Study of Donepezil in Female Breast Cancer Survivors With Cognitive Dysfunction

Wake Forest University (WFU)

Status and phase

Completed

Phase 2

Conditions

Sleep Disorders

Cognition Disorders

Breast Cancer

Anxiety Disorder

Depression

Fatigue

Treatments

Drug: Placebo

Drug: donepezil hydrochloride

Study type

Interventional

Funder types

Other

NIH

Identifiers

NCT01466270

U10CA081851 (U.S. NIH Grant/Contract)

IRB00019792-1

REBACCCWFU 97211 (Other Identifier)

Details and patient eligibility

About

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.

Full description

OBJECTIVES:

Primary

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

Secondary

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.

Enrollment

62 patients

Sex

Female

Ages

18+ years old

Volunteers

No Healthy Volunteers

Inclusion criteria

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.

Exclusion criteria

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.