Overview

This phase Ib trial tests the safety, best dose, and effectiveness of SONALA-001 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, to kill tumor cells. SONALA-001 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 with MRgFUS may be safe, tolerable, and/or effective in treating patients with progressive or recurrent glioblastoma.

Eligibility

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