Background <p>The clinical demand for reirradiation is increasing; however, evidence for dose guidance to estimate normal tissue toxicity is lacking. The goal of the REPAIR trial is to determine the maximally tolerated dose (MTD) of reirradiation in the thorax, implemented by sequentially increasing the normal tissue recovery factors applied to previously delivered dose.</p> Methods <p>This multi-institution phase I dose-escalation study for patients undergoing thoracic reirradiation will use a time-to-event continual reassessment method (TITE-CRM). The MTD of reirradiation in this trial is represented by the recovery factor equation associated with a 35% or lower rate of Common Terminology Criteria for Adverse Events (CTCAE) grade 3–5 treatment-related toxicity occurring within 1&#xa0;year of treatment. Accrual will start at level 1 (recovery factor = 10% at 6&#xa0;months + 0.75% per month thereafter). Patients (n = 48) will be assigned to recovery factors 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 3–5 toxicity of 35% or less. Patients with recurrence, metastasis, or new primary malignancies in the thorax requiring radiation and who have previously received radiotherapy to the thorax, where reirradiation is expected to exceed the dose constraints used for de novo treatments, are eligible.</p> Discussion <p>This study will provide information on the safety of dose escalation for thoracic reirradiation using the concept of recovery after radiation.</p> Trial Registration <p>Clinicaltrials.gov identifier: NCT06558175 (registration date August 14, 2024).</p>