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

Early Phase 1

Completed

• 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
• Interventions: Drug: Donepezil

• Registration Number: NCT00452868
• Lead Sponsor: Wake Forest University Health Sciences

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.

Study Timeline

• Study Start: 2006-06
• Study First Submitted: 2007-03-27
• Study First Submitted QC: 2007-03-27
• Study First Posted: 2007-03-28
• Primary Completion: 2010-02
• Study Completion: 2010-02
• Results First Submitted: 2012-08-31
• Results First Submitted QC: 2013-01-24
• Results First Posted: 2013-02-28
• Status Verified: 2018-08
• Last Update Submitted: 2018-08-08
• Last Update Posted: 2018-09-07

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 14

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Donepozil	Donepezil	Donepezil 5 milligrams a day for 6 weeks

Primary Outcome Measures

Name	Time	Method
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.

Trial Locations

Locations (2)

Wake Forest University Comprehensive Cancer Center; 🇺🇸 Winston-Salem, North Carolina, United States

Tufts-NEMC Cancer Center; 🇺🇸 Boston, Massachusetts, United States