Featured Clinical Study
A Dose Escalation and Expansion Study of Sonodynamic Therapy With SONALA-001 in Combination With Exablate 4000 Type-2 MR-guided Focused Ultrasound in Patients With Recurrent or Progressive Glioblastoma Multiforme
Study Sponsor: SonALAsense, Inc.
Study website: https://www.sonalasense.com/phase-2-rgbm-sdt-202
Study Number: NCT05370508
Tumor Type: Recurrent or Progressive glioblastoma (GBM)
Age Group: Adults
Gender: Female & Male
Study Phase: Phase 1/Phase 2
Published Date: 03/27/2023
GENERAL OVERVIEW
Detailed Overview
The goals of this study are to evaluate the safety, preliminary efficacy (progression free survival), Dose-Limiting Toxicities (DLTs), and to determine the Recommended Phase 2 Dose (RP2D) of SONALA-001 in combination with MRI-guided focused ultrasound (MRgFUS), termed Sonodynamic therapy (SDT).
This is evaluated through the use of a new investigational intravenous infusion of SONALA-001 in combination with Exablate Type-2 MRI-guided focused ultrasound in patients with recurrent or progressive GBM.
ELIGIBILITY
Inclusion Criteria
You may be eligible if you:
- are eighteen years or older
- have a primary GBM that has recurred or progressed and resection is not indicated
- have had previous treatment with at least standard-of-care radiotherapy (RT) and temozolomide (only if tumor has at least partial methylation of the MGMT promoter)
- are able to care for yourself
- have adequate organ and marrow function
- have an understanding, ability, and willingness to fully comply with study procedures and restrictions
Exclusion Criteria
You may not be eligible if you:
- have a secondary glioblastoma with IDH1 mutations (i.e., glioblastoma that progressed from low-grade diffuse astrocytoma or AA)
- tumor is located in your brainstem or infratentorial region (lower part) of your brain
- have had a prior surgical resection for recurrent or progressed GBM
- are unable to undergo an MRI (e.g., presence of a pacemaker)
- have a malignant disease, other than that being treated in this study
- have a known history of Human Immunodeficiency Virus (HIV)
- have a known history of Hepatitis B or known active Hepatitis C virus
STUDY DETAILS
Patient Participation Requirements
On the day of treatment, patients will receive SONALA-001 (intravenous aminolevlulinic acid (ALA)) through a peripheral or centrally placed intravenous line by rapid infusion samples over the course of 10-20 minutes. Over the course of the next 24 hours, blood will be drawn periodically to determine how ALA is processed within the body.
After about 7 hours the patient will be brought to the radiology section of the hospital and receive placement of a stereotactic head frame. The patient is then brought to the MRI section of the radiology unit in the hospital. Their head will then be placed within the Exablate 4000, Type 2.0 device helmet against a flexible membrane and an MRI will be performed.
During the next 2-3 hours the patient will receive MRI-guided focused ultrasound to the tumor area. No surgery is required.
After the procedure, the patient’s head is freed from the device helmet and the stereotactic head frame is removed.
The patient will be escorted out of the MRI room for observation and blood draws. The patient will then continue to have assessments for 3-4 weeks after treatment(s) for safety and to evaluate the effect on the tumor.
Depending on when the patient joins the study, they may have one treatment or multiple treatments given about one month apart.
Mechanism of Action
ALA is known to be able to cross the Blood Brain Barrier (BBB) and accumulate in malignant brain tumors in a form which makes the tumor sensitive to light. When SONALA-001 is administered intravenously and combined with MRI-guided Focused Ultrasound, a burst of light is produced that results in the death of glioma cells without damage to normal brain tissue.
Possible Risks and Side Effects
Side effects of intravenous SONALA-001 are still being investigated though may be similar to oral ALA, which may include the side effects listed below.
Side effects of Sonodynamic Therapy with SONALA-001 in combination with the Exablate Type-2 may include the following:
- Fever
- Low blood pressure
- Nausea/Vomiting
- Diarrhea
- Chills
- Light sensitivity
- Skin redness, itching, or pain
- Abnormal liver enzymes
Study Compensation
SonALAsense will pay for all costs not covered by insurance. In addition, SonALAsense will pay for all clinical trial expenses for participants including travel, parking, and meals.
Study Data
Recently, Dr. Sheng-Kai Wu and Dr. Kullervo Hynynen from the Sunnybrook Health Sciences Centre demonstrated that three (aminolevulinic acid) ALA sonodynamic therapy (SDT) treatments resulted in the complete disappearance of the L9 glioma in a rat model, with 100% survival of the animals.
A first-in-human Phase 0/1 clinical trial at the Ivy Brain Tumor Center (NCT04559685) was conducted to investigate the feasibility, safety, and biological effects of ALA SDT using intravenous SONALA-001 in combination with the Exablate Type-2 device in patients with recurrent high-grade glioma (rHGG). 9 patients were treated in 3 increasing energy dose cohorts. In this energy dose-escalation clinical trial, half of the rHGG tumor volume was targeted with SDT and the untreated half served as an internal control. Maximal surgical resection was undertaken 4 days after SDT and SDT-treated tumor tissue and control tumor tissue were examined and compared for evidence of SDT-induced effects. No serious drug-or device-related adverse events were reported.
Preliminary data from the first 10 patients treated in this Phase 0/1 clinical trial in rHGG were presented at the European Society for Medical Oncology and the Society for Neuro-Oncology in 2022. The data from 10 patients showed that the average tumor cell death was significantly higher in SDT-treated tumor vs. control tumor tissue. These preliminary human data support the concept that ALA SDT-treated animal glioma model effects may be successfully translated to human rGBM patients.
STUDY LOCATIONS & CONTACTS
Arizona
Ivy Brain Tumor Center
350 W Thomas Road
Phoenix, AZ 85103
Jamie Sanders
602-406-8605
research@ivybraintumorcenter.org
New York
NYU Langone
530 1st Ave. Skirball 85
New York, NY 10016
Shannon Ciprut
212-263-2441
shannon.ciprut@nyulangone.org
Ohio
Cleveland Clinic
9500 Euclid Avenue, CA-51
Cleveland, OH 44195
Teresa Allison
216-445-8797
ALLISOT@ccf.org
Texas
MD Anderson
Mendelsohn Faculty Center
1515 Holcombe Blvd, Unit 442
Houston, TX 77030
Summer Stovall, RN, BSN, CCRP
713-792-2400
Sstovall@mdanderson.org
