Abstract 381TiP
Background
Glioblastoma (GBM) is a poor prognosis malignant glioma. After surgical resection, standard therapy consists of concomitant radiotherapy (RT) and temozolomide (TMZ) followed by TMZ alone. Dendritic cells (DCs) are the most potent professional antigen-presenting cells capable of generating a specific immune response against various cancers. Multiple phase I/II trials and at least three meta-analysis showed improved survival (OS) and progression-free survival (PFS) with DC vaccination in High-grade gliomas (HGGs) patients. Since 2001, we have treated over 80 advanced melanoma patients with a tumor lysate-loaded autologous DC vaccine, obtaining a clinical benefit of 54.1% with a favourable toxicity profile. In patients developing antitumor immunity, DC vaccination increased the amount of intratumoral activated cytotoxic T lymphocytes and decreases the number of FoxP3 positive regulatory T cells. Based on these data we have developed a phase II protocol with DC vaccine concomitant to standard RT-CT in patients udergone radical surgery for GBM.
Trial design
This is a single-arm phase II trial evaluating progression free-survival (PFS) and safety of a DC vaccination integrated to standard therapy in resected GBM patients. All Patients will receive a dendritic cell vaccine loaded with autologous tumor homogenate for up to one year. The vaccine administration will start at the end of the RT-CT (Induction Phase) and then will be alternated to TMZ cycles (Maintenance Phase). Treatment schedule: DC Vaccine: 10x106 cells administered intradermally on weeks 1, 2, 3, 4, 7, 11, 15, ...and every 28 days TMZ: 150-200mg/m2/day administered orally from day 1 to 5 on weeks: 5,9,13,...and every 28 days Primary end points are PFS and safety, among secondary end points there are the in vitro (Elispot, Plasma Cytokines, Tumor tissue analysis) and in vivo (DTH skin test) Immune response evaluations. A Simon's two-stage design has been used for the sample size calculation. In the first stage, 9 patients will be accrued and a total of 28 patients will be enrolled Time to events (PFS and OS) will be calculated with the Kaplan-Meier method and the analysis will be performed on the eligible population.
Clinical trial identification
EudraCT 2020-003755-15.
Editorial acknowledgement
Legal entity responsible for the study
IRCCS Istituto Romagnolo per lo Studio dei Tumori (IRST) \"Dino Amadori\", Meldola, Italy.
Funding
Has not received any funding.
Disclosure
All authors have declared no conflicts of interest.