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

• Sponsor: Wake Forest University Health Sciences (Other)
• Overall Status: Completed
• CT.gov ID: NCT00452868
• Collaborator: National Cancer Institute (NCI) (NIH)
• Enrollment: 14
• Locations: 2
• Arm: 1
• Actual Duration (Months): 44.1
• Patients Per Site: 7
• Patients Per Site Per Month: 0.2

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
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	Drug: Donepezil	Early Phase 1

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 Design

• Study Type: Interventional
• Actual Enrollment: 14 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Supportive Care
• Official Title: A Pilot Study of Donepezil Hydrochloride in Pediatric Brain Tumor Survivors After Cranial Irradiation
• Actual Study Start Date: Jun 1, 2006
• Actual Primary Completion Date: Feb 1, 2010
• Actual Study Completion Date: Feb 1, 2010

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Donepozil Donepezil 5 milligrams a day for 6 weeks	Drug: Donepezil; Donepezil 5 milligrams a day for 6 weeks

Outcome Measures

Primary Outcome Measures

1. 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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 8 Years to 17 Years
• Sexes Eligible for Study: All
• Accepts 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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Tufts-NEMC Cancer Center	Boston	Massachusetts	United States	02111
2	Wake Forest University Comprehensive Cancer Center	Winston-Salem	North Carolina	United States	27157-1096

Sponsors and Collaborators

• Wake Forest University Health Sciences
• National Cancer Institute (NCI)

Investigators

• Study Chair: Sharon M. Castellino, MD, FAAP, Wake Forest University Health Sciences

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Wake Forest University Health Sciences
• ClinicalTrials.gov Identifier: NCT00452868
• Other Study ID Numbers: CDR0000537049; P30CA012197; CCCWFU-91305; CCCWFU-IRB-00000258
• First Posted: Mar 28, 2007
• Last Update Posted: Sep 7, 2018
• Last Verified: Aug 1, 2018

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by Wake Forest University Health Sciences: 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
• Additional relevant MeSH terms: Nervous System Neoplasms; Central Nervous System Neoplasms; Neurotoxicity Syndromes; Donepezil

Study Results

Participant Flow

Recruitment Details	patients were registered from 9/11/2006 to 5/14/2009
Pre-assignment Detail	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.

Arm/Group Title	Donepezil
Arm/Group Description	Patients less than 35 kilograms(kg): Donepezil 5 milligrams (mg) orally once every alternate day. Patients greater than 35 kg Donepezil 5 mg orally once per day. If there are no adverse effects noted on review of symptoms, the dose will be increased to 5 mg daily for patients < 35 kg. And to 10 mg/day for patients > 35 kg. This evaluation and dose escalation may be done as early as week 4. For all, donepezil will be administered 24 weeks.
Period Title: Overall Study
STARTED	13
COMPLETED	11
NOT COMPLETED	2

Baseline Characteristics

Arm/Group Title	Donepezil
Arm/Group Description
Overall Participants	13
Age (Count of Participants)
<=18 years	13 100%
Between 18 and 65 years	0 0%
>=65 years	0 0%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	12.81 (3)
Sex: Female, Male (Count of Participants)
Female	6 46.2%
Male	7 53.8%
Region of Enrollment (participants) [Number]
United States	13 100%

Outcome Measures

1. Primary Outcome

Title	Neurocognitive Function as Measured by the Neurocognitive Battery at 24 Weeks
Description	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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Donepezil
Arm/Group Description
Measure Participants	11
Mean (Standard Deviation) [units on a scale]	10 (3)

Adverse Events

Arm/Group Title	Donepezil
Arm/Group Description
All Cause Mortality
	Donepezil
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Donepezil
	Affected / at Risk (%)	# Events
Total	3/11 (27.3%)
Gastrointestinal disorders
vomiting	2/11 (18.2%)	2
General disorders
Dehydration	1/11 (9.1%)	1
ataxia	1/11 (9.1%)	1
Other (Not Including Serious) Adverse Events
	Donepezil
	Affected / at Risk (%)	# Events
Total	11/ (NaN)
Ear and labyrinth disorders
Dizziness	1/11 (9.1%)	1
Neuropathy: cranial: CN VIII Hearing and balance	1/11 (9.1%)	1
Eye disorders
Occular/Visual	2/11 (18.2%)	2
Gastrointestinal disorders
Nausea	6/11 (54.5%)	6
Diarrhea	5/11 (45.5%)	5
Incontenence, anal	1/11 (9.1%)	1
General disorders
Anorexia	5/11 (45.5%)	5
Fatigue	10/11 (90.9%)	10
Pain: Abdomen NOS	4/11 (36.4%)	4
Pain: Back	1/11 (9.1%)	1
Pain: Extremity-limb	1/11 (9.1%)	1
Infections and infestations
Fever (in the absence of neutropenia)	1/11 (9.1%)	1
Infection	1/11 (9.1%)	1
Infection with unknown ANC: Bronchus	1/11 (9.1%)	1
Infection with unknown ANC: Nerv-peripheral	1/11 (9.1%)	1
Infection with unknown ANC: Urinary tract NOS	1/11 (9.1%)	1
Musculoskeletal and connective tissue disorders
Muscle weakness, generalized: whole body	1/11 (9.1%)	1
Pain: Muscle	5/11 (45.5%)	5
Muscle weakness, generalid or specfic ara (not due to neuropathy): Left sided	1/11 (9.1%)	1
Nervous system disorders
Neurology	2/11 (18.2%)	2
Pain: Head/headache	1/11 (9.1%)	1
Confusion	1/11 (9.1%)	1
Psychiatric disorders
Personality/behavioral	1/11 (9.1%)	1
Insomnia	4/11 (36.4%)	4
Speech Impairment	1/11 (9.1%)	1
Mood Alteration: Agitation	1/11 (9.1%)	1
Extrapyramidal/involuntary movement/restlessness	1/11 (9.1%)	1
Renal and urinary disorders
Incontinence, urinary	1/11 (9.1%)	1
Skin and subcutaneous tissue disorders
Pain: Skin	1/11 (9.1%)	1
Vascular disorders
Hemorrhag, pulmonary/upper respiratory: nose	1/11 (9.1%)	1

Limitations/Caveats

small number (11) analyzed

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.