GlioblastomaPhase 1/2NCT00115440
BNCT to Treat Glioma That Has Progressed Following Radiotherapy
A Phase 1/2 study testing Bononophenylalanine (BPA)-based BNCT in people with Glioblastoma and Anaplastic Astrocytoma, run by Boneca Corporation at 1 site in Finland.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Glioblastoma, Anaplastic Astrocytoma
- What is being tested?
- Bononophenylalanine (BPA)-based BNCT
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 22 participants
- Where
- 1 siteFinland
- Study dates
- Mar 2001to Jan 2009
- Phase
- Phase 1/2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Show all 18Show fewer
- 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
Trial locations and contacts
1 site in 1 country.
Finland1 site
Department of Oncology, Helsinki University Central Hospital
Helsinki, FIN-00029
About this study
Official title: BPA-Mediated Boron Neutron Capture Therapy (BNCT) in the Treatment of Glioblastoma or Anaplastic Astrocytoma Progressing After Conventional External Beam Radiotherapy
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.
Read the 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).
- Conditions
- Glioblastoma, Anaplastic Astrocytoma
- Being tested
- Bononophenylalanine (BPA)-based BNCT
- Keywords
- glioblastoma, anaplastic astrocytoma, boron neutron capture therapy, radiation therapy, boronophenylalanine
- Medical subject headings
- Glioblastoma, Astrocytoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Bononophenylalanine (BPA)-based BNCTRadiation
Boronophenylalanine is infused into a peripheral vein prior to neutron irradiation.
| Study group | Role | What they receive |
|---|---|---|
| A | Experimental | Active treatment arm. Receives: Radiation: Bononophenylalanine (BPA)-based BNCT |
What is being measured
The primary outcome is the main question the study is designed to answer.
safety
Measured: 3 years
Secondary outcomes (3)
survival
Measured: 3 years
adverse effects of BNCT
Measured: 3 years
quality-of-life
Measured: 3 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 Jun 2005 (estimated)
- Study startMar 2001
- Primary completionDec 2008
- Study completionJan 2009
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for GlioblastomaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 22 participants (actual)
Sponsor and investigators
- Lead sponsor
- Boneca Corporation
- Sponsor type
- Industry (pharma, biotech, devices)
- Investigators
- Heikki T Joensuu, M.D., prof., Principal investigator, Helsinki University Central Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00115440
- Sponsor's protocol ID
- FIN-BNCT-03/2000
- Other IDs
- BNCT P-03
- Status last verified
- Sep 2007
- First submitted
- 22 Jun 2005
- Last updated
- 28 Jan 2009
- Results posted
- No
- Data monitoring committee
- No
Publications
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.
PubMed 15236879Joensuu 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.
PubMed 12749708
Study at a glance
From the registry record, last updated by the sponsor on 28 Jan 2009. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- BPA-Mediated Boron Neutron Capture Therapy (BNCT) in the Treatment of Glioblastoma or Anaplastic Astrocytoma Progressing After Conventional External Beam Radiotherapy
- ClinicalTrials.gov ID
- NCT00115440
- Acronym / sponsor ID
- FIN-BNCT-03/2000
- Conditions
- Glioblastoma, Anaplastic Astrocytoma
- Keywords
- glioblastoma, anaplastic astrocytoma, boron neutron capture therapy, radiation therapy, boronophenylalanine
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 22 participants (actual)
- Lead sponsor
- Boneca CorporationIndustry (pharma, biotech, devices)
- Study start
- Mar 2001
- Primary completion
- Dec 2008 (actual)
- Study completion
- Jan 2009 (actual)
- First posted
- 23 Jun 2005 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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).
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| A | Experimental | Radiation: Bononophenylalanine (BPA)-based BNCTActive treatment arm. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- 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.
Key exclusion criteria (18 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Bononophenylalanine (BPA)-based BNCTBoronophenylalanine is infused into a peripheral vein prior to neutron irradiation. | Radiation | A |
Primary outcome
safety
Time frame: 3 years
3 secondary outcomes
survival
Time frame: 3 years
adverse effects of BNCT
Time frame: 3 years
quality-of-life
Time frame: 3 years
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 28 Jan 2009.
- Background: PubMed 15236879Kouri 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 publication: PubMed 12749708Joensuu 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Heikki T Joensuu, M.D., prof. principal investigator
Helsinki University Central Hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Bononophenylalanine (BPA)-based BNCT in people with Glioblastoma and Anaplastic Astrocytoma, run by Boneca Corporation at 1 site in Finland.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 18 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 28 Jan 2009. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Finland. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
safety (time frame: 3 years). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00115440, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 28 Jan 2009.