Phase 3 Randomized Placebo Controlled Clinical Trial of Donepezil - WF 97116

A randomized, placebo controlled, double-blind, parallel group Phase 3 design will be used to
assess the effect of 24 weeks of donepezil on cognitive function (memory) in breast cancer
survivors who report having cognitive dysfunction and demonstrate memory impairment 1-5 year
post chemotherapy. Patients who meet the eligibility criteria will be stratified by age (<50,
50-59, 60-69, ≥70) and randomized to donepezil or placebo with equal probability.

Inclusion Criteria:

- Women ≥18 years old with history of invasive breast cancer

- Must have completed at least 4 cycles of adjuvant/neo-adjuvant cytotoxic chemotherapy
between 1 and 5 years prior to registration (Ongoing herceptin or other chronic HER 2
directed therapies are allowed).

- 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 plan to continue
for the duration of the study (9 months)

- 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) if dose is stable over previous 12
weeks.

- Self-reported cognitive problem plus a measured memory deficit (score <7 on single
trial of Eligibility Pre-screen HVLT-R Form C).

- Prior treatment with > 4 cycles of adjuvant/neo-adjuvant cytotoxic chemotherapy

- ECOG performance status 0-2

- Ability to understand and the willingness to sign a written informed consent document.

- Must be able to speak English.

Exclusion Criteria:

- Evidence or suspected recurrent or metastatic disease. Prior brain irradiation is not
allowed.

- Patients may not currently be taking Ketoconazole or Quinidine

- 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.

- History of allergic reactions attributed to compounds of similar chemical or biologic
composition to donepezil. Hypersensitivity to donepezil.

- Uncontrolled intercurrent illness including, but not limited to, ongoing or active
infection, symptomatic congestive heart failure, unstable angina pectoris, recent
myocardial infarction, cardiac arrhythmia.

- Traumatic brain injury, multiple sclerosis, acute severe fatigue, chronic fatigue
syndrome or fibromyalgia.

- Psychiatric illness/social situations that would limit compliance with study
requirements including but not limited to a history of schizophrenia, psychosis or
substance abuse.

- Untreated current severe depression. Currently treated depression is permitted if
treatment is stable.

- 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.