Clinical trial NCT01466270: Study of Donepezil in Female Breast Cancer Survivors With Cognitive Dysfunction
Official title: A Feasibility Study of Donepezil in Female Breast Cancer Survivors With Self-Reported Cognitive Dysfunction Following Chemotherapy
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Anxiety Disorder
Breast Cancer
Cognition Disorders
Depression
Fatigue
Sleep Disorders
Keywords: fatigue
sleep disorders
depression
anxiety disorder
cognitive/functional effects
breast cancer
cancer survivor
Lead sponsor: Wake Forest University Health Sciences
Sponsor class: OTHER
Collaborators: name: National Cancer Institute (NCI)
First posted: 2011-11-06
Enrollment: 62
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.

Detailed 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.

Eligibility criteria: 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.

Primary outcomes:
measure: Retention
timeFrame: 24 Weeks
measure: Compliance
timeFrame: 24 weeks
Secondary outcomes:
measure: HVLT-IR
timeFrame: 24 weeks
measure: Fatigue
timeFrame: 24 weeks
Other outcomes:
Locations:
Study officials:
affiliation: Wake Forest University Health Sciences
name: Julia A. Lawrence
role: PRINCIPAL_INVESTIGATOR
References: