Boron Neutron Capture Therapy (BNCT) as Treatment of Glioblastoma

This study has been terminated.
(Slow accrual)
Sponsor:
Information provided by:
Boneca Corporation
ClinicalTrials.gov Identifier:
NCT00115453
First received: June 22, 2005
Last updated: August 14, 2008
Last verified: August 2008
  Purpose

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.


Condition Intervention Phase
Glioblastoma
Radiation: irradiation
Phase 1
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Boron Neutron Capture Therapy in the Treatment of Glioblastoma Multiforme

Resource links provided by NLM:


Further study details as provided by Boneca Corporation:

Primary Outcome Measures:
  • safety [ Time Frame: 3 years ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • tumor response [ Time Frame: one year ] [ Designated as safety issue: No ]
  • effect on brain tissue [ Time Frame: 3 years ] [ Designated as safety issue: No ]

Enrollment: 50
Study Start Date: May 1999
Study Completion Date: August 2008
Primary Completion Date: August 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: A
Active treatment arm.
Radiation: irradiation
Boronophenylalanine is infused into a peripheral vein prior to neutron irradiation.

Detailed Description:

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).

  Eligibility

Ages Eligible for Study:   18 Years to 75 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Histologically confirmed glioblastoma multiforme
  • Supratentorial location
  • At least 30% of the tumor volume has been removed at craniotomy as judged from a pre/perioperative MRI
  • Ability to understand the concept of investigational therapy
  • Tolerates dexamethasone treatment
  • Adequate anti-epileptic medication
  • BNCT can be delivered within 6 weeks from the date of brain surgery
  • A written informed consent

Exclusion Criteria:

  • Age less than 18 or greater than 75
  • The tumor infiltrates into the optic chiasm or into the deep parts of the brain prohibiting delivery of an adequate radiation dose with BNCT
  • Prior radiation therapy to the brain
  • Prior chemotherapy, immunotherapy, or gene therapy
  • Karnofsky performance score <70
  • Severe cardiac, liver, or kidney failure
  • Severe infection
  • A cardiac pace-maker, or a metal implant in the head and neck region that will prohibit MRI examination
  • Pregnancy or lactation
  • Phenylketonuria
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00115453

Locations
Finland
Department of Oncology, Helsinki University Central Hospital
Helsinki, Finland, FIN-00029
Sponsors and Collaborators
Boneca Corporation
Investigators
Principal Investigator: Heikki Joensuu, M.D., prof. Helsinki University Central Hospital
  More Information

Additional Information:
Publications:
Responsible Party: CEO Markku Pohjola, BONECA Ltd, Tukholmankatu 8
ClinicalTrials.gov Identifier: NCT00115453     History of Changes
Other Study ID Numbers: BNCT-P01
Study First Received: June 22, 2005
Last Updated: August 14, 2008
Health Authority: Finland: Finnish Medicines Agency

Keywords provided by Boneca Corporation:
glioblastoma
boron neutron capture therapy
boronophenylalanine
brain tumor

Additional relevant MeSH terms:
Glioblastoma
Astrocytoma
Glioma
Neoplasms, Neuroepithelial
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms, Nerve Tissue

ClinicalTrials.gov processed this record on August 26, 2014