Donepezil in Treating Young Patients With Primary Brain Tumors Previously Treated With Radiation Therapy to the Brain

Wake Forest University (WFU)

Status and phase: Completed; Early Phase 1

Conditions: Brain and Central Nervous System Tumors; Radiation Toxicity; Psychosocial Effects of Cancer and Its Treatment; Neurotoxicity; Cognitive/Functional Effects; Long-term Effects Secondary to Cancer Therapy in Children

Treatments: Drug: Donepezil

Study type: Interventional

Funder types: Other; NIH

Identifiers

NCT00452868

P30CA012197 (U.S. NIH Grant/Contract)

CCCWFU-IRB-00000258 (Other Identifier)

CDR0000537049

CCCWFU-91305 (Other Identifier)

Details and patient eligibility

About

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.

Full 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.

Enrollment: 14 patients

Sex: All

Ages: 8 to 17 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Supportive Care

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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14 participants in 1 patient group

Donepozil

Experimental group

Description:

Donepezil 5 milligrams a day for 6 weeks

Treatment:

Drug: Donepezil