Phase I Study of Escalated Pharmacologic Dose, of Oral Folinic Acid in Combination With Temozolomide, According to Stupp R. Regimen, in Patients With Operated Grade-IV Astocytoma and a Non-methylated Gene Status of MGMT.
Glioblastoma treated by Stupp regimen (Temozolomide + radiation therapy) have a different
outcome depending on the methylation status of MGMT gene: when the gene is unmethylated, the
repair process is active and the prognostic poor. In pre-clinical models, it has been
demonstrated that Folic acid could re-methylate the MGMT gene and therefore the repair
process to radiation and temozolomide could be limited, allowing a better prognosis. The
proposed phase-1 study will explore the safety and efficacy of escalated doses of oral
Folinic acid concomitantly with Stupp regimen. To determine the MTD is the main objective of
the study, then the toxicty profile, the RDP2 and the methylation process efficacy at the
MGMT gene level.
Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Maximal Tolerated Dose
maximal tolerated dose 3x3 patients inclusion(modified Fibonnacci dose escalation )
Mario CAMPONE, MD, PhD
Institut Cancerologie de l'Ouest
France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)