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

Phase	Type	Status	Age	Sponsor	Protocol IDs
Phase III	Supportive care	Active	18 and over	NCI	CCCWFU-91105 WFU 91105, NCT00369785

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

U.S.A.
Georgia
	Augusta
	MBCCOP - Medical College of Georgia Cancer Center
		Angela Goebel, BS	Ph:  706-721-8944
Illinois
	Chicago
	John H. Stroger, Jr. Hospital of Cook County
		Howard Zaren, MD, FACS	Ph:  312-864-5202
	Decatur
	CCOP - Central Illinois
		James Wade, MD	Ph:  217-876-6617
			Email: jlwade3@sbcglobal.net
Indiana
	South Bend
	CCOP - Northern Indiana CR Consortium
		Alicia Dombkowski	Ph:  574-647-7390 800-284-7370
Iowa
	Cedar Rapids
	Cedar Rapids Oncology Associates
		Clinical Trials Office - Cedar Rapids Oncology Associates	Ph:  319-363-2690
Louisiana
	New Orleans
	MBCCOP - LSU Health Sciences Center
		Robert Veith, MD	Ph:  504-896-9740
	Shreveport
	Feist-Weiller Cancer Center at Louisiana State University Health Sciences
		Glenn Mills, MD	Ph:  318-813-1442
			Email: gmills@lsuhsc.edu
Michigan
	Ann Arbor
	CCOP - Michigan Cancer Research Consortium
		Philip Stella, MD	Ph:  734-712-1000
	Royal Oak
	CCOP - Beaumont
		David Decker, MD, FACP	Ph:  248-551-6900
			Email: ddecker@beaumont.edu
Missouri
	Springfield
	CCOP - Cancer Research for the Ozarks
		John Goodwin, MD	Ph:  417-889-8099
			Email: jgoodwin@sprg.mercy.net
	St. Louis
	CCOP - Heartland Research Consortium
		Alan Lyss, MD	Ph:  314-996-5514
			Email: jmr2166@bjc.org
	CCOP - St. Louis-Cape Girardeau
		Bethany Sleckman, MD	Ph:  314-251-6573
New York
	East Syracuse
	CCOP - Hematology-Oncology Associates of Central New York
		Colleen Sweeney	Ph:  315-472-7504 ext. 2129
North Carolina
	Burlington
	Alamance Cancer Center at Alamance Regional Medical Center
		Janak Choksi, MD	Ph:  336-538-7737
	Elkin
	Hugh Chatham Memorial Hospital
		Clinical Trials Office - Hugh Chatham Memorial Hospital	Ph:  336-527-7577
			Email: info@hughchatham.org
	Goldsboro
	Southeastern Medical Oncology Center - Goldsboro
		James Atkins, MD	Ph:  919-580-0000
			Email: jatkins@cancersmoc.com
	Lenoir
	Caldwell Memorial Hospital
		Theodore Yaeger, MD, FACRO	Ph:  828-759-4960
	Winston-Salem
	Wake Forest University Comprehensive Cancer Center
		Clinical Trials Office - Wake Forest University Comprehensive Cancer Center	Ph:  336-713-6771
Pennsylvania
	Wynnewood
	CCOP - Main Line Health
		Maria Hendricks, MSN, RN	Ph:  610-645-2649
South Carolina
	Greenville
	Cancer Centers of the Carolinas - Eastside
		Clinical Trials Office - Cancer Centers of the Carolinas	Ph:  864-241-6251
	Spartanburg
	CCOP - Upstate Carolina
		Clinical Trials Office - CCOP - Upstate Carolina	Ph:  800-486-5941
South Dakota
	Sioux Falls
	CCOP - Sioux Community Cancer Consortium
		Loren Tschetter, MD	Ph:  605-328-8044
			Email: tidemanb@siouxvalley.org
Texas
	Houston
	University of Texas M.D. Anderson CCOP Research Base
		Monica Loghin, MD	Ph:  713-745-4098
Wisconsin
	Green Bay
	CCOP - St. Vincent Hospital Cancer Center, Green Bay
		Clinical Trials Office - CCOP - St. Vincent Hospital Cancer Center, Green Bay	Ph:  920-433-8889

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		2009-07-05
NCI Grant/Contract Number		CA12197, CA81851

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