Local targeted alpha therapy using 225Ac‑DOTA‑SP for newly diagnosed WHO grade 3–4 glioma

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)

This trial tests a local peptide‑guided alpha‑particle treatment (225Ac‑DOTA‑SP) in adults 18–80 with newly diagnosed WHO grade 3–4 glioma after initial surgery and radiochemotherapy to see if it safely targets residual tumor and improves local control.

Quick facts

• Phase: Not applicable
• Study type: Interventional
• Enrollment: 35 (estimated)
• Ages: 18 Years to 80 Years
• Sex: All
• Sponsor: Medical University of Warsaw (Academic / other)
• Drugs / interventions: chemotherapy, radiation
• Locations: 2 sites (Warsaw, Poland and 1 other locations)
• Trial ID: NCT07488754 on ClinicalTrials.gov

What this trial studies

Researchers deliver [225Ac]Ac‑DOTA‑SP directly into the tumor cavity or surrounding area after standard surgery and radiochemotherapy so the peptide can bind neurokinin‑1 receptors on glioma cells and emit highly localized alpha radiation. The study is a single‑arm interventional protocol enrolling adults with histologically confirmed WHO grade 3–4 glioma, Karnofsky performance status ≥70, and no imaging evidence of progression or radiation necrosis. Outcomes focus on safety and local tumor control with serial MRI and clinical follow‑up to monitor response and adverse events. Treatment is performed at specialist neurosurgical centers under radiation‑safety procedures.

Who should consider this trial

Good fit: Ideal candidates are adults 18–80 with histologically confirmed WHO grade 3–4 glioma who have completed first‑line surgery and radiochemotherapy, have Karnofsky ≥70, no MRI evidence of progression or radiation necrosis, and do not require urgent surgery.

Not a fit: Patients with low‑grade glioma, active progression or recurrence, radiation‑induced necrosis, poor performance status, or need for emergency surgery are unlikely to benefit from this intervention.

Why it matters

Potential benefit: If successful, this approach could deliver potent, focused radiation to residual tumor cells while limiting exposure to healthy brain, potentially improving local control and survival.

How similar studies have performed: While alpha‑emitter radiotherapies such as 225Ac‑PSMA have shown promising results in other cancers, intratumoral peptide‑directed alpha therapy for high‑grade glioma remains early and has not yet been validated in large clinical trials.

Eligibility criteria

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.

Where this trial is running

Warsaw, Poland and 1 other locations

• Department of Neurosurgery, Medical University of Warsaw, Banacha 1a — Warsaw, Poland, Poland (Recruiting)
• Department of Neurosurgery, National Instiute of Oncology, W.K. Roentgena 5 — Warsaw, Poland, Poland (Recruiting)

Study contacts

• Principal investigator: Przemysław Kunert, Professor MD PhD — Medical University of Warsaw
• Study coordinator: Przemysław Kunert, Professor MD PhD

Conditions Glioblastoma; High-Grade Glioma; alpha emitter; glioblastoma; local therapy; 225-Ac; high-grade glioma