Meningioma
Conditions
Keywords
Recurrent meningioma, RLT, PET PSMA
Brief summary
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.
Interventions
OTHERPET PSMA
PET PSMA ; 1 by subject before surgery
Sponsors
Hospices Civils de Lyon
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
DIAGNOSTIC
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 85 Years
Healthy volunteers
No
Inclusion criteria
* 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
Exclusion criteria
* 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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Significant expression of PSMA | 1 month | To estimate the percentage of patients with meningioma with significant PSMA expression in PSMA ligand PET |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Significant expression of PSMA and grade of meningioma in anatomopathological analysis | 3 months after the surgery | To evaluate the percentage of patients with significant PSMA expression in PSMA ligand PET scans as a function of the grade of meningioma defined by anatomopathological analysis. |
| Measurement of PSMA expression at 120 min and somatostatin receptors in PET quantified in SUV units on the PET console | 1 month | To evaluate the association between PSMA expression measurement in meningioma PSMA ligand PET and somatostatin receptor expression measurement in \[68Ga\]DOTATOC PET in the subgroup of patients undergoing both examinations. |
| 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) | 1 month | To evaluate the association between PSMA expression measurement in meningioma PSMA ligand PET and tumor growth measurement measured by MRI in the subgroup of patients undergoing both examinations. |
| Measurement of PSMA expression in PET is quantified in SUV units at acquisitions at different time points | 1 month | To evaluate the washout rate of the PSMA PET tracer by performing multiple acquisitions at different time points in the subgroup of patients performing the different PET acquisitions. |
| PSMA tracer fixation measurements in PET at different time points in SUV (at 120, 210 and 300 minutes) and the tumor volume | 1 month | Estimate the mean dose of Lu-177-labeled PSMA deposited in the tumor from PSMA ligand PET imaging in the subgroup of patients performing the different PET acquisitions. |
| 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 | 3 months | Evaluate the association between the measurement of PSMA expression in PSMA ligand PET of meningiomas and the immunohistochemical measurement of PSMA expression on the surgical specimen in the subgroup of operated patients. |
Countries
France
Contacts
CONTACTFLAUS ANTHIME, Dr
CONTACTMANSUY Adeline
Outcome results
None listed