Sonodynamic Therapy with ExAblate System in Glioblastoma Patients

NCT04845919 | Completed Phase 2

• 1 other identifier: Sonic ALA
• Study Type: interventional
• Target: 5
• Locations: 1 country
• Sites: 1

Brief 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 15-21 days after SDT, according to the clinical and radiological status. The main goal of the present study is to investigate the safety and feasibility of SDT in patients affected by GBMs attained with low-frequency FUS. In particular: Safety will be evaluated by patient examination and MRI images during the treatment, and by follow-up MRI and clinical and neurological visits. To evaluate feasibility, the extent of the sonicated area will be calculated at the end of the procedure in order to evaluate the targeted area. Secondary objective of the trial is to assess the efficacy of the SDT procedure in terms of tumor regression and/or cell apoptosis and necrosis.

Conditions

Glioblastoma Multiforme

Keywords

Sonodynamic therapy,; focused ultrasound,; 5-aminolevulinic acid

Outcome Measures

Primary Outcomes (1)

• Presence of hemorrhage, edema or other damages

  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

  10 days after the procedure

Secondary Outcomes (2)

• Rate of neurological deficits

  10 days after the procedure

• Radiological response to treatment

  10 days after the procedure

Study Arms (1)

5-ALA mediated sonodynamic therapy

EXPERIMENTAL

Drug: 5-Aminolevulinic Acid

Interventions

5-Aminolevulinic Acid DRUG

SDT treatment with 5-ALA using the ExAblate Model 4000 Type-2 "Neuro-System".

5-ALA mediated sonodynamic therapy

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Men or women, age between 18 and 75 years, inclusive.
• Suspected primary lobar Glioblastoma clearly measurable on the basis of Response Assessment in Neuro-Oncology (RANO) criteria
• Newly diagnosed brain glioblastomas located in a surgically accessible brain region for resection
• The targeted tumor resection volume measures between 1 cm and 6 cm in diameter.
• Karnofsky rating 70-100.
• 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.
• No contraindication to MRI.
• No contraindication to brain surgery.
• Contraceptive use by both male and female subjects consistent with local regulations regarding the methods of contraception for those participating in clinical studies.
• Male participants: Male participants must agree that, if their partner is at risk of becoming pregnant, they will use an effective method of contraception. The participants must agree to use the contraception during the whole period of the study and for 12 weeks after the study intervention injection.

You may not qualify if:

• Brain glioblastoma presenting with the following characteristics:
• Brain edema and/or mass effect that causes midline shift of more than 15 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 arrhythmia
• Cardiac pacemaker

Sponsors & Collaborators

• Fondazione I.R.C.C.S. Istituto Neurologico Carlo Besta: lead

Study Sites (1)

Foundation IRCCS Carlo Besta Neurological Institute

Milan, Italy, 20133, Italy

Location

Related Publications (4)

• Bonosi L, Marino S, Benigno UE, Musso S, Buscemi F, Giardina K, Gerardi R, Brunasso L, Costanzo R, Iacopino DG, Maugeri R. Sonodynamic therapy and magnetic resonance-guided focused ultrasound: new therapeutic strategy in glioblastoma. J Neurooncol. 2023 May;163(1):219-238. doi: 10.1007/s11060-023-04333-3. Epub 2023 May 14.

  PMID: 37179515 BACKGROUND

• Pellegatta S, Corradino N, Zingarelli M, Porto E, Gionso M, Berlendis A, Durando G, Maffezzini M, Musio S, Aquino D, DiMeco F, Prada F. The Immunomodulatory Effects of Fluorescein-Mediated Sonodynamic Treatment Lead to Systemic and Intratumoral Depletion of Myeloid-Derived Suppressor Cells in a Preclinical Malignant Glioma Model. Cancers (Basel). 2024 Feb 15;16(4):792. doi: 10.3390/cancers16040792.

  PMID: 38398183 BACKGROUND

• Keating GF, Chesney KM, Patel N, Kilburn L, Fonseca A, Packer RJ, Challa C, O'Brien PF, Donoho DA, Myseros JS, Oluigbo C, Keating RF, Syed HR. MR-guided focused ultrasound in pediatric neurosurgery: current insights, technical challenges, and lessons learned from 45 treatments at Children's National Hospital. Neurosurg Focus. 2024 Sep 1;57(3):E6. doi: 10.3171/2024.6.FOCUS24332.

  PMID: 39217632 BACKGROUND

• Huangfu L, Zha B, Li P, Wang L, Liu X, Cui H, Li Y, Wu J, Shi S, Yang Y, Sun X, Gao S, Li H, Yang D, Zheng Y. A phase I clinical trial of sonodynamic therapy combined with radiotherapy for brainstem gliomas. Int J Cancer. 2025 Mar 1;156(5):1005-1014. doi: 10.1002/ijc.35218. Epub 2024 Oct 8.

  PMID: 39377640 BACKGROUND

MeSH Terms

Conditions

Glioblastoma

Interventions

Aminolevulinic Acid

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Levulinic Acids; Keto Acids; Carboxylic Acids; Organic Chemicals; Amino Acids; Amino Acids, Peptides, and Proteins

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: OTHER
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 2, 2021
• First Posted: April 15, 2021
• Study Start: February 22, 2023
• Primary Completion: October 30, 2024
• Study Completion: October 30, 2024
• Last Updated: November 12, 2024

Record last verified: 2024-11

Data Sharing

• IPD Sharing: Will not share

Locations

IT (1)