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

NCT ID: NCT00369785

Last Updated: 2021-10-20

Study Results

Results available

Outcome measurements, participant flow, baseline characteristics, and adverse events have been published for this study.

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE3

Total Enrollment

198 participants

Study Classification

INTERVENTIONAL

Study Start Date

2008-02-29

Study Completion Date

2012-07-01

Brief Summary

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RATIONALE: Donepezil may help lessen confusion and fatigue and improve mood and quality of life in patients who have undergone radiation therapy for brain tumors. It is not yet known whether donepezil is more effective than a placebo in lessening side effects of radiation therapy in patients with brain tumors.

PURPOSE: This randomized phase III trial is studying donepezil to see how well it works in lessening side effects of radiation therapy compared with a placebo in patients who have undergone radiation therapy for brain tumors.

Detailed Description

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OBJECTIVES:

Primary

* 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

* 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.

Conditions

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Brain Tumors Metastatic Disease

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

SUPPORTIVE_CARE

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors

Study Groups

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Arm I - Donepezil

Weeks 1-6: One 5 mg tablet orally donepezil hydrochloride Weeks 7-24: Two 5mg tablets per day

Group Type EXPERIMENTAL

donepezil hydrochloride

Intervention Type DRUG

Weeks 1-6: One tablet Donepezil 5 mg given daily Weeks 7-24: Two Donepezil 5 mg tablets given daily

Arm II - Control

Weeks 1-6: One placebo tablet per day Weeks 7-24: Two placebo tablets per day

Group Type PLACEBO_COMPARATOR

Placebo

Intervention Type DRUG

Weeks 1-6: One tablet per day Weeks 7-24: Two tablets per day

Interventions

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donepezil hydrochloride

Weeks 1-6: One tablet Donepezil 5 mg given daily Weeks 7-24: Two Donepezil 5 mg tablets given daily

Intervention Type DRUG

Placebo

Weeks 1-6: One tablet per day Weeks 7-24: Two tablets per day

Intervention Type DRUG

Other Intervention Names

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Donepezil

Eligibility Criteria

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Inclusion Criteria

* Adults \>18 years old.
* Life expectancy of at least \> 30 weeks.
* Must have received a prior course of at least 30 Gy fractionated whole or partial brain irradiation for treatment of a primary brain tumor or metastatic disease to the brain.
* Must have completed radiation \> 6 months prior to enrollment and have no radiographic evidence of brain disease, or stable brain disease defined as no evidence of tumor progression in the 3 months prior to enrollment.
* Patients who have undergone one or more treatments with single fraction stereotactic radiosurgery (SRS) in addition to whole or partial brain irradiation are eligible, as long as the SRS was completed \> 6 months prior to registration if NED or stable disease.
* Radiation treatment records must be available for all prior radiation treatments (external beam and/or SRS).
* Patients who have received PCI (prophylactic cranial irradiation) are eligible.
* Karnofsky Performance Status must be \> 60 or ECOG 0-2.
* Treatment with steroids, anti-cholinergics, anti-epileptics, anti-depressants, and /or sedatives/benzodiazepines is acceptable, but the patient must be on a stable or decreasing dose at the time of study entry.
* Patients using narcotic analgesics on a stable dose and/or prn basis are eligible.
* Patients currently on a stable dose of Methylphenidate or Dextramphetamine are eligible.
* For patients with brain metastases, if extracranial primary or metastatic disease is present, it must have responded to local and/or systemic treatment. Must be stable in the 3 months prior to enrollment.
* Must not be receiving chemotherapy at the time of enrollment.
* Patient must not have any planned therapy, including surgery, brain radiation of any type, chemotherapy, or immunotherapy during the next 30 weeks for brain or extracranial primary metastatic disease.
* Hormonal therapy for patients with breast or prostate cancer is acceptable.
* Breast patients receiving therapy with Herceptin are allowed.
* Patients must be able to give informed consent to participate in the study, including signing the consent form.
* Patients must have a telephone.

Exclusion Criteria

* Patients cannot be currently taking dementia drugs, cognitive enhancers, neuroleptics, and/or anti-parkinsonian agents. For patients who have used these drugs in the past, they must not have used them in the 2 weeks prior to enrolling on the study.
* Hypersensitivity to donepezil.
* Patients may not currently be taking Ketoconazole or Quindine
* Arrythmias including bradycardia or heartblock
* Patients who have received, GliaSite or other type of brain brachytherapy, (Gliadel Wafers permitted) convection enhanced delivery of immunotoxins, and/or any other investigational modalities for treatment of their brain tumor. The effects of donepezil on the developing human fetus at the recommended therapeutic dose are unknown. For this reason, women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately.
* It is unknown whether donepezil is excreted in breast milk, for this reason women who are currently breast-feeding are not eligible for this study.
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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National Cancer Institute (NCI)

NIH

Sponsor Role collaborator

Wake Forest University Health Sciences

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Stephen Rapp, PhD

Role: PRINCIPAL_INVESTIGATOR

Wake Forest University Health Sciences

Locations

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Associates in Womens Health, PA - North Review

Wichita, Kansas, United States

Site Status

Cancer Center of Kansas, PA - Medical Arts Tower

Wichita, Kansas, United States

Site Status

Cancer Center of Kansas, PA - Wichita

Wichita, Kansas, United States

Site Status

CCOP - Wichita

Wichita, Kansas, United States

Site Status

Via Christi Cancer Center at Via Christi Regional Medical Center

Wichita, Kansas, United States

Site Status

Central Maine Comprehensive Cancer Center at Central Maine Medical Center

Lewiston, Maine, United States

Site Status

New Hampshire Oncology - Hematology, PA - Hooksett

Hooksett, New Hampshire, United States

Site Status

Lakes Region General Hospital

Laconia, New Hampshire, United States

Site Status

Don Monti Comprehensive Cancer Center at North Shore University Hospital

Manhasset, New York, United States

Site Status

CCOP - MeritCare Hospital

Fargo, North Dakota, United States

Site Status

Trinity CancerCare Center

Minot, North Dakota, United States

Site Status

Summa Center for Cancer Care at Akron City Hospital

Akron, Ohio, United States

Site Status

MetroHealth Cancer Care Center at MetroHealth Medical Center

Cleveland, Ohio, United States

Site Status

United States Air Force Medical Center - Wright-Patterson

Wright-Patterson Air Force Base, Ohio, United States

Site Status

Thompson Cancer Survival Center

Knoxville, Tennessee, United States

Site Status

Gundersen Lutheran Center for Cancer and Blood

La Crosse, Wisconsin, United States

Site Status

Countries

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United States

Related Links

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https://nctn-data-archive.nci.nih.gov/

Data Available: Select individual patient-level data form this trial can be requested from the NCTN/NCORP Data Archive

Other Identifiers

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U10CA081851

Identifier Type: NIH

Identifier Source: secondary_id

View Link

REBACCCWFU 91105

Identifier Type: OTHER

Identifier Source: secondary_id

IRB00000551

Identifier Type: -

Identifier Source: org_study_id