractions, or 40 Gy in 10 fractions.
Continue regular medical care immunotherapy. Other than being an anti-PD-1 or anti-PD-L1 immunotherapy, the agent, dose, and schedule is not specified by protocol.
Stanford University, School of Medicine
Palo Alto, California, United States
Progression-free Survival
Defined as percentage of participants without disease progression or death at 24 weeks from date of study entry, assessed per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. Complete Response (CR): Disappearance of all target lesions Partial Response (PR): ≥30% decrease in the sum of the longest diameter of target lesions Overall Response (OR): CR + PR
Time frame: 24 weeks from study entry
Change in Circulating Tumor Deoxyribonucleic Acid Levels as Measured Using CAncer Personalized Profiling by Deep Sequencing
Will correlate with radiographic response. Plasma biomarkers (e.g. cell free deoxyribonucleic acid level) will be summarized using medians and interquartile ranges; changes in biomarkers will be assessed using the Wilcoxon signed rank test. Correlation of biomarkers with radiographic response will be evaluated using a Wilcoxon rank sum test on patients with and without the event of interest. If feasible, these analyses will be supplemented by more formal analyses with the Cox model.
Time frame: Baseline (pre-treatment)
Change in Immune Marker Levels as Measured From Peripheral Blood Using Flow Cytometry Performed by the Human Immune Monitoring Core at Stanford University
Change in immune marker levels was measured using flow cytometry performed by the Human Immune Monitoring Core at Stanford University. These changes will correlate with radiographic response.
Time frame: Pre-radiation (up to 14 days before RT) and post-radiation (up to 14 days after completion of RT)
Number of Participants With Acute (0-6 Months) and Late (> 6 Months) Grade 3-5 Toxicity
This outcome measured the number of participants who experienced Grade 3-5 acute (0-6 months) and late (\>6 months) toxicities, assessed using the Common Terminology Criteria for Adverse Events (CTCAE) version 4, through up to 4 years after study entry.
Time frame: Up to 4 years after study entry
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Overall Survival
The electronic medical record was monitored for patient deaths.
Time frame: Time from study entry to death, assessed up to 4 years after study entry