Background: The emergence of MTA in oncology has revolutionized the phase I design paradigm. The usual dose-limiting toxicity (DLT) endpoint is an oversimplification of the complex toxicity profile resulting in loss of information. Moreover, MTAs can induce less DLTs but more multiple moderate toxicities that may lead to dose reduction in long lasting treatment. We thus sought to develop a new toxicity endpoint, the Total Toxicity Profile (TTP), to incorporate multiple toxicities. Methods: We reanalysed the phase I trial that evaluated erlotinib (75, 100, 125, 150 mg/m²) in children with brain stem glioma (NCT00418327). Only 2/21 patients experienced protocol defined DLTs, but multiple moderate toxicities were observed. The TTP endpoint is a weighted combination of all toxicities experienced by the patient (Euclidean norm of the weights), where the weights (ranging from 0 to 10) reflect the clinical importance of each grade and type of toxicity. The weights and the acceptable toxicity target (target TTP) were elicited from 3 clinicians using hypothetical patient cohorts with various toxicity outcomes. They were asked to make a decision of where the next cohort of patients would be treated: higher, lower or same dose level. The target TTP was defined as the mean of TTPs of the cohorts associated with a decision to repeat the dose. We used the TTP-driven Quasi-Likelihood Continual Reassessment Method (QL-CRM) to re-estimate the recommended dose. Results: Clinicians identified 5 main dermatological toxicity types possibly attributable to erlotinib. The consensus weights (table below) as well as the target TTP (set at 4.66) were easily obtained, confirming the feasibility of the process. The weights differed from the CTCAE grades, confirming the interest of the approach. The recommended dose based on the retrospective analysis of all grades toxicity was lower than that identified by the DLT-driven CRM (100 instead of 125mg/m²). Conclusions: By neglecting multiple moderate toxicities, DLT-driven designs may over-estimate the recommended dose when investigating MTA. Our proposal is an appealing alternative design for MTA.