BNCT to Treat Glioma That Has Progressed Following Radiotherapy

Sponsor

Boneca Corporation (Industry)

Overall Status

Completed

CT.gov ID

NCT00115440

Collaborator

(none)

Enrollment

Location

Arm

94.1

Duration (Months)

0.2

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Glioblastoma Anaplastic Astrocytoma	Radiation: Bononophenylalanine (BPA)-based BNCT	Phase 1/Phase 2

Detailed Description

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).

Study Design

Study Type:

Interventional

Actual Enrollment :

22 participants

Allocation:

Non-Randomized

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Study Start Date :

Mar 1, 2001

Actual Primary Completion Date :

Dec 1, 2008

Actual Study Completion Date :

Jan 1, 2009

Arms and Interventions

Arm	Intervention/Treatment
Experimental: A Active treatment arm.	Radiation: Bononophenylalanine (BPA)-based BNCT Boronophenylalanine is infused into a peripheral vein prior to neutron irradiation.

Arm

Intervention/Treatment

Experimental: A

Active treatment arm.

Radiation: Bononophenylalanine (BPA)-based BNCT

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

Outcome Measures

Primary Outcome Measures

safety [3 years]

Secondary Outcome Measures

survival [3 years]
adverse effects of BNCT [3 years]
quality-of-life [3 years]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Histologically confirmed supratentorial glioblastoma or anaplastic astrocytoma.
Recurred tumor after surgery and radiotherapy or tumor progressing after radiotherapy.
Recurrence/progression has been confirmed by serial MRI scans and a biopsy, or by debulking surgery.
The World Health Organization performance status <2.
WBC >2,500/mm3, platelet count >75,000/mm3, serum creatinine <180 umol/L.
A written informed consent

Exclusion Criteria:

Age less than 18
Tumor infiltrates into the brain stem or the optic tracts
The majority of tumor tissue consists of grade II glioma with only a focal grade III component
A minimum gross tumor dose of 17 Gy (W) is not obtained in dose-planning
Less than 6 months has elapsed from the last date of external irradiation
Less than 4 weeks has elapsed from the last cancer chemotherapy dose prior to giving BNCT
The total conventional radiation therapy dose given is more than 61 Gy or less than 50

Gy, or one of nonconventional fractionation schemes has been used (conventional:

1.8-2.0 Gy/day, 5 days per week, weekly dose 9 to 10 Gy)

More than approximately 1/3 of the total brain volume has been within the 90% isodose
Gliomas where the enhancing tumor volume is larger than 2/3 of the volume of one hemisphere in the MRI examination preceding BNCT
More than one radiotherapy course has been given to the brain tumor
Untreated congestive heart failure or renal failure
Uncontrolled brain oedema despite the use of corticosteroids
A cardiac pace-maker or an unremovable metal implant present in the head and neck region that will interfere with MRI-based dose-planning
Restlessness or inability to lie in a cast for 30 to 60 minutes
Clinical follow-up after therapy cannot be arranged
Pregnancy
Inability to understand treatment options
Unwillingness to take part in the follow-up schedule