Official Title: “A Pilot Study of Donepezil Hydrochloride in Pediatric Brain Tumor Survivors After Cranial Irradiation”

RATIONALE: Donepezil may decrease the side effects caused by radiation therapy to the brain.

PURPOSE: This clinical trial is studying how well donepezil works in treating young patients with primary brain tumors previously treated with radiation therapy to the brain.

Study Type: Interventional

Study Design: Supportive Care, Open Label, Active Control

OBJECTIVES:

Primary - Determine the impact of donepezil hydrochloride on cognitive function in pediatric patients with primary brain tumors previously treated with cranial radiotherapy.

Secondary - Assess health-related quality of life of patients treated with this drug. - Assess function and quality of life of the families of patients treated with this drug. - Determine the physiologic effects of radiotherapy on cerebrovascular hemodynamics in patients treated with this drug. - Determine the toxicity of donepezil hydrochloride in these patients.

OUTLINE: This is a multicenter, pilot, open-label, controlled study.

Patients receive oral donepezil hydrochloride once daily or once every other day for up to 24 weeks in the absence of disease progression or unacceptable toxicity. After completion of 6 weeks of study therapy, patients are evaluated for toxicity. Patients experiencing no adverse effects from treatment may continue receiving donepezil hydrochloride at a higher dose for 18 more weeks.

Patients undergo measurement of cognitive function (by neurocognitive testing), behavioral adjustment and social competency (by parent-reported questionnaires), health-related quality of life (by child- and parent-reported questionnaires), and vascular dynamics (by transcranial Doppler ultrasound) at baseline and at weeks 12, 24, and 36. Family function and family quality of life are assessed at baseline and at week 24.

PROJECTED ACCRUAL: A total of 35 patients will be accrued for this study.

Intervention(s) in this Clinical Trial

• Drug: donepezil hydrochloride
• Procedure: cognitive assessment
• Procedure: psychosocial assessment and care
• Procedure: quality-of-life assessment
• Procedure: ultrasound imaging

Primary Measures

• Effect of donepezil hydrochloride on neurocognitive function as measured by the neurocognitive battery at 24 weeks

Secondary Measures

• Comparison of baseline dynamic vascular analysis (DVA™) indices in pediatric patients who score < 70 vs pediatric patients who score > 70 on the Peabody Picture Vocabulary Test-3
• Correlation of changes in DVA™ indices with changes in cognitive function
• Health-related quality of life (QOL) as measured by Child Report of QOL and Pediatric QOL Inventory (parent and child components) at baseline and at 12, 24, and 36 weeks
• Family impact as measured by Life Events, Pediatric Inventory for Parents, and Impact on Family at week 24
• Toxicity as measured by NCI CTCAE v3.0
• Barriers to recruitment and retention of pediatric patients

DISEASE CHARACTERISTICS:

• Prior diagnosis of primary brain tumor
• No type 2 neurofibromatosis
• Underwent fractionated radiotherapy (≥ 23.4 Gy) with or without surgery or chemotherapy for the brain tumor at least 1 year ago
• No stereotactic radiosurgery as sole treatment
• No evidence of disease progression by MRI

PATIENT CHARACTERISTICS:

• Karnofsky or Lansky performance status 70-100%
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception
• Baseline IQ ≥ 70 on Peabody Picture Vocabulary Test-3
• Stable weight within the past 6 months with no concern of weight loss
• Vision aids and hearing aids must be used for all neuropsychologic/neurocognitive tests, If indicated
• Able to speak English
• No attention-deficit/hyperactivity disorder before cancer diagnosis
• No uncontrolled seizures or uncontrolled endocrinopathies
• No uncontrolled comorbidities

PRIOR CONCURRENT THERAPY:

• See Disease Characteristics
• More than 6 weeks since prior donepezil hydrochloride, EGb761, methylphenidate hydrochloride, other stimulants, or any other cognitive function-enhancing drug
• No steroid dose greater than physiologic replacement (18-30 mg/m² hydrocortisone or equivalent)
• No other concurrent anticholinergic drugs

Gender Eligibility for this Clinical Trial: Both

Minimum Age for this Clinical Trial: 8 Years

Maximum Age for this Clinical Trial: 17 Years

Are Healthy Volunteers Accepted for this Clinical Trial?: No

Lead Sponsor: Wake Forest University

Overall Clinical Trial Officials and Contacts

Sharon M. Castellino, MD, FAAP Study Chair Wake Forest University  

Information obtained from ClinicalTrials.gov on July 02, 2009

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00452868

Study ID Number: CDR0000537049

ClinicalTrials.gov Identifier: NCT00452868

Health Authority: Unspecified

Clinical trial summary from the National Cancer Institute's PDQ® database