Back to resultsBNCT to Treat Glioma That Has Progressed Following Radiotherapy
Primary Purpose
Glioblastoma, Anaplastic Astrocytoma
Status
Completed
Phase
Phase 1
Locations
Finland
Study Type
Interventional
Intervention
Bononophenylalanine (BPA)-based BNCT
Sponsored by
About this trial
This is an interventional treatment trial for Glioblastoma focused on measuring glioblastoma, anaplastic astrocytoma, boron neutron capture therapy, radiation therapy, boronophenylalanine
Eligibility Criteria
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
Sites / Locations
- Department of Oncology, Helsinki University Central Hospital
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
A
Arm Description
Active treatment arm.
Outcomes
Primary Outcome Measures
safety
Secondary Outcome Measures
survival
adverse effects of BNCT
quality-of-life
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT00115440
Brief Title
BNCT to Treat Glioma That Has Progressed Following Radiotherapy
Official Title
BPA-Mediated Boron Neutron Capture Therapy (BNCT) in the Treatment of Glioblastoma or Anaplastic Astrocytoma Progressing After Conventional External Beam Radiotherapy
Study Type
Interventional
2. Study Status
Record Verification Date
September 2007
Overall Recruitment Status
Completed
Study Start Date
March 2001 (undefined)
Primary Completion Date
December 2008 (Actual)
Study Completion Date
January 2009 (Actual)
3. Sponsor/Collaborators
Name of the Sponsor
Boneca Corporation
4. Oversight
Data Monitoring Committee
No
5. 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.
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).
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Glioblastoma, Anaplastic Astrocytoma
Keywords
glioblastoma, anaplastic astrocytoma, boron neutron capture therapy, radiation therapy, boronophenylalanine
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
22 (Actual)
8. Arms, Groups, and Interventions
Arm Title
A
Arm Type
Experimental
Arm Description
Active treatment arm.
Intervention Type
Radiation
Intervention Name(s)
Bononophenylalanine (BPA)-based BNCT
Intervention Description
Boronophenylalanine is infused into a peripheral vein prior to neutron irradiation.
Primary Outcome Measure Information:
Title
safety
Time Frame
3 years
Secondary Outcome Measure Information:
Title
survival
Time Frame
3 years
Title
adverse effects of BNCT
Time Frame
3 years
Title
quality-of-life
Time Frame
3 years
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Heikki T Joensuu, M.D., prof.
Organizational Affiliation
Helsinki University Central Hospital
Official's Role
Principal Investigator
Facility Information:
Facility Name
Department of Oncology, Helsinki University Central Hospital
City
Helsinki
ZIP/Postal Code
FIN-00029
Country
Finland
12. IPD Sharing Statement
Citations:
PubMed Identifier
15236879
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.
Results Reference
background
PubMed Identifier
12749708
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.
Results Reference
result
Links:
URL
http://www.boneca.fi
Description
Boneca Corporation is a Finnish company that provides BNCT.
Learn more about this trial
BNCT to Treat Glioma That Has Progressed Following Radiotherapy
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