Phase 2 VISTA combines valproic acid, irinotecan, and simvastatin for recurrent malignant glioma

This prospective, open-label Phase 2 study from Inova Health Care Services evaluates a three-drug repurposed regimen in recurrent malignant glioma. Valproic acid has histone deacetylase-inhibitory and antiseizure activity, irinotecan inhibits topoisomerase I, and simvastatin inhibits HMG-CoA reductase, affecting cholesterol and isoprenoid synthesis. Treatment is organized in 21-day cycles, with dosing and sequencing specified by the protocol.

The study has recurrent glioblastoma and recurrent IDH-mutant glioma cohorts, including grade 4 IDH-mutant astrocytoma. Eligibility includes recent radiographic progression and measurable enhancing disease, with prior-treatment requirements differing between cohorts. The aim is to characterize safety and look for tumor response or sustained disease control from a metabolic, epigenetic, and cytotoxic combination using established drugs. Treatment at recurrence remains individualized and may include repeat surgery, selected re-irradiation, alkylating chemotherapy, or bevacizumab for appropriate indications; the fact that these study drugs are familiar does not establish that their combination is effective or low-risk.