A Randomized Phase II Trial of Hypo-fractionated Intensity-Modulated Radiation Therapy (IMRT) Utilizing 2.5 Gy/Fraction Versus Standard- Fractionated IMRT, Concurrent With Carboplatin/Paclitaxel and Followed by Consolidation Durvalumab, for Subjects With Stage III Non-Small Cell Lung Cancer.

[BACKGROUND] Locoregional control remains suboptimal for patients with stage III non-small cell lung cancer (NSCLC) who receive standard-of-care concurrent chemoradiation, with standard-fractionated radiation treatment (RT) delivered at 2 Gy/fraction. Hypo-fractionated RT is effectively used as a standard-of-care treatment option in several different cancers and allows escalation of the biological effective dose (BED) to the tumor, without increasing the overall treatment time. In NSCLC, hypo-fractionated RT regimens have been investigated in early phase trials and found to be feasible if performed with careful attention to the dose received by adjacent critical structures.

[METHODS] The study is a randomized, phase II clinical trial designed to evaluate the feasibility, toxicity and efficacy of hypo-fractionated RT to 62.5 Gy in 25 fractions (2.5 Gy/fraction) in stage III NSCLC subjects, compared to the current standard-of care 6-week RT regimen (2 Gy/fraction), with concurrent systemic chemotherapy and consolidation immunotherapy. Our primary objective is to compare locoregional control between hypo-fractionated RT versus standard fractionated RT. Secondary objectives include comparing acute and late toxicities, progression free survival, overall survival, and quality of life.

[CONCLUSIONS] This study will assess the safety and feasibility of hypo-fractionated RT at 2.5 Gy/fraction with concurrent chemotherapy and consolidation immunotherapy and is the first prospective, randomized clinical trial, to our knowledge, to compare the efficacy of hypo-fractionated RT versus standard-fractionated RT for patients with stage III non-small cell lung cancer.