Glioblastoma, Astrocytoma, IDH-Mutant, Grade 4
Conditions
Brief summary
The goal of this clinical trial 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 tumors in patients with recurrent glioblastoma and adults with recurrent IDH-mutated gliomas
Detailed description
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
Interventions
Day 1 40mg/kg/dose PO BID and simvastatin at 40mg PO daily
D2 irinotecan 180mg/m2 IV and VPA 40mg/kg/dose PO BID, simvastatin at 40mg PO daily
Day3-21 Continuous simvastatin starting at 40mg daily PO
Sponsors
Study design
Eligibility
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Assessing Efficacy as Measured By Response Rate Of Valproic acid, Irinotecan, and Simvastatin in Recurrent Glioma | through study completion, an average of 6 months from start of treatment | The response is defined as a confirmed complete response (CR) or partial response (PR) defined by RANO 2.0. Response rate will be calculated as the number of observed response (PR or CR) divided by all treated subjects in the arm. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Assessing Safety and Adverse Event Rates Of Valproic Acid, Irinotecan, And Simvastatin in Recurrent Glioma | through end of study, average 9 months from start of treatment | Adverse events will be reported for all patients who receive at least one dose of study medicine. |
Countries
United States
Contacts
Inova Health Care Services