Phase I/IIa Study of Concomitant Radiotherapy With Olaparib and Temozolomide in Unresectable High Grade Gliomas Patients
Status:
Recruiting
Trial end date:
2022-06-30
Target enrollment:
Participant gender:
Summary
The Stupp protocol is the standard treatment of glioblastoma multiform (GBM) which prognosis
remains poor.
The non-dividing nature of normal brain cells provides an opportunity to enhance the
therapeutic ratio by combining radiation with inhibitors of replication-specific DNA repair
pathways such poly(ADP-ribose) polymerase (PARP) inhibitors, thus inducing more cytotoxic
effects of DNA-damage related to treatment modalities, including alkylating reagents like
temozolomide (TMZ).
Olaparib, a potent PARP inhibitor, overcomes apoptotic resistance and sensitizes GBM cells
for death receptor-mediated apoptosis induced by TRAIL (Tumor necrosis factor-Related
Apoptosis Inducing Ligand). Moreover, inhibition of PARP activity increases cellular
sensitivity to ionizing radiation: it was even suggested to be more pronounced in tumors than
in normal tissue.
Lastly, progress in technical imaging and intensity-modulated-radiotherapy (IMRT) techniques
provide new possibilities for sparing healthy tissues.