Clinical trial NCT00452868: Donepezil in Treating Young Patients With Primary Brain Tumors Previously Treated With Radiation Therapy to the Brain
Official title: A Pilot Study of Donepezil Hydrochloride in Pediatric Brain Tumor Survivors After Cranial Irradiation
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: EARLY_PHASE1
Conditions: Brain and Central Nervous System Tumors
Cognitive/Functional Effects
Long-term Effects Secondary to Cancer Therapy in Children
Neurotoxicity
Psychosocial Effects of Cancer and Its Treatment
Radiation Toxicity
Keywords: cognitive/functional effects
neurotoxicity
long-term effects secondary to cancer therapy in children
psychosocial effects of cancer and its treatment
radiation toxicity
childhood central nervous system germ cell tumor
childhood choroid plexus tumor
childhood craniopharyngioma
childhood grade I meningioma
childhood grade II meningioma
childhood grade III meningioma
childhood spinal cord neoplasm
childhood brain stem glioma
childhood cerebellar astrocytoma
childhood medulloblastoma
childhood supratentorial primitive neuroectodermal tumor
childhood visual pathway and hypothalamic glioma
childhood subependymal giant cell astrocytoma
childhood ependymoma
childhood cerebral astrocytoma/malignant glioma
Lead sponsor: Wake Forest University Health Sciences
Sponsor class: OTHER
Collaborators: name: National Cancer Institute (NCI)
First posted: 2007-03-28
Enrollment: 14
Sex: ALL
Minimum age (years): 8
Maximum age (years): 17
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: SUPPORTIVE_CARE

Brief summary: 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.

Detailed description: 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.

Eligibility criteria: Inclusion Criteria:

* 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
* Karnofsky or Lansky performance status 70-100%
* Fertile patients willing to 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
* More than 6 weeks since prior donepezil hydrochloride, EGb761, methylphenidate hydrochloride, other stimulants, or any other cognitive function-enhancing drug

Exclusion Criteria:

* Stereotactic radiosurgery as sole treatment
* Evidence of disease progression by MRI
* Pregnant or nursing
* Attention-deficit/hyperactivity disorder before cancer diagnosis
* Uncontrolled seizures or uncontrolled endocrinopathies
* Uncontrolled comorbidities
* Steroid dose greater than physiologic replacement (18-30 mg/m² hydrocortisone or equivalent)
* Use of concurrent anticholinergic drugs

Primary outcomes:
measure: Neurocognitive Function as Measured by the Neurocognitive Battery at 24 Weeks
timeFrame: 24 weeks
Secondary outcomes:
Other outcomes:
Locations:
city: Boston
country: United States
facility: Tufts-NEMC Cancer Center
state: Massachusetts
city: Winston-Salem
country: United States
facility: Wake Forest University Comprehensive Cancer Center
state: North Carolina
Study officials:
affiliation: Wake Forest University Health Sciences
name: Sharon M. Castellino, MD, FAAP
role: STUDY_CHAIR
References: