Boron Neutron Capture Therapy (BNCT) as Treatment of Glioblastoma

Sponsor

Boneca Corporation (Industry)

Overall Status

Terminated

CT.gov ID

NCT00115453

Collaborator

(none)

Enrollment

Location

Arm

111

Duration (Months)

0.5

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Glioblastoma	Radiation: irradiation	Phase 1/Phase 2

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).

Study Design

Study Type:

Interventional

Actual Enrollment :

50 participants

Allocation:

Non-Randomized

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

Boron Neutron Capture Therapy in the Treatment of Glioblastoma Multiforme

Study Start Date :

May 1, 1999

Actual Primary Completion Date :

Aug 1, 2008

Actual Study Completion Date :

Aug 1, 2008

Arms and Interventions

Arm	Intervention/Treatment
Experimental: A Active treatment arm.	Radiation: irradiation Boronophenylalanine is infused into a peripheral vein prior to neutron irradiation.

Arm

Intervention/Treatment

Experimental: A

Active treatment arm.

Radiation: irradiation

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

Outcome Measures

Primary Outcome Measures

safety [3 years]

Secondary Outcome Measures

tumor response [one year]
effect on brain tissue [3 years]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 75 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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