Medical Experiment - Assessment of Efficacy & Safety of Local, Targeted Therapy With Neuropeptide Labelled With Alpha Emitter [225Ac]Ac-DOTA-SP (TAT) as Supplementary Therapy Following Standard Treatment Of Glioma (WHO G3-G4)
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 发起方
- 入组人数
- 35
- 试验地点
- 2
- 主要终点
- 1. Number of patients experiencing clinical progression (as defined below)
研究概览
简要总结
Brain tumors account for 1.35% of all cancers and cause 2.2% of cancer-related deaths. Gliomas are the most common type, comprising 40-90% of central nervous system tumors in different age groups. The incidence of malignant gliomas is approximately 0.5-2 per 100,000 people annually. Standard treatments include surgical resection, radiotherapy, and chemotherapy, yet overall survival remains low, typically 1-3 years post-diagnosis. The study highlights the pressing need for novel treatment strategies, particularly given the infiltrative nature of gliomas and the potential for targeted therapies using neuropeptides.The aim of this study is to assess the efficacy and safety of local targeted therapy with [225Ac]Ac-DOTA-SP in newly diagnosed glioblastoma following standard treatment.It is an interventional study without a control group, initiated by the researcher. Patients included are aged 18-80 with WHO G3-G4 glioma post-first-line treatment, not requiring immediate surgery and meeting specific MRI criteria.Patients will receive a maximum of six cycles of [225Ac]Ac-DOTA-SP, involving pre-treatment assessments, local administration of the agent after ensuring catheter patency, and continuous monitoring. Blood tests and neurological evaluations will be performed regularly.Outcome will be assessed by measuring overall survival (OS) and progression-free survival (PFS). The study anticipates improvements in both OS and PFS when compared to current treatments, contributing to critical insights into targeted alpha therapy's effectiveness in glioblastoma.Treatment with [225Ac]Ac-DOTA-SP previously indicated few significant side effects, primarily transient issues like seizures. Patients will be closely monitored throughout the study to identify any adverse effects promptly.The estimated study duration is three years, with biological material collected for histopathological and genetic analysis during surgical reoperation.Data will be anonymized to protect patient confidentiality, stored securely, and made available only for the scope of the study.Led by Prof. Przemysław Kunert, the research team includes multiple co-investigators from neurosurgery and nuclear medicine departments.
详细描述
- Background Brain tumors account for approximately 1.35% of all cancers and are responsible for 2.2% of cancer-related deaths. Gliomas are the most common primary brain tumors and, depending on age group, represent 40%-90% of central nervous system tumors. The incidence of malignant gliomas is estimated at 0.5-2 cases per 100,000 persons per year. These tumors occur more frequently in men, most often in the fifth and sixth decades of life. In Poland, approximately 1,300 patients are diagnosed with gliomas annually, including about 600 with malignant disease.
Current standard treatment consists of surgery, radiotherapy, and chemotherapy. Nevertheless, prognosis remains poor, with median survival ranging from 1 to 3 years depending on tumor type. Despite treatment, disease progression commonly occurs, and chemotherapy provides only a modest extension of survival. These limitations underscore the need for novel therapeutic strategies.
Given the infiltrative nature of gliomas, an effective treatment should diffuse throughout the tumor and selectively bind to neoplastic cells. Peptide-based targeted therapy appears particularly promising in this context. Many tumors express membrane receptors at high levels, allowing the use of radioisotope-labeled peptides for diagnosis and therapy. This approach is already applied in selected lymphomas and neuroendocrine tumors.
In gliomas, particularly WHO grade II-IV, increased expression of neurokinin-1 (NK-1) receptors has been observed. Substance P, the natural ligand for NK-1 receptors, demonstrates rapid diffusion and binding to glioma cells. A derivative of substance P developed at the Institute of Nuclear Medicine, University Hospital Basel, showed that more than 95% of gliomas exhibit elevated NK-1 receptor expression, confirming its potential for targeted therapy.
Substance P may be labeled with beta-emitting isotopes such as 90Y and 177Lu. However, due to their longer tissue range, these isotopes may pose a risk to adjacent critical brain structures. This limitation prompted interest in alpha emitters such as 213Bi and 225Ac, which have high energy but very short tissue penetration.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •age 18-80;
- •histologically confirmed diffuse glioma (CNS WHO G3-G4);
- •after standard treatment with biopsy or resection, radiotherapy and/or chemotherapy;
- •no sign of progression or radiation necrosis;
- •functional state >70 according to Karnofsky's performance scale (KPS);
- •ability to give informed consent to participate in the study.
排除标准
- •low-grade glioma;
- •progression or recurrence defined as: deterioration of the patient's condition according to the Karnofsky Performance Scale, worsening of neurological function, progressive neurological deficit, need to initiate or increase corticosteroid dose by >50%, progression or recurrence assessed on MRI (RANO criteria);
- •radiation-induced necrosis secondary to radiotherapy; may occur within the first 3 months after radiotherapy (exception: a patient after resection of radiation necrosis - not earlier than 4 weeks post-surgery, after a follow-up MRI);
- •need for emergency surgery (e.g., acute increase in intracranial pressure);
- •significant postoperative complications, e.g., KPS < 70, wound infection, cerebrospinal fluid leak;
- •leak into the ventricular system >10% during the catheter patency check;
- •open/ventricle-connected resection cavity;
- •catheter obstruction;
- •estimated life expectancy under 3 months;
- •patients without preserved logical/verbal contact;
- •lack of cooperation from the patient;
- •inability to give informed, voluntary consent to participate in the study;
- •patients enrolled in another medical trial;
- •patients who received any other investigational drug within 1 month prior to the first dose;
- •prior treatment with [225Ac]Ac-DOTA-SP;
- •breastfeeding or pregnant women;
- •severe comorbid organ diseases that, in the Investigator's opinion, significantly increase the procedural risk.
研究组 & 干预措施
Experimental : HGG treated with alpha emitter [225Ac]Ac-DOTA-SP (TAT) after standard therapy
Patients with high-grade gliomas (WHO G3-G4) after standard therapy who are treated with local, targeted therapy with alpha emitter [225Ac]Ac-DOTA-SP (TAT)
干预措施: Radiation: Local, targeted therapy with alpha emitter [225Ac]Ac-DOTA-SP (TAT) (Radiation)
结局指标
主要结局
1. Number of patients experiencing clinical progression (as defined below)
时间窗: From enrollment to 18 months
Clinical progression defined by: * reduction in Karnofsky Performance Scale result below 70% OR * new focal neurological deficit or exacerbation of existing deficit OR * necessity to use or increase dexamethasone dose by 50% or more.
次要结局
- 2. Number of patients experiencing radiological progression (as defined below)(From enrollment to 18 months)
- 3. Number of patients experiencing local radiological progression (as defined below)(From enrollment to 18 months)