Sonodynamic Therapy With ExAblate System in Glioblastoma Patients

• Status: Not yet recruiting
• Trial end date: 2022-12-01
• Target enrollment: 0
• Participant gender: All

Summary

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 glioblastomas using the ExAblate Model 4000 Type-2 "Neuro-System".

Patients will be consented, screened, and will undergo study SDT treatment with 5-ALA using the ExAblate Model 4000 Type-2 "Neuro-System". After SDT treatment, patients will perform a strict neuro-radiological follow-up (minimum of 2 MRI) and undergo tumor resection 14-21 days after SDT, according to the clinical and radiological status.

The main goal of the present study is to investigate the antitumor effects of SDT in patients affected by HGGs attained with low-frequency focused ultrasound.

• Safety will be evaluated by patient examination and MRI during the treatment, and by follow-up by daily clinical visits and MRI every 3 days. Data on the safety versus adverse effects of this treatment will be acquired during each visit through a combination of MRI evaluations, clinical assessments and neurological examinations.

• Feasibility will be evaluated performing serial MRI after SDT treatment evaluating tumor size, morphology and peri-lesional edema until tumor resection.

Efficacy is not a primary endpoint. To evaluate the treatment effect, for each subject, the following data will be collected:

• Tumor volume changes after SDT according to sonicated tumors volumes (by imaging).

• Histology after tumor resection, comprising assessment of apoptosis and necrosis.

• Phase: N/A
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Fondazione I.R.C.C.S. Istituto Neurologico Carlo Besta
• Treatments: Aminolevulinic Acid

Criteria

Inclusion Criteria:

• Suspected primary lobar Glioblastoma clearly measurable on the basis of Response

• Assessment in Neuro-Oncology (RANO) criteria

• Brain glioblastomas located in a surgically accessible brain region for resection

• The targeted tumor resection volume measures between 1cm and 5cm in diameter.

• Karnofsky rating 70-100

• American Society of Anesthesiologists (ASA) score 1-3

• Able to attend all study visits

• No previous brain surgery

• No previous radiation treatment

• No previous systemic treatment for the tumor

• Able and willing to give informed consent

Exclusion Criteria:

• 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)

• 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

• 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

• Severe hypertension

• Anti-coagulant therapy or medications known to increase risk of hemorrhage within washout period prior to treatment

• History of a bleeding disorder, coagulopathy or with a history of spontaneous tumor hemorrhage

• Abnormal level of platelets (<100000) or international normalized ratio (INR) >1.3

• Cerebral or systemic vasculopathy

• Known allergy sensitivity or contraindications to gadolinium

• Contraindications to MRI such as non-MRI-compatible implanted devices

• Subjects not fitting comfortably into the MRI scanner

• Difficulty lying supine and still for up to 4 hours in the MRI unit or claustrophobia

• Positive pregnancy test (for pre-menopausal women)

• Severely impaired renal function with estimated glomerular filtration rate <30 mL/min/1.73m2 and/or on dialysis

• Respiratory: chronic pulmonary disorders, e.g. severe emphysema, chronic obstructive pulmonary disease (COPD), pulmonary vasculitis, or other causes of reduced pulmonary vascular cross-sectional area.

• Any illness or medical condition that in the investigator's opinion precludes participation in this study

• Patients unable to sign a consent form