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

NCT06975332 | Recruiting

• 1 other identifier: KB/86/2024
• Study Type: interventional
• Target: 35
• Locations: 1 country
• Sites: 2

Brief 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.

Conditions

Glioblastoma; High-Grade Gliomas; Grade III Astrocytoma; Grade III Glioma

Keywords

alpha emitter; glioblastoma recurrence; local therapy; 225-Ac; high-grade glioma recurrence

Outcome Measures

Primary Outcomes (1)

• Number of patients experiencing clinical progression (as defined below)

  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.

  From enrollment to 18 months

Secondary Outcomes (2)

• Number of patients experiencing radiological progression (as defined below)

  From enrollment to 18 months

• Number of patients experiencing local radiological progression (as defined below)

  From enrollment to 18 months

Study Arms (1)

High-grade glioma recurrence treated with alpha emitter [225Ac]Ac-DOTA-SP (TAT)

EXPERIMENTAL

Patients with high-grade gliomas (WHO G3-G4) recurrence who are treated with local, targeted therapy with alpha emitter \[225Ac\]Ac-DOTA-SP (TAT)

Radiation: Local, targeted therapy with alpha emitter [225Ac]Ac-DOTA-SP (TAT)

Interventions

Local, targeted therapy with alpha emitter [225Ac]Ac-DOTA-SP (TAT) RADIATION

Local, targeted therapy with alpha emitter \[225Ac\]Ac-DOTA-SP (TAT) administered to the post-resection cavity or tumour via Rickham reservoir using induced diffusion.

High-grade glioma recurrence treated with alpha emitter [225Ac]Ac-DOTA-SP (TAT)

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Medical University of Warsaw: lead

Study Sites (2)

Department of Neurosurgery, Medical University of Warsaw, Banacha 1a

Warsaw, Poland, 02-097, Poland

RECRUITING

Department of Neurosurgery, National Instiute of Oncology, W.K. Roentgena 5

Warsaw, Poland, 02-781, Poland

RECRUITING

Related Publications (7)

• Hilario A, Ramos A, Perez-Nunez A, Salvador E, Millan JM, Lagares A, Sepulveda JM, Gonzalez-Leon P, Hernandez-Lain A, Ricoy JR. The added value of apparent diffusion coefficient to cerebral blood volume in the preoperative grading of diffuse gliomas. AJNR Am J Neuroradiol. 2012 Apr;33(4):701-7. doi: 10.3174/ajnr.A2846. Epub 2011 Dec 29.

  PMID: 22207304 BACKGROUND

• Sykova E, Nicholson C. Diffusion in brain extracellular space. Physiol Rev. 2008 Oct;88(4):1277-340. doi: 10.1152/physrev.00027.2007.

  PMID: 18923183 BACKGROUND

• Cordier D, Forrer F, Bruchertseifer F, Morgenstern A, Apostolidis C, Good S, Muller-Brand J, Macke H, Reubi JC, Merlo A. Targeted alpha-radionuclide therapy of functionally critically located gliomas with 213Bi-DOTA-[Thi8,Met(O2)11]-substance P: a pilot trial. Eur J Nucl Med Mol Imaging. 2010 Jul;37(7):1335-44. doi: 10.1007/s00259-010-1385-5. Epub 2010 Feb 16.

  PMID: 20157707 BACKGROUND

• Cordier D, Forrer F, Kneifel S, Sailer M, Mariani L, Macke H, Muller-Brand J, Merlo A. Neoadjuvant targeting of glioblastoma multiforme with radiolabeled DOTAGA-substance P--results from a phase I study. J Neurooncol. 2010 Oct;100(1):129-36. doi: 10.1007/s11060-010-0153-5. Epub 2010 Mar 10.

  PMID: 20217458 BACKGROUND

• Krolicki L, Bruchertseifer F, Kunikowska J, Koziara H, Pawlak D, Kulinski R, Rola R, Merlo A, Morgenstern A. Dose escalation study of targeted alpha therapy with [225Ac]Ac-DOTA-substance P in recurrence glioblastoma - safety and efficacy. Eur J Nucl Med Mol Imaging. 2021 Oct;48(11):3595-3605. doi: 10.1007/s00259-021-05350-y. Epub 2021 Apr 15.

  PMID: 33860346 BACKGROUND

• Krolicki L, Bruchertseifer F, Kunikowska J, Koziara H, Krolicki B, Jakucinski M, Pawlak D, Apostolidis C, Mirzadeh S, Rola R, Merlo A, Morgenstern A. Safety and efficacy of targeted alpha therapy with 213Bi-DOTA-substance P in recurrent glioblastoma. Eur J Nucl Med Mol Imaging. 2019 Mar;46(3):614-622. doi: 10.1007/s00259-018-4225-7. Epub 2018 Nov 29.

  PMID: 30498897 BACKGROUND

• Krolicki L, Kunikowska J, Bruchertseifer F, Kulinski R, Pawlak D, Koziara H, Rola R, Morgenstern A, Merlo A. Locoregional Treatment of Glioblastoma With Targeted alpha Therapy: [ 213 Bi]Bi-DOTA-Substance P Versus [ 225 Ac]Ac-DOTA-Substance P-Analysis of Influence Parameters. Clin Nucl Med. 2023 May 1;48(5):387-392. doi: 10.1097/RLU.0000000000004608. Epub 2023 Mar 1.

  PMID: 36854309 BACKGROUND

MeSH Terms

Conditions

Glioblastoma; Astrocytoma

Condition Hierarchy (Ancestors)

Glioma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue

Study Officials

• Przemysław Kunert, Professor

  Department of Neurosurgery, Medical University of Warsaw, Poland

  PRINCIPAL INVESTIGATOR

• Joanna Kunikowska, Professor

  Department of Nuclear Medicine, Medical University of Warsaw, Poland

  STUDY DIRECTOR

Central Study Contacts

Przemysław Kunert, Professor

CONTACT

+48 22 599 2575; przemyslaw.kunert@wum.edu.pl

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 14, 2025
• First Posted: May 16, 2025
• Study Start: October 9, 2024
• Primary Completion (Estimated): September 1, 2026
• Study Completion (Estimated): September 1, 2027
• Last Updated: May 16, 2025

Record last verified: 2025-05

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL
• Time Frame: from study conclusion in Sep 2027
• Access Criteria: Data access will be provided to any researchers possessing access to published articles as supplementary materials or via e-mail on reasonable request.

Locations

PL (2)