VISTA: A phase 2 study of Valproic acid, Irinotecan, and Simvastatin Applied to Recurrent Glioma

Gliomas are the most common primary cancer of the brain. When gliomas recur after initial treatment, there are no treatments proven to prolong survival and no accepted standard of care. Combining irinotecan, a traditional chemotherapy with adequate brain penetration, and two repurposed generic drugs, valproic acid and simvastatin, to make the chemotherapy work better, may be effective for recurrent gliomas. This is a prospective clinical trial in two cohorts of patients, adults with recurrent glioblastoma and adults with recurrent IDH-mutated gliomas. The objective is to see if the combination of valproic acid, irinotecan, and simvastatin causes these tumors to stabilize or shrink, which is a sign that these combinations are effective against these tumors.  

Inova Schar Cancer
8081 Innovation Park Drive
Fairfax, VA22031

• Age 18 or over
• 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
• ANC > 1.5, Hgb > 8, Platelets > 100
• Tbili < 1.5X ULN
• AST/ALT < 3X ULN
• KPS at least 70  

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