Low-Intensity Focused Ultrasound Therapy with 5-ALA (Sonodynamic Therapy) for the Treatment of Recurrent Glioblastoma

Inclusion Criteria

• Disease status and disease parameters: * Suspected recurrent glioblastoma that is clearly measurable based on the modified Response Assessment in Neuro-Oncology (RANO) criteria * The tumor lesion needs to comprise at least 1 contrast-enhancing lesion with a volume of ≥ 2 cm^3 and ≤ 20 cm^3 of targeted treatment area * Tumor tissue to be treated is in a surgically accessible brain region for resection * The brain tumor to be treated must be in the treatment envelope of the Neuronavigation-Guided Focused Ultrasound System (NaviFUS) system (30 mm to 90 mm from the inner skull table) * Recurrence will be assessed by imaging and confirmed by consensus at tumor board
• Men or women between the ages of 18-80 years of age at the time of consent
• No contraindication to repeat brain surgery
• Karnofsky performance score of 70-100
• Able to undergo an MRI with contrast
• Able to swallow oral medications
• Willingness and ability to comply with scheduled visits, treatment plans, lifestyle considerations, laboratory tests, and other procedures
• Ability to understand and the willingness to sign a written informed consent document (personally or by the legally authorized representative, if applicable)
• Participants who received prior chemotherapy, radiation therapy, immunotherapy, and/or another investigational therapy must have recovered (Common Terminology Criteria for Adverse Events [CTCAE] grade ≤ 1 or baseline) from the acute effects of the therapy or therapies) except for residual alopecia or grade 2 peripheral neuropathy prior to registration
• Absolute neutrophil count (ANC) ≥ 1000/mm^3
• Platelets ≥ 100,000/mm^3
• Hemoglobin ≥ 11 g/dL for women and ≥ 12 g/dL for men Participants may receive erythrocyte transfusions to achieve this hemoglobin level at the discretion of the investigator
• International normalized ratio (INR) ≤ 1.4
• Creatinine clearance (CrCl) ≥ 60 mL/min/1.73 m^2 as estimated by the Cockcroft-Gault (C-G) equation. If estimated CrCl is abnormal, accurate measurement should be obtained by 24-hour CrCl
• Bilirubin ≤ 1.5 x upper limit of normal (ULN) (except in patients with Gilbert's disease, where bilirubin to 2.0 x ULN is allowed)
• Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 3 x ULN
• Alkaline phosphatase ≤ 3 x ULN
• Estimated glomerular filtration rate ≥ 30 mL/min/1.73m^2

Exclusion Criteria

• Known sensitivity or allergy to 5-ALA
• Simultaneous use of other potentially phototoxic substances (e.g. tetracyclines, sulfonamides, fluoroquinolones, hypericin extracts)
• Diagnosis of porphyria
• Hypersensitivity against porphyrins
• Pregnancy
• Significant cardiac disease or coagulopathy
• Herniation / intractable seizure / other clinical indications requiring urgent resection
• Known active systemic bacterial infection (requiring intravenous [IV] antibiotics at time of initiating study treatment), fungal infection, or detectable viral infection (such as known human immunodeficiency virus positivity or with known active hepatitis B or C (for example, hepatitis B surface antigen positive)
• Have had a recent ( ≤ 3 months prior to registration) transient ischemic attack or stroke
• Significant vascular disease (e.g. aortic aneurysm)
• Evidence of bleeding diathesis or coagulopathy
• Need for systemic anticoagulation which cannot be held for 3 days prior to SDT
• Unstable angina and/or congestive heart failure (New York Heart [NYH] class III or class IV) within 6 months prior to registration
• Severe hypertension (systolic ≥ 180 mm Hg; diastolic ≥ 120 mm Hg) despite anti-hypertensive medications
• Transmural myocardial infarction within 6 months prior to registration
• Serious and inadequately controlled cardiac arrhythmia
• Acute exacerbation of chronic obstructive pulmonary disease
• Has serious and/or uncontrolled preexisting medical condition(s) that, in the judgment of the investigator, would preclude participation in this study
• Treatment with another investigational drug or investigational procedure within 30 days prior to registration or within 5 half-lives of the investigational product, whichever is longer
• Brain edema and/or mass effect that causes midline shift of more than 15 mm
• Evidence of recent (within 30 days prior to registration) intracranial hemorrhage
• Calcifications or metallic implanted objects in the focused ultrasound sonication path
• Scalp atrophy or scars at the expected location of transducer
• Cerebral or systemic vasculopathy
• Need for or currently on dialysis
• Respiratory: chronic pulmonary disorders (e.g., severe emphysema, chronic obstructive pulmonary disease [COPD], pulmonary vasculitis, or other causes of reduced pulmonary vascular cross-sectional area)
• Receipt of radiotherapy ≤ 21 days prior to registration
• Receipt of chemotherapy ≤ 21 days prior to registration
• Prior treatment with sonodynamic therapy
• Concurrent use of Optune device
• Concurrent use of supplements or medications with substantial antioxidant effects (including sulfhydryl-containing medications such as captopril or supplements such as N-acetylcysteine, or high doses of vitamins with antioxidant activity such as C or E)
• Known sensitivity to gadolinium