[Lu]Lu-DOTATATE for Recurrent Meningioma (LUMEN-1, EORTC-2334-BTG): Study Protocol for a Randomized Phase II Trial.

There are no established treatment options for patients with meningioma recurring after surgery and radiotherapy. Somatostatin receptor type 2 (SSTR2) is highly expressed in meningiomas, and SSTR2-targeting radionuclide therapy with [Lu]Lu-DOTATATE has shown potential activity in the treatment of meningioma in uncontrolled and small studies. EORTC-2334-BTG (LUMEN-1, NCT06326190) is a randomized, multicenter, phase II trial in patients with recurrent World Health Organization (WHO) grade 1, 2, or 3 meningioma. In total, 136 patients will be randomized in a 2:1 ratio to [Lu]Lu-DOTATATE (≤4 doses of 7.4 GBq given every 4 wk) or local standard of care (hydroxyurea, bevacizumab, sunitinib, octreotide, everolimus, or observation). The main eligibility criteria include age 18 y or older; neuropathologically confirmed meningioma of WHO grade 1, 2, or 3; WHO performance score of 0-2; measurable disease on MRI (≥10 × 10 mm); radiologically documented progression of any existing tumor (growth > 25% or new lesions) or appearance of new lesions within the last 2 y; SSTR positivity by PET imaging (SUV > 2.3); at least 1 prior surgery and at least 1 line of radiotherapy; and no prior systemic therapy. The primary efficacy endpoint is locally assessed progression-free survival according to Response Assessment in Neuro-Oncology MRI meningioma criteria, and secondary endpoints include radiologic response rate, overall survival, safety, health-related quality of life, and neurologic function. The trial protocol includes a comprehensive exploratory translational research program with dosimetry and imaging-based and tissue-based investigations. LUMEN-1 was activated in March 2025 and will enroll patients in 35 sites in 10 countries across Europe, with primary endpoint collection planned after 2 y and study completion after 5 y. To our knowledge, EORTC-2334-BTG (LUMEN-1, NCT06326190) is the first prospective randomized trial investigating the efficacy of [Lu]Lu-DOTATATE in patients with recurrent meningioma.