Phase III Double Blind, Placebo Controlled Study of Donepezil in the Irradiated Brain

Inclusion 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

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

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