Phase I Factorial Study Of Temozolomide Plus Memantine, Mefloquine, And Metformin As Post-Radiation Adjuvant Therapy For Newly Diagnosed Glioblastoma.

2044Background: Repurposing non-cancer drugs may represent a new source of novel therapies for glioblastoma (GBM). Memantine, mefloquine, and metformin have putative anticancer activity potentially relevant to gliomas. The aim of this phase I factorial study was to determine the maximum tolerated doses (MTD) of combinations of these agents with temozolomide (TMZ) for newly diagnosed GBM. Methods: Adults (≥18 years of age) with newly diagnosed GBM who received chemoradiation with TMZ, with no progressive disease on post-treatment imaging, were eligible. The patients were sequentially enrolled to one of seven treatment arms (doublet, triplet, or quadruplet therapy with TMZ combined with mefloquine, memantine, and/or metformin). Dose-limiting toxicities (DLTs) were determined over the first 28 days of treatment, using a 3+3 study design. Results: Of 85 enrolled patients, 81 patients completed the MTD period. The final MTDs for doublet therapy arms (TMZ plus 1 drug) were memantine 20 mg twice a day (BID), mef...