Sonodynamic Therapy in Patients With Recurrent GBM

The combination of 5-ALA (Gleolan) and LIFU is collectively known as sonodynamic therapy (SDT). SDT is an investigational therapy that will be administered 1-3 weeks before surgery for recurrent GBM. Researchers seek to determine the safety and feasibility of this therapy as well as measure its effectiveness to elicit tumor-cell death. All participants are expected to stay overnight in the hospital following administration of SDT to monitor for adverse events.

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 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 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.
• Has adequate bone marrow and organ function as defined by the following laboratory values (as assessed by the local laboratory for eligibility):

Hematological

• 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

Renal & Hepatic

• 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
• Estimated glomerular filtration rate ≥30mL/min/1.73m2

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 7 days prior to SDT
• Unstable angina and/or congestive heart failure (NYH Class III or Class IV; see section 13.2) 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, 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