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Boron

Boronophenylalanine is infused into a peripheral vein prior to neutron irradiation.

irradiation

Heikki Joensuu, M.D., prof.

Boron Neutron Capture Therapy (BNCT) is an experimental radiation therapy technique that is based on the principle of irradiating boron atoms with neutrons. When neutrons have relatively low energy, boron atoms that have been targeted to cancerous tissue using a suitable boron carrier (an amino acid derivative called BPA, boronophenylalanine) will capture the neutrons. As a result from the neutron capture the boron atoms will split into two, producing helium and lithium ions. The helium and lithium ions, in turn, have only a short pathlength in tissue (about 5 micrometers) and will deposit their cell damaging effect mainly within the tumor provided that the boron carrier (BPA) has accumulated in the tumor. In practice, the study participants will receive BPA as an approximately 2-hour intravenous infusion, following which the tumor is irradiated with low energy (epithermal) neutrons obtained from a nuclear reactor at the BNCT facility. BNCT requires careful radiation dose planning, but neutron irradiation will last approximately only for one hour. In this study BNCT is given only once. The study hypothesis is that glioblastoma tissue may accumulate the boron carrier compound, and glioblastoma might respond to BNCT.

This is a single BNCT-facility, non-randomized, non-comparative, prospective, open-label, phase I/II trial to determine the value of BNCT in the treatment of subjects who have undergone surgery for glioblastoma, but glioblastoma has not been treated with radiation therapy or chemotherapy. The neutron irradiation site is the FiR 1 reactor site, located at Otaniemi, Espoo, Finland, about 6 kilometers from the Helsinki University Central Hospital, Helsinki, where patient evaluation and post-irradiation care will take place.

BPA is infused as a fructose complex (BPA-F) into a peripheral vein over 2 hours prior to neutron irradiation. Blood samples will be taken before starting the BPA infusion, and thereafter at 20 to 40 minute intervals during the infusion, following infusion, and after delivering neutron irradiation to monitor the blood boron concentration. The blood samples will be analyzed for boron to estimate the average blood boron level during neutron irradiation. The first 12 patients are treated using a BPA dose of 290 mg/kg, following which the dose of BPA is increased stepwise to 500 mg/kg, provided that unacceptable toxicity will not occur.

All patients will be evaluated for response using CT or magnetic resonance imaging (MRI).

Boron Neutron Capture Therapy (BNCT) as Treatment of Glioblastoma

Boron Neutron Capture Therapy in the Treatment of Glioblastoma Multiforme

Boneca Corporation

CEO Markku Pohjola

Symptoms and General Pathology

Recurrence

Oligodendroglioma

Disease Attributes

Anaplastic Astrocytoma

Anaplastic Oligodendroglioma

Radiation dose: 9 Gy-Eq

* Investigational product, boronophenylalanine, DMX-101 500mg/kg/3hr
* Investigational Device, DM-BTPS, DM-BNCT - neutron irradiation to reach maximum BNCT dose in brain of 9 Gy-Eq

Radiation dose: 11 Gy-Eq

* Investigational product, boronophenylalanine, DMX-101 500mg/kg/3hr
* Investigational Device, DM-BTPS, DM-BNCT - neutron irradiation to reach maximum BNCT dose in brain of 11 Gy-Eq

Radiation dose: 13 Gy-Eq

* Investigational product, boronophenylalanine, DMX-101 500mg/kg/3hr
* Investigational Device, DM-BTPS, DM-BNCT - neutron irradiation to reach maximum BNCT dose in brain of 13Gy-Eq

Patients will be infused DMX-101 intravenously at a dose of 500mg/kg/hr over 3 hours. Thereafter, patient will receive neutron irradiation simultaneously for a certain period of time based on his Boronophenylalanine (BPA) concentration in the blood.

500mg/kg/3hr followed by neutron irradiation to reach maximum brain dose of 9Gy-Eq

500mg/kg/3hr followed by neutron irradiation to reach maximum brain dose of 11Gy-Eq

500mg/kg/3hr followed by neutron irradiation to reach maximum brain dose of 13Gy-Eq

Moonkyoung Kim

Gi Taek Yee, M.D., Ph.D.

Woo Kim, M.D., Ph.D.

This is a multi-centered, radiation dose escalation, open, exploratory, Phase 1/2a clinical trial on the safety, efficacy and pharmacokinetic characteristics of BNCT in patients with recurrent high-grade gliomas.

The Phase I clinical study is to explore the adequate radiation dose level of BNCT based on confirmation of the maximum tolerated dose (radiation dose) of BNCT in patients with recurrent high-grade gliomas and characterize the safety, efficacy and pharmacokinetics.

To evaluate the primary objective of tolerability, subject population with history of exposure to a similar treatment recurrent high-grade glioma who received prior standard radiotherapy will be recruited.

The Phase IIa is to confirm the efficacy and safety after irradiation of radiation dose confirmed in the Phase I clinical study. To evaluate the primary objective of efficacy, subject population with glioblastoma (The 2021 WHO Classification of Tumors of the Central Nervous System, Glioblastoma IDH-wild type, WHO Grade 4) will be recruited.

The subject receives the study drug administration and neutron irradiation in the BNCT clinic with all procedures performed under the control by the investigator affiliated to the study site. 500 mg/kg of the study drug is intravenously administered over 3 hours at a constant rate and neutron irradiation starts at 1 hour after the end of the study drug administration according to the previously established neutron irradiation plan.

All patients will be evaluated for response using magnetic resonance imaging (MRI) using RANO and modified RANO criteria.

In the Phase I clinical study, the 3+3 dose escalation design is applied to evaluate the dose limiting toxicity (DLT) and 3 study subjects are enrolled to each group (Group 1, Group 2, Group 3). Depending on whether or not DLT occurs, 3 subjects at minimum to 18 subjects at maximum are enrolled.

However, in the event a subject assigned a subject number withdraws from the study before starting BNCT or within 90 days from starting BNCT for reasons other than safety, up to 3 additional subjects can be enrolled for each dose group, resulting in 27 subjects at maximum allowed for enrollment for the Phase I clinical study.

In the Phase IIa clinical study, up to 12 subjects are enrolled. However, subjects who are included in a group that has received the radiation dose confirmed as the maximum tolerated dose (MTD) in the Phase 1 clinical study AND satisfy all inclusion/exclusion criteria of the Phase IIa are included in the number of subjects of Phase IIa.

Studying the Safety, Efficacy, and Pharmacokinetic Characteristics of BNCT in Patients With Recurrent High-grade Gliomas

A Multi-centered, Radiation Dose Escalation, Open, Exploratory, Phase 1/2a Clinical Trial on the Safety, Efficacy and Pharmacokinetic Characteristics of BNCT(Boron Neutron Capture Therapy) in Patients With Recurrent High-grade Gliomas

To explore the adequate radiation dose level of BNCT based on confirmation of the maximum tolerated dose (radiation dose) of BNCT in patients with recurrent high-grade gliomas

Percentage of patients that are free from progressive disease for 6 months per modified RANO criteria

Percentage of patients that are free from progressive disease for 6 months per RANO criteria

Median duration of progression free survival according to modified RANO criteria

Median duration of progression free survival according to RANO criteria

ORR will be defined as the percentage of patients with complete response (CR) or partial response (PR) according to the modified RANO criteria.

ORR will be defined as the percentage of patients with complete response (CR) or partial response (PR) according to the RANO criteria.

Median duration of overall survival for patients that are alive

Percentage of patients that are alive for 1 year

The analysis is conducted using the Noncompartmental Analysis Method, and the results are summarized for each group in terms of descriptive statistics including the mean, standard deviation, minimum, median, and maximum values.

Dawonmedax Co., Ltd.

Head and Neck Neoplasms

boronophenylalanine-based BNCT

Heikki T Joensuu, M.D., prof.

Boron Neutron Capture Therapy (BNCT) is an experimental radiation therapy technique which is based on the principle of irradiating boron atoms with neutrons. When neutrons have relatively low energy, boron atoms that have been targeted to cancerous tissue using a suitable boron carrier (an amino acid derivative called BPA, boronophenylalanine) will capture the neutrons. As a result from the neutron capture the boron atoms will split into two, producing helium and lithium ions. The helium and lithium ions, in turn, have only a short pathlength in tissue (about 5 micrometers) and will deposit their cell damaging effect mainly within the tumor provided that the boron carrier (BPA) has accumulated in the tumor. In practice, the study participants will receive BPA as an approximately 2-hour intravenous infusion, following which the tumor is irradiated with low energy (epithermal) neutrons obtained from a nuclear reactor at the BNCT facility. BNCT requires careful radiation dose planning, but neutron irradiation will last approximately only for one hour. In this study BNCT will be repeated, and the 2 treatments will be given 3 to 5 weeks apart. The study hypothesis is that head and neck cancers that have recurred following conventional radiotherapy might accumulate the boron carrier compound, and might respond to BNCT.

This is a single BNCT-facility, non-randomized, non-comparative, open-label, phase I to II trial to determine the value of BNCT in the treatment of inoperable, irradiated, locally advanced cancers of the head and neck region. An attempt to perform 18F-labeled boronophenylalanine (18F-BPA) SPECT or PET imaging will be made before BNCT. Patients whose tumor uptake is \>2.5 times that of the corresponding normal head and neck tissue will be enrolled, and treated with a single fraction BPA-based BNCT twice, 3 to 5 weeks apart. Another 18F-BPA SPECT or PET study may be performed 1 to 3 months after BNCT to determine the SPECT/PET response.

The neutron irradiation site is the FiR 1 reactor site, located at Otaniemi, Espoo, Finland, about 6 kilometers from the Helsinki University Central Hospital, Helsinki, where patient evaluation and post-irradiation care will take place.

Prior to BNCT, BPA is infused as a fructose complex (l-BPA-F) into a peripheral vein over 2 hours. Blood samples will be taken for monitoring whole blood boron concentration before starting the BPA infusion, and thereafter at 20 to 40 minute intervals during the infusion, following infusion, and after delivering neutron irradiation. The blood samples will be analyzed for blood boron concentration to estimate the average blood boron concentration during neutron irradiation.

All patients will be evaluated for response using CT or magnetic resonance imaging (MRI).

Boronophenylalanine (BPA)-Based Boron Neutron Capture Therapy (BNCT) in the Treatment Head and Neck Tumors

Boronophenylalanine (BPA)-Based Boron Neutron Capture Therapy (BNCT) in the Treatment of Inoperable and Irradiated Head and Neck Tumors: A Feasibility Study

professor

Bononophenylalanine (BPA)-based BNCT

Boron Neutron Capture Therapy (BNCT) is an experimental radiation therapy technique which is based on the principle of irradiating boron atoms with neutrons. When neutrons have relatively low energy, boron atoms that have been targeted to cancerous tissue using a suitable boron carrier (an amino acid derivative called BPA, boronophenylalanine) will capture the neutrons. As a result from the neutron capture the boron atoms will split into two, producing helium and lithium ions. The helium and lithium ions, in turn, have only a short pathlength in tissue (about 5 micrometers) and will deposit their cell damaging effect mainly within the tumor provided that the boron carrier (BPA) has accumulated in the tumor. In practice, the study participants will receive BPA as an approximately 2-hour intravenous infusion, following which the tumor is irradiated with low energy (epithermal) neutrons obtained from a nuclear reactor at the BNCT facility. BNCT requires careful radiation dose planning, but neutron irradiation will last approximately only for one hour. In this study BNCT is given once. The study hypothesis is that anaplastic astrocytomas and glioblastomas that have recurred following conventional radiotherapy might accumulate the boron carrier compound, and might respond to BNCT.

This is a single BNCT-facility, non-randomized, non-comparative, prospective, open-label, phase I/II study to determine the value of BNCT in the treatment of inoperable, irradiated, progressing anaplastic astrocytomas or glioblastomas following conventional radiation therapy. The neutron irradiation site is the FiR 1 reactor site, located at Otaniemi, Espoo, Finland, about 6 kilometers from the Helsinki University Central Hospital, Helsinki, where patient evaluation and post-irradiation care will take place.

BPA is infused as a fructose complex (BPA-F) into a peripheral vein over 2 hours prior to neutron irradiation. Blood samples will be taken before starting the BPA infusion, and thereafter at 20 to 40 minute intervals during the infusion, following infusion, and after delivering neutron irradiation to monitor the blood boron concentration. The blood samples will be analyzed for boron to estimate the average blood boron level during neutron irradiation. A minimum tumor dose of 17 Gy (W) is given while limiting the normal brain maximum peak dose to 8 Gy (W), and the average normal brain dose to 6 Gy (W). The first 10 patients will be given BPA 290 mg/kg, following which the BPA dose will be escalated in cohorts of 3 subjects gradually up to 450 mg/kg, provided that protocol-specified unacceptable toxicity will not occur.

All patients will be evaluated for response using CT or magnetic resonance imaging (MRI).

BNCT to Treat Glioma That Has Progressed Following Radiotherapy

BPA-Mediated Boron Neutron Capture Therapy (BNCT) in the Treatment of Glioblastoma or Anaplastic Astrocytoma Progressing After Conventional External Beam Radiotherapy

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Boron Neutron Capture Therapy (BNCT) as Treatment of Glioblastoma	NCT00115453	Glioblastoma	irradiation	18 Years - 75 Years	Boneca Corporation
Studying the Safety, Efficacy, and Pharmacokinetic Characteristics of BNCT in Patients With Recurrent High-grade Gliomas	NCT05737212	Recurrent High-... Recurrent Gliob... Recurrent Anapl... Recurrent Anapl...	500mg/kg/3hr fo... 500mg/kg/3hr fo... 500mg/kg/3hr fo...	19 Years - 80 Years	Dawonmedax Co., Ltd.
Boronophenylalanine (BPA)-Based Boron Neutron Capture Therapy (BNCT) in the Treatment Head and Neck Tumors	NCT00114790	Head and Neck C...	boronophenylala...	18 Years -	Boneca Corporation
BNCT to Treat Glioma That Has Progressed Following Radiotherapy	NCT00115440	Glioblastoma Anaplastic Astr...	Bononophenylala...	18 Years -	Boneca Corporation
BNCT to Treat Glioma That Has Progressed Following Radiotherapy	NCT00115440	Glioblastoma Anaplastic Astr...	Bononophenylala...	18 Years -	Boneca Corporation
Boronophenylalanine (BPA)-Based Boron Neutron Capture Therapy (BNCT) in the Treatment Head and Neck Tumors	NCT00114790	Head and Neck C...	boronophenylala...	18 Years -	Boneca Corporation

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