Meningioma Clinical Trial
Official title:
Combination of Alpelisib and Trametinib in Progressive Refractory Meningiomas: Phase 1 Study
Aggressive growing meningiomas resistant to multiple surgeries and radiotherapy constitute an
unmet pharmaceutical need in neurooncology, leading to a fatal issue within a few months.
Grade II-III meningiomas progression-free survival (PFS) 6 is at 10-15%. Median PFS grade III
meningioma is approximate 3 years.
Alpelisib is a well-tolerated Phosphoinositide 3-kinase α (Pi3Kα) specific inhibitor.
However, phosphatidylinositol-3-kinase (PI3K) and the mammalian target of rapamycin (mTOR)
inhibition does not induce apoptosis in vitro and induces an antiproliferative effect without
any radiologic response in most treated patients.
Trametinib, a mekinist (MEK) inhibitor is currently used in combined treatment for recurrent
melanomas in clinical practice with a good clinical tolerance at 1-2 mg daily. In vitro, on
meningioma primary cell culture, Trametinib induces cell apoptosis via caspase activity.
These results strongly suggest the relevance to combine Alpelisib and Trametinib in
aggressive and recurrent meningiomas.
Alpelisib and Trametinib combination has not been studied to date, despite each drugs have
been separately studied in phase 3.
Multicenter, open label, dose-finding phase I study of Alpelisib in combination with
Trametinib administered at a fixed dose (1.5 mg daily), both drugs will be administered
daily. Starting dose of Alpelisib will be 160mg/day and will be increased to 200mg/day or
decreased to 120mg/day depending of grade 3-4 adverse events occurrence, to determine maximal
tolerated dose (MTD) and recommended dose.
Primary Objective is to determine the safety profile and tolerability of Alpelisib and
Trametinib given in combination in patients with aggressive and refractory meningiomas in
terms of Dose-Limiting Toxicities (DLT, assessed during cycle 1).
n/a
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