Pilot Study of Sonodynamic Therapy With 5-ALA for the Treatment of Recurrent Glioblastoma Using Neuronavigation-Guided Low-Intensity Focused Ultrasound
Patients diagnosed with glioblastoma (GBM) are faced with limited treatment options. This pilot study will evaluate the safety and feasibility of combining an investigational drug called 5-ALA with neuronavigation-guided low-intensity focused ultrasound (LIFU) for patients who have recurrent GBM. Focused ultrasound (FUS) can be used to non-invasively destroy tumor tissue while preserving normal tissue. When FUS is combined with 5-ALA, this combinatorial approach is called sonodynamic therapy (SDT), and this investigational therapy is being tested for its ability to cause damage to GBM cells. SDT will take place prior to surgery for recurrent GBM.
⁃ 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