ELUMEN (Phase IIb)

Investigator physician: Pr Antoine VERGER

Evaluation of the addition of Everolimus to ¹⁷⁷Lu-DOTATATE in the treatment of grades 2 and 3 refractory meningioma: a phase IIb clinical trial

Grade 2 and 3 refractory meningioma

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 I), and meningiomas at high risk of aggressive behavior (grade II/atypical and III/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 II and III 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 II and III 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 II and III 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 II and III meningioma but the present study does not aim to compare the radioactive and non-radioactive analogues.

The hypothesis of this study is by adding everolimus by blocking the m-Tor pathway, will potentiate the effect of ¹⁷⁷Lu-Dotatate by increasing the radiosensitivity of tumor cells and thus extend the PFS-6 in refractory grades 2 and 3 meningioma patients.

Therapy: Everolimus®
Study status: Not yet recruiting
Clinical Trial number: NCT06126588
Funding: InCA