Clinical trial NCT00115453: Boron Neutron Capture Therapy (BNCT) as Treatment of Glioblastoma
Official title: Boron Neutron Capture Therapy in the Treatment of Glioblastoma Multiforme
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
PHASE2
Conditions: Glioblastoma
Keywords: glioblastoma
boron neutron capture therapy
boronophenylalanine
brain tumor
Lead sponsor: Boneca Corporation
Sponsor class: INDUSTRY
First posted: 2005-06-23
Enrollment: 50
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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.

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 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

Primary outcomes:
measure: safety
timeFrame: 3 years
Secondary outcomes:
measure: tumor response
timeFrame: one year
measure: effect on brain tissue
timeFrame: 3 years
Other outcomes:
Locations:
city: Helsinki
country: Finland
facility: Department of Oncology, Helsinki University Central Hospital
Study officials:
affiliation: Helsinki University Central Hospital
name: Heikki Joensuu, M.D., prof.
role: PRINCIPAL_INVESTIGATOR
References:
citation: Kouri M, Kankaanranta L, Seppala T, Tervo L, Rasilainen M, Minn H, Eskola O, Vahatalo J, Paetau A, Savolainen S, Auterinen I, Jaaskelainen J, Joensuu H. Undifferentiated sinonasal carcinoma may respond to single-fraction boron neutron capture therapy. Radiother Oncol. 2004 Jul;72(1):83-5. doi: 10.1016/j.radonc.2004.03.016.
citation: Joensuu H, Kankaanranta L, Seppala T, Auterinen I, Kallio M, Kulvik M, Laakso J, Vahatalo J, Kortesniemi M, Kotiluoto P, Seren T, Karila J, Brander A, Jarviluoma E, Ryynanen P, Paetau A, Ruokonen I, Minn H, Tenhunen M, Jaaskelainen J, Farkkila M, Savolainen S. Boron neutron capture therapy of brain tumors: clinical trials at the finnish facility using boronophenylalanine. J Neurooncol. 2003 Mar-Apr;62(1-2):123-34. doi: 10.1007/BF02699939.