Accelerator-based BNCT (Boron Neutron Capture Therapy) for Head and Neck Carcinoma.

NCT07058116 | Recruiting Phase 1 DMC

• 2 other identifiers: HN-BNCT-01-20242024-515036-71-00
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 1

Brief Summary

This phase I study of an accelerator-based boron neutron capture therapy (BNCT) in the treatment of locally recurrent head and neck carcinoma, is sponsored by HUS, Haartmaninkatu 4, Helsinki, Finland and Neutron Therapeutics Finland OY, Kanavaranta 9 FIN-00290 Helsinki. The indication is for patients with head and neck carcinoma that has recurred locally after conventional radiation therapy. The primary objective is to demonstrate the safety of accelerator-based neutron radiation using the nuBeam Suite in delivering BNCT. The secondary objective is the ability to deliver the planned radiation dose to the target site and the ability to plan the trial treatment using the trial treatment planning software, position and target the tumor site using the robotic table in conjunction with the CT scanner and calculate the required radiation dose for each planned BNCT trial treatment. To establish these objectives, the following parameters will be controlled:

• Objective response rate
• Duration of response.
• The clinical benefit rate (includes complete response, partial response, and stabilized disease for a minimum of 8 weeks since the date of the first BNCT).
• Locoregional recurrence-free survival.
• Progression-free survival.
• Overall survival.
• Quality of life. The maximum sample size is 10 study subjects evaluable for safety. The study does not involve randomization. Regarding the target population, the study subjects must fulfill each of the inclusion criteria:
• Patient has provided a written informed consent as approved by the EC prior to study specific screening procedures, with the understanding that the patient has the right to withdraw from the study at any time, without prejudice.
• ≥ 18 years of age at the time of enrollment.
• Histologically confirmed head and neck carcinoma.
• Inoperable cancer, prior surgery may or may not have been done.
• Prior radiotherapy or chemoradiotherapy has been given.
• Anticipated life expectancy of at least 6 months
• Presence of distant metastases.
• World Health Organization (WHO) performance status \> 2
• Concurrent uncontrolled localized cancer other than head and neck carcinoma or overtly metastatic cancer.
• The patient has access to a non-experimental, effective treatment option and is a suitable candidate for such therapy.
• Concomitant chemotherapy.
• Concurrent experimental therapy or participation in a trial with an experimental therapy within 3 months prior to study inclusion.
• Less than 3 months since prior radiation therapy.
• Major surgery within 4 weeks prior to study inclusion.
• Unremovable metal implants present in the head and neck region that will interfere with CT/MRI-based dose-planning.
• Known sensitivity to the study drug.
• One or more of the following:
• Blood hemoglobin \< 100 g/L, neutrophils \< 1.5 x 109/L, platelet count \< 120 x 109/L
• Serum/plasma creatinine \> 1.5 x Upper Limit of Normal (ULN)
• Serum bilirubin 2.0 \> ULN
• Serum ALT and/or AST \> 2.0 x ULN
• Serum alkaline phosphatase \> 2.5 x ULN
• Serious uncontrolled infection or other serious uncontrolled concomitant disease.
• Collagen vascular disease or a disease that is considered to increase radiosensitivity of normal tissues to radiation (e.g., ataxia-telangiectasia)
• Patient is unwilling or unable to comply with the CIP required follow-up visits for the duration of the study.
• Untreated or severe treated congestive heart failure, cardiac pacemaker, or renal failure.
• Restlessness or inability to lie in a cast for about 30 minutes.
• Clinical follow-up after therapy cannot be arranged or the patient is not willing to participate in the follow-up.
• Known pregnancy, breastfeeding, or planning of pregnancy; for women of childbearing potential, a negative pregnancy test must be obtained prior to enrollment.
• The patient is not able to understand the nature of the study and trial treatment options.
• Phenylketonuria
• Fructose intolerance.

Conditions

Head and Neck Carcinoma

Keywords

L-Boronophenylalanine; BNCT; Boron Neutron Capture Therapy; Head and Neck Carcinoma; Neutron Therapeutics; Helsinki University Hospital

Outcome Measures

Primary Outcomes (1)

• Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability]

  The primary objective is to assess the safety of accelerator-based neutron radiation using the nuBeam Suite, and explicitly, the nuBeam Treatment Delivery System (TDS) in delivering BNCT to treat cancer patients. Safety/toxicity of neutron radiation delivered by the nuBeam TDS will be assessed using the Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 at one month after the last BNCT trial treatment.

  The expected duration to the primary outcome is 13 months. The primary safety endpoint is 1 month after the final/2nd BNCT trial treatment of the last study subject. Study subject enrollment is anticipated to take 12 months.

Secondary Outcomes (3)

• Trial Irradiation Success for the nuBeam TDS

  The expected duration to the primary outcome is 13 months. The primary safety endpoint is 1 month after the final/2nd BNCT trial treatment of the last study subject. Study subject enrollment is anticipated to take 12 months.

• Procedure success of the nuBeam Suite

  The expected duration to the primary outcome is 13 months. The primary safety endpoint is 1 month after the final/2nd BNCT trial treatment of the last study subject. Study subject enrollment is anticipated to take 12 months.

• Treatment effectiveness

  The expected duration to the primary outcome is 13 months. The primary safety endpoint is 1 month after the final/2nd BNCT trial treatment of the last study subject. Study subject enrollment is anticipated to take 12 months.

Study Arms (1)

Single group - Dose escalation study

EXPERIMENTAL

Two BNCT trial treatments are scheduled to be administered to each study subject with a 4-week time interval between the 2 trial treatments (a range from 3.0 to 6.0 weeks is allowed for the interval). Neutron irradiations are given at the Helsinki University Hospital BNCT facility (Helsinki, Finland) using the nuBeam Suite. The nuBeam Treatment Delivery System within the nuBeam Suite delivers a neutron beam that has suitable energy and flux for clinical BNCT. The Instructions for Use/User Guide(s) containing the detailed instructions for using the system will be followed for the delivery of neutron irradiation for each BNCT trial treatment. The basic steps for the irradiation procedure are: 1. Neutron source preparation/calibration 2. CT imaging of the target region 3. Positioning of the study subject 4. Irradiation to the planned trial treatment dose 5. Close-out/Shutdown Each BNCT trial treatment will be carried out according to the trial treatment plan.

Drug: L-Boronophenylalanine intravenous administration

Interventions

L-Boronophenylalanine intravenous administration DRUG

L-BPA will be complexed with fructose to form L-BPA-fructose (L-BPA-F) to increase solubility, and 400 mg/kg of L-BFA as complexed with fructose (L-BPA-F) will then be administered intravenously at a concentration of L-BPA 30 g/L over 2 hours before neutron irradiation.

Also known as: Neutron Irradiation

Single group - Dose escalation study

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• The patient considered for the study has provided a written informed consent as approved by the EC prior to study specific screening procedures, with the understanding that the patient has the right to withdraw from the study at any time, without prejudice.
• ≥ 18 years of age at the time of enrollment.
• Histologically confirmed head and neck carcinoma.
• Inoperable cancer, prior surgery may or may not have been done.
• Prior radiotherapy or chemoradiotherapy has been given.
• Anticipated life expectancy of at least 6 months.

You may not qualify if:

• Patients who fulfill any of the following criteria will be excluded:
• Presence of distant metastases.
• World Health Organization (WHO) performance status \> 2 (see Appendix 2).
• Concurrent uncontrolled localized cancer other than head and neck carcinoma or overtly metastatic cancer.
• The patient has access to a non-experimental, effective treatment option and is a suitable candidate for such therapy.
• Concomitant chemotherapy.
• Less than 3 months since prior radiation therapy.
• Unremovable metal implants present in the head and neck region that will interfere with CT/MRI-based dose-planning.
• Known sensitivity to the study drug.
• One or more of the following:
• Blood hemoglobin \< 100 g/L, neutrophils \< 1.5 x 109/L, platelet count \< 120 x 109/L
• Serum/plasma creatinine \> 1.5 x Upper Limit of Normal (ULN)
• Serum bilirubin 2.0 \> ULN
• Serum ALT and/or AST \> 2.0 x ULN
• Serum alkaline phosphatase \> 2.5 x ULN

Sponsors & Collaborators

• Neutron Therapeutics, LLC: lead
• Helsinki University Central Hospital: collaborator

Study Sites (1)

Helsinki University Hospital

Helsinki, 00290, Finland

RECRUITING

Related Publications (26)

• Salama JK, Vokes EE, Chmura SJ, Milano MT, Kao J, Stenson KM, Witt ME, Haraf DJ. Long-term outcome of concurrent chemotherapy and reirradiation for recurrent and second primary head-and-neck squamous cell carcinoma. Int J Radiat Oncol Biol Phys. 2006 Feb 1;64(2):382-91. doi: 10.1016/j.ijrobp.2005.07.005. Epub 2005 Oct 5.

  PMID: 16213104 BACKGROUND

• Igaki H, Murakami N, Nakamura S, Yamazaki N, Kashihara T, Takahashi A, Namikawa K, Takemori M, Okamoto H, Iijima K, Chiba T, Nakayama H, Takahashi A, Kaneda T, Takahashi K, Inaba K, Okuma K, Nakayama Y, Shimada K, Nakagama H, Itami J. Scalp angiosarcoma treated with linear accelerator-based boron neutron capture therapy: A report of two patients. Clin Transl Radiat Oncol. 2022 Feb 18;33:128-133. doi: 10.1016/j.ctro.2022.02.006. eCollection 2022 Mar.

  PMID: 35252597 BACKGROUND

• Bokstein F, Blumenthal DT, Corn BW, Gez E, Matceyevsky D, Shtraus N, Ram Z, Kanner AA. Stereotactic radiosurgery (SRS) in high-grade glioma: judicious selection of small target volumes improves results. J Neurooncol. 2016 Feb;126(3):551-7. doi: 10.1007/s11060-015-1997-5. Epub 2015 Nov 24.

  PMID: 26603164 BACKGROUND

• Kawabata S, Suzuki M, Hirose K, Tanaka H, Kato T, Goto H, Narita Y, Miyatake SI. Accelerator-based BNCT for patients with recurrent glioblastoma: a multicenter phase II study. Neurooncol Adv. 2021 May 20;3(1):vdab067. doi: 10.1093/noajnl/vdab067. eCollection 2021 Jan-Dec.

  PMID: 34151269 BACKGROUND

• Hirose K, Konno A, Hiratsuka J, Yoshimoto S, Kato T, Ono K, Otsuki N, Hatazawa J, Tanaka H, Takayama K, Wada H, Suzuki M, Sato M, Yamaguchi H, Seto I, Ueki Y, Iketani S, Imai S, Nakamura T, Ono T, Endo H, Azami Y, Kikuchi Y, Murakami M, Takai Y. Boron neutron capture therapy using cyclotron-based epithermal neutron source and borofalan (10B) for recurrent or locally advanced head and neck cancer (JHN002): An open-label phase II trial. Radiother Oncol. 2021 Feb;155:182-187. doi: 10.1016/j.radonc.2020.11.001. Epub 2020 Nov 11.

  PMID: 33186684 BACKGROUND

• Barth RF, Zhang Z, Liu T. A realistic appraisal of boron neutron capture therapy as a cancer treatment modality. Cancer Commun (Lond). 2018 Jun 19;38(1):36. doi: 10.1186/s40880-018-0280-5.

  PMID: 29914575 BACKGROUND

• Stupp R, Taillibert S, Kanner A, Read W, Steinberg D, Lhermitte B, Toms S, Idbaih A, Ahluwalia MS, Fink K, Di Meco F, Lieberman F, Zhu JJ, Stragliotto G, Tran D, Brem S, Hottinger A, Kirson ED, Lavy-Shahaf G, Weinberg U, Kim CY, Paek SH, Nicholas G, Bruna J, Hirte H, Weller M, Palti Y, Hegi ME, Ram Z. Effect of Tumor-Treating Fields Plus Maintenance Temozolomide vs Maintenance Temozolomide Alone on Survival in Patients With Glioblastoma: A Randomized Clinical Trial. JAMA. 2017 Dec 19;318(23):2306-2316. doi: 10.1001/jama.2017.18718.

  PMID: 29260225 BACKGROUND

• H, Järvinen and W. Voorbraak (eds.),Recommendations for the Dosimetry of Boron Neutron Capture Therapy, NRG Report 21425/03.55339/C, Petten, The Netherlands, 2003

  BACKGROUND

• Kawabata S, Hiramatsu R, Kuroiwa T, Ono K, Miyatake S. Boron neutron capture therapy for recurrent high-grade meningiomas. J Neurosurg. 2013 Oct;119(4):837-44. doi: 10.3171/2013.5.JNS122204. Epub 2013 Jun 28.

  PMID: 23808536 BACKGROUND

• Menendez PR, Roth BM, Pereira MD, Casal MR, Gonzalez SJ, Feld DB, Santa Cruz GA, Kessler J, Longhino J, Blaumann H, Jimenez Rebagliati R, Calzetta Larrieu OA, Fernandez C, Nievas SI, Liberman SJ. BNCT for skin melanoma in extremities: updated Argentine clinical results. Appl Radiat Isot. 2009 Jul;67(7-8 Suppl):S50-3. doi: 10.1016/j.apradiso.2009.03.020. Epub 2009 Mar 27.

  PMID: 19375342 BACKGROUND

• Wang LW, Chen YW, Ho CY, Hsueh Liu YW, Chou FI, Liu YH, Liu HM, Peir JJ, Jiang SH, Chang CW, Liu CS, Lin KH, Wang SJ, Chu PY, Lo WL, Kao SY, Yen SH. Fractionated Boron Neutron Capture Therapy in Locally Recurrent Head and Neck Cancer: A Prospective Phase I/II Trial. Int J Radiat Oncol Biol Phys. 2016 May 1;95(1):396-403. doi: 10.1016/j.ijrobp.2016.02.028. Epub 2016 Feb 13.

  PMID: 27084657 BACKGROUND

• Suzuki M, Kato I, Aihara T, Hiratsuka J, Yoshimura K, Niimi M, Kimura Y, Ariyoshi Y, Haginomori S, Sakurai Y, Kinashi Y, Masunaga S, Fukushima M, Ono K, Maruhashi A. Boron neutron capture therapy outcomes for advanced or recurrent head and neck cancer. J Radiat Res. 2014 Jan 1;55(1):146-53. doi: 10.1093/jrr/rrt098. Epub 2013 Aug 16.

  PMID: 23955053 BACKGROUND

• Aihara T, Morita N, Kamitani N, Kumada H, Ono K, Hiratsuka J, Harada T. BNCT for advanced or recurrent head and neck cancer. Appl Radiat Isot. 2014 Jun;88:12-5. doi: 10.1016/j.apradiso.2014.04.007. Epub 2014 Apr 21.

  PMID: 24799334 BACKGROUND

• Kato I, Fujita Y, Maruhashi A, Kumada H, Ohmae M, Kirihata M, Imahori Y, Suzuki M, Sakrai Y, Sumi T, Iwai S, Nakazawa M, Murata I, Miyamaru H, Ono K. Effectiveness of boron neutron capture therapy for recurrent head and neck malignancies. Appl Radiat Isot. 2009 Jul;67(7-8 Suppl):S37-42. doi: 10.1016/j.apradiso.2009.03.103. Epub 2009 Apr 2.

  PMID: 19409799 BACKGROUND

• Kankaanranta L, Seppala T, Koivunoro H, Saarilahti K, Atula T, Collan J, Salli E, Kortesniemi M, Uusi-Simola J, Valimaki P, Makitie A, Seppanen M, Minn H, Revitzer H, Kouri M, Kotiluoto P, Seren T, Auterinen I, Savolainen S, Joensuu H. Boron neutron capture therapy in the treatment of locally recurred head-and-neck cancer: final analysis of a phase I/II trial. Int J Radiat Oncol Biol Phys. 2012 Jan 1;82(1):e67-75. doi: 10.1016/j.ijrobp.2010.09.057. Epub 2011 Feb 6.

  PMID: 21300462 BACKGROUND

• Kankaanranta L, Seppala T, Koivunoro H, Saarilahti K, Atula T, Collan J, Salli E, Kortesniemi M, Uusi-Simola J, Makitie A, Seppanen M, Minn H, Kotiluoto P, Auterinen I, Savolainen S, Kouri M, Joensuu H. Boron neutron capture therapy in the treatment of locally recurred head and neck cancer. Int J Radiat Oncol Biol Phys. 2007 Oct 1;69(2):475-82. doi: 10.1016/j.ijrobp.2007.03.039. Epub 2007 Aug 6.

  PMID: 17689034 BACKGROUND

• Barth RF, Vicente MG, Harling OK, Kiger WS 3rd, Riley KJ, Binns PJ, Wagner FM, Suzuki M, Aihara T, Kato I, Kawabata S. Current status of boron neutron capture therapy of high grade gliomas and recurrent head and neck cancer. Radiat Oncol. 2012 Aug 29;7:146. doi: 10.1186/1748-717X-7-146.

  PMID: 22929110 BACKGROUND

• Kim YS. Reirradiation of head and neck cancer in the era of intensity-modulated radiotherapy: patient selection, practical aspects, and current evidence. Radiat Oncol J. 2017 Mar;35(1):1-15. doi: 10.3857/roj.2017.00122. Epub 2017 Mar 31.

  PMID: 28395502 BACKGROUND

• Chow LQM, Haddad R, Gupta S, Mahipal A, Mehra R, Tahara M, Berger R, Eder JP, Burtness B, Lee SH, Keam B, Kang H, Muro K, Weiss J, Geva R, Lin CC, Chung HC, Meister A, Dolled-Filhart M, Pathiraja K, Cheng JD, Seiwert TY. Antitumor Activity of Pembrolizumab in Biomarker-Unselected Patients With Recurrent and/or Metastatic Head and Neck Squamous Cell Carcinoma: Results From the Phase Ib KEYNOTE-012 Expansion Cohort. J Clin Oncol. 2016 Nov 10;34(32):3838-3845. doi: 10.1200/JCO.2016.68.1478. Epub 2016 Sep 30.

  PMID: 27646946 BACKGROUND

• Argiris A, Li Y, Forastiere A. Prognostic factors and long-term survivorship in patients with recurrent or metastatic carcinoma of the head and neck. Cancer. 2004 Nov 15;101(10):2222-9. doi: 10.1002/cncr.20640.

  PMID: 15452834 BACKGROUND

• De Felice F, Polimeni A, Valentini V, Brugnoletti O, Cassoni A, Greco A, de Vincentiis M, Tombolini V. Radiotherapy Controversies and Prospective in Head and Neck Cancer: A Literature-Based Critical Review. Neoplasia. 2018 Mar;20(3):227-232. doi: 10.1016/j.neo.2018.01.002. Epub 2018 Feb 12.

  PMID: 29448084 BACKGROUND

• Peng G, Wang T, Yang KY, Zhang S, Zhang T, Li Q, Han J, Wu G. A prospective, randomized study comparing outcomes and toxicities of intensity-modulated radiotherapy vs. conventional two-dimensional radiotherapy for the treatment of nasopharyngeal carcinoma. Radiother Oncol. 2012 Sep;104(3):286-93. doi: 10.1016/j.radonc.2012.08.013. Epub 2012 Sep 17.

  PMID: 22995588 BACKGROUND

• Nutting CM, Morden JP, Harrington KJ, Urbano TG, Bhide SA, Clark C, Miles EA, Miah AB, Newbold K, Tanay M, Adab F, Jefferies SJ, Scrase C, Yap BK, A'Hern RP, Sydenham MA, Emson M, Hall E; PARSPORT trial management group. Parotid-sparing intensity modulated versus conventional radiotherapy in head and neck cancer (PARSPORT): a phase 3 multicentre randomised controlled trial. Lancet Oncol. 2011 Feb;12(2):127-36. doi: 10.1016/S1470-2045(10)70290-4. Epub 2011 Jan 12.

  PMID: 21236730 BACKGROUND

• Marur S, Forastiere AA. Head and Neck Squamous Cell Carcinoma: Update on Epidemiology, Diagnosis, and Treatment. Mayo Clin Proc. 2016 Mar;91(3):386-96. doi: 10.1016/j.mayocp.2015.12.017.

  PMID: 26944243 BACKGROUND

• Torre LA, Bray F, Siegel RL, Ferlay J, Lortet-Tieulent J, Jemal A. Global cancer statistics, 2012. CA Cancer J Clin. 2015 Mar;65(2):87-108. doi: 10.3322/caac.21262. Epub 2015 Feb 4.

  PMID: 25651787 BACKGROUND

• Siegel RL, Miller KD, Jemal A. Cancer Statistics, 2017. CA Cancer J Clin. 2017 Jan;67(1):7-30. doi: 10.3322/caac.21387. Epub 2017 Jan 5.

  PMID: 28055103 BACKGROUND

Study Officials

• Angel Estrada, PhD

  Neutron Therapeutics

  STUDY CHAIR

Central Study Contacts

Anu Anttonen, MD, PhD

CONTACT

358 50 4279911; anu.anttonen@hus.fi

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 26, 2025
• First Posted: July 10, 2025
• Study Start: May 8, 2025
• Primary Completion: November 30, 2025
• Study Completion: January 30, 2026
• Last Updated: July 10, 2025

Record last verified: 2025-06

Data Sharing

• IPD Sharing: Will not share

Locations

FI (1)