Alternate Title
Basic Trial Information
Objectives
Entry Criteria
Expected Enrollment
Outcomes
Outline
Trial Contact Information
Registry Information

Alternate Title

Donepezil in Treating Patients Who Have Undergone Radiation Therapy for Brain Tumors

Basic Trial Information

Objectives

Primary

1. Compare the effect of donepezil hydrochloride vs placebo, in terms of improving neurocognitive symptom cluster (i.e., cognitive impairment, subjective confusion, and fatigue), in patients who have undergone partial- or whole-brain irradiation for brain tumors.

Secondary

1. Compare the effect of these regimens on mood and quality of life in these patients.

Entry Criteria

Disease Characteristics:

• Diagnosis of primary or metastatic brain tumor

• Completed a course of ≥ 30 Gy fractionated whole-brain irradiation or large-field partial-brain irradiation for primary or metastatic brain tumor ≥ 6 months prior to study entry
  • Meets the following criteria:
    • Single-fraction stereotactic radiosurgery as a boost after external-beam radiotherapy
    • No polifeprosan 20 with carmustine implant (Gliadel wafers), GliaSite®, or other type of brain brachytherapy
    • No convection-enhanced delivery of immunotoxins
    • No other investigational modalities as adjuvant therapy after external-beam radiotherapy

• Must have treatment records (total dose, dose per fraction, and isodose curves) available for all prior radiotherapy (external-beam radiotherapy, brachytherapy, and/or stereotactic radiosurgery)

• Patients receiving prophylactic cranial irradiation are eligible

• No radiographic evidence of brain disease OR stable brain disease, defined as no evidence of tumor progression within the past 3 months

• No brain metastases with progressive extracranial primary or metastatic disease
  • Extracranial primary or metastatic disease must be stable or have responded to local and/or systemic treatment within the past 3 months

Prior/Concurrent Therapy:

• See Disease Characteristics
• More than 2 weeks since prior and no other concurrent dementia drugs, cognitive enhancers, neuroleptics, and/or anti-parkinsonian agents
• Concurrent steroids, anti-cholinergics, anti-epileptics, anti-depressants, and/or sedatives/benzodiazepines allowed provided patient is on a stable or decreasing dose
• Concurrent narcotic analgesics allowed provided the patient is on a stable dose and/or prn basis
• No other planned therapy, including surgery, brain irradiation of any type, chemotherapy, or immunotherapy, for the next 30 weeks for brain or extracranial primary metastatic disease
  • Concurrent trastuzumab (Herceptin®) for breast cancer allowed
  • Concurrent hormonal therapy for breast or prostate cancer allowed
• No concurrent bethanechol, ketoconazole, quinidine, or succinylcholine
• No prior GliaSite or other type of brain brachytherapy, convection enhanced delivery of immunotoxins, and/or any other investigational modalities for treatment of brain tumor
  • Gliadel wafers allowed
• No concurrent chemotherapy

Patient Characteristics:

• Life expectancy ≥ 30 weeks
• Karnofsky performance status 60-100%
• Patients must have a phone
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception
• No sick sinus syndrome or supraventricular arrhythmias
• No hypersensitivity to donepezil hydrochloride

Expected Enrollment

A total of 200 patients will be accrued for this study.

Outcomes

Fatigue, subjective confusion, and cognitive performance at 24 weeks

Mood at 24 weeks
Quality of life at 24 weeks

Outline

This is a prospective, double-blind, placebo-controlled, randomized, multicenter study. Patients are stratified according to prior brain irradiation type (whole-brain vs partial-brain) and study site. Patients are randomized to 1 of 2 treatment arms.

• Arm I: Patients receive oral donepezil hydrochloride once or twice daily for up to 24 weeks in the absence of unacceptable toxicity.

• Arm II: Patients receive oral placebo once or twice daily for up to 24 weeks in the absence of unacceptable toxicity.

Patients complete self-reported questionnaires (quality of life, fatigue, subjective confusion, neurocognitive battery, and mood) at baseline and 12 and 24 weeks.

Trial Contact Information

Trial Lead Organizations

Wake Forest University CCOP Research Base

Stephen Rapp, PhD, Principal investigator		Ph: 336-716-6995 Email: srapp@wfubmc.edu

Registry Information
Official Title		Phase III Double Blind, Placebo Controlled Study of Donepezil in the Irradiated Brain
Trial Start Date		2008-01-01
Trial Completion Date		2010-06-30 (estimated)
Registered in ClinicalTrials.gov		NCT00369785
Date Submitted to PDQ		2006-04-28
Information Last Verified		2011-12-22
NCI Grant/Contract Number		CA12197, CA81851

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