Exploratory Evaluation of AR-42 Histone Deacetylase Inhibitor in the Treatment of Vestibular Schwannoma and Meningioma

Study Summary

This will be a multi-center, proof of concept phase 0 study to assess the suppression of p-AKT in Vestibular Schwannoma (VS) and meningiomas by AR-42 in adult patients undergoing tumor resection. AR-42 is a small molecule which crosses the blood brain barrier (BBB) in rodents, but the investigators are not certain yet if it will penetrate human VS. Meningiomas are outside the BBB, but seem to be unusually resistant to all current medical treatments. The primary endpoint of the bioactivity of suppression of p-AKT by AR-42 was selected as drug activity seems more informative than bioavailability. Our preclinical data and others have shown dose dependent suppression of p-AKT by AR-42 in both VS and meningiomas.

Primary Outcome

The phospho-AKT/AKT ratio was used to estimate the activity of AKT, a kinase, at the core of resected tumors. Quantitation of the normalized p-AKT/AKT ratio is depicted as a percentage relative to the untreated VS2 set as 100%. For example, a value under 100% indicates a lower level of AKT activity relative to untreated VS2 tumors. Phosphorylated AKT, or phospho-AKT, is the activated form of AKT. These measurements were derived from the core of the resected tumors.

Interventions

• DRUG AR-42