This phase I/II trial tests the safety and efficacy of split-course adaptive radiation therapy in combination with immunotherapy with or without chemotherapy for the treatment of patients with stage IV lung cancer or lung cancer that that has spread to nearby tissue or lymph nodes (locally advanced). Radiation therapy is a standard cancer treatment that uses high energy rays to kill cancer cells and shrink tumors. Split-course adaptive radiation therapy uses patient disease response to alter the intensity of the radiation therapy. Immunotherapy with monoclonal antibodies such as pembrolizumab, ipilimumab, cemiplimab, atezolizumab or nivolumab may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Chemotherapy drugs like carboplatin, pemetrexed, and paclitaxel work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving split-course adaptive radiation therapy with standard treatments like immunotherapy and chemotherapy may be more effective at treating stage IV or locally advanced lung cancer than giving them alone.
Age >= 18 years at time of informed consent
• Histologically documented or cytologically confirmed diagnosis of stage IVA or IVB (M1b or M1c) or locally advanced (not eligible for standard of care [SOC] chemoradiation) non-small cell lung cancer with evaluable disease per Response Evaluation Criteria in Solid Tumors (RECIST) version (v) 1.1 criteria
Available tumor material (< 6 months old) adequate for confirmation of programmed cell death 1 ligand 1 (PD-L1) expression per local standard of care testing
Eastern Cooperative Oncology Group (ECOG) performance status of 0-2
Mixed small cell histology
Confirmed candidate (per study physician) for alternative systemic therapy if preferred by treating physician (i.e. mEGFR, ALK, KRAS G12C or ROS1 mutations). Testing not required for enrollment
Brain metastases that would require administration of whole brain radiotherapy for management on required screening brain MRI within 21 days of day 1 of study treatment
Symptomatic malignant ascites or malignant pleural effusion (sampling not required). Pleural metastases are allowed if deemed targetable with radiotherapy
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Treatment groupsSee each treatment group below.
Vanderbilt-Ingram Cancer Center
Lead sponsor
National Cancer Institute (NCI)
Collaborator
Varian Medical Systems
Collaborator