Local, Targeted Therapy With Alpha Emitter [225Ac]Ac-DOTA-SP (TAT) In Newly Diagnosed Glioma (WHO G3-G4)

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.

Sex

All

Minimum age

18 Years

Maximum age

80 Years

Inclusion Criteria:

* 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.

Exclusion Criteria:

* 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.

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