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

Official Title: “Phase III Double Blind, Placebo Controlled Study of Donepezil in the Irradiated Brain”

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.

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.

Intervention(s) in this Clinical Trial

• Drug: donepezil hydrochloride
  • Given orally
• Other: placebo
  • Given orally

Arms, Groups and Cohorts in this Clinical Trial

• Experimental: Arm I
  • Patients receive oral donepezil hydrochloride once or twice daily for up to 24 weeks in the absence of unacceptable toxicity.
• Placebo Comparator: Arm II
  • Patients receive oral placebo once or twice daily for up to 24 weeks in the absence of unacceptable toxicity.

Primary Measures

• Fatigue, subjective confusion, and cognitive performance at 24 weeks
  • Safety Issue?: No

Secondary Measures

• Mood at 24 weeks
  • Safety Issue?: No
• Quality of life at 24 weeks
  • Safety Issue?: No

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

Gender Eligibility for this Clinical Trial: Both

Minimum Age for this Clinical Trial: 18 Years

Maximum Age for this Clinical Trial: N/A

Are Healthy Volunteers Accepted for this Clinical Trial?: No

Lead Investigator: Wake Forest University Other

Overall Clinical Trial Officials and Contacts

Stephen Rapp, PhD Principal Investigator Wake Forest University  

Information obtained from ClinicalTrials.gov on February 09, 2012

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00369785

Study ID Number: CDR0000485228

ClinicalTrials.gov Identifier: NCT00369785

Health Authority: Unspecified

Clinical trial summary from the National Cancer Institute's PDQ® database