MODERN-LUNG: A phase 2 study of a moderately hypofractionated schedule of chemoradiation followed by immunotherapy for unresectable locally advanced non-small cell lung cancer

Background: Moderately hypofractionated radiotherapy entails higher doses per fraction given over shorter treatment time, and thus is more convenient for patients and provides economic benefits for both patients and the health care sector Faster treatment delivery has become more tolerable due to advances in radiation technology and established as the standard of care in many breast and prostate cancer treatments Lung cancer is a common cancer that is associated with high morbidity and mortality and is particularly prevalent in the elderly and socially disadvantaged and Aboriginal groups In Australia, the standard of care for the treatment of unresectable stage 3 non-small cell lung cancer (NSCLC) is 6 weeks of radiotherapy (2 Gy per fraction) given concurrently with platinum-based doublet chemotherapy (CRT) followed by immunotherapy for up to 12 months However, in the UK, a 4-week schedule of moderately hypofractionated radiotherapy (2 75 Gy per fraction) with chemotherapy has been commonly used Because of the priority to reduce hospital visits during the COVID 19 pandemic, some hospitals in Australia are using the 4-week schedule, but there are no published data on the tolerability of this shorter CRT schedule with immunotherapy and there are no phase 3 data comparing it directly with a 6-week schedule The aim of this single-arm phase 2 study is to establish tolerability of the 4-week schedule prior to proceeding with a phase 3 trial comparing 4 weeks with 6 weeks It will be multi-institutional study across NSW and other states Aims: To assess the toxicity of using a 4-week schedule ofCRT followed by immunotherapy in unresectable stage 3 NSCLC Methods: A minimum of 50 patients will be recruited from the clinic to receive a 4-week schedule of CRT followed by immunotherapy for unresectable stage 3 NSCLC All assessments, treatment delivery, and follow-up will be according to local guidelines Toxicities and treatment outcomes will be measured The primary endpoint is the incidence of major toxicities pertaining to thoracic radiotherapy, including Grade = 3 pneumonitis and Grade = 3 esophagitis Statistics: There are stopping rules to the study if thresholds for severe esophagitis and pneumonitis incidence are exceeded Outcomes will be analyzed according to descriptive and Kaplan-Meier method statistics Current status of the study:Await local ethics approval of protocol in August 2020 and start recruitment atCMNby October 2020 Multisite recruitment by November 2020