Boronophenylalanine (BPA)-Based Boron Neutron Capture Therapy (BNCT) in the Treatment Head and Neck Tumors

Sponsor

Boneca Corporation (Industry)

Overall Status

Completed

CT.gov ID

NCT00114790

Collaborator

(none)

Enrollment

Location

Arm

Duration (Months)

0.3

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 will be repeated, and the 2 treatments will be given 3 to 5 weeks apart. The study hypothesis is that head and neck cancers that have recurred following conventional radiotherapy might accumulate the boron carrier compound, and might respond to BNCT.

Condition or Disease	Intervention/Treatment	Phase
Head and Neck Cancer	Radiation: boronophenylalanine-based BNCT	Phase 1/Phase 2

Detailed Description

This is a single BNCT-facility, non-randomized, non-comparative, open-label, phase I to II trial to determine the value of BNCT in the treatment of inoperable, irradiated, locally advanced cancers of the head and neck region. An attempt to perform 18F-labeled boronophenylalanine (18F-BPA) SPECT or PET imaging will be made before BNCT. Patients whose tumor uptake is >2.5 times that of the corresponding normal head and neck tissue will be enrolled, and treated with a single fraction BPA-based BNCT twice, 3 to 5 weeks apart. Another 18F-BPA SPECT or PET study may be performed 1 to 3 months after BNCT to determine the SPECT/PET response.

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.

Prior to BNCT, BPA is infused as a fructose complex (l-BPA-F) into a peripheral vein over 2 hours. Blood samples will be taken for monitoring whole blood boron concentration before starting the BPA infusion, and thereafter at 20 to 40 minute intervals during the infusion, following infusion, and after delivering neutron irradiation. The blood samples will be analyzed for blood boron concentration to estimate the average blood boron concentration during neutron irradiation.

All patients will be evaluated for response using CT or magnetic resonance imaging (MRI).

Study Design

Study Type:

Interventional

Actual Enrollment :

30 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

Boronophenylalanine (BPA)-Based Boron Neutron Capture Therapy (BNCT) in the Treatment of Inoperable and Irradiated Head and Neck Tumors: A Feasibility Study

Study Start Date :

Dec 1, 2003

Actual Primary Completion Date :

Oct 1, 2008

Actual Study Completion Date :

Jan 1, 2012

Arms and Interventions

Arm	Intervention/Treatment
Experimental: BNCT. Boronophenylalanine-based BNCT.	Radiation: boronophenylalanine-based BNCT Boronophenylalanine is infused into a peripheral vein prior to neutron irradiation.

Arm

Intervention/Treatment

Experimental: BNCT.

Boronophenylalanine-based BNCT.

Radiation: boronophenylalanine-based BNCT

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

Outcome Measures

Primary Outcome Measures

treatment response [1 year]

Secondary Outcome Measures

time to progression [2 years]
safety [2 years]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Histologically confirmed, malignant head and neck cancer.
Inoperable tumor, prior surgery may or may not have been done.
Prior radiotherapy or chemoradiotherapy has been given.
If prior SPECT or PET with 18F-BFA has been done, BPA needs to accumulate at least 2.5 times more in the tumor than in the corresponding contralateral normal tissue.
WHO performance status <3.
WBC >2,500/mm3, platelets >75,000/mm3, serum creatinine <180 umol/L.
A written informed consent.

Exclusion Criteria:

Lymphoma or other tumor type that is expected to respond to cancer chemotherapy or to a dose of conventional radiation therapy that can be safely given.
A non-experimental, effective treatment option is available.
Expected survival less than 3 months.
Concomitant systemic chemotherapy (prior cancer chemotherapy is allowed).
Other concurrent experimental therapy, or such therapy is being planned to be given.
Less than 3 months since prior radiation therapy.
Untreated or severe, treated congestive heart failure or renal failure.
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 or the patient is not willing to participate in follow-up.
Pregnancy.
Age less than 18.
The patient is not able to understand the treatment options.