This early phase I trial tests the safety, best dose, and effectiveness of SONALA-001 or 5-ALA HCL in combination with magnetic resonance imaging-guided focused ultrasound (MRgFUS), also called sonodynamic therapy, in treating patients with glioblastoma that is growing, spreading, or getting worse (progressive) or that has come back after a period of improvement (recurrent). Sonodynamic therapy is a non-invasive combination therapy that uses low-intensity ultrasound, such as MRgFUS, to activate a drug, such as SONALA-001 or 5-ALA HCL, to kill tumor cells. SONALA-001 or 5-ALA HCL binds to the tumor and may help the sonodynamic therapy target the tumor. MRgFUS is an image-guided, non-invasive technique that uses high energy ultrasound from the Exablate 4000 Type 2.0 device to kill tumors without damaging surrounding healthy tissue. Giving sonodynamic therapy using SONALA-001 or 5-ALA HCL with MRgFUS may be safe, tolerable, and/or effective in treating patients with progressive or recurrent glioblastoma.
PRIMARY OBJECTIVE: I. To characterize the safety and toxicity after treatment with aminolevulinic acid intravenous formulation SONALA-001 (SONALA-001) or orally administered aminolevulinic acid hydrochloride (5-ALA HCL) in combination with MRgFUS in subjects with progressive or recurrent glioblastoma (rGBM). SECONDARY OBJECTIVES: I. To evaluate the preliminary antitumor activity as assessed by objective response rate (ORR; proportion of patients with complete or partial response) per Response Assessment in Neuro-Oncology (RANO) 2.0 guidelines. II. To evaluate preliminary signals of activity as measured by clinical benefit rate (CBR) (proportion of patients with complete response, partial response or stable disease), progression-free survival (PFS), PFS rate at 6 months, and overall survival (OS). OUTLINE: Patients receive SONALA-001 intravenously (IV) over 15 minutes or 5-ALA HCL orally (PO) and undergo transcranial MRgFUS 3-8 hours after infusion on day 1 of each cycle. Cycles repeat every 42 days in the absence of disease progression or unacceptable toxicity. Additionally, patients undergo a computed tomography (CT) of the brain prior to treatment and blood sample collection and magnetic resonance imaging (MRI) throughout the study. After completion of study treatment, patients are followed up at 30 days, and then every 3 to 6 months for up to 3 years after registration.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
8
Undergo blood sample collection
Undergo CT
Ancillary studies
Undergo MRI
Undergo transcranial MRgFUS
Given PO
Mayo Clinic in Rochester
Rochester, Minnesota, United States
RECRUITINGIncidence of adverse events (AEs)
Defined per the Common Terminology Criteria for Adverse Events (CTCAE) version (v) 5 as AEs considered to be at least possibly related to study treatment. The maximum grade for each type of AE will be recorded for each patient, and frequency tables will be reviewed to determine patterns (by dose level and overall).
Time frame: Up to 30 days after last dose of study treatment
Incidence of grade 3 or higher non-hematologic AEs
Defined per the CTCAE v5 as AEs considered to be at least possibly related to study treatment. The maximum grade for each type of AE will be recorded for each patient, and frequency tables will be reviewed to determine patterns (by dose level and overall).
Time frame: Up to 30 days after last dose of study treatment
Incidence of grade 4 or higher AE
Defined per the CTCAE v5 as AEs considered to be at least possibly related to study treatment. The maximum grade for each type of AE will be recorded for each patient, and frequency tables will be reviewed to determine patterns (by dose level and overall).
Time frame: Up to 30 days after last dose of study treatment
Dose-limiting event (DLE)
AEs will be evaluated using CTCAE v5. The target DLE rate is \< 33%.
Time frame: During first 6 weeks of therapy [first cycle of treatment (cycle length = 42 days)]
Maximum tolerated dose (MTD)
Will be defined as the highest safety-tolerated dose level where at most one patient out of six experiences a DLE.
Time frame: Up to 6 weeks
Overall response rate (ORR)
Assessed by the proportion of patients with complete or partial response.
Time frame: Up to 3 years
Clinical benefit rate
Assessed by the proportion of patients with complete response, partial response or stable disease.
Time frame: Up to 3 years
Progression-free survival (PFS)
Defined as the time from registration to the earliest date of documentation of disease progression, relapse, or death due to any cause.
Time frame: Up to 3 years
PFS at 6 months (PFS6)
The PFS6 rate will be estimated as the number of patients who are progression-free and alive at 6 months.
Time frame: At 6 months
Overall survival (OS)
Defined as the time from registration to death due to any cause.
Time frame: Up to 3 years
Time to response
Defined as the time from registration to the first incidence of a response, estimated in patients who have achieved a response (PR or CR).
Time frame: Up to 3 years
Duration of response
Defined as the time from response to progression or death, whichever occurs first estimated among patients who have achieved objective response (PR or CR).
Time frame: Up to 3 years
Duration of clinical benefit
Defined as the time from response to progression or death, whichever occurs first, estimated among patients who achieved clinical benefit (stable disease, PR, or CR).
Time frame: Up to 3 years
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