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.