Boron Neutron Capture Therapy (BNCT) Combined With Cetuximab in the Treatment of Locally Recurred Head and Neck Cancer

Phase 1

Terminated

• Conditions: Head and Neck Cancer
• Interventions: Radiation: BNCT; Drug: cetuximab

• Registration Number: NCT00927147
• Lead Sponsor: Boneca Corporation

Brief Summary

The purpose of the study is to investigate efficacy and safety boron neutron capture therapy (BNCT) administered in combination with cetuximab in the treatment of head and neck cancer that has recurred locally following conventional cancer treatment (surgery and radiation therapy). Boron neutron capture therapy is a special form of radiation therapy, which is based on interaction between boron atoms taken up by the cancerous tissue and neutron irradiation. The boron atoms, located within cancer cells, may capture low-energy neutrons obtained from a nuclear accelerator, which results in splitting up (fission) of the boron atoms, and a high radiation effect within the tumor. Cetuximab is an antibody directed against certain proteins found on cancer cell surface (epidermal growth factor receptors). When administered immediately after BNCT, cetuximab may or may not improve treatment efficacy.

Detailed Description

This is a single-center, non-randomized, non-comparative, open-label, phase I/II trial to determine safety and efficacy of BNCT in the treatment of nonoperable, irradiated, locally advanced cancers of the head and neck region. Patients will be treated with a single-fraction boronophenylalanine (BPA)-based BNCT. All patients will be evaluated for response using CT or magnetic resonance imaging (MRI).

Neutron irradiation will first be planned based on the available tumor imaging examinations, following which the head and body position will be determined for irradiation, and head fixation will be prepared and tested. On the irradiation day 400 mg/m2 L-BPA-F will be infused intravenously over 2 hours. Cetuximab doses will be administered following completion of BNCT. The cetuximab doses will be escalated in cohorts of 3 patients.

Study Timeline

• Study Start: 2009-06
• Study First Submitted: 2009-06-21
• Study First Submitted QC: 2009-06-23
• Study First Posted: 2009-06-24
• Primary Completion: 2013-06
• Study Completion: 2013-06
• Status Verified: 2017-01
• Last Update Submitted: 2017-01-30
• Last Update Posted: 2017-01-31

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 17

Inclusion Criteria

• Histologically confirmed invasive squamous cell carcinoma of the head and neck
• Inoperable tumor or the patient is not a candidate for surgery for medical reasons; prior surgery may or may not have been done
• Prior radiotherapy or chemoradiotherapy has been given to the tumor
• If prior 18F-boronophenylalanine (BPA) PET (positron emission tomography)has been done, BPA needs to accumulate at least 2 times more in the tumor than in the corresponding normal tissue
• A written informed consent

Exclusion Criteria

• Presence of distant metastases
• A non-experimental, effective treatment op-tion is available
• WHO performance status >3
• WBC <2,500/mm3, platelets <75,000/mm3, serum creatinine >180 umol/L
• Concomitant systemic cancer chemotherapy (except cetuximab).
• Other concurrent experimental therapy
• Less than 1 month since prior radiation therapy
• Untreated or severe treated congestive heart failure or renal failure
• A cardiac pace-maker or unremovable metal implants 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
• Known allergy/hypersensitivity to cetuximab

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
BNCT plus cetuximab	BNCT	Patients treated with BNCT followed by cetuximab administration
BNCT plus cetuximab	cetuximab	Patients treated with BNCT followed by cetuximab administration

Primary Outcome Measures

Name	Time	Method
Response rate	December 2010

Secondary Outcome Measures

Name	Time	Method
Safety	December 2010
Duration of treatment response	December 2010
Time to progression	December 2010
Survival	December 2010
Adverse events	December 2010

Trial Locations

Locations (1)

Department of Oncology, Helsinki University Central Hospital; 🇫🇮 Helsinki, Finland