A Phase 1 Single Center Clinical Trial Evaluating Safety of 5-Aminolevulinic Acid (5-ALA) Combined With CV01 Delivery of Ultrasound for Sonodynamic Therapy (SDT) in Patients With Newly Diagnosed High-Grade Glioma (HGG) Prior to Resection and Standard Adjuvant Therapy
This trial is designed to evaluate safety and explore possible efficacy of 5-aminolevulinic acid hydrochloride (5-ALA HCl, Gliolan®) with CV01 delivery of ultrasound for sonodynamic therapy in patients with newly diagnosed high-grade glioma prior to resection and standard adjuvant therapy. The study will accrue 10 evaluable high-grade glioma patients. Patients who qualify will receive sonodynamic therapy (5 ALA combined with CV01-delivered sonication) 2 to 5 days prior to standard resection, with one study magnetic resonance imaging being performed between sonodynamic therapy and resection. Resection will be followed by standard radio-/chemotherapy. All patients will be followed up in-study for toxicities and adverse events for 28 days.
• Age ≥ 18 years
• WHO Performance Status of 0-2
• Patients with cranial MRI displaying typical features of high-grade glioma on imaging or histologically proven high-grade glioma including GBM, anaplastic astrocytoma (AA), anaplastic oligodendroglioma (AO). No previous tumor specific treatment such as surgery (apart from biopsy), radio- or chemotherapy, antiangiogenic or immunotherapy.
• Planned debulking or cytoreductive surgery
• The following laboratory values at study entry
‣ Absolute neutrophil count (ANC) ≥ 1500 cells/mm3
⁃ Platelet count ≥ 100,000 cells/mm3
⁃ Hemoglobin (Hgb) \> 10g/dL
⁃ AST and ALT ≤ 2.5 x Upper Limit of Normal (ULN)
⁃ Total bilirubin ≤ 1.5 x ULN
⁃ Creatine clearance (CrCL) as estimated by Cockcroft-Gault equation of
‣ ≥ 40 mL/min
⁃ Blood clotting within acceptable limits according to investigator
• For female and male patients and their female partners of childbearing/reproductive potential: Willingness to apply highly effective contraception (Pearl index \<1) during the entire study and in female patients for 6 months after the last application of Gliolan® and in male patients and their female partners for 3 months after the last application of Gliolan®.
• Ability to understand and provide informed consent