Sonodynamic therapy using Focused Ultrasound and 5-ala in the treatment of glioblastomas.

Phase 1

• Conditions: IV degree lobar glioblastoma with a diameter of less than 5 cm.; MedDRA version: 20.0Level: PTClassification code 10018336Term: GlioblastomaSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); Therapeutic area: Diseases [C] - Nervous System Diseases [C10]

• Registration Number: EUCTR2021-003374-30-IT
• Lead Sponsor: FONDAZIONE IRCCS ISTITUTO NEUROLOGICO CARLO BESTA

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2021-10-19
• Last Update Posted: 2 March 2022

Recruitment & Eligibility

• Status: Authorised-recruitment may be ongoing or finished
• Sex: All
• Target Recruitment: 10

Inclusion Criteria

Criteria Inclusion: CH patients
- age between 18-60 years;
- both genders;
- diagnosis of grade IV lobar glioblastoma with a diameter of less than 5 cm;
- diagnosis confirmed with magnetic resonance examination;
- no contraindication to the magnetic resonance examination;
- no contraindications to surgery.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 10
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

Exclusion Criteria

Exclusion Criteria
1. Brain glioblastoma presenting with the following characteristics:
¿ Brain edema and/or mass effect that causes midline shift of more than 10 mm
¿ Evidence of recent intracranial hemorrhage within the targeted tumor volume
¿ Calcifications in the focused ultrasound sonication path (system tools may not
tailor the treatment around these calcifications)
2. The sonication pathway to the tumor involves either:
¿ more than 30% of the skull area traversed by scars, scalp disorders (e.g. eczema),
or atrophy of the scalp
¿ Clips, shunts, or other metallic implanted objects in the skull or the brain
3. Cardiac disease or unstable hemodynamic status including:
¿ Documented myocardial infarction within six months of enrolment
¿ Unstable angina on medication
¿ Congestive heart failure
¿ Left ventricular ejection fraction < 50%
¿ Right-to-left, bidirectional, or transient right-to-left cardiac shunts
¿ History of a hemodynamically unstable cardiac arrythmia
¿ Cardiac pacemaker
4. Severe hypertension
5. Anti-coagulant therapy or medications known to increase risk of hemorrhage within
washout period prior to treatment
6. History of a bleeding disorder, coagulopathy or with a history of spontaneous tumor
hemorrhage
7. Abnormal level of platelets (<100000) or INR >1.3
8. Cerebral or systemic vasculopathy
9. Known allergy sensitivity or contraindications to gadolinium
10. Contraindications to MRI such as non-MRI-compatible implanted devices
14
11. Subjects not fitting comfortably into the MRI scanner
12. Difficulty lying supine and still for up to 4 hours in the MRI unit or claustrophobia
13. Positive pregnancy test (for pre-menopausal women)
14. Severely impaired renal function with estimated glomerular filtration rate
<30mL/min/1.73m2 and/or on dyalisis
15. Respiratory: chronic pulmonary disorders, e.g. severe emphysema, COPD, pulmonary
vasculitis, or other causes of reduced pulmonary vascular cross-sectional area.
16. Any illness or medical condition that in the investigator’s opinion precludes participation
in this study
17. Patients unable to sign a consent form

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Timepoint(s) of evaluation of this end point: 12 months;Main Objective: The goal of this prospective, non-randomized, single-arm study is to evaluate the safety and feasibility of sonodynamic therapy with 5-aminolevulinic acid in patients with newly diagnosed cerebral<br>glioblastomas using the ExAblate Model 4000 Type-2 Neuro-System”.;Secondary Objective: Efficacy of the treatment, the following data will be collected for each subject:<br>- Overall tumor volume (for images)<br>- Immunohistochemical staining dedicated to the detection of cellular apoptosis and<br>necrosis, as well as angiogenesis and inflammation;Primary end point(s): safety