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

Phase 3
18 Years
Not Enrolling
Brain and Central Nervous System Tumors, Cognitive/Functional Effects, Fatigue, Metastatic Cancer, Psychosocial Effects of Cancer and Its Treatment, Radiation Toxicity

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Trial Information

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



- 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


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

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.

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

Inclusion Criteria


- 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

- 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

- 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


- 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


- 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

- Gliadel wafers allowed

- No concurrent chemotherapy

Type of Study:


Study Design:

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Supportive Care

Outcome Measure:

Fatigue, subjective confusion, and cognitive performance at 24 weeks

Outcome Time Frame:

24 weeks

Safety Issue:


Principal Investigator

Stephen Rapp, PhD

Investigator Role:

Principal Investigator

Investigator Affiliation:

Wake Forest University


United States: Federal Government

Study ID:




Start Date:

January 2008

Completion Date:

June 2012

Related Keywords:

  • Brain and Central Nervous System Tumors
  • Cognitive/Functional Effects
  • Fatigue
  • Metastatic Cancer
  • Psychosocial Effects of Cancer and Its Treatment
  • Radiation Toxicity
  • cognitive/functional effects
  • fatigue
  • psychosocial effects of cancer and its treatment
  • radiation toxicity
  • tumors metastatic to brain
  • adult brain stem glioma
  • adult central nervous system germ cell tumor
  • adult choroid plexus tumor
  • adult craniopharyngioma
  • adult mixed glioma
  • adult anaplastic meningioma
  • meningeal melanocytoma
  • adult meningeal hemangiopericytoma
  • adult grade I meningioma
  • adult grade II meningioma
  • adult grade III meningioma
  • adult papillary meningioma
  • adult anaplastic oligodendroglioma
  • adult oligodendroglioma
  • adult pineoblastoma
  • adult pineocytoma
  • adult anaplastic astrocytoma
  • adult diffuse astrocytoma
  • adult glioblastoma
  • adult giant cell glioblastoma
  • adult gliosarcoma
  • adult pilocytic astrocytoma
  • adult ependymoblastoma
  • adult medulloblastoma
  • adult supratentorial primitive neuroectodermal tumor (PNET)
  • adult anaplastic ependymoma
  • adult ependymoma
  • adult myxopapillary ependymoma
  • adult subependymoma
  • Fatigue
  • Neoplasm Metastasis
  • Neoplasms
  • Neoplasms, Second Primary
  • Nervous System Neoplasms
  • Central Nervous System Neoplasms
  • Radiation Injuries



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