DOSINDYGO: DOSe finding for INtraoperative photoDYnamic therapy of GliOblastoma

Abstract

Glioblastoma is a malignant brain tumor with a poor prognosis. Currently, complete resection is rarely feasible, since tumor cells usually infiltrate the surrounding brain. Recently, the INDYGO clinical trial has been achieved to assess the toxicity of photodynamic therapy (PDT) delivered intraoperatively to treat newly diagnosed glioblastoma. Today, we believe that the PDT effect obtained in the INDYGO clinical trial can be improved by a higher light dose. The DOSINDYGO clinical trial aims to achieve a light-dose escalation increasing up to four times the initial light dose used in the INDYGO trial. An increase of both light power and treatment time should allow to treat deeper in the surrounding tissues (up to 8mm) and thus decrease the recurrence risk. First light dose will be reached by doubling the treatment time used in the INDYGO trial, the other one will be achieved by increasing light power only. This methodology was chosen in order to maintain an acceptable treatment time for anesthesia but also to prevent higher fluence rate that could induce a lower tolerance as observed in our preclinical results. Primary endpoint will be to determine the optimum light-dose regarding the ratio efficacy and tolerance of the treatment. Primary criterion is the assessment of the progression free survival within the bed border’s cavity. Finally, although no adverse effect has been noticed during the INDYGO trial, increasing light dose in this DOSINDYGO trial could result in other direct and indirect biological effects.