Study of Donepezil in Female Breast Cancer Survivors With Cognitive Dysfunction

A Feasibility Study of Donepezil in Female Breast Cancer Survivors With Self-Reported Cognitive Dysfunction Following Chemotherapy

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.

Study Overview

• Status: Completed
• Conditions: Depression; Breast Cancer; Fatigue; Cognition Disorders; Sleep Disorders; Anxiety Disorder
• Intervention / Treatment: Drug: Placebo; Drug: donepezil hydrochloride

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.

• Study Type: Interventional
• Enrollment (Actual): 62
• Phase: Phase 2

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: QUADRUPLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Arm I; Patients receive donepezil hydrochloride PO QD.	Drug: donepezil hydrochloride; Given PO; Other Names: Donepezil
PLACEBO_COMPARATOR: Arm II; Patients receive placebo PO QD.	Drug: Placebo; Given PO

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Retention	Retention is the percentage of participants who stay in the study for 24 weeks.	24 Weeks
Compliance	Compliance is the percentage of pills taken while on study (based on returned diaries)	24 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
HVLT-IR	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.	24 weeks
Fatigue	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.	24 weeks

Collaborators and Investigators

• Sponsor: Wake Forest University Health Sciences
• Collaborators: National Cancer Institute (NCI)
• Investigators: Principal Investigator: Julia A. Lawrence, Wake Forest University Health Sciences

Study record dates

Study Major Dates

• Study Start (ACTUAL): July 1, 2012
• Primary Completion (ACTUAL): October 1, 2013
• Study Completion (ACTUAL): October 1, 2013

Study Registration Dates

• First Submitted: November 2, 2011
• First Submitted That Met QC Criteria: November 2, 2011
• First Posted (ESTIMATE): November 6, 2011

Study Record Updates

• Last Update Posted (ACTUAL): October 20, 2021
• Last Update Submitted That Met QC Criteria: September 27, 2021
• Last Verified: September 1, 2021

More Information

Terms related to this study

• Keywords: breast cancer; fatigue; depression; cancer survivor; anxiety disorder; cognitive/functional effects; sleep disorders
• Additional Relevant MeSH Terms: Behavioral Symptoms; Mental Disorders; Pathologic Processes; Nervous System Diseases; Skin Diseases; Neoplasms; Neoplasms by Site; Neurologic Manifestations; Neurocognitive Disorders; Breast Diseases; Depression; Breast Neoplasms; Fatigue; Disease; Sleep Wake Disorders; Anxiety Disorders; Parasomnias; Cognitive Dysfunction; Cognition Disorders; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Cholinergic Agents; Enzyme Inhibitors; Nootropic Agents; Cholinesterase Inhibitors; Donepezil
• Other Study ID Numbers: IRB00019792-1; U10CA081851 (U.S. NIH Grant/Contract); REBACCCWFU 97211 (OTHER: NCI)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes