VISTA: Valproic Acid, Irinotecan, and Simvastatin for Recurrent Glioma

This is a prospective clinical trial in two cohorts of patients, adults with recurrent glioblastoma and adults with recurrent IDH-mutated gliomas.

The study evaluates the efficacy of valproic acid, irinotecan, and simvastatin in recurrent glioma by measuring response rate.

The study treatment is as follow: Study Treatment

• 21-day cycles
• D1 VPA 40mg/kg/dose PO BID and simvastatin at 40mg PO daily
• D2 VPA 40mg/kg/dose PO BID, simvastatin at 40mg PO daily, and irinotecan 180mg/m2 IV
• D3-21 Continuous simvastatin starting at 40mg daily PO

Inclusion criteria

• Diagnosis of glioblastoma or IDH-mutated glioma by WHO 2021 classification
• For glioblastoma, at least one prior treatment, which needs to include temozolomide and/or radiation
• For IDH-mutated glioma, prior treatment with both radiation and alkylating chemotherapy
• Evidence of progression by RANO 2.0 criteria on MRI within last four weeks
• At least 1 enhancing measurable lesion

Exclusion criteria

• Use of an enzyme-inducing antiepileptic or other strong inducer of CYP3A4
• Prior treatment with irinotecan
• Prior use of valproic acid within 2 months
• Anticancer treatment within 4 weeks, 6 weeks if nitrosourea
• Active bacterial or fungal infection requiring systemic treatment
• Pregnancy
• Known mitochondrial disease