Sonodynamic Therapy With ExAblate System in Glioblastoma Patients (Sonic ALA)
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|ClinicalTrials.gov Identifier: NCT04845919|
Recruitment Status : Not yet recruiting
First Posted : April 15, 2021
Last Update Posted : April 15, 2021
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.
|Condition or disease||Intervention/treatment||Phase|
|Glioblastoma Multiforme||Drug: 5-Aminolevulinic Acid||Not Applicable|
Despite progress made in many cancer treatments, high-grade gliomas (HGG) remain an extraordinary challenge. Their aggressive and infiltrative nature, the limited efficacy and inherent risk of surgical resection combined with radiotherapy, and the difficulty in delivering anticancer drugs to the brain, make the prognosis for patients with gliomas grim. Therefore, new and less-invasive alternatives to existing procedures are needed.
Sonodynamic therapy (SDT) represents an emerging approach that offers the possibility of non-invasively eradicating solid tumors in a site-directed manner. It involves the delivery of a non-toxic chemical agent that selectively accumulates into target areas and the subsequent exposure of the targeted tissue to relatively low-intensity ultrasound. These procedures (sensitization and ultrasound exposure) are both per se harmless, but, when combined, result in activation of the chemical agent and subsequent cytotoxic events limited to the target tissue volume. SDT offers significant advantages because ultrasound energy can be tightly focused and delivered through the intact skull to deep areas of the brain, depending on the frequency. SDT is achieved by focusing low-intensity and low-frequency ultrasound, which, as opposite to high-intensity ultrasonic beams, can be focused effectively within the whole intracranial space with the currently available device (ExAblate 4000, Insightec, Haifa, Israel). This would enable to target also tumors in the peripheral area of the intracranial space.
5-ALA is a protoporhyrin IX (PpIX) precursor that selectively accumulates in HGGs because of an enhanced uptake and metabolism from tumor cells. It is used for intra-operative guidance in surgery as tumoral tissues shows an exceeding fluorescence under certain light conditions due to PpIX accumulation, as compared to the normal surrounding parenchyma. It is therefore a good candidate for SDT. 5-ALA can exert sonodynamic effects against HGGs, as it has been shown in several pre-clinical studies. Unpublished pre-clinical data on a safety experiment conducted at the University of Virginia showed that SDT with 5-ALA was not exerting a toxic effect to the normal brain.
The idea of the present study is to investigate the antitumor effects of SDT in patients affected by HGGs attained with low-frequency focused ultrasound. Focused ultrasound under MRI-guidance can be safely delivered through an intact human skull to perform SDT in combination with 5-ALA with a low risk of transient adverse effects, as evaluated during follow-up visits, post-procedural serial MRI and histology.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||5 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||A Pilot Study to Evaluate the Safety and Feasibility of Sonodynamic Therapy Using the ExAblate MRI-Guided Focused Ultrasound in the Treatment of Cerebral Glioblastomas.|
|Estimated Study Start Date :||May 2021|
|Estimated Primary Completion Date :||May 2021|
|Estimated Study Completion Date :||December 2022|
|Experimental: 5-ALA mediated sonodynamic therapy||
Drug: 5-Aminolevulinic Acid
SDT treatment with 5-ALA using the ExAblate Model 4000 Type-2 "Neuro-System".
- Presence of hemorrhage, oedema or other damages [ Time Frame: 10 days after the procedure ]MR images will be acquired before the procedure and will also be used to guide the FUS treatment; new MRI scans will be acquired at immediately after and at 24 hours, 5 days and 10 days after the procedure and will be analyzed to identify any focal alteration within the treatment's radius compatible with hemorrhages, necrosis, oedema, inflammation or other damages
- Rate of neurological deficits [ Time Frame: 10 days after the procedure ]Patients will be clinically evaluated to identify any change in their clinical picture or new onset of neurological symptoms/deficits,
- Radiological response to treatment [ Time Frame: 10 days after the procedure ]Tumor volume at baseline will be assessed for each patient as gadolinium-enhancing parenchymal regions before any follow-up scan. Post-treatment tumor volumes will be assessed at all follow-up MRI scans, and radiological response to sonodynamic therapy -i.e. the change in pathological volume after the treatment- will be determined by confronting baseline and follow-up scans by the RANO Criteria.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04845919
|Contact: Francesco Prada, MD||+39022394 ext firstname.lastname@example.org|
|Contact: Renato Mantegazza, MD||+39022394 ext email@example.com|