A Study of the Boron Neutron Capture Therapy (BNCT) Using B10 L-BPA in Malignant Brain Tumors

Inclusion Criteria:

1. Age of 18 years and older.

2. Patients with malignant brain tumors confirmed by histological and/or medicalimaging, classified as WHO Grade 3 or 4 according to the World Health Organizationof tumors of the central nervous system (CNS) classification, excluding those withhistologically confirmed Grade 3 intracranial ependymoma, medulloblastoma, andprimary CNS lymphoma.

3. There must be a time interval ≥ 3 months between prior radiation therapy and thescheduled BNCT.

4. There must be a time interval ≥ 1 month between receipt of antitumor drugs and thescheduled BNCT.

5. Within 4 weeks prior to the screening visit, measurable disease by magneticresonance imaging (MRI) and/or computed tomography (CT) scan showing a volume ≦ 250cm^3, longest dimension < 7 cm.

6. At least one measurable lesion that can be assessed by RECIST v1.1.

7. Eastern Cooperative Oncology Group (ECOG) Performance Score ≤ 2.

8. Life expectancy ≥ 3 months in the opinion of the investigator.

9. Adequate organ functions as defined below:

• Hemoglobin ≥ 8.0 g/dL.

• White blood cell (WBC) count ≥ 2.5 x 10^3/μL.

• Neutrophil count ≥ 1.5 × 10^3/μL.

• Platelet count ≥ 80 × 10^3/μL.

• Aspartate aminotransferase (AST) ≤ 2.5 × upper limit of normal (ULN).

• Alanine aminotransferase (ALT) ≤ 2.5 × ULN.

• Serum creatinine ≤ 1.5 × ULN

• Estimated glomerular filtration rate(eGFR) ≥ 15 mL / min / 1.73m^2

10. Female subjects with reproductive potential must have a negative result of serumpregnancy test at the screening visit and urine pregnancy test before the B10 L-BPAadministration. However, if the subject has been menopausal for at least 2 years (more than 24 months since the last menstrual period) or uses surgical birthcontrol, testing is not required.

11. Female subject with childbearing potential as well as male subject with reproductivepotential must agree to refrain from unprotected sex and use 2 methods of highlyeffective contraception with their partner (e.g. barrier contraceptives [malecondom, female condom, or diaphragm plus spermicide], intrauterine device, hormonalmethods [hormone shot or injection, implants, combination oral contraceptives, orpatches]) for ≥ 6 months after the BNCT until the end of this study.

12. Physically and mentally capable of participating in the study and willing to adhereto study procedures.

13. Provision of signed informed consent.

Exclusion Criteria:

1. Patients with malignant brain tumors complicated by any of the following conditions:

• Extracranial metastases.

• Multiple intracranial lesions on both sides.

2. The investigator assesses that the subject has concurrent infections or othermalignant tumors and is not suitable to participate in the trial.

3. Patients with malignant brain tumors are considered eligible for standard surgicaltreatment that is effective against the tumor.

4. A time interval less than 3 months from previous radiation therapy for intracranialregion.

5. A time interval less than 3 months from last brain surgery (excluding drainageprocedures and biopsy) and less than 1 month from previous chemotherapy.

6. The adverse event of previous anti-tumor therapy were NCI-CTCAE V5.0 gradeevaluation ≧ Class 3 (excluding alopecia and peripheral neuropathy).

7. Received or expect to receive any investigational drug, biologic or device within 1month prior to the scheduled BNCT.

8. Patients receiving or expected to receive vascular endothelial growth factorinhibitors (except bevacizumab) or live attenuated vaccines within 1 month prior tothe scheduled BNCT.

9. Patients received major surgery within 1 month prior to the scheduled BNCT or arestill recovering from a previous surgery. The investigator will evaluate thesubject's condition when the subject receives major surgery. Major surgery isdefined as procedure that requires general anaesthesia and/or anticipatedhospitalization longer than 24 hours, with significant risk of blood loss orcomplications. Examples include heart surgery, organ transplants, and prolongedoperations such as certain back surgeries. Procedures such as stent implantation,biopsy, endoscopy, and day surgery are excluded.

10. Patients who had radiation myelitits or radiation necrosis of the brain/brain stem.

11. Patient who is prone to vascular rupture during the trial as assessed by theinvestigator. The Patient will be eligible for the study if they have undergonestent implantation and obtained consent from the investigator.

12. Patients with severe congestive heart failure or renal failure, as well asmyocardial infarction, unstable angina, or poorly controlled arrhythmia within 6months prior to the scheduled BNCT.

13. Severe comorbidities, including but not limited to poorly controlled epilepsy,poorly controlled diabetes mellitus, poorly controlled hypertension; chronic lungdiseases (e.g., obstructive pneumonia, interstitial pneumonia, pulmonary fibrosis,and severe emphysema); kidney diseases (e.g., chronic renal failure, acute renalfailure and nephrotic syndrome); cardiac diseases (e.g., New York Heart Association [NYHA] Functional Classification Class III or IV); phenylketonuria; and/or othersevere conditions in the opinion of the investigator.

14. Suspected or known hypersensitivity (including allergy) to boron or any component ofthe study drug or contrast media.

15. Subject with hereditary fructose intolerance.

16. With a cardiac pacemaker or will interfere with MRI-based or CT-based dose-planningor tumor response evaluation.

17. Restless subjects who are unable to lie or sit in a cast for more than 30 minutes.

18. Any medical or psychiatric conditions that, in the opinion of the investigator, mayinterfere with optimal participation in the study or place the subject at increasedrisk of adverse events (AEs).

19. Female subject who is planning to be pregnant or lactating during the study period.

20. Subject who is considered unfit to participate in the clinical study as assessed bythe investigator.

21. Subject who has received prior BNCT.