Sonodynamic therapy using SONALA-001 or 5-ALA with MRI-guided focused ultrasound for progressive or recurrent glioblastoma

MC240704 Pilot Dose Escalation and Expansion Study of Sonodynamic Therapy With Aminolevulinic Acid Hydrochloride (5-ALA HCl Or SONALA-001) in Combination With Exablate 4000 Type 2.0 MR-Guided Focused Ultrasound (MRgFUS) in Patients With Progressive or Recurrent Glioblastoma Multiforme (RGBM)

This trial tries giving SONALA-001 (IV) or 5-ALA (oral) together with MRI-guided focused ultrasound to see if the combination is safe and can help people whose glioblastoma has progressed or come back.

Quick facts

• Phase: Early Phase 1
• Study type: Interventional
• Enrollment: 8 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Mayo Clinic (Academic / other)
• Locations: 1 site (Rochester, Minnesota)
• Trial ID: NCT07076472 on ClinicalTrials.gov

What this trial studies

This is an early Phase I trial testing sonodynamic therapy, which combines a tumor-localizing drug (SONALA-001 intravenously or oral 5-ALA) with magnetic resonance-guided focused ultrasound (MRgFUS) to activate the drug and target tumor cells without open surgery. Participants receive the drug, then undergo transcranial MRgFUS 3–8 hours later on day 1 of each 42-day cycle, with imaging and blood tests used to monitor response and safety. The primary goal is to characterize safety and toxicity; secondary measures include tumor response by RANO 2.0, progression-free survival, and overall survival. Patients are followed for safety at 30 days after treatment and then every 3–6 months for up to 3 years.

Who should consider this trial

Good fit: Adults (≥18 years) with progressive or recurrent glioblastoma not suitable for resection, who have had prior radiotherapy and have ECOG performance status 0–2 and adequate blood and liver function, are the intended candidates.

Not a fit: Patients who are surgical candidates, have very poor organ function or blood counts, a life expectancy under 12 weeks, cannot have MRI, or have other contraindications to the drug or ultrasound are unlikely to benefit or be eligible.

Why it matters

Potential benefit: If successful, this approach could offer a noninvasive, tumor-targeted treatment that may slow tumor growth or extend survival while limiting damage to surrounding healthy brain tissue.

How similar studies have performed: This sonodynamic approach is relatively novel for glioblastoma: 5-ALA is established for fluorescence-guided surgery and there are encouraging preclinical and very early clinical signals for sonodynamic methods, but robust evidence in recurrent GBM is limited.

Eligibility criteria

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

Where this trial is running

Rochester, Minnesota

• Mayo Clinic in Rochester — Rochester, Minnesota, United States (Recruiting)

Study contacts

• Principal investigator: Terence C. Burns, MD, PhD — Mayo Clinic
• Study coordinator: Clinical Trials Referral Office

Conditions Progressive Glioblastoma; Recurrent Glioblastoma