P07.12.B REPURPOSING DRUGS IN RESEARCH AND CANCER CLINICAL TRIALS (REDIRECCT); PHASE 0 PITAVASTATIN IN GLIOBLASTOMA PATIENTS.

Abstract BACKGROUND Glioblastoma (GB) is an aggressive brain tumor with very limited treatment options. Pitavastatin, a statin approved for treatment of hypercholesterolemia, demonstrated strong cytotoxic effects in patient-derived GB cells in vitro and its physico-chemical properties suggest blood-brain barrier (BBB) permeability. We tested in which concentration pitavastatin reaches GB in patients. MATERIAL AND METHODS 10 patients were included, 2 patients with primary, 6 with recurrent GB and 2 with metastasis received pitavastatin for six days prior to planned surgery. A 3 + 3 dose-escalation design (16 mg, 32 mg, 48 mg) was used. Tumor samples from gadolinium-enhancing and tumor-infiltrating brain (TIB) as well as plasma samples were analyzed using LC-MS RESULTS High dose pitavastatin was well tolerated. Mean concentrations at 16 mg, 32 mg, and 48 mg were 0.125 μM, 0.144 μM, and 0.168 μM in the gadolinium-enhancing tumor; and 0.136 μM, 0.148 μM, and 0.204 μM in TIB. For breast cancer metastasis, the concentrations were 0.32 μM in the gadolinium-enhancing tumor and 0.11 μM in TIB. For lung cancer metastasis, the concentrations were 0.26 μM in the gadolinium-enhancing tumor and 0.17 μM in TIB.. Plasma-to-tumor ratios ranged from 3.1 to 0.4. Clinically relevant concentrations for synergy with temozolomide were achieved in TIB tissue, suggesting potential therapeutic impact beyond areas with BBB disruption. CONCLUSION Short-term high-dose pitavastatin achieves therapeutic concentrations in GB infiltrated tissue, supporting its potential as an adjunct therapy. Further investigation in Phase I/II trials is warranted.