SUNSET: SBRT for Ultra-central NSCLC- a Safety and Efficacy Trial

This multi-centre phase I dose-escalation study will use a time-to-event continual reassessment method (TIT-CRM). Accrual will start at level 1 (60 Gy in 8 fractions). Patients will be assigned to treatment doses using the TITE-CRM model. The model will use all available information from previously accrued patients to assign the highest dose with a predicted risk of grade 3 toxicity of 30% or less.

This study will use a time-to-event continual reassessment method (TITE-CRM). The study design is based on RTOG 0813 (described above), but with a more cautious approach, since the patients herein may constitute a high-risk subset of the patients enrolled in RTOG 0813. The modifications include a starting dose (60 Gy in 8 fractions) herein that is lower than the safe dose for central tumors as determined by RTOG 0813 (60 Gy in 5 fractions), and longer follow-up period during which patients are considered at-risk for toxicity, (i.e. two years herein vs. one year in RTOG 0813). The primary endpoint of this study is the maximally tolerated dose (MTD) of radiotherapy for ultracentral tumors. The MTD is the dose of radiotherapy associated with a \<30% rate of grade 3-5 toxicity occurring within 2 years of treatment. Local Progression, Regional nodal progression, Distant metastases, Progression-Free Survival, Overall survival, patient reported outcomes and quality of life. The correlative objectives of this study are to determine the prognostic value of ctDNA levels measured pre-treatment, at the end of treatment and 3- and 12-months after treatment.