Dose Optimized BNCT for Head and Neck Cancer

Study Overview
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Brief Summary
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The goal of this clinical trial is to evaluate the safety of applying BNCT with the dose optimization in patients with recurrent head and neck cancer. The main questions it aims to answer are: - Dose optimized BNCT are conducted safety in these patients. Participants will receive dose optimized BNCT regulated as 12, 15, 18 Gy-Eq of the mucosal dose.

Official Title
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Safety Cohort Study for Dose Optimization of Accelerator-based BPA-BNCT in Patients With Unresectable Locally Recurrent Squamous Cell Carcinoma of the Head and Neck (ST-BNCT2001)

Conditions
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Head and Neck Cancer, Squamous Cell Carcinoma

Intervention / Treatment
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* Radiation: Accelerator-based BNCT with borofalan(10B)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Signed written informed consent to participate in the clinical trial on their own free will. Aged over 20 years at the time of consent obtaining. ECOG performance status (PS) of 0-2. Histologically confirmed a primary lesion of Head and Neck cancer. Following condition: Locally Recurrent Head and Neck Squamous Cell Carcinoma after chemo radiotherapy or radiation therapy. Primary Head or Neck Squamous Cell Carcinoma with no indicated of radical radiation therapy for the target lesions. More than one the target lesions based on RECIST (version 1.1) Local recurrent lesion localized to unilateral. Received a fractionated radiation therapy with total doses of ≥40 and ≤80 Gy at around 2 Gy per daily fraction at target lesion sites or an equivalent biologically effective dose. ≥50 days have passed since the last irradiation date of the prior radiation therapy at target lesion sites to the day of scheduled BNCT Have an estimated survival of ≥90 days after BNCT. Estimated able to receive the minimum tumor dose at least 20Gy-Eq. Screening test values that meet the following criteria. No abnormal findings of clinical concern in chest X-ray exam. Exclusion Criteria: Active multiple primary cancers. Distant metastatic lesions. Active infections requiring systemic treatment. Serious complications. Poorly controlled diabetes mellitus. Poorly controlled hypertension. Chronic lung diseases. Kidney diseases. Cardiac diseases. Other serious complications. Phenylketonuria. Hereditary fructose intolerance. Current or past medical history of serious hypersensitivity to drugs or contrast media. Myocardial infarction, unstable angina, or poorly controlled arrhythmia within 6 months prior to the scheduled BNCT. Grade ≥3 (CTCAE v4.0) symptom at the target site. Tumor invasion of the carotid artery or adjacent to over half of the carotid artery. Dental caries whose treatment has not been completed. Received antitumor drugs within 4 weeks prior to the scheduled BNCT. Participating in a clinical study of an unapproved drug except 18F-F BPA-PET/CT examinations within 4 weeks prior to the scheduled BNCT. Implanted with a cardiac pacemaker, ventricular assist device, or the like. Inability to immobilize at a right position during irradiation by the investigator (subinvestigator) Pregnant or who are breastfeeding during the period of the clinical trial. Mental illness or mental conditions. Poorly controlled epilepsy. Unable to comply with the protocol and to attend follow-up visits. With a history of BNCT. Considered unfit to participate in this clinical trial as assessed by the investigator.

Ages Eligible for Study
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Minimum Age: 20 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Dose-optimized BNCT with borofalan(10B)<br> | Radiation: Accelerator-based BNCT with borofalan(10B)<br>* Patients will be treated with BNCT regulated as 12, 15, or 18 Gy-Eq of the mucosal maximum dose.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Adverse events (Absence and presence of serious adverse events) | Grade 3 or higher adverse events as evaluated in CTCAEv5.1 Number of participants with severe adverse events due to an excess of tissue tolerance dose | Within 90days after the completion of BNCT | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective response rate: ORR | ORR within 90 days after the completion of BNCT is evaluated using RECIST guidelines (version 1.1). ORR is defined as the percentage of subjects with CR and PR in the target lesions among all eligible subjects. | Within 90 days after the completion of BNCT | 
| Duration of Response | The duration of the response is the time from the confirmed achievement of CR or PR (whichever is recorded first) to the date of initial objectively confirmed recurrence or exacerbation. | Within 2 years after the completion of BNCT | 
| Disease control rate (DCR) | DCR is evaluated using RECIST guidelines (version 1.1). DCR is defined as the proportion of subjects with CR, PR, or SD in the target lesions among all eligible subjects. | Within 90 days after the completion of BNCT | 
| Overall survival (OS) | OS is defined as the time from the day of the completion of BNCT to death due to all causes. The survey period will be up to the completion of the follow-up survey for all subjects. | Within 2 years after the completion of BNCT or up to the end of this study | 
| Progression-Free Survival (PFS) | PFS is defined as the time from the day of the completion of BNCT to the date of initial confirmed PD. The survey period will be up to the completion of the follow-up survey for all subjects. | Within 2 years after the completion of BNCT or up to the end of this study | 
| Late Adverse Events | The late Adverse Events are defined as the medical occurrence of the study from the treatment periods to the follow-up periods. | From 90 days to 2 years after the completion of BNCT | 
| Quality of life (QOL) Score Based on EORTC QLQ C30 and H&N35. | QOL score is assessed with EORTC QLQ C30 and H&N35 in the follow-up period. Results are scored as a specified manner by EORTC and changes in scores during the follow up period are evaluated | Within 2 years after the completion of BNCT or up to the end of this study | 
| Quality-Adjusted Life Year (QALY) | QOL and life year are multiplied to calculate the QALY. QOL score based on EQ-5D-5L in Japanese version. | Within 2 years after the completion of BNCT or up to the end of this study |