Official Title: “Adjunctive Donepezil Therapy and Genetic Risk Factors of Cognitive Dysfunction in Brain Tumor Survivors”

A significant number of brain tumor patients who received radiation or chemotherapy have thinking problems as a result of their treatment. The purpose of this study is to find out if treatment with Aricept (donepezil) may improve some aspects of thinking abilities in patients with brain tumors who received radiation or chemotherapy. This research will also study whether persons having particular genes for a blood-borne substance called apolipoprotein E (APOE) are more likely to have thinking problems after radiation or chemotherapy treatment for their brain tumors. The findings of this study will help us find out whether Aricept can improve thinking abilities after cancer treatment, and whether some of the thinking difficulties may be in part related to having certain genes.

Study Type: Interventional

Study Design: Treatment, Open Label, Single Group Assignment, Efficacy Study

Study Primary Completion Date: October 2010

A significant proportion of brain tumor patients treated with radiation or chemotherapy who are in disease remission experience cognitive sequelae from their treatment. Cognitive dysfunction can be of sufficient severity to interfere with their ability to function at premorbid professional and social levels. There are, however, no approved pharmacological interventions for improving cognitive functions in cancer patients who display treatment-related cognitive deficits. Donepezil, an acetylcholinesterase inhibitor, has been shown to provide cognitive and functional benefits in patients with Alzheimer's disease, vascular dementia, and in patients with other neurological diseases without known cholinergic deficiency.

The proposed pilot study will examine the efficacy of donepezil in improving cognitive functions in adult brain tumor patients treated with radiation and/or chemotherapy who have mild to moderate cognitive difficulties. Neuropsychological measures of executive, psychomotor speed, attention, and memory abilities will be administered prior to, during and following donepezil therapy. The proposed study will also test the hypothesis that the apolipoprotein E (APOE) e-4 allele correlates with the development of cognitive impairment after radiation or chemotherapy treatments. The proposed investigation is unprecedented and may provide preliminary information about (1) a pharmacological therapy that could improve cognitive functions in this population, and (2) a genetic risk factor that may increase vulnerability to radiation or chemotherapy-induced cognitive decline.

Intervention(s) in this Clinical Trial

• Other: donepezil and questionaires
  • Patients will undergo a brief cognitive evaluation prior to (baseline/Time 1), Cognitive Re-Evaluation (about 12 weeks after Time 1), Cognitive Re-Evaluation (about 12 weeks after Time 2) ,Cognitive Re-Evaluation (about 6 months after discontinuation of Donepezil). Then pt will be tx with donepezil, an acetylcholinesterase inhibitor. They will undergo a four-week dose titration (i.e., 5mg QD during weeks 1-4) to reach a final dose of 10mg QD of oral donepezil there after for a maximum of 24 weeks.

Arms, Groups and Cohorts in this Clinical Trial

• Experimental: 1
  • donepezil and questionaires

Primary Measures

• The primary goal of this study is to assess the efficacy of donepezil in improving executive abilities and psychomotor speed in adult brain tumor patients who have undergone cranial irradiation and/or chemotherapy.
  • Time Frame: conclusion of study
    Safety Issue?: No

Secondary Measures

• This study will also assess the efficacy of donepezil in improving other cognitive domains such as attention, memory, and general cognition in this population.
  • Time Frame: conclusion of study
    Safety Issue?: No
• The study will also explore the possibility that the possession of the apolipoprotein E (APOE) є-4 allele is associated with the development of cognitive difficulties following cranial radiation and/or chemotherapy treatments.
  • Time Frame: conclusion of study
    Safety Issue?: No

Inclusion Criteria:

• diagnosed with a brain tumor and treated with cranial irradiation and/or chemotherapy, and in stable remission of their disease at the time of enrollment.
• completed radiation and/or chemotherapy treatment at least 6 months prior to being enrolled in the study.
• who obtain a Mini-Mental Status Examination (MMSE) score ranging from 18 to 28 at the time of enrollment.
• are at least 18 years of age.
• are English speaking.
• have capacity to give consent

Exclusion Criteria:

• Patients with active or progressive disease on recent MRI of the brain either at the time of enrollment, or during the study period.
• with a pre-existing uncontrolled seizure disorder, or significant renal or hepatic impairment.
• taking the following medications: antipsychotics, psychostimulants.
• patients who have been on selective serotonin re-uptake inhibitors (SSRIs) for less than 3 months at the time of enrollment.
• with uncontrolled behavioral or mood disturbances.
• have their anticonvulsant medication(s) or dosage(s) changed less than 30 days prior to enrollment.
• currently receiving donepezil or other cholinesterase inhibitors.
• who is pregnant.
• unable to cooperate or complete cognitive tests.

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 Sponsor: Memorial Sloan-Kettering Cancer Center

Overall Clinical Trial Officials and Contacts

Denise Correa, PhD Principal Investigator Memorial Sloan-Kettering Cancer Center  

Overall Contact: Denise Correa, PhD  corread@mskcc.org

Information obtained from ClinicalTrials.gov on July 02, 2009

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00594633

Study ID Number: 04-122

ClinicalTrials.gov Identifier: NCT00594633

Health Authority: United States: Institutional Review Board

Memorial Sloan-Kettering Cancer Center