Combination of Everolimus and 177Lu-DOTATATE in the Treatment of Grades 2 and 3 Refractory Meningioma: a Phase IIb Clinical Trial
Meningioma, the most common intracranial primary tumor of the central nervous system predominantly affects people in their fifties. Meningiomas are generally subdivided into two entities: a priori non-aggressive meningiomas (grade 1), and meningiomas at high risk of aggressive behavior (grade 2/atypical and 3/anaplastic). The current conventional treatments for meningioma are surgery and radiotherapy. When these treatments are no longer feasible, meningiomas are considered refractory irrespectively of grade, and in these rare entities, the therapeutic arsenal is reduced to the few treatments that have shown limited efficacy. Refractory, and particularly grades 2 and 3 meningiomas, have very poor prognoses with a progression-free survival at 6 months (PFS-6) of 26%. The European Response Assessment in Neuro-Oncology group (RANO) recommends that in any new, grades 2 and 3 meningioma, therapy that achieves a PFS-6 \>30% in phase II trials be considered promising. In Nuclear Medicine, Peptide Receptor Radionuclide Therapy (PRRT) with 177Lu-DOTATATE, currently used on a compassionate basis in refractory meningioma, deploys an octreotide-like effect, and appears very promising, with preliminary PFS-6 of 94% and an overall survival at 12 months (OS-12) of 88% in grade 1 meningioma. However, its PFS-6 is reduced to 28% with an OS-12 of 65% in WHO grades 2 and 3 meningioma. Recently the non-radiolabeled octreotide and everolimus combination however achieved a PFS-6 of 55% and an OS-12 of 75% in a population of 90% WHO grades 2 and 3 meningioma.
• Adult patient \< 80 years old, who received a complete comprehensive briefing about the trial and signed the informed consent
• Eligible patient for compassional access program (National Multidisciplinary Neuro-Oncology board to Lutathera ® traitement
• WHO performance status ≤ 3
• Patient with grade 2 and 3 meningioma, substantiated by histology, not amenable to surgery or radiotherapy, with clinical or radiological progression
• Clinical deterioration or at least 10% of tumor growth rate, defined as the product of the two largest diameters of the target lesion within 6 months
• Expressing somatostatin receptors as determined by 68Ga-DOTATOC PET (lesion uptake ≥ liver uptake and/or 1.7 fold SUVpeak of the controlateral meninges).
• Patient that underwent a brain MRI and 68Ga-DOTATOC PET within the last 2 months.
• Effective contraception required for women of childbearing age.
• Patient with social security cover.