Boron Neutron Capture Therapy With B10 L-BPA for Unresectable Recurrent Head and Neck Cancers

Inclusion Criteria:

1. Subject aged 18-80 (inclusive).

2. Histologically or cytologically confirmed diagnosis of head and neck cancers with nodistant metastasis in subjects as follows:

3. Unresectable recurrent or persistent squamous cell carcinoma (SCC) aftercompleting one of the following frontline therapies:

• Standard concurrent chemoradiotherapy with a platinum-containing regimen.
• Curative induction chemotherapy with a platinum-containing regimen,followed by radiation therapy.
• Radiation therapy alone in the prior treatment for those who are unfit fora platinum-containing regimen or reject chemotherapy for the treatment oflocoregional recurrence.
• Concurrent chemoradiotherapy with a cetuximab-containing regimen in theprior treatment for those who are unfit for a platinum-containing regimenor reject other chemotherapy for the treatment of locoregional recurrence.

2. Unresectable recurrent or persistent non-squamous cell carcinoma (nSCC) afterreceiving any type of frontline therapies.

3. Subjects who are unsuitable for systemic therapies, or subjects who refuse systemictherapies.

4. Receipt of prior radiation therapy between 40 Gray (Gy) and 75 Gy at the targetlesion(s) for SCC patients and no more than 75 Gy at the target lesion(s) for nSCCpatients.

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

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

7. Measurable disease by magnetic resonance imaging (MRI) and/or computed tomography (CT) scan and ≤ 7 cm in the longest dimension.

8. At least one measurable lesion that can be assessed by RECIST version 1.1.

9. Eastern Cooperative Oncology Group (ECOG) Performance Score of 0-2.

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

11. Adequate organ functions as defined below:

• Hemoglobin ≥ 8.0 g/dL.

• White blood cell (WBC) count ≥ 2.5 x 103/μL.

• Neutrophil count ≥ 1.5 × 103/μL.

• Platelet count ≥ 80 × 103/μL.

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

• Alanine aminotransferase (ALT) ≤ 2.5 × ULN.

• Serum creatinine ≤ 1.5 × ULN.

12. Negative serology test for human immunodeficiency virus (HIV) infection.

13. Female subject with reproductive potential must have a negative result of serumpregnancy test at the screening visit and urine pregnancy test before the B10 L-BPAadministration.

14. 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]) until the end of this study.

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

16. Provision of signed informed consent.

Exclusion Criteria:

1. Presence of secondary cancer with the exception of carcinoma in situ and skincancers after curative surgery.

2. Synchronous multiple head and neck cancers outside the field of neutron beamirradiation.

3. Distant metastasis outside of the head and neck region.

4. Imaging studies, e.g., CT, MRI, demonstrating tumor invasion into the carotidartery.

5. Unsuitable for the BNCT, as assessed by the investigator based on theinvestigator-determined computed tomography angiography (CTA) of head and neck insuspected cases of tumor invasion into the carotid artery.

6. Presence of any ≥ Grade 3 toxicity (e.g., mucositis, stomatitis, and skininflammation) at the prior irradiation area, as assessed by the NCI-CTCAE version 5.0.

7. Presence of ≥ Grade 3 cataract, as assessed by the NCI-CTCAE version 5.0.

8. Active infections requiring systemic treatment within 2 weeks of the screeningvisit.

9. Myocardial infarction, unstable angina, or poorly controlled arrhythmia within 6months prior to the scheduled BNCT.

10. Severe comorbidities including but not limited to poorly controlled epilepsy, poorlycontrolled diabetes mellitus, poorly controlled hypertension, chronic lung diseases,e.g., obstructive pneumonia, interstitial pneumonia, pulmonary fibrosis, and severeemphysema, kidney diseases, e.g., chronic renal failure, acute renal failure, andnephrotic syndrome, cardiac diseases, e.g., New York Heart Association (NYHA)Functional Classification Class III or IV, and/or other severe conditions in theopinion of the investigator.

11. Suspected or known hypersensitivity (including allergy) to any of B10 L-BPAcomponents (e.g., L-phenylalanine) or contrast media.

12. History of prior BNCT.

13. Subject with hereditary fructose intolerance.

14. Subject with phenylketonuria.

15. Presence of any dental conditions necessitating tooth extraction within 2 weeksbefore and after the BNCT, as assessed by the dentist.

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

17. 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).

18. Received any investigational drug or device or have participated in a clinical studywithin 4 weeks prior to the screening visit.

19. History of substance or alcohol abuse within 6 months prior to the screening visit.

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

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