Overview

This Phase I/II study, titled 'A Phase I/II Study to Evaluate Safety and Efficacy of the Boron Neutron Capture Therapy (BNCT) using B10 L-BPA as Boron Carrier in Malignant Brain Tumors.', aims to assess the efficacy of B10 L-BPA with BNCT in patients with malignant brain tumors. The primary objective is to evaluate the safety and efficacy of BNCT with B10 L-BPA for malignant brain tumors treatment, using the Response Evaluation Criteria in Solid Tumors, Version 1.1 (RECIST v1.1) as the standard for assessment.

Eligibility

Inclusion Criteria:

1. Age of 20 years and older.
2. Patients with malignant brain tumors confirmed by histological and/or medical imaging, classified as WHO Grade 3 or 4 according to the World Health Organization of tumors of the central nervous system (CNS) classification, excluding those with histologically confirmed Grade 3 intracranial ependymoma, medulloblastoma, and primary CNS lymphoma.
3. There must be a time interval ≥ 3 months between prior radiation therapy and the scheduled BNCT.
4. There must be a time interval ≥ 1 month between receipt of antitumor drugs and the scheduled BNCT.
5. Within 4 weeks before the scheduled BNCT, measurable disease by magnetic resonance imaging (MRI) and/or computed tomography (CT) scan showing a volume ≦ 250 cm^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 serum

    pregnancy test at the screening visit and urine pregnancy test before the B10 L-BPA administration. However, if the subject has been menopausal for at least 2 years (more than 24 months since the last menstrual period) or uses surgical birth control, testing is not required.

11. Female subject with childbearing potential as well as male subject with reproductive potential must agree to refrain from unprotected sex and use 2 methods of highly effective contraception with their partner (e.g. barrier contraceptives [male condom, female condom, or diaphragm plus spermicide], intrauterine device, hormonal methods [hormone shot or injection, implants, combination oral contraceptives, or patches]) 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 adhere to 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 other

   malignant tumors and is not suitable to participate in the trial.

3. Patients with malignant brain tumors are considered eligible for standard surgical treatment that is effective against the tumor.
4. A time interval less than 3 months from previous radiation therapy for intracranial region.
5. A time interval less than 3 months from last brain surgery (excluding drainage procedures and biopsy) and less than 1 month from previous chemotherapy.
6. The adverse event of previous anti-tumor therapy were NCI-CTCAE V5.0 grade evaluation ≧ Class 3 (excluding alopecia and peripheral neuropathy).
7. Received or expect to receive any investigational drug, biologic or device within 1 month prior to the scheduled BNCT.
8. Patients receiving or expected to receive vascular endothelial growth factor inhibitors (except bevacizumab) or live attenuated vaccines within 1 month prior to the scheduled BNCT.
9. Patients received major surgery within 1 month prior to the scheduled BNCT or are still recovering from a previous surgery. The investigator will evaluate the subject's condition when the subject receives major surgery. Major surgery is defined as procedure that requires general anaesthesia, including heart surgery, organ transplants, and long operations such as some back surgeries, excluding stent implantation, biopsy, and day surgery.
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 the investigator. The Patient will be eligible for the study if they have undergone stent implantation and obtained consent from the investigator.
12. Patients with severe congestive heart failure or renal failure, as well as myocardial infarction, unstable angina, or poorly controlled arrhythmia within 6 months prior to the scheduled BNCT.
13. Severe comorbidities including but not limited to poorly controlled epilepsy, poorly controlled diabetes mellitus, poorly controlled hypertension, chronic lung diseases, e.g., obstructive pneumonia, interstitial pneumonia, pulmonary fibrosis, and severe emphysema, kidney diseases, e.g., chronic renal failure, acute renal failure, phenylketonuria and nephrotic syndrome, cardiac diseases, e.g., New York Heart Association (NYHA) Functional Classification Class III or IV), phenylketonuria and/or other severe conditions in the opinion of the investigator.
14. Suspected or known hypersensitivity (including allergy) to boron or any component of the 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-planning or 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, may interfere with optimal participation in the study or place the subject at increased risk 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 by the investigator.
21. Subject who has received prior BNCT.