Sonodynamic Therapy With SONALA-001 or 5-ALA HCL and Magnetic Resonance Guided Focused Ultrasound for the Treatment of 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.

Inclusion criteria

• Age ≥ 18 years
• Diagnosis of recurrent or progressive glioblastoma (as defined in 2021 World Health Organization [WHO] Classification of Tumors of the Central Nervous System; Louis, Perry, et al. 2021) for which resection is not indicated as assessed by the study physician
• Radiographic evidence of disease which may be measurable or non-measurable
• Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0, 1 or 2
• Previous treatment with radiotherapy (RT)
• Have a life expectancy of ≥ 12 weeks
• Hemoglobin ≥ 9.0 g/dL (obtained ≤ 15 days prior to registration)
• Absolute neutrophil count (ANC) ≥ 1500/mm^3 (obtained ≤ 15 days prior to registration)
• Platelet count ≥ 100,000/mm^3 (obtained ≤ 15 days prior to registration)
• Total bilirubin ≤ 1.5 x upper limit of normal (ULN) (obtained ≤ 15 days prior to registration)
• Alanine aminotransferase (ALT) and aspartate transaminase (AST) ≤ 3 x ULN (≤ 5 x ULN for patients with liver involvement) (obtained ≤ 15 days prior to registration)
• Albumin ≥ 3 g/dL (obtained ≤ 15 days prior to registration)
• Potassium ≥ lower limit of normal (LLN) (obtained ≤ 15 days prior to registration)
• Serum total calcium ≥ LLN (obtained ≤ 15 days prior to registration)
• Creatinine ≤ 1.5 x ULN OR calculated creatinine clearance ≥ 60 mL/min using the Cockcroft-Gault formula (obtained ≤ 15 days prior to registration)
• Negative pregnancy test done ≤ 8 days prior to registration, for persons of childbearing potential only
• Provide written informed consent
• Willing to participate in the neuro-oncology biorepository [Institutional Review Board (IRB) 12-003458, principal investigator (PI): Jann Sarkaria, MD, PhD] for collecting and archiving biospecimens samples on neuro-oncology patients
• Willing to return to enrolling institution for follow-up (during the active monitoring phase of the study)

Exclusion criteria

• Any of the following because this study involves an investigational agent, the genotoxic, mutagenic, and teratogenic effects of which on the developing fetus and newborn are unknown:

• Pregnant persons
• Nursing persons
• Persons of childbearing potential (and persons able to father a child) who are unwilling to employ adequate contraception
• Recurrence ≤ 4 weeks after the completion of RT, defined from the imaging assessment immediately after completion of RT
• Three or more prior systemic treatments for recurrent or progressing disease
• Diagnosis of porphyria, or hypersensitivity to porphyrins
• Failure to recover to grade 1 or baseline from any adverse events (AEs) (Common Terminology Criteria for Adverse Events [CTCAE] version [v] 5.0) related to prior anticancer therapy

• EXCEPTIONS: Alopecia, lymphopenia, peripheral neuropathy, and ototoxicity ≤ grade 3)
• Known history of the following conditions:

• Allergy to gadolinium contrast agents
• Patients known to be HIV positive and currently receiving antiretroviral therapy

• NOTE: Patients known to be HIV positive, but without clinical evidence of an immunocompromised state, are eligible for this trial
• Inability to undergo MRI scans
• Uncontrolled intercurrent illness including, but not limited to:

• Ongoing or active infection
• Patients with platelet count < 100
• Symptomatic congestive heart failure
• Unstable angina pectoris
• Cardiac arrhythmia
• Or psychiatric illness/social situations that would limit compliance with study requirements
• History of myocardial infarction ≤ 6 months, or congestive heart failure requiring use of ongoing maintenance therapy for life-threatening ventricular arrhythmias
• Co-morbid systemic illnesses or other severe concurrent disease which, in the judgment of the investigator, would make the patient inappropriate for entry into this study or interfere significantly with the proper assessment of safety and toxicity of the prescribed regimens