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 (ALA SDT GLIOMA 401)

Inclusion Criteria:

1. Age ≥ 18 years

2. WHO Performance Status of 0-2

3. Patients with cranial MRI displaying typical features of high-grade glioma onimaging or histologically proven high-grade glioma including GBM, anaplasticastrocytoma (AA), anaplastic oligodendroglioma (AO). No previous tumor specifictreatment such as surgery (apart from biopsy), radio- or chemotherapy,antiangiogenic or immunotherapy.

4. Planned debulking or cytoreductive surgery

5. The following laboratory values at study entry

6. Absolute neutrophil count (ANC) ≥ 1500 cells/mm3

7. Platelet count ≥ 100,000 cells/mm3

8. Hemoglobin (Hgb) > 10g/dL

9. AST and ALT ≤ 2.5 x Upper Limit of Normal (ULN)

10. Total bilirubin ≤ 1.5 x ULN

11. Creatine clearance (CrCL) as estimated by Cockcroft-Gault equation of ≥ 40 mL/min

12. Blood clotting within acceptable limits according to investigator

13. For female and male patients and their female partners of childbearing/reproductivepotential: Willingness to apply highly effective contraception (Pearl index <1)during the entire study and in female patients for 6 months after the lastapplication of Gliolan® and in male patients and their female partners for 3 monthsafter the last application of Gliolan®.

14. Ability to understand and provide informed consent

Exclusion Criteria:

1. Infra-tentorial tumors

2. Patients who have clinically significant edema or tumor mass effect requiring urgentintervention (e.g., surgery, initiation of steroids, escalating doses of steroids)

3. Women who are pregnant or breastfeeding

4. Inability to undergo MRI or receive gadolinium (Gd)

5. Hypersensitivity to 5-ALA or porphyrins

6. Average skull thickness at the treatment field > 10 mm from standard navigation CTs.The treatment field is defined as the various locations on the head where thetransducer will be coupled to the patient. The average skull thickness at eachtreatment field will be determined through post-processing the thin cut headcomputed tomography (CT) scan (without contrast).

7. Hemorrhagic or ischemic stroke (including transient ischemic attacks) and centralnervous system bleeding in the preceding 6 months that are not related to gliomabiopsy. History of prior intratumoral bleeding is not an exclusion criterion;however, all patient's navigation CTs will be reviewed for the presence of freshblood.

8. Participation in another interventional clinical trial during this trial or within 4weeks before entry into this trial

9. Known acute or chronic types of porphyria

10. Gastrointestinal disorder that negatively affects absorption

11. Known active hepatitis B or C (Note: testing is not required)

12. Known Human Immunodeficiency Virus (HIV) infection (Note: testing is not required)

13. Unable to avoid photosensitising drugs (eg, St. John's wort, griseofulvin, thiazidediuretics, sulfonylureas, phenothiazines, sulfonamides, quinolones, andtetracyclines) for up to 2 weeks following 5-ALA administration

14. Any other concurrent severe and/or uncontrolled concomitant medical condition thatcould compromise participation in the study (e.g, clinically significant pulmonarydisease, clinically significant psychiatric or neurological disorder, active oruncontrolled infection)

15. Diagnosis of other invasive cancer (except basal cell carcinoma/squamous cellcarcinoma of the skin) within the last 5 years; adequately treated carcinoma in situis allowed

16. Patient has a condition the investigator believes would interfere with the abilityto provide informed consent or comply with study instructions, or that mightconfound the interpretation of the study results or put the patient at undue risk

17. Patients who are dependent on the sponsor, investigator or trial site

18. Patients who are committed to an institution by virtue of an order issued either bythe judicial or the administrative authorities