Resectable Stage IIA to IIIB Non-small Cell Lung Cancer Clinical Trial
Official title:
An Open Label, Randomized Study of Neoadjuvant Nivolumab and Chemotherapy, With or Without Sub-ablative Stereotactic Body Radiation Therapy, for Resectable Stage IIA to IIIB Non-small Cell Lung Cancer
An open label, randomized study of neoadjuvant nivolumab and chemotherapy, with or without sub-ablative stereotactic body radiation therapy, for resectable stage IIA to IIIB non-small cell lung cancer
Primary Objective - To compare the complete pathological response rate after 3 cycles of neoadjuvant nivolumab and platinum-based doublet chemotherapy vs. the same regimen with the addition of sub-ablative stereotactic radiation therapy (8 Gy x 3) directed at the primary lung tumor. Secondary Objectives - To characterize the rate of Major Pathological Response (MPR), defined as ≤ 10% residual viable tumor cells at the time of surgical resection in the primary tumor and lymph nodes, as assessed by local pathology laboratory. - To characterize rates of Event Free Survival (EFS), defined as survival without documented disease progression per RECIST v1.1 that precludes surgery for local or distant disease recurrence. Exploratory Objectives - To characterize the rate of pathological downstaging of biopsy confirmed positive lymph nodes not in the stereotactic body radiation therapy (SBRT) field. - To characterize rates of Disease-Free Survival (DFS), defined as survival without local or distant recurrence or occurrence of new primary NSCLC. - To characterize rates of Overall Survival (OS) after study enrollment. - To characterize the incidence of adverse events, graded according to National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) version 5.0. - To describe surgical safety and the incidence and severity of surgery-related adverse events. - To characterize rates of clearance of ctDNA (circulating tumor DNA) following neoadjuvant therapy and definitive surgical treatment - To evaluate whole tumor RNAseq (RNA-sequencing) from pre- and post- treatment tissue samples to assess for predictors and signatures of pathologic response. - To evaluate of gene expression in pre- and post-treatment blood samples to assess for predictors and signatures of complete pathologic response. - To assess the expression characteristics of PD-L1, infiltrating immune cells and TMB (tumor mutational burden), and their association with clinical outcomes. ;