Accelerator-based BNCT (Boron Neutron Capture Therapy) for Head and Neck Carcinoma.

This phase I study of an accelerator-based boron neutron capture therapy (BNCT) in the treatment of locally recurrent head and neck carcinoma, is sponsored by HUS, Haartmaninkatu 4, Helsinki, Finland and Neutron Therapeutics Finland OY, Kanavaranta 9 FIN-00290 Helsinki.

The indication is for patients with head and neck carcinoma that has recurred locally after conventional radiation therapy.

The primary objective is to demonstrate the safety of accelerator-based neutron radiation using the nuBeam Suite in delivering BNCT.

The secondary objective is the ability to deliver the planned radiation dose to the target site and the ability to plan the trial treatment using the trial treatment planning software, position and target the tumor site using the robotic table in conjunction with the CT scanner and calculate the required radiation dose for each planned BNCT trial treatment.

To establish these objectives, the following parameters will be controlled:

• Objective response rate
• Duration of response.
• The clinical benefit rate (includes complete response, partial response, and stabilized disease for a minimum of 8 weeks since the date of the first BNCT).
• Locoregional recurrence-free survival.
• Progression-free survival.
• Overall survival.
• Quality of life.

The maximum sample size is 10 study subjects evaluable for safety.

The study does not involve randomization.

Regarding the target population, the study subjects must fulfill each of the inclusion criteria:

1. Patient has provided a written informed consent as approved by the EC prior to study specific screening procedures, with the understanding that the patient has the right to withdraw from the study at any time, without prejudice.
2. ≥ 18 years of age at the time of enrollment.
3. Histologically confirmed head and neck carcinoma.
4. Inoperable cancer, prior surgery may or may not have been done.
5. Prior radiotherapy or chemoradiotherapy has been given.
6. Anticipated life expectancy of at least 6 months

Patients who fulfill any of the following criteria will be excluded:

1. Presence of distant metastases.

2. World Health Organization (WHO) performance status > 2

3. Concurrent uncontrolled localized cancer other than head and neck carcinoma or overtly metastatic cancer.

4. The patient has access to a non-experimental, effective treatment option and is a suitable candidate for such therapy.

5. Concomitant chemotherapy.

6. Concurrent experimental therapy or participation in a trial with an experimental therapy within 3 months prior to study inclusion.

7. Less than 3 months since prior radiation therapy.

8. Major surgery within 4 weeks prior to study inclusion.

9. Unremovable metal implants present in the head and neck region that will interfere with CT/MRI-based dose-planning.

10. Known sensitivity to the study drug.

11. One or more of the following:

    • Blood hemoglobin < 100 g/L, neutrophils < 1.5 x 109/L, platelet count < 120 x 109/L
    • Serum/plasma creatinine > 1.5 x Upper Limit of Normal (ULN)
    • Serum bilirubin 2.0 > ULN
    • Serum ALT and/or AST > 2.0 x ULN
    • Serum alkaline phosphatase > 2.5 x ULN

12. Serious uncontrolled infection or other serious uncontrolled concomitant disease.

13. Collagen vascular disease or a disease that is considered to increase radiosensitivity of normal tissues to radiation (e.g., ataxia-telangiectasia)

14. Patient is unwilling or unable to comply with the CIP required follow-up visits for the duration of the study.

15. Untreated or severe treated congestive heart failure, cardiac pacemaker, or renal failure.

16. Restlessness or inability to lie in a cast for about 30 minutes.

17. Clinical follow-up after therapy cannot be arranged or the patient is not willing to participate in the follow-up.

18. Known pregnancy, breastfeeding, or planning of pregnancy; for women of childbearing potential, a negative pregnancy test must be obtained prior to enrollment.

19. The patient is not able to understand the nature of the study and trial treatment options.

20. Phenylketonuria

21. Fructose intolerance.

There is one investigational device included as part of this study. The nuBeam Suite has two main components, the Treatment Delivery System and the nuBeam Dose Engine.

The study drug included in this study is L-boronophenylalanine fructose (L-BPA Fructose)