Donepezil in Treating Patients Who Have Undergone Radiation Therapy for Brain Tumors - Full Text View

Sponsor:	Wake Forest University
Collaborator:	National Cancer Institute (NCI)
Information provided by:	National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:	NCT00369785

Purpose

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.

Condition	Intervention	Phase
Brain and Central Nervous System Tumors Cognitive/Functional Effects Fatigue Metastatic Cancer Psychosocial Effects of Cancer and Its Treatment Radiation Toxicity	Drug: donepezil hydrochloride Other: placebo	Phase III

Study Type:	Interventional
Study Design:	Supportive Care, Randomized, Double-Blind, Placebo Control
Official Title:	Phase III Double Blind, Placebo Controlled Study of Donepezil in the Irradiated Brain

Resource links provided by NLM:

MedlinePlus related topics: Brain Cancer Cancer

Drug Information available for: E 2020 Donepezil

U.S. FDA Resources

Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:

Fatigue, subjective confusion, and cognitive performance at 24 weeks [ Designated as safety issue: No ]

Secondary Outcome Measures:

Mood at 24 weeks [ Designated as safety issue: No ]
Quality of life at 24 weeks [ Designated as safety issue: No ]

Estimated Enrollment:	200
Study Start Date:	January 2008
Estimated Primary Completion Date:	June 2010 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Arm I: Experimental Patients receive oral donepezil hydrochloride once or twice daily for up to 24 weeks in the absence of unacceptable toxicity.	Drug: donepezil hydrochloride Given orally
Arm II: Placebo Comparator Patients receive oral placebo once or twice daily for up to 24 weeks in the absence of unacceptable toxicity.	Other: placebo Given orally

Detailed Description:

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.

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00369785

Show 24 Study Locations

Sponsors and Collaborators

Wake Forest University

National Cancer Institute (NCI)

Investigators

Principal Investigator:

Stephen Rapp, PhD

Wake Forest University

More Information

Additional Information:

Clinical trial summary from the National Cancer Institute's PDQ® database This link exits the ClinicalTrials.gov site

No publications provided

Responsible Party:	Wake Forest University Comprehensive Cancer Center ( Edward G. Shaw )
Study ID Numbers:	CDR0000485228, CCCWFU-91105
Study First Received:	August 24, 2006
Last Updated:	January 15, 2010
ClinicalTrials.gov Identifier:	NCT00369785 History of Changes
Health Authority:	Unspecified

Keywords provided by National Cancer Institute (NCI):

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
adult melanocytic lesion
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)

Additional relevant MeSH terms:

Nootropic Agents
Neurotransmitter Agents
Fatigue
Molecular Mechanisms of Pharmacological Action
Physiological Effects of Drugs
Nervous System Diseases
Enzyme Inhibitors
Central Nervous System Neoplasms
Cholinergic Agents
Pharmacologic Actions
Signs and Symptoms

Cholinesterase Inhibitors
Neoplastic Processes
Neoplasms
Pathologic Processes
Neoplasms by Site
Therapeutic Uses
Donepezil
Neoplasm Metastasis
Central Nervous System Agents
Nervous System Neoplasms

ClinicalTrials.gov processed this record on February 08, 2010