Sonodynamic Therapy in Patients With Recurrent GBM

Eligibility Criteria

• 1. 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 ≥ 6 cm3 and ≤ 20 cm3 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 NaviFUS system (30 mm to 80 mm from the inner skull table)
• * Recurrence will be assessed by imaging and confirmed by consensus at tumor board
• 2. Men or women between the ages of 18-80 years of age at the time of consent
• 3. No contraindication to repeat brain surgery
• 4. Karnofsky Performance Score of 70-100
• 5. Able to undergo an MRI with contrast
• 6. Able to swallow oral medications
• 7. Willingness and ability to comply with scheduled visits, treatment plans, lifestyle considerations, laboratory tests, and other procedures.
• 8. Ability to understand and the willingness to sign a written informed consent document (personally or by the legally authorized representative, if applicable).
• 9. 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.
• 10. Has adequate bone marrow and organ function as defined by the following laboratory values (as assessed by the local laboratory for eligibility):
• * Absolute neutrophil count (ANC) ≥1000/mm3
• * Platelets ≥ 100,000/mm3
• * 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.
• * INR ≤ 1.4
• * Creatinine clearance CrCl ≥ 60 mL/min/1.73 m2 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 ULN (except in patients with Gilbert's disease, where bilirubin to 2.0x ULN is allowed).
• * AST and ALT ≤ 3 x ULN
• * Alkaline phosphatase ≤ 3 x ULN
• * GGT ≤ 3 x ULN
• * Estimated glomerular filtration rate ≥30mL/min/1.73m2
• 1. Known sensitivity or allergy to 5-ALA
• 2. Simultaneous use of other potentially phototoxic substances (e.g. tetracyclines, sulfonamides, fluoroquinolones, hypericin extracts)
• 3. Diagnosis of porphyria
• 4. Hypersensitivity against porphyrins
• 5. Pregnancy
• 6. Significant cardiac disease or coagulopathy
• 7. Herniation / intractable seizure / other clinical indications requiring urgent resection
• 8. 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)
• 9. Have had a recent (≤3 months prior to registration) transient ischemic attack or stroke
• 10. Significant vascular disease (e.g. aortic aneurysm)
• 11. Evidence of bleeding diathesis or coagulopathy
• 12. Need for systemic anticoagulation which cannot be held for 7 days prior to SDT
• 13. Unstable angina and/or congestive heart failure (NYH Class III or Class IV; see section 13.2) within 6 months prior to registration
• 14. Severe hypertension (systolic ≥ 180 mm Hg; diastolic ≥ 120 mm Hg) despite anti-hypertensive medications
• 15. Transmural myocardial infarction within 6 months prior to registration
• 16. Serious and inadequately controlled cardiac arrhythmia
• 17. Acute exacerbation of chronic obstructive pulmonary disease
• 18. Has serious and/or uncontrolled preexisting medical condition(s) that, in the judgment of the investigator, would preclude participation in this study
• 19. 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
• 20. Brain edema and/or mass effect that causes midline shift of more than 15 mm
• 21. Evidence of recent (within 30 days prior to registration) intracranial hemorrhage
• 22. Calcifications or metallic implanted objects in the focused ultrasound sonication path
• 23. Scalp atrophy or scars at the expected location of transducer
• 24. Cerebral or systemic vasculopathy
• 25. Need for or currently on dialysis
• 26. Respiratory: chronic pulmonary disorders (e.g., severe emphysema, COPD, pulmonary vasculitis, or other causes of reduced pulmonary vascular cross-sectional area).
• 27. Receipt of radiotherapy ≤21 days prior to registration
• 28. Receipt of chemotherapy ≤ 21 days prior to registration
• 29. Prior treatment with sonodynamic therapy
• 30. Concurrent use of Optune device
• 31. 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)
• 32. Known sensitivity to gadolinium