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

Summary

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 recurrent glioblastoma. It is an interventional study without a control group, initiated by the researcher. Patients included are aged 18-80 with recurrent WHO G3-G4 glioma post-first-line treatment, not requiring immediate surgery and meeting specific MRI progression 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.

Eligibility

Inclusion Criteria:

* age 18-80;
* histologically confirmed diffuse glioma (CNS WHO G3-G4);
* after standard treatment with biopsy or resection, radiotherapy and/or chemotherapy;
* tumour progression as defined by RANO 2.0 on MRI (hyperintense lesion on MRI or increase of maximal transverse diameter of tumour or increase on volumetric measurement, local progression by continuity in proximity of 4 cm to primary lesion after resection, stable lesion progression on MRI \>25% in time between two consecutive MRIs or any new lesion on MRI; to differentiate progression from pseudoprogression a biopsy may be needed, especially within 12 weeks from radiotherapy);
* unifocal lesion;
* after resection: tumour volume \<50 ml AND tumour tissue thickness on contrast-enhanced T1 MRI \<1 cm;
* after biopsy: tumour median diameter \<2 cm;
* functional state \>70 according to Karnofsky's performance scale (KPS);
* ability to give informed consent to participate in the study.

Exclusion criteria:

* necessity of urgent surgery (e.g., sudden increase in intracranial pressure);
* significant postoperative complications: e.g., Karnofsky's performance scale (KPS) \<70, wound infection, cerebrospinal fluid leak;
* ventricular shunt leak \>10% during a control patency test;
* open/communicating resection cavity;
* mass effect on CT scan or MRI with midline shift of more than 5 mm and/or nausea, vomiting, altered consciousness, or clinically significant papilledema;
* catheter obstruction;
* predicted life expectancy less than 3 months;
* patients without preserved logical-verbal contact or uncooperative;
* inability to provide informed, voluntary consent to participate in the study;
* patients participating in another medical experiment;
* patients who have taken any other investigational drug within 1 month of the first dose;
* prior treatment with \[225Ac\]Ac-DOTA-SP;
* breastfeeding or pregnancy;
* severe diseases of other organs that, in the opinion of the Investigator, significantly increase the risk of the procedure.

Conditions5

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