Study of Donepezil in Female Breast Cancer Survivors With Cognitive Dysfunction

This study has been completed.
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Wake Forest NCORP Research Base Identifier:
First received: November 2, 2011
Last updated: December 31, 2014
Last verified: December 2014

RATIONALE: Donepezil hydrochloride may help lessen cognitive dysfunction caused by chemotherapy.

PURPOSE: This phase II trial is studying donepezil hydrochloride in treating cognitive dysfunction after chemotherapy in female breast cancer survivors.

Condition Intervention Phase
Anxiety Disorder
Breast Cancer
Cognition Disorders
Sleep Disorders
Drug: donepezil hydrochloride
Drug: Placebo
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Feasibility Study of Donepezil in Female Breast Cancer Survivors With Self-Reported Cognitive Dysfunction Following Chemotherapy

Resource links provided by NLM:

Further study details as provided by Wake Forest NCORP Research Base:

Primary Outcome Measures:
  • Retention [ Time Frame: 24 Weeks ] [ Designated as safety issue: No ]
    Retention is the percentage of participants who stay in the study for 24 weeks.

  • Compliance [ Time Frame: 24 weeks ] [ Designated as safety issue: No ]
    Compliance is the percentage of pills taken while on study (based on returned diaries)

Secondary Outcome Measures:
  • HVLT-IR [ Time Frame: 24 weeks ] [ Designated as safety issue: No ]
    Hopkins verbal learning test - immediate recall is the number of words (of 12) than can be remembers during three tries. The total score ranges from 0 to 36. Higher is better.

  • Fatigue [ Time Frame: 24 weeks ] [ Designated as safety issue: No ]
    Fatigue is quantified by the FACIT-Fatigue scale. It consists of 13 questions answered on a 0 to 4 point scale. The fatigue score is the sum of the responses (some reverse scored) so that higher values represent less fatigue.

Enrollment: 62
Study Start Date: April 2012
Study Completion Date: October 2013
Primary Completion Date: October 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Arm I
Patients receive donepezil hydrochloride PO QD.
Drug: donepezil hydrochloride
Given PO
Other Name: Donepezil
Placebo Comparator: Arm II
Patients receive placebo PO QD.
Drug: Placebo
Given PO

Detailed Description:



  • Determine the feasibility of conducting a randomized placebo-controlled clinical trial for cognitive symptoms in female breast cancer survivors.


  • Estimate the variability of the clinical outcomes (FACT-Cognition Perceived Cognitive Impairment subscale, neurocognitive battery, FACIT-Fatigue, FACT Cog Total Score, PROMIS Fatigue, Epworth Sleepiness Scale, Beck Depression Inventory, Beck Anxiety Inventory, and RAND Short Form-36).
  • Estimate the within patient correlation over time of the clinical outcomes.
  • Obtain preliminary estimates of the effect of donepezil on the primary and secondary outcome variables.
  • Correlate the reports of fatigue, sleep disturbance, and mood with measures of cognitive symptoms and neurocognitive test performance.
  • Document the severity of cognitive symptoms and functional impairment in female breast cancer survivors who enroll on this pilot study.
  • Correlate cognitive symptoms with cognitive test performance.
  • Document the toxicities associated with donepezil hydrochloride use.

OUTLINE: This is a randomized, double-blind, placebo-controlled, multicenter study. Patients are stratified according to menopausal status (pre- vs peri-/post-menopausal) and time since end of chemotherapy (12-36 months vs 36.01-60 months).

Arm I: Patients receive donepezil hydrochloride orally (PO) once daily (QD).

Arm II: Patients receive placebo PO QD.

In both arms treatment continues for 24 weeks.

Patients complete the entire battery of neurocognitive tests and questionnaires (FACT-Cognition Perceived Cognitive Impairment subscale, neurocognitive battery, FACIT-Fatigue, FACT Cog Total Score, PROMIS Fatigue, Epworth Sleepiness Scale, Beck Depression Inventory, Beck Anxiety Inventory, and RAND Short Form-36) at baseline (pre-treatment), 24 weeks (end of medication), and 36 weeks (end of wash-out).

After completion of therapy, patients are followed at 12 weeks.


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


  • Adults >18 years old.
  • Female with history of invasive breast cancer
  • Must have completed adjuvant chemotherapy between 1 and 5 years prior to registration
  • Received at least 4 cycles of cytotoxic chemotherapy
  • Documentation of prior chemotherapy
  • Patients receiving ongoing hormonal therapy for breast cancer must be on the same hormonal agent for at least 3 months prior to study registration and continue for the duration of the study (9 months)
  • Karnofsky Performance Status must be > 60 or ECOG 0-2.
  • Use of psychotropic medications (anti-depressants, anxiolytics, sleeping aids, narcotics) is permitted. Patient will be asked to list any that have been taken within the last 3 days on the recent medication sheet.
  • Patients must be able to give informed consent to participate in the study, including signing the consent form.
  • Self-reported cognitive disruption (FACT-Cog Version 3 Perceived Cognitive Impairments sub-score of < 63)
  • Negative serum pregnancy test within 10 days prior to registration for women of child-bearing potential.


  • Evidence or suspected recurrent or metastatic disease
  • History of dementia, Alzheimer's disease, multi-infarct dementia or CVA (history of transient ischemic attack (TIA is allowed)
  • Current use of donepezil, galantamine, rivastigmine, tacrine, memantine, methylphenidate, dextroamphetamine, or any other specific cognition enhancing drugs.are not allowed. For patients who have used these medications they must not have used them within 4 weeks prior to registration.

Patients may not currently be taking Ketoconazole or Quinidine

  • Hypersensitivity to donepezil.
  • Use of investigational medications within the last 30 days.
  • Prior brain metastasis
  • Traumatic brain injury, multiple sclerosis or recent myocardial infarction
  • History of schizophrenia, psychosis or substance abuse
  • Untreated current severe depression. (Currently treated depression is permitted if treatment is stable.)
  • Acute severe fatigue, chronic fatigue syndrome or fibromyalgia.
  • History of hepatic or renal dysfunction or disease
  • Pregnant women are excluded from this study. The effects of donepezil on the developing human fetus at the recommended therapeutic dose are unknown. For this reason and because donepezil is known to be teratogenic, women of child-bearing potential 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 study 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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its identifier: NCT01466270

United States, North Carolina
Wake Forest Cancer Center CCOP Research Base
Winston Salem, North Carolina, United States, 27157
Sponsors and Collaborators
Wake Forest NCORP Research Base
National Cancer Institute (NCI)
Principal Investigator: Julia A. Lawrence Comprehensive Cancer Center of Wake Forest University
  More Information

Responsible Party: Wake Forest NCORP Research Base Identifier: NCT01466270     History of Changes
Other Study ID Numbers: CCCWFU 97211  U10CA081851 
Study First Received: November 2, 2011
Results First Received: December 31, 2014
Last Updated: December 31, 2014
Health Authority: United States: Institutional Review Board

Keywords provided by Wake Forest NCORP Research Base:
sleep disorders
anxiety disorder
cognitive/functional effects
breast cancer
cancer survivor

Additional relevant MeSH terms:
Anxiety Disorders
Breast Neoplasms
Cognition Disorders
Breast Diseases
Mental Disorders
Neoplasms by Site
Nervous System Diseases
Neurocognitive Disorders
Pathologic Processes
Skin Diseases
Sleep Wake Disorders
Cholinergic Agents
Cholinesterase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Neurotransmitter Agents
Nootropic Agents
Physiological Effects of Drugs processed this record on May 23, 2016