NCT02822573|CompletedPhase 3ResultsDMCFDA Drug

Phase 3 Randomized Placebo Controlled Clinical Trial of Donepezil

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A Phase 3 Randomized Placebo Controlled Clinical Trial of Donepezil in Chemotherapy Exposed Breast Cancer Survivors With Cognitive Impairment

Wake Forest University Health Sciences ClinicalTrials.gov

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4 other identifiers

IRB000417073UG1CA189824-04S1WF-97116NCI-2016-01050

Study Type

interventional

Target

276

Locations

1 country

Sites

278

Timeline

RegisteredJul 2016

StartedMay 2017

CompletionJul 2022

Brief Summary

This study is to compare the safety and effects of donepezil (Aricept) for patients reporting cognitive or memory issues after receiving chemotherapy for breast cancer. Patients will receive either donepezil or placebo for 24 weeks. The primary objective is to see if memory improves with the use of donepezil during the study.

Trial Health

On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment

276

participants targeted

Target at P50-P75 for phase_3

Timeline

Completed

Started May 2017

Longer than P75 for phase_3

Geographic Reach

1 country

278 active sites

Status

completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

5.2 years study duration

First Submitted

Initial submission to the registry

June 30, 2016

Completed

4 days until next milestone

First Posted

Study publicly available on registry

July 4, 2016

Completed

11 months until next milestone

Study Start

First participant enrolled

May 30, 2017

Completed

5.2 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

July 29, 2022

Completed

Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

July 29, 2022

Completed

1.1 years until next milestone

Results Posted

Study results publicly available

September 13, 2023

Completed

Last Updated

September 13, 2023

Status Verified

July 1, 2023

Enrollment Period

5.2 years

First QC Date

June 30, 2016

Results QC Date

July 24, 2023

Last Update Submit

August 17, 2023

Conditions

Cognitive Dysfunction Memory Impairment

Keywords

DonepezilCognitionBreast Cancer

Outcome Measures

Primary Outcomes (1)

Hopkins Verbal Learning Test-Revised (HVLT-R) - Total
Hopkins Verbal Learning Test-Revised (HVLT-R): The HVLT-R measures verbal learning and memory. It consists of a 12-item word list which is read to patients on three successive learning trials. Free recall scores are recorded for each learning trial. After a 20-minute interval during which patients complete other non-interfering tasks and questionnaires they are asked to recall the target words. Range is 0-36 with higher values representing better verbal learning and memory.
Baseline, Weeks 12, 24, 36

Secondary Outcomes (6)

Digit Symbol Coding Results
Baseline, Weeks 12, 24, 36
PROMIS 7-item Fatigue Scale Converted to T-scale Results
Baseline, Weeks 12, 24, 36
FACT-Cognition (Version 3): Perceived Cognitive Impairment
Baseline, Weeks 12, 24, 36
Controlled Oral Word Association Test (COWA) Results
Baseline, Weeks 12, 24, 36
Trail Making Test, Parts A & B (TMT-A, TMT-B) Results
Baseline, Weeks 12, 24, 36
+1 more secondary outcomes

Study Arms (2)

Donepezil

ACTIVE COMPARATOR

Participants will be asked to take one 5 mg tablet of donepezil daily for 6 weeks followed by two 5 mg tablets daily for 18 weeks. After 24 weeks, participants will begin a 12 week wash-out period.

Drug: Donepezil 5 mg

Placebo

PLACEBO COMPARATOR

Participants will be asked to take one tablet of matching placebo daily for 6 weeks followed by two tablets daily for 18 weeks. After 24 weeks, participants will begin a 12 week wash-out period.

Drug: Placebo

Interventions

Donepezil 5 mgDRUG

Participants will be asked to take one 5 mg tablet of donepezil daily for 6 weeks followed by two 5mg tablets daily for 18 weeks. After 24 weeks, participants will begin a 12 week wash-out period.

Also known as: Aricept

Donepezil

PlaceboDRUG

Participants will be asked to take one tablet of matching placebo daily for 6 weeks followed by two tablets daily for 18 weeks. After 24 weeks, participants will begin a 12 week wash-out period.

Also known as: Sugar Pill

Placebo

Eligibility Criteria

Age18 Years - 75 Years

Sexfemale

Healthy VolunteersNo

Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

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 human epidermal growth factor receptor 2 (HER2) 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. Patients who were previously on one of these psychotropic medications and have subsequently discontinued the drug must have been off the medication for at least 4 weeks prior to enrollment. Patients who have been on a psychotropic medication for at least 12 weeks but have recently switched to a medicine in the same class (for example, switching from one selective serotonin reuptake inhibitor (SSRI) antidepressant to a different SSRI antidepressant) need to be on a stable dose of the new medication for at least 4 weeks prior to enrollment to be eligible.
Self-reported cognitive problem plus a measured memory deficit (score \<7 on single trial of Eligibility Pre-screen Hopkins Verbal Learning Test - Revised (HVLT-R) Form 3).
Eastern Cooperative Oncology Group (ECOG) performance status 0-2
Ability to understand and the willingness to sign a written informed consent document.
Must be able to speak English.
Patients currently taking a moderate risk corrected QT interval (QTc) prolongation medication (see Appendix A) are allowed if one of the following criteria are met: 1) The moderate risk QTc prolongation medication is stopped. The patient should be off the moderate risk QTc prolongation medication for at least 5 half-lives before starting study drug. 2) Patients that continue using a moderate risk QTc prolongation medication must have a normal QTc interval (≤ 460 milliseconds) on a screening ECG following informed consent and prior to study enrollment. These patients will also be monitored at designated study follow-up visits per Section 7.5 (monitored 3-7 days after initiating study drug, at week 3, and 3-7 days after the study drug dose increase with ECG's to assess the QTc interval; the QTc level must be ≤ 500 milliseconds at these time points in order to continue on the study drug). 3) Moderate risk QTc prolongation medications that are only taken occasionally may be stopped at the discretion of the treating site physician. Patients must be off medication for at least 5 half-lives prior to starting study drug to be eligible.
Patients currently taking a moderate risk bradycardia-causing agent (see Appendix B) are allowed if one of the following criteria are met: 1) The moderate risk bradycardia-causing agent is stopped. The patient should be off the moderate risk bradycardia-causing agent for at least 5 half-lives before starting study drug. 2) Patients that continue using a moderate risk bradycardia-causing agent must have a resting heart rate ≥ 55 beats per minute at screening following informed consent. These patients' resting heart rate will be monitored 3-7 days after initiating study drug, at week 3, and 3-7 days after the study drug dose increase per Section 7.5. 3) Moderate risk bradycardia-causing agents that are only taken occasionally may be stopped at the discretion of the treating site physician. Patients must be off medication for at least 5 half-lives prior to starting study drug to be eligible.

You may not qualify if:

Evidence or suspected recurrent or metastatic disease.
Prior brain irradiation is not allowed.
Planned therapy (surgery, radiation, chemotherapy, or immunotherapy) while on the study for brain and/or extracranial primary/metastatic disease.
Hypersensitivity to donepezil or piperidine derivatives
Current use of ceritinib
Current use of Succinylcholine/Acetylcholinesterase Inhibitors(as listed in Appendix C). For patients who have used these medications, they must not have used them within 4 weeks prior to enrollment.
Current use of high-risk QTc prolonging medication(s). See Appendix D
Current use of quinidine or systemic ketoconazole (topical ketoconazole is acceptable to use while on study).
History of dementia, Alzheimer's disease, multi-infarct dementia or clinically significant Cerebrovascular Accident (history of transient ischemic attack (TIA) is allowed).
Current use of donepezil, galantamine, rivastigmine, tacrine, memantine, methylphenidate, dextroamphetamine, or any other specific cognition enhancing drug(s). For patients who have used these medications, they must not have used them within 4 weeks prior to pre-screening. Patients who plan to start taking a cognition enhancing drug while on this study are also excluded.
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.
Major medical conditions that affect cognition, 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.
+7 more criteria

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Wake Forest University Health Scienceslead
National Cancer Institute (NCI)collaborator

Study Sites (278)

Kaiser Permanente-Anaheim

Anaheim, California, 92806, United States

Location

Kaiser Permanente-Deer Valley Medical Center

Antioch, California, 94531, United States

Location

Kaiser Permanente-Baldwin Park

Baldwin Park, California, 91706, United States

Location

Kaiser Permanente-Bellflower

Bellflower, California, 90706, United States

Location

Kaiser Permanente-Fontana

Fontana, California, 92335, United States

Location

Kaiser Permanente-Fremont

Fremont, California, 94538, United States

Location

Fresno Cancer Center

Fresno, California, 93720, United States

Location

Kaiser Permanente-Fresno

Fresno, California, 93720, United States

Location

Kaiser Permanente - Harbor City

Harbor City, California, 90710, United States

Location

Kaiser Permanente-Irvine

Irvine, California, 92618, United States

Location

Kaiser Permanente Los Angeles Medical Center

Los Angeles, California, 90027, United States

Location

Kaiser Permanente West Los Angeles

Los Angeles, California, 90034, United States

Location

Kaiser Permanente-Modesto

Modesto, California, 95356, United States

Location

Kaiser Permanente-Oakland

Oakland, California, 94611, United States

Location

Kaiser Permanente-Ontario

Ontario, California, 91761, United States

Location

Kaiser Permanente - Panorama City

Panorama City, California, 91402, United States

Location

Kaiser Permanente-Rancho Cordova Cancer Center

Rancho Cordova, California, 95670, United States

Location

Kaiser Permanente-Richmond

Richmond, California, 94801, United States

Location

Kaiser Permanente-Riverside

Riverside, California, 92505, United States

Location

Kaiser Permanente-Roseville

Roseville, California, 95661, United States

Location

The Permanente Medical Group-Roseville Radiation Oncology

Roseville, California, 95678, United States

Location

Kaiser Permanente Downtown Commons

Sacramento, California, 95814, United States

Location

Kaiser Permanente-South Sacramento

Sacramento, California, 95823, United States

Location

South Sacramento Cancer Center

Sacramento, California, 95823, United States

Location

Kaiser Permanente - Sacramento

Sacramento, California, 95825, United States

Location

Kaiser Permanente-San Diego Zion

San Diego, California, 92120, United States

Location

Kaiser Permanente-San Francisco

San Francisco, California, 94115, United States

Location

Kaiser Permanente-Santa Teresa-San Jose

San Jose, California, 95119, United States

Location

Kaiser Permanente San Leandro

San Leandro, California, 94577, United States

Location

Kaiser Permanente-San Marcos

San Marcos, California, 92078, United States

Location

Kaiser Permanente-San Rafael

San Rafael, California, 94903, United States

Location

Kaiser San Rafael-Gallinas

San Rafael, California, 94903, United States

Location

Kaiser Permanente Medical Center - Santa Clara

Santa Clara, California, 95051, United States

Location

Kaiser Permanente-Santa Rosa

Santa Rosa, California, 95403, United States

Location

Kaiser Permanente-South San Francisco

South San Francisco, California, 94080, United States

Location

Kaiser Permanente-Stockton

Stockton, California, 95210, United States

Location

Kaiser Permanente Medical Center-Vacaville

Vacaville, California, 95688, United States

Location

Kaiser Permanente-Vallejo

Vallejo, California, 94589, United States

Location

Kaiser Permanente-Walnut Creek

Walnut Creek, California, 94596, United States

Location

Kaiser Permanente-Woodland Hills

Woodland Hills, California, 91367, United States

Location

Penrose-Saint Francis Healthcare

Colorado Springs, Colorado, 80907, United States

Location

Rocky Mountain Cancer Centers-Penrose

Colorado Springs, Colorado, 80907, United States

Location

Kaiser Permanente-Franklin

Denver, Colorado, 80205, United States

Location

Porter Adventist Hospital

Denver, Colorado, 80210, United States

Location

Kaiser Permanente-Rock Creek

Lafayette, Colorado, 80026, United States

Location

Littleton Adventist Hospital

Littleton, Colorado, 80122, United States

Location

Kaiser Permanente-Lone Tree

Lone Tree, Colorado, 80124, United States

Location

Longmont United Hospital

Longmont, Colorado, 80501, United States

Location

Parker Adventist Hospital

Parker, Colorado, 80138, United States

Location

Helen F Graham Cancer Center

Newark, Delaware, 19713, United States

Location

Medical Oncology Hematology Consultants PA

Newark, Delaware, 19713, United States

Location

Christiana Care Health System-Christiana Hospital

Newark, Delaware, 19718, United States

Location

Beebe Health Campus

Rehoboth Beach, Delaware, 19971, United States

Location

TidalHealth Nanticoke / Allen Cancer Center

Seaford, Delaware, 19973, United States

Location

Holy Cross Hospital

Fort Lauderdale, Florida, 33308, United States

Location

Hawaii Cancer Care Inc - Waterfront Plaza