unresectable squamous cell carcinoma of the head and neck refractory to standard treatments
Conditions
Interventions
Patients will be administered borofalan(10B) intravenously at 200 mg/kg/h for 2 h. The blood boron concentration will be measured after 2 h, and will be used to calculate the optimized thermal neutron
Sponsors
Department of Radiation Oncology, Southern Tohoku BNCT Research Center
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Document consent by his/her own free will. 2. 20 years old or older. 3. ECOG performance status of 0-2. 4. The primary lesion is histologically head and neck cancer. 5. Any participant who meets any of the following criteria refractory to standard treatments. - Patients with locally recurrent head and neck squamous cell carcinoma after chemoradiotherapy or radiation. - Patients with primary locally recurrent head and neck squamous cell carcinoma refractory to standard treatments such as radical chemoradiotherapy, and prior radiation therapy. 6. Patients who have at least one measurable lesion in the target lesion site based on RECIST (version 1.1) 7. Patients with unilateral local recurrent lesion(s). 8. Patients with radiation therapy, fractionation around 2Gy/day, total dose within the range of 40 Gy and Radiation therapy, over 40 Gy of total biologically effective dose; 2Gy/day. 9. 50 days or more have passed since the last irradiation date of prior radiation therapy for the evaluation target lesion site to the scheduled date of BNCT. 10. Over 90 days of survival is expected after BNCT. 11. Patients that able to receive at least 20 Gy-Eq (expected tumor minimum dose) for the evaluation target lesion site on the prior simulation with the CT images at screening test. 12. Any participant who meets any of the following criteria. Supportive therapies (G-CSF and blood transfusion), which might affect the following tests within 14 days before the screening tests are prohibited. - Kidney function Serum creatinine level <= 1.2mg/dL for male; serum creatinine level <= 1.0mg/dL for female) - Liver function AST <= 5 x ULN ALT <= 5 x ULN - Hemoglobin >= 8.0 g/dL - Platelet count >= 80,000/microL - White blood cell count >= 2,500/microL - Neutrophil count >= 1,500/microL
Exclusion criteria
Exclusion criteria: 1. Patients (Pts) with active multiple cancers, not including lesions equivalent to carcinoma in situ or skin cancer considered healed 2. Pts with distant metastasis 3. Pts with active infections requiring systemic treatment 4. Pts with significant complications - Poorly uncontrolled diabetes - Poorly uncontrolled hypertension - Chronic lung disease - Kidney disease - Heart disease - Serious complications 5. Pts with phenylketonuria 6. Pts with hereditary fructose intolerance 7. Pts who have complications and a medical history with severe hypersensitivity reactions in drugs and contrast agents 8. Pts with myocardial infarction, unstable angina, uncontrolled arrhythmia within 6 months 9. Pts with over Grade 3 (CTCAE v4.0) in the target lesion site 10. Pts with the tumors invade the carotid artery or adjacent to more than halfway through the carotid artery, and considered not to manage the normal tissue between the carotid artery and membrane mucosa or skin by the treatments 11. Pts with decayed and untreated teeth 12. Pts with the administration of antineoplastic drug within 3weeks prior to the scheduled date of BNCT 13. Pts who were enrolled in unapproved drugs clinical study except for 18F-FBPA-PET/CT or who are participating in this clinical study within 4 weeks prior to the scheduled date of BNCT. Or patients will participate in unapproved drugs clinical study except for 18F-FBPA-PET/CT other clinical study during this study 14. Pts who have a cardiac pacemaker and auxiliary artificial heart 15. Pts who are considered unable to be fixed position during irradiation 16. Pts who complicated with psychiatric disorder or mental manifestation 17. Pts with poorly uncontrolled epilepsy 18. Pts who unable to comply with this clinical protocol and receive follow-up care 19. Other conditions that in the opinion of the investigator would preclude the subject's participation in a clinical study
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Locoregional progression-free survival within 2 years after BNCT | — |
Secondary
| Measure | Time frame |
|---|---|
| 1. Response rate Evaluate tumor response within 180 days. 2. Duration of response From the time that the measurement criteria are first met for CR or PR until the first date that recurrent or the progressive disease is objectively documented. 3. Disease control rate Evaluate tumor response within 180 days. 4. Overall survival The time to death from any cause. 5. Progression-free survival The time to the date of first documented PD. 6. QOL assessment based on EORTC-QLQ-C30 and HN35. QOL assessment in the post-treatment observation period. 7. Quality-adjusted life year (QALY) To calculate the QALY, QOL assessment is used in EQ-5D-5L Japanese version. 8. Adverse events The occurrence of acute adverse events within 90 days after BNCT, and the occurrence of late adverse events 90 days after BNCT. 9. 18F-FDG-PET If available before the start of BNCT, and Day 90 or 180, evaluate changes in SUV. 10. 18F-FBPA-PET If available before the start of BNCT, and Day 90 or 180, evaluate changes in SUV. 11. Boron concentration change in whole blood and blood plasma Two hours later after the administration of Borofalan (10B), right after neutron irradiation, 30 minutes later after the administration, evaluate boron concentration in whole blood and blood plasma. 12. Immune responsiveness in the tumor tissue assessments If available, perform a biopsy before the start of BNCT and Day 3-5. Evaluate PD-L1 IHC and immune responsiveness on single staining protocol. 13. Changes cytokine level in blood If available, evaluate changes cytokine level in blood before the start of BNCT, Day 1, 3, 14, 30, 90. 14. Genetic mutation and expression analysis If available, perform a biopsy before the start of BNCT and Day 3-5, then extract neoplasm DNA and RNA, and miRNA from blood specimen and analysis tumor gene mutation and gene expression. 15. Metabolome analysis If available, evaluate changes metabolic product in blood before the start of BNCT, Day 1, 3. | — |
Countries
Japan
Contacts
Public ContactKatsumi Hirose
Southern Tohoku BNCT Research Center Department of Radiation Oncology
Outcome results
None listed