Ablative radiation therapy to restrain everything safely treatable (ARREST): study protocol for a phase I trial treating polymetastatic cancer with stereotactic radiotherapy

BackgroundPatients with polymetastatic cancer are most often treated with systemic therapy to improve overall survival and/or delay progression, with palliative radiotherapy reserved for sites of symptomatic disease. Stereotactic ablative radiotherapy (SABR) has shown promise in the treatment of oligometastatic disease, but the utility of SABR in treating all sites of polymetastatic disease has yet to be evaluated. This study aims to evaluate the maximally tolerated dose (MTD) of SABR in patients with polymetastatic disease.MethodsUp to 48 patients with polymetastatic cancer (>10 sites) will be enrolled on this phase I, modified 3+3 design trial. Eligible patients will have exhausted (or refused) standard systemic therapy options. SABR will be delivered as an escalating number of weekly fractions of 6Gy, starting at 6Gyx2 weekly fractions (dose level 1). The highest dose level (dose level 4) will be 6Gyx5 weekly fractions. Feasibility and safety of SABR will be evaluated 6weeks following treatment using a composite endpoint of successfully completing treatment as well as toxicity outcomes.DiscussionThis study will be the first to explore delivering SABR in patients with polymetastatic disease. SABR will be planned using the guiding principles of: strict adherence to dose constraints, minimization of treatment burden, and minimization of toxicity. As this represents a novel use of radiotherapy, our phase I study will allow for careful selection of the MTD for exploration in future studies.Trial registrationThis trial was prospectively registered in ClinicalTrials.gov as NCT04530513 on August 28, 2020.