Local, Targeted Therapy With Alpha Emitter [225Ac]Ac-DOTA-SP (TAT) In Newly Diagnosed Glioma (WHO G3-G4)
Trial statusRecruiting
Trial phaseNot applicable
Trial typeInterventional
Biological sexAll
Age18-80
SponsorMedical University of Warsaw
About this trial
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.
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
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;
Disqualifiers
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);
Trial design
Design model
Single group
Treatments tested in this trial
Radiation: Local, targeted therapy with alpha emitter [225Ac]Ac-DOTA-SP (TAT)
RadiationLocal, targeted therapy with alpha emitter \[225Ac\]Ac-DOTA-SP (TAT) administered to the post-resection cavity or tumour via Rickham reservoir using induced diffusion.
Treatment groups
35 Participants
are divided into 1 treatment groupGroup A: Experimental : HGG treated with alpha emitter [225Ac]Ac-DOTA-SP (TAT) after standard therapyExperimental treatment 1 intervention
Trial outcomes
Primary outcomes
1
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.
Time frame
From enrollment to 18 monthsSecondary outcomes
1
2. Number of patients experiencing radiological progression (as defined below)
Radiological progression assessed on contrast-enhanced cerebral MRI: * any new contrast-enhanced lesion OR * 25% or more increase in contrast-enhancing lesions despite stable or increasing steroid dose OR * significant increase in non-enhancing FLAIR/T2W lesions, not attributable to other non-tumour causes.
Time frame
From enrollment to 18 months2
3. Number of patients experiencing local radiological progression (as defined below)
Local radiological progression assessed on contrast-enhanced cerebral MRI: * any new contrast-enhanced lesion within 4 cm from resection cavity OR * 25% or more increase in contrast-enhancing lesions within 4 cm from resection cavity despite stable or increasing steroid dose.
Time frame
From enrollment to 18 monthsSponsors and contacts
Click on the lead sponsor to view all of their trials.
Source ClinicalTrials.gov