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
Conditions
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
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.
Interventions
DRUGDonepezil
Donepezil 5 milligrams a day for 6 weeks
Sponsors
National Cancer Institute (NCI)
Wake Forest University Health Sciences
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
SUPPORTIVE_CARE
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
8 Years to 17 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Neurocognitive Function as Measured by the Neurocognitive Battery at 24 Weeks | 24 weeks | Delis-Kaplan Executive Function System Tower Total Scaled Score, range is 1-19 with the higher score being a better outcome. |
Countries
United States
Participant flow
Recruitment details
patients were registered from 9/11/2006 to 5/14/2009
Pre-assignment details
13 unique patients were recruited, one patient twice after failing to start therapy the first time, two patients were not evaluable, leaving 11 patients for analysis.
Participants by arm
| Arm | Count |
|---|---|
| Donepezil | 13 |
| Total | 13 |
Baseline characteristics
| Characteristic | Donepezil |
|---|---|
| Age, Categorical <=18 years | 13 Participants |
| Age, Categorical >=65 years | 0 Participants |
| Age, Categorical Between 18 and 65 years | 0 Participants |
| Age, Continuous | 12.81 years STANDARD_DEVIATION 3 |
| Region of Enrollment United States | 13 participants |
| Sex: Female, Male Female | 6 Participants |
| Sex: Female, Male Male | 7 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 11 / — |
| serious Total, serious adverse events | 3 / 11 |
Outcome results
Primary
Neurocognitive Function as Measured by the Neurocognitive Battery at 24 Weeks
Delis-Kaplan Executive Function System Tower Total Scaled Score, range is 1-19 with the higher score being a better outcome.
Time frame: 24 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Donepezil | Neurocognitive Function as Measured by the Neurocognitive Battery at 24 Weeks | 10 units on a scale | Standard Deviation 3 |