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

This Phase II study, titled "A Phase II Study to Evaluate the Efficacy and Safety of Boron Neutron Capture Therapy (BNCT) Using B10 L-BPA in Patients with Unresectable Recurrent Head and Neck Cancers," aims to assess the efficacy and safety of B10 L-BPA-based BNCT in this patient population. The primary objective is to evaluate its efficacy, while secondary objectives include assessing safety, survival outcomes, tumor response, and the pharmacokinetics (PK) profile of B10 L-BPA and boron.


Eligibility Criteria:
Inclusion Criteria:

1. Subject aged 18-80 (inclusive).
2. Histologically or cytologically confirmed diagnosis of head and neck cancers with no distant metastasis in subjects as follows:

   1. Unresectable recurrent or persistent squamous cell carcinoma (SCC) after completing 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 for a platinum-containing regimen or reject chemotherapy for the treatment of locoregional recurrence.
      * Concurrent chemoradiotherapy with a cetuximab-containing regimen in the prior treatment for those who are unfit for a platinum-containing regimen or reject other chemotherapy for the treatment of locoregional recurrence.
   2. Unresectable recurrent or persistent non-squamous cell carcinoma (nSCC) after receiving any type of frontline therapies.
3. Subjects who are unsuitable for systemic therapies, or subjects who refuse systemic therapies.
4. Receipt of prior radiation therapy between 40 Gray (Gy) and 75 Gy at the target lesion(s) for SCC patients and no more than 75 Gy at the target lesion(s) for nSCC patients.
5. There must be a time interval ≥ 3 months between prior radiation therapy and the scheduled BNCT.
6. There must be a time interval ≥ 1 month between receipt of antitumor drugs and the scheduled 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 serum pregnancy test at the screening visit and urine pregnancy test before the B10 L-BPA administration.
14. 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 \[hormone shot or injection, implants, combination oral contraceptives, or patches\]) until the end of this study.
15. Physically and mentally capable of participating in the study and willing to adhere to study procedures.
16. Provision of signed informed consent.

Exclusion Criteria:

1. Presence of secondary cancer with the exception of carcinoma in situ and skin cancers after curative surgery.
2. Synchronous multiple head and neck cancers outside the field of neutron beam irradiation.
3. Distant metastasis outside of the head and neck region.
4. Imaging studies, e.g., CT, MRI, demonstrating tumor invasion into the carotid artery.
5. Unsuitable for the BNCT, as assessed by the investigator based on the investigator-determined computed tomography angiography (CTA) of head and neck in suspected cases of tumor invasion into the carotid artery.
6. Presence of any ≥ Grade 3 toxicity (e.g., mucositis, stomatitis, and skin inflammation) 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 screening visit.
9. Myocardial infarction, unstable angina, or poorly controlled arrhythmia within 6 months prior to the scheduled BNCT.
10. 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, and nephrotic syndrome, cardiac diseases, e.g., New York Heart Association (NYHA) Functional Classification Class III or IV, and/or other severe conditions in the opinion of the investigator.
11. Suspected or known hypersensitivity (including allergy) to any of B10 L-BPA components (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 weeks before 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, may interfere with optimal participation in the study or place the subject at increased risk of adverse events (AEs).
18. Received any investigational drug or device or have participated in a clinical study within 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 by the investigator.