Alternate Title
Basic Trial Information
Objectives
Entry Criteria
Expected Enrollment
Outcomes
Outline
Published Results
Related Publications
Trial Contact Information
Registry Information

Alternate Title

Boron Neutron Capture Therapy Following Surgery in Treating Patients With Glioblastoma Multiforme Removed During Surgery

Basic Trial Information

Phase	Type	Status	Age	Sponsor	Protocol IDs
Phase I	Treatment	Closed	50 and over	Other	EORTC-11961 NCT00004015

Objectives

1. Determine systemic and local toxicity of borocaptate sodium with boron neutron capture therapy (BNCT) following craniotomy with gross total resection in patients with glioblastoma multiforme.
2. Determine the qualitative and quantitative dose-limiting toxicity and maximum tolerated dose of this regimen in these patients.
3. Determine the maximum tolerated radiation dose of BNCT in cranial localization to healthy tissues in these patients under defined conditions.

Entry Criteria

Disease Characteristics:

• Histologically proven glioblastoma multiforme for which conventional radiotherapy would be of little or no benefit



• Gross total resection of tumor confirmed by postoperative MRI performed within 48 hours of surgery



• Evaluable preoperative and postoperative MRI films with and without contrast must be available



• No prior brain malignancy



• No prior craniotomy except for glioblastoma

Prior/Concurrent Therapy:

Biologic therapy:

• No prior biologic therapy for glioblastoma multiforme
• No concurrent biologic therapy

Chemotherapy:

• No prior chemotherapy for glioblastoma multiforme
• No concurrent chemotherapy

Endocrine therapy:

• No prior endocrine therapy for glioblastoma multiforme except corticosteroids
• No concurrent endocrine therapy

Radiotherapy:

• See Disease Characteristics
• No prior radiotherapy for glioblastoma multiforme
• No prior radiotherapy to head and neck
• No other concurrent radiotherapy

Surgery:

• See Disease Characteristics
• Prior stereotactic biopsy allowed for glioblastoma multiforme

Patient Characteristics:

Age:

• 50 and over

Performance status:

• Karnofsky 70-100%

Life expectancy:

• Not specified

Hematopoietic:

• Not specified

Hepatic:

• Bilirubin, SGOT, SGPT, and alkaline phosphatase no greater than 2.5 times normal unless caused by reversible reaction to antiseizure medication

Renal:

• Blood urea nitrogen and creatinine no greater than 2.5 times upper limit of normal

Cardiovascular:

• No severe heart disease (e.g., congestive heart failure, angina pectoris)

Pulmonary:

• No severe dyspnea at time of diagnosis
• No severe obstructive or restrictive lung disease

Other:

• No other concurrent malignant tumor
• No severe gastrointestinal disease or active peptic ulcer disease
• No uncontrolled endocrine disease
• No serious mental disease, organic brain disease (e.g., preexisting epilepsy or serious aphasia), or legally incapacitated patients

Expected Enrollment

Approximately 30-36 patients will be accrued for this study.

Outcomes

Acute toxicity as measured by NCIC-Common Toxicity Criteria up to 30 days after the first BSH administration

Late toxicity as measured by RTOC and EORTC late radiation morbidity scale from 90 days after completion of irradiation treatment until death
Overall survival as measured by Logrank until death

Outline

This is a dose escalation, multicenter study.

Within 6 weeks of surgery, patients receive borocaptate sodium followed 12-18 hours later by neutron irradiation. Treatment repeats daily for 4 days.

Cohorts of 3-9 patients receive escalating doses of neutron irradiation. The maximum tolerated dose is defined as the dose preceding that at which 3 or more patients experience dose limiting toxicity.

Patients are followed weekly for 4 weeks, monthly for 2 months, every 6 weeks for 15 months and then every 3 months thereafter.

Verbakel WF, Sauerwein W, Hideghety K, et al.: Boron concentrations in brain during boron neutron capture therapy: in vivo measurements from the phase I trial EORTC 11961 using a gamma-ray telescope. Int J Radiat Oncol Biol Phys 55 (3): 743-56, 2003.[PUBMED Abstract]

Hideghéty K, Sauerwein W, Haselsberger K, et al.: Postoperative treatment of glioblastoma with BNCT at the petten irradiation facility (EORTC protocol 11,961). Strahlenther Onkol 175 (Suppl 2): 111-4, 1999.[PUBMED Abstract]

Gabel D, Touw D, Stecher-Rasmussen F, et al.: Quality control of Na2B12H11SH, a drug boron neutron capture therapy in EORTC trial 11961. [Abstract] Ann Oncol 9(suppl 2): 129, 1998.

Hideghéty K, Sauerwein W, Wittig A, et al.: Tissue uptake of BSH in patients with glioblastoma in the EORTC 11961 phase I BNCT trial. J Neurooncol 62 (1-2): 145-56, 2003 Mar-Apr.[PUBMED Abstract]

Hideghety W, Sauerwein W, DeVries M, et al.: Post-operative treatment of glioblastoma with boron neutron capture therapy at the European High Flux Reactor Petten (EORTC protocol 11961). [Abstract] Ann Oncol 9(suppl 2): 129, 1998.

Sauerwein W, Hideghety K, De Vries M, et al.: Boron neutron capture therapy (BNCT) for the treatment of glioblastoma (EORTC protocol 11961). [Abstract] Radiother Oncol 48(suppl 1): s157, 1998.

Sauerwein W, Hideghety K, De Vries M, et al.: Conducting phase I clinical trial in binary treatment modality: methodical questions for the evaluation of boron neutron capture therapy. [Abstract] Ann Oncol 9(suppl 2): 129, 1998.

Vos MJ, Turowski B, Zanella FE, et al.: Radiologic findings in patients treated with boron neutron capture therapy for glioblastoma multiforme within EORTC trial 11961. Int J Radiat Oncol Biol Phys 61 (2): 392-9, 2005.[PUBMED Abstract]

Haselsberger K, Pendl G, Sauerwein W, et al.: BNCT for glioblastoma in Europe: design of the EORTC protocol 11961 and clinical course of the first patient. [Abstract] J Neurooncol 39 (2): A-P155, 147, 1998.

Wittig A, Moss RL, Stecher-Rasmussen F, et al.: Neutron activation of patients following boron neutron capture therapy of brain tumors at the high flux reactor (HFR) Petten (EORTC Trials 11961 and 11011). Strahlenther Onkol 181 (12): 774-82, 2005.[PUBMED Abstract]

Verbakel WF, Hideghety K, Morrissey J, et al.: Towards in vivo monitoring of neutron distributions for quality control of BNCT. Phys Med Biol 47 (7): 1059-72, 2002.[PUBMED Abstract]

Hüsing J, Sauerwein W, Hideghéty K, et al.: A scheme for a dose-escalation study when the event is lagged. Stat Med 20 (22): 3323-34, 2001.[PUBMED Abstract]

Rassow J, Stecher-Rasmussen F, Voorbraak W, et al.: Comparison of quality assurance for performance and safety characteristics of the facility for Boron Neutron Capture therapy in Petten/NL with medical electron accelerators. Radiother Oncol 59 (1): 99-108, 2001.[PUBMED Abstract]

Sauerwein W, Moss R, Rassow J, et al.: Organisation and management of the first clinical trial of BNCT in Europe (EORTC protocol 11961).EORTC BNCT study group. Strahlenther Onkol 175 (Suppl 2): 108-11, 1999.[PUBMED Abstract]

Gabel D, Philipp KH, Wheeler FJ, et al.: The compound factor of the 10B(n,alpha)7Li reaction from borocaptate sodium and the relative biological effectiveness of recoil protons for induction of brain damage in boron neutron capture therapy. Radiat Res 149 (4): 378-86, 1998.[PUBMED Abstract]

Pignol JP, Oudart H, Chauvel P, et al.: Selective delivery of 10B to soft tissue sarcoma using 10B-L-borophenylalanine for boron neutron capture therapy. Br J Radiol 71 (843): 320-3, 1998.[PUBMED Abstract]

Trial Contact Information

Trial Lead Organizations

European Organization for Research and Treatment of Cancer

Wolfgang Sauerwein, MD, PhD, Study coordinator		Ph: 49-201-723-2052 Email: w.sauerwein@uni-essen.de

Registry Information
Official Title		Postoperative Treatment of Glioblastoma with BNCT at the Petten Irradiation Facility
Trial Start Date		2002-06-14
Registered in ClinicalTrials.gov		NCT00004015
Date Submitted to PDQ		1999-07-29
Information Last Verified		2006-05-02

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