Design
toxicity
The RALLY study is a multicenter, interventional, non-randomized, open-label and non-comparative study. A classical 3 + 3 dose escalation model with four cohorts will be used, enrolling three patients in each cohort (Fig. Dose escalation example. Green circles represent patients that did not experience a dose-limiting toxicity at a given dose. Red circles represent patients that did experience a dose-limiting toxicity. The y-axis represents the dose to the non-tumourous liver tissue. In this example, two patients in the 80 Gy cohort experienced a dose-limiting toxicity, meaning the maximal tolerable dose is found and set to 70 Gy (with 18 patients included). The escalation will halt if no maximal tolerable dose is found after 80 Gy. Note that the last safe cohort will always include six patientsInclusion of patients in the next cohort will be performed if (i) all patients have received the treatment dose at least six weeks prior and (ii) the Data and Safety Monitoring Board (see Monitoring) has scrutinized the toxicity data and gave permission to proceed.