Measurement of PSMA Expression in Vivo in Recurrent Meningiomas by PET Imaging: a Preliminary Study to a Therapeutic Trial Using Radioligand Therapy (RLT)

Обзор

Meningioma is the most common intracerebral tumor in adults. Conventional treatment includes surgery and external beam radiation therapy. However, when multiple surgeries and radiation therapy sessions fail to control tumor progression, no standard treatment is adopted. Therefore, refractory multi-recurrent meningiomas remain an unmet medical need and warrant the search for new therapies. In this respect, radioligand therapy (RLT) with LUTATHERA is used in the context of early compassionate access. RLT is based on the combination of a vector molecule directed specifically at a target (here the somatostatin receptors), with a radioactive isotope emitting particles destroying the targeted cells, and possibly their neighbors (here Lutetium 177). This treatment is indicated only if positron emission tomography (PET) imaging of somatostatin receptors is positive, excluding patients. In terms of efficacy, this treatment allows disease control in recurrences for low grade (grade 1) but has an insufficient effect in most aggressive meningiomas (grade 2, 3). RLT targeting the prostate specific membrane antigen (PSMA) prolongs the survival of patients with metastatic prostate cancer that significantly expresses PSMA, presenting a tumor signal higher than the hepatic signal in PET with PSMA ligands. PSMA is a transmembrane receptor, overexpressed in tumor cells and endothelial cells of neovascularization of various solid tumors. Initial results in immunohistochemistry (IHC) suggest that PSMA is expressed by neovascularization of meningiomas in a manner correlated with grades and recurrence. This is partly explained by the highly vascular nature of these lesions and has been iconographed by clinical cases in PSMA PET confirming in vivo an overexpression of PSMA. This overexpression of PSMA within meningiomas could offer a therapeutic alternative in RLT in patients where Lutathera is not suitable. However, there is no systematic study of the frequency and intensity of PSMA expression by PSMA ligand PET in recurrent meningiomas. The aim of the study is to evaluate the frequency of significant in vivo PSMA expression in recurrent meningiomas via PSMA ligand PET. We consider that at least 50% of recurrent meningiomas should have a significant level of PSMA expression in PSMA ligand PET to justify a therapeutic RLT trial targeting PSMA. In addition, as an exploratory study, in the subgroup of operated patients, an IHC analysis will be performed to explore the association between the PET signal and PSMA expression and confirm the specificity of the signal.

Вмешательства

• Другое PET PSMA
  PET PSMA ; 1 by subject before surgery

Первичные конечные точки

• Significant expression of PSMA [Срок оценки: 1 month]

Вторичные конечные точки (6)

• Significant expression of PSMA and grade of meningioma in anatomopathological analysis [Срок оценки: 3 months after the surgery]
• Measurement of PSMA expression at 120 min and somatostatin receptors in PET quantified in SUV units on the PET console [Срок оценки: 1 month]
• Measurement of PSMA PET expression quantified in SUV units at 120 min on the Siemens PET console and tumor growth measurement measured by MRI (% variation in tumor volume between the last two MRIs) [Срок оценки: 1 month]
• Measurement of PSMA expression in PET is quantified in SUV units at acquisitions at different time points [Срок оценки: 1 month]
• PSMA tracer fixation measurements in PET at different time points in SUV (at 120, 210 and 300 minutes) and the tumor volume [Срок оценки: 1 month]
• Measurement of PSMA expression in PET is quantified in units of Standardized uptake value (SUV) at 120 min and the measurement of PSMA expression in immunohistochemistry on the surgical specimen [Срок оценки: 3 months]

Критерии участия

Критерии включения

• Adult patient (≥18 years old),
• Beneficiary or entitled to a social security scheme
• Patient who has agreed to participate in the study and signed written informed consent
• Patients with histologically proven meningioma that has recurred after surgery and/or radiotherapy and/or systemic treatment

Критерии исключения

• Contraindication to \[18F\]PSMA PET scan: hypersensitivity to the active substance or to any of the excipients (ethanol, sodium chloride injection, and sodium ascorbate), according to the SPC sheet (https://www.ema.europa.eu/fr/documents/product-information/pylclari-epar-product-information\_fr.pdf).
• Antiangiogenic treatment within 60 days prior to inclusion
• Impossible to follow-up for 12 months
• Pregnant, parturient, or breastfeeding women. A pregnancy test will be performed before inclusion for women of childbearing age within 48 hours prior to the examination. -Individuals deprived of their liberty by a judicial or administrative decision
• Individuals receiving psychiatric care
• Individuals admitted to a health or social care facility for purposes other than research
• Adults subject to a legal protection measure (guardianship, curatorship)
• Subjects participating in another interventional research study that includes an exclusion period still in effect at the time of inclusion.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Не применимо

Модель

Одна группа

Маскирование

Открытое

Основная цель

Диагностика

Центры проведения

Франция · 1 центр

• Hôpital Louis Pradel — Bron

Идентификаторы

NCT: NCT07428213 · 69HCL24_1208 · 2026-A00403-48

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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