AUTHOR=Pace Andrea , Lombardi Giuseppe , Villani Veronica , Benincasa Dario , Abbruzzese Claudia , Cestonaro Ilaria , CorrĂ  Martina , Padovan Marta , Cerretti Giulia , Caccese Mario , Silvani Antonio , Gaviani Paola , Giannarelli Diana , Ciliberto Gennaro , Paggi Marco G. TITLE=Efficacy and safety of chlorpromazine as an adjuvant therapy for glioblastoma in patients with unmethylated MGMT gene promoter: RACTAC, a phase II multicenter trial JOURNAL=Frontiers in Oncology VOLUME=13 YEAR=2023 URL=https://www.frontiersin.org/journals/oncology/articles/10.3389/fonc.2023.1320710 DOI=10.3389/fonc.2023.1320710 ISSN=2234-943X ABSTRACT=Introduction

Drug repurposing is a promising strategy to develop new treatments for glioblastoma. In this phase II clinical trial, we evaluated the addition of chlorpromazine to temozolomide in the adjuvant phase of the standard first-line therapeutic protocol in patients with unmethylated MGMT gene promoter.

Methods

This was a multicenter phase II single-arm clinical trial. The experimental procedure involved the combination of CPZ with standard treatment with TMZ in the adjuvant phase of the Stupp protocol in newly-diagnosed GBM patients carrying an unmethylated MGMT gene promoter. Progression-free survival was the primary endpoint. Secondary endpoints were overall survival and toxicity.

Results

Forty-one patients were evaluated. Twenty patients (48.7%) completed 6 cycles of treatment with TMZ+CPZ. At 6 months, 27 patients (65.8%) were without progression, achieving the primary endpoint. Median PFS was 8.0 months (95% CI: 7.0-9.0). Median OS was 15.0 months (95% CI: 13.1-16.9). Adverse events led to reduction or interruption of CPZ dosage in 4 patients (9.7%).

Discussion

The addition of CPZ to standard TMZ in the first-line treatment of GBM patients with unmethylated MGMT gene promoter was safe and led to a longer PFS than expected in this population of patients. These findings provide proof-of-concept for the potential of adding CPZ to standard TMZ treatment in GBM patients with unmethylated MGMT gene promoter.

Clinical trial registration

https://clinicaltrials.gov/study/NCT04224441, identifier NCT04224441.