Measurement of PSMA Expression in Vivo in Recurrent Meningiomas by PET Imaging: a Preliminary Study to a Therapeutic Trial Using Radioligand Therapy (RLT)
试验速览
- 阶段
- 不适用
- 状态
- 尚未招募
- 入组人数
- 40
- 试验地点
- 1
- 主要终点
- Significant expression of PSMA
研究概览
简要总结
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Diagnostic
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 85 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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
排除标准
- •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.
研究组 & 干预措施
Adult patients with recurrent meningioma
Adult patients with recurrent meningioma
干预措施: PET PSMA (Other)
结局指标
主要结局
Significant expression of PSMA
时间窗: 1 month
To estimate the percentage of patients with meningioma with significant PSMA expression in PSMA ligand PET
次要结局
- Significant expression of PSMA and grade of meningioma in anatomopathological analysis(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(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)(1 month)
- Measurement of PSMA expression in PET is quantified in SUV units at acquisitions at different time points(1 month)
- PSMA tracer fixation measurements in PET at different time points in SUV (at 120, 210 and 300 minutes) and the tumor volume(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(3 months)