Phase 3 Randomized Placebo Controlled Clinical Trial of Donepezil (Remember)

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

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.

Study Overview

• Status: Completed
• Conditions: Cognitive Dysfunction; Memory Impairment
• Intervention / Treatment: Drug: Donepezil 5 mg; Drug: Placebo

Detailed Description

Randomized, double-blind, placebo-controlled study with 24 weeks of exposure to drug or placebo followed by a 12 week wash-out period. 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. A total of 276 patients will be enrolled (138 per arm). We expect an accrual rate of 7-10 participants per month based on our prior feasibility study. We expect the study to be complete within 40 months.

Participants will be asked to take one 5mg tablet of donepezil or one tablet of matching placebo orally once a day for 6 weeks followed by two 5mg tablets (10mg total) of donepezil or two placebo tablets orally once a day for 18 weeks. After 24 weeks, participants will begin a 12 week wash-out period.

Time points for performing study assessments. Participants will be administered the cognitive battery of tests and questionnaires at baseline, week 12, week 24 and week 36. In addition, a single vial of blood will be drawn at baseline for apolipoprotein E (APOE) genotyping and subsequent bioassays (pending supplemental funding).

• Study Type: Interventional
• Enrollment (Actual): 276
• Phase: Phase 3

Contacts and Locations

Study Locations

• United States
  • California
    • Anaheim, California, United States, 92806
      • Kaiser Permanente-Anaheim
    • Antioch, California, United States, 94531
      • Kaiser Permanente-Deer Valley Medical Center
    • Baldwin Park, California, United States, 91706
      • Kaiser Permanente-Baldwin Park
    • Bellflower, California, United States, 90706
      • Kaiser Permanente-Bellflower
    • Fontana, California, United States, 92335
      • Kaiser Permanente-Fontana
    • Fremont, California, United States, 94538
      • Kaiser Permanente-Fremont
    • Fresno, California, United States, 93720
      • Kaiser Permanente-Fresno
    • Fresno, California, United States, 93720
      • Fresno Cancer Center
    • Harbor City, California, United States, 90710
      • Kaiser Permanente - Harbor City
    • Irvine, California, United States, 92618
      • Kaiser Permanente-Irvine
    • Los Angeles, California, United States, 90027
      • Kaiser Permanente Los Angeles Medical Center
    • Los Angeles, California, United States, 90034
      • Kaiser Permanente West Los Angeles
    • Modesto, California, United States, 95356
      • Kaiser Permanente-Modesto
    • Oakland, California, United States, 94611
      • Kaiser Permanente-Oakland
    • Ontario, California, United States, 91761
      • Kaiser Permanente-Ontario
    • Panorama City, California, United States, 91402
      • Kaiser Permanente - Panorama City
    • Rancho Cordova, California, United States, 95670
      • Kaiser Permanente-Rancho Cordova Cancer Center
    • Richmond, California, United States, 94801
      • Kaiser Permanente-Richmond
    • Riverside, California, United States, 92505
      • Kaiser Permanente-Riverside
    • Roseville, California, United States, 95678
      • The Permanente Medical Group-Roseville Radiation Oncology
    • Roseville, California, United States, 95661
      • Kaiser Permanente-Roseville
    • Sacramento, California, United States, 95814
      • Kaiser Permanente Downtown Commons
    • Sacramento, California, United States, 95823
      • Kaiser Permanente-South Sacramento
    • Sacramento, California, United States, 95823
      • South Sacramento Cancer Center
    • Sacramento, California, United States, 95825
      • Kaiser Permanente - Sacramento
    • San Diego, California, United States, 92120
      • Kaiser Permanente-San Diego Zion
    • San Francisco, California, United States, 94115
      • Kaiser Permanente-San Francisco
    • San Jose, California, United States, 95119
      • Kaiser Permanente-Santa Teresa-San Jose
    • San Leandro, California, United States, 94577
      • Kaiser Permanente San Leandro
    • San Marcos, California, United States, 92078
      • Kaiser Permanente-San Marcos
    • San Rafael, California, United States, 94903
      • Kaiser San Rafael-Gallinas
    • San Rafael, California, United States, 94903
      • Kaiser Permanente-San Rafael
    • Santa Clara, California, United States, 95051
      • Kaiser Permanente Medical Center - Santa Clara
    • Santa Rosa, California, United States, 95403
      • Kaiser Permanente-Santa Rosa
    • South San Francisco, California, United States, 94080
      • Kaiser Permanente-South San Francisco
    • Stockton, California, United States, 95210
      • Kaiser Permanente-Stockton
    • Vacaville, California, United States, 95688
      • Kaiser Permanente Medical Center-Vacaville
    • Vallejo, California, United States, 94589
      • Kaiser Permanente-Vallejo
    • Walnut Creek, California, United States, 94596
      • Kaiser Permanente-Walnut Creek
    • Woodland Hills, California, United States, 91367
      • Kaiser Permanente-Woodland Hills
  • Colorado
    • Colorado Springs, Colorado, United States, 80907
      • Penrose-Saint Francis Healthcare
    • Colorado Springs, Colorado, United States, 80907
      • Rocky Mountain Cancer Centers-Penrose
    • Denver, Colorado, United States, 80210
      • Porter Adventist Hospital
    • Denver, Colorado, United States, 80205
      • Kaiser Permanente-Franklin
    • Lafayette, Colorado, United States, 80026
      • Kaiser Permanente-Rock Creek
    • Littleton, Colorado, United States, 80122
      • Littleton Adventist Hospital
    • Lone Tree, Colorado, United States, 80124
      • Kaiser Permanente-Lone Tree
    • Longmont, Colorado, United States, 80501
      • Longmont United Hospital
    • Parker, Colorado, United States, 80138
      • Parker Adventist Hospital
  • Delaware
    • Newark, Delaware, United States, 19713
      • Helen F Graham Cancer Center
    • Newark, Delaware, United States, 19713
      • Medical Oncology Hematology Consultants PA
    • Newark, Delaware, United States, 19718
      • Christiana Care Health System-Christiana Hospital
    • Rehoboth Beach, Delaware, United States, 19971
      • Beebe Health Campus
    • Seaford, Delaware, United States, 19973
      • TidalHealth Nanticoke / Allen Cancer Center
  • Florida
    • Fort Lauderdale, Florida, United States, 33308
      • Holy Cross Hospital
  • Hawaii
    • 'Aiea, Hawaii, United States, 96701
      • Pali Momi Medical Center
    • Honolulu, Hawaii, United States, 96813
      • Queen's Medical Center
    • Honolulu, Hawaii, United States, 96813
      • Hawaii Cancer Care Inc - Waterfront Plaza
    • Honolulu, Hawaii, United States, 96813
      • Queen's Cancer Cenrer - POB I
    • Honolulu, Hawaii, United States, 96813
      • Straub Clinic and Hospital
    • Honolulu, Hawaii, United States, 96813
      • University of Hawaii Cancer Center
    • Honolulu, Hawaii, United States, 96817
      • Hawaii Cancer Care Inc-Liliha
    • Honolulu, Hawaii, United States, 96817
      • Queen's Cancer Center - Kuakini
    • Honolulu, Hawaii, United States, 96826
      • Kapiolani Medical Center for Women and Children
    • Honolulu, Hawaii, United States, 96819
      • Kaiser Permanente Moanalua Medical Center
  • Idaho
    • Boise, Idaho, United States, 83712
      • Saint Luke's Cancer Institute - Boise
    • Fruitland, Idaho, United States, 83619
      • Saint Luke's Cancer Institute - Fruitland
    • Meridian, Idaho, United States, 83642
      • Saint Luke's Cancer Institute - Meridian
    • Nampa, Idaho, United States, 83686
      • Saint Luke's Cancer Institute - Nampa
    • Twin Falls, Idaho, United States, 83301
      • Saint Luke's Cancer Institute - Twin Falls
  • Illinois
    • Bloomington, Illinois, United States, 61704
      • Illinois CancerCare-Bloomington
    • Canton, Illinois, United States, 61520
      • Illinois CancerCare-Canton
    • Centralia, Illinois, United States, 62801
      • Centralia Oncology Clinic
    • Danville, Illinois, United States, 61832
      • Carle on Vermilion
    • Decatur, Illinois, United States, 62526
      • Decatur Memorial Hospital
    • Decatur, Illinois, United States, 62526
      • Cancer Care Specialists of Illinois - Decatur
    • Effingham, Illinois, United States, 62401
      • Crossroads Cancer Center
    • Effingham, Illinois, United States, 62401
      • Carle Physician Group-Effingham
    • Galesburg, Illinois, United States, 61401
      • Illinois CancerCare-Galesburg
    • Kewanee, Illinois, United States, 61443
      • Illinois CancerCare-Kewanee Clinic
    • Mattoon, Illinois, United States, 61938
      • Carle Physician Group-Mattoon/Charleston
    • Ottawa, Illinois, United States, 61350
      • Illinois CancerCare-Ottawa Clinic
    • Pekin, Illinois, United States, 61554
      • Illinois CancerCare-Pekin
    • Peoria, Illinois, United States, 61615
      • Illinois CancerCare-Peoria
    • Peru, Illinois, United States, 61354
      • Illinois CancerCare-Peru
    • Urbana, Illinois, United States, 61801
      • Carle Cancer Center
    • Urbana, Illinois, United States, 61801
      • The Carle Foundation Hospital
  • Iowa
    • Cedar Rapids, Iowa, United States, 52402
      • Physicians' Clinic of Iowa PC
    • Des Moines, Iowa, United States, 50309
      • Iowa Methodist Medical Center
    • Des Moines, Iowa, United States, 50314
      • Mercy Medical Center - Des Moines
    • Des Moines, Iowa, United States, 50309
      • Medical Oncology and Hematology Associates-Des Moines
    • Des Moines, Iowa, United States, 50314
      • Broadlawns Medical Center
    • Des Moines, Iowa, United States, 50316
      • Iowa Lutheran Hospital
    • West Des Moines, Iowa, United States, 50266-7700
      • Methodist West Hospital
  • Kansas
    • Chanute, Kansas, United States, 66720
      • Cancer Center of Kansas - Chanute
    • El Dorado, Kansas, United States, 67042
      • Cancer Center of Kansas - El Dorado
    • Fort Scott, Kansas, United States, 66701
      • Cancer Center of Kansas - Fort Scott
    • Independence, Kansas, United States, 67301
      • Cancer Center of Kansas-Independence
    • Kingman, Kansas, United States, 67068
      • Cancer Center of Kansas-Kingman
    • Manhattan, Kansas, United States, 66502
      • Cancer Center of Kansas-Manhattan
    • McPherson, Kansas, United States, 67460
      • Cancer Center of Kansas - McPherson
    • Newton, Kansas, United States, 67114
      • Cancer Center of Kansas - Newton
    • Parsons, Kansas, United States, 67357
      • Cancer Center of Kansas - Parsons
    • Salina, Kansas, United States, 67401
      • Cancer Center of Kansas - Salina
    • Wellington, Kansas, United States, 67152
      • Cancer Center of Kansas - Wellington
    • Wichita, Kansas, United States, 67214
      • Ascension Via Christi Hospitals Wichita
    • Wichita, Kansas, United States, 67208
      • Cancer Center of Kansas-Wichita Medical Arts Tower
    • Wichita, Kansas, United States, 67214
      • Cancer Center of Kansas - Wichita
    • Wichita, Kansas, United States, 67208
      • Associates In Womens Health
    • Winfield, Kansas, United States, 67156
      • Cancer Center of Kansas - Winfield
  • Kentucky
    • Bardstown, Kentucky, United States, 40004
      • Flaget Memorial Hospital
    • Lexington, Kentucky, United States, 40504
      • Saint Joseph Radiation Oncology Resource Center
    • Lexington, Kentucky, United States, 40509
      • Saint Joseph Hospital East
    • London, Kentucky, United States, 40741
      • Saint Joseph London
  • Louisiana
    • Alexandria, Louisiana, United States, 71301
      • Christus Saint Frances Cabrini Hospital
    • Baton Rouge, Louisiana, United States, 70805
      • LSU Health Baton Rouge-North Clinic
    • Baton Rouge, Louisiana, United States, 70809
      • Louisiana Hematology Oncology Associates LLC
    • Baton Rouge, Louisiana, United States, 70809
      • Mary Bird Perkins Cancer Center
    • Baton Rouge, Louisiana, United States, 70809
      • Our Lady of the Lake Physicians Group - Medical Oncology
    • New Orleans, Louisiana, United States, 70121
      • Ochsner Medical Center Jefferson
    • New Orleans, Louisiana, United States, 70112
      • University Medical Center New Orleans
    • New Orleans, Louisiana, United States, 70112
      • Louisiana State University Health Science Center
    • Shreveport, Louisiana, United States, 71105
      • CHRISTUS Highland Medical Center
  • Michigan
    • Ann Arbor, Michigan, United States, 48106
      • Saint Joseph Mercy Hospital
    • Brighton, Michigan, United States, 48114
      • Saint Joseph Mercy Brighton
    • Brighton, Michigan, United States, 48114
      • IHA Hematology Oncology Consultants-Brighton
    • Canton, Michigan, United States, 48188
      • Saint Joseph Mercy Canton
    • Canton, Michigan, United States, 48188
      • IHA Hematology Oncology Consultants-Canton
    • Caro, Michigan, United States, 48723
      • Caro Cancer Center
    • Chelsea, Michigan, United States, 48118
      • Saint Joseph Mercy Chelsea
    • Chelsea, Michigan, United States, 48118
      • IHA Hematology Oncology Consultants-Chelsea
    • Clarkston, Michigan, United States, 48346
      • Hematology Oncology Consultants-Clarkston
    • Clarkston, Michigan, United States, 48346
      • Newland Medical Associates-Clarkston
    • Dearborn, Michigan, United States, 48124
      • Beaumont Hospital - Dearborn
    • Escanaba, Michigan, United States, 49829
      • Green Bay Oncology - Escanaba
    • Farmington Hills, Michigan, United States, 48336
      • Beaumont Hospital - Farmington Hills
    • Flint, Michigan, United States, 48503
      • Hurley Medical Center
    • Flint, Michigan, United States, 48503
      • Genesee Cancer and Blood Disease Treatment Center
    • Flint, Michigan, United States, 48503
      • Genesee Hematology Oncology PC
    • Flint, Michigan, United States, 48503
      • Genesys Hurley Cancer Institute
    • Grand Rapids, Michigan, United States, 49503
      • Spectrum Health at Butterworth Campus
    • Grand Rapids, Michigan, United States, 49503
      • Mercy Health Saint Mary's
    • Grosse Pointe, Michigan, United States, 48230
      • William Beaumont Hospital-Grosse Pointe
    • Livonia, Michigan, United States, 48154
      • Saint Mary Mercy Hospital
    • Muskegon, Michigan, United States, 49444
      • Mercy Health Mercy Campus
    • Pontiac, Michigan, United States, 48341
      • Saint Joseph Mercy Oakland
    • Pontiac, Michigan, United States, 48341
      • Newland Medical Associates-Pontiac
    • Reed City, Michigan, United States, 49677
      • Spectrum Health Reed City Hospital
    • Royal Oak, Michigan, United States, 48073
      • William Beaumont Hospital-Royal Oak
    • Saginaw, Michigan, United States, 48601
      • Ascension Saint Mary's Hospital
    • Saginaw, Michigan, United States, 48604
      • Oncology Hematology Associates of Saginaw Valley PC
    • Tawas City, Michigan, United States, 48764
      • Ascension Saint Joseph Hospital
    • Traverse City, Michigan, United States, 49684
      • Munson Medical Center
    • Troy, Michigan, United States, 48085
      • William Beaumont Hospital - Troy
    • West Branch, Michigan, United States, 48661
      • Saint Mary's Oncology/Hematology Associates of West Branch
    • Wyoming, Michigan, United States, 49519
      • Metro Health Hospital
    • Ypsilanti, Michigan, United States, 48197
      • IHA Hematology Oncology Consultants-Ann Arbor
  • Minnesota
    • Burnsville, Minnesota, United States, 55337
      • Fairview Ridges Hospital
    • Coon Rapids, Minnesota, United States, 55433
      • Mercy Hospital
    • Edina, Minnesota, United States, 55435
      • Fairview Southdale Hospital
    • Fridley, Minnesota, United States, 55432
      • Unity Hospital
    • Maple Grove, Minnesota, United States, 55369
      • Fairview Clinics and Surgery Center Maple Grove
    • Maplewood, Minnesota, United States, 55109
      • Saint John's Hospital - Healtheast
    • Maplewood, Minnesota, United States, 55109
      • Minnesota Oncology Hematology PA-Maplewood
    • Minneapolis, Minnesota, United States, 55415
      • Hennepin County Medical Center
    • Minneapolis, Minnesota, United States, 55407
      • Abbott-Northwestern Hospital
    • Minneapolis, Minnesota, United States, 55454
      • Health Partners Inc
    • New Ulm, Minnesota, United States, 56073
      • New Ulm Medical Center
    • Robbinsdale, Minnesota, United States, 55422
      • North Memorial Medical Health Center
    • Saint Louis Park, Minnesota, United States, 55416
      • Park Nicollet Clinic - Saint Louis Park
    • Saint Paul, Minnesota, United States, 55101
      • Regions Hospital
    • Saint Paul, Minnesota, United States, 55102
      • United Hospital
    • Shakopee, Minnesota, United States, 55379
      • Saint Francis Regional Medical Center
    • Stillwater, Minnesota, United States, 55082
      • Lakeview Hospital
    • Waconia, Minnesota, United States, 55387
      • Ridgeview Medical Center
    • Willmar, Minnesota, United States, 56201
      • Rice Memorial Hospital
    • Woodbury, Minnesota, United States, 55125
      • Minnesota Oncology Hematology PA-Woodbury
    • Wyoming, Minnesota, United States, 55092
      • Fairview Lakes Medical Center
  • Mississippi
    • Columbus, Mississippi, United States, 39705
      • Baptist Memorial Hospital and Cancer Center-Golden Triangle
    • New Albany, Mississippi, United States, 38652
      • Baptist Memorial Hospital and Cancer Center-Union County
    • Oxford, Mississippi, United States, 38655
      • Baptist Memorial Hospital and Cancer Center-Oxford
    • Southhaven, Mississippi, United States, 38671
      • Baptist Memorial Hospital and Cancer Center-Desoto
  • Missouri
    • Jefferson City, Missouri, United States, 65109
      • Capital Region Southwest Campus
    • Saint Louis, Missouri, United States, 63131
      • Missouri Baptist Medical Center
    • Springfield, Missouri, United States, 65804
      • Mercy Hospital Springfield
  • Nebraska
    • Kearney, Nebraska, United States, 68847
      • CHI Health Good Samaritan
  • North Carolina
    • Asheboro, North Carolina, United States, 27203
      • Randolph Hospital
    • Asheville, North Carolina, United States, 28801
      • Mission Hospital
    • Asheville, North Carolina, United States, 28816
      • Hope Women's Cancer Centers-Asheville
    • Asheville, North Carolina, United States, 28803
      • AdventHealth Infusion Center Asheville
    • Belmont, North Carolina, United States, 28012
      • Gaston Hematology and Oncology Associates-Belmont
    • Chapel Hill, North Carolina, United States, 27599
      • UNC Lineberger Comprehensive Cancer Center
    • Clemmons, North Carolina, United States, 27012
      • Wake Forest University at Clemmons
    • Clinton, North Carolina, United States, 28328
      • Southeastern Medical Oncology Center-Clinton
    • Gastonia, North Carolina, United States, 28054
      • CaroMont Regional Medical Center
    • Gastonia, North Carolina, United States, 28054
      • Gaston Hematology and Oncology Associates
    • Goldsboro, North Carolina, United States, 27534
      • Southeastern Medical Oncology Center-Goldsboro
    • Greensboro, North Carolina, United States, 27403
      • Cone Health Cancer Center
    • Hendersonville, North Carolina, United States, 28791
      • Margaret R Pardee Memorial Hospital
    • Hendersonville, North Carolina, United States, 28792
      • AdventHealth Hendersonville
    • Jacksonville, North Carolina, United States, 28546
      • Southeastern Medical Oncology Center-Jacksonville
    • Winston-Salem, North Carolina, United States, 27157
      • Wake Forest University Health Sciences
  • North Dakota
    • Bismarck, North Dakota, United States, 58501
      • Sanford Bismarck Medical Center
    • Fargo, North Dakota, United States, 58122
      • Sanford Roger Maris Cancer Center
    • Fargo, North Dakota, United States, 58122
      • Sanford Broadway Medical Center
  • Ohio
    • Belpre, Ohio, United States, 45714
      • Strecker Cancer Center-Belpre
    • Cincinnati, Ohio, United States, 45220
      • Good Samaritan Hospital - Cincinnati
    • Cincinnati, Ohio, United States, 45242
      • Bethesda North Hospital
    • Cincinnati, Ohio, United States, 45247
      • TriHealth Cancer Institute-Westside
    • Cincinnati, Ohio, United States, 45255
      • TriHealth Cancer Institute-Anderson
    • Columbus, Ohio, United States, 43214
      • Riverside Methodist Hospital
    • Columbus, Ohio, United States, 43214
      • Columbus Oncology and Hematology Associates Inc
    • Findlay, Ohio, United States, 45840
      • Armes Family Cancer Center
    • Marietta, Ohio, United States, 45750
      • Marietta Memorial Hospital
    • Newark, Ohio, United States, 43055
      • Licking Memorial Hospital
  • Oregon
    • Portland, Oregon, United States, 97227
      • Kaiser Permanente Northwest
  • Pennsylvania
    • Danville, Pennsylvania, United States, 17822
      • Geisinger Medical Center
    • Hazleton, Pennsylvania, United States, 18201
      • Geisinger Medical Center-Cancer Center Hazleton
    • Lewisburg, Pennsylvania, United States, 17837
      • Geisinger Medical Oncology-Lewisburg
    • Pottsville, Pennsylvania, United States, 17901
      • Geisinger Cancer Services-Pottsville
    • Scranton, Pennsylvania, United States, 18510
      • Community Medical Center
    • Selinsgrove, Pennsylvania, United States, 17870
      • Geisinger Medical Oncology-Selinsgrove
    • Wilkes-Barre, Pennsylvania, United States, 18711
      • Geisinger Wyoming Valley/Henry Cancer Center
  • South Carolina
    • Anderson, South Carolina, United States, 29621
      • AnMed Health Cancer Center
    • Boiling Springs, South Carolina, United States, 29316
      • Prisma Health Cancer Institute - Spartanburg
    • Easley, South Carolina, United States, 29640
      • Prisma Health Cancer Institute - Easley
    • Gaffney, South Carolina, United States, 29341
      • Gibbs Cancer Center-Gaffney
    • Georgetown, South Carolina, United States, 29440
      • Tidelands Georgetown Memorial Hospital
    • Greenville, South Carolina, United States, 29605
      • Prisma Health Cancer Institute - Faris
    • Greenville, South Carolina, United States, 29615
      • Prisma Health Cancer Institute - Eastside
    • Greenville, South Carolina, United States, 29605
      • Prisma Health Cancer Institute - Butternut
    • Greenwood, South Carolina, United States, 29646
      • Self Regional Healthcare
    • Greer, South Carolina, United States, 29650
      • Prisma Health Cancer Institute - Greer
    • Greer, South Carolina, United States, 29651
      • Gibbs Cancer Center-Pelham
    • Seneca, South Carolina, United States, 29672
      • Prisma Health Cancer Institute - Seneca
    • Spartanburg, South Carolina, United States, 29303
      • Spartanburg Medical Center
    • Union, South Carolina, United States, 29379
      • MGC Hematology Oncology-Union
  • South Dakota
    • Sioux Falls, South Dakota, United States, 57117-5134
      • Sanford USD Medical Center - Sioux Falls
    • Sioux Falls, South Dakota, United States, 57104
      • Sanford Cancer Center Oncology Clinic
  • Tennessee
    • Memphis, Tennessee, United States, 38120
      • Baptist Memorial Hospital and Cancer Center-Memphis
    • Memphis, Tennessee, United States, 38120
      • Baptist Memorial Hospital for Women
    • Memphis, Tennessee, United States, 38120
      • Family Cancer Center-Memphis
    • Nashville, Tennessee, United States, 37208
      • Meharry Medical College
  • Wisconsin
    • Burlington, Wisconsin, United States, 53105
      • Aurora Cancer Care-Southern Lakes VLCC
    • Chippewa Falls, Wisconsin, United States, 54729
      • Marshfield Clinic-Chippewa Center
    • Eau Claire, Wisconsin, United States, 54701
      • Marshfield Medical Center-EC Cancer Center
    • Fond Du Lac, Wisconsin, United States, 54937
      • Aurora Health Center-Fond du Lac
    • Germantown, Wisconsin, United States, 53022
      • Aurora Health Care Germantown Health Center
    • Grafton, Wisconsin, United States, 53024
      • Aurora Cancer Care-Grafton
    • Green Bay, Wisconsin, United States, 54311
      • Aurora BayCare Medical Center
    • Green Bay, Wisconsin, United States, 54301
      • Saint Vincent Hospital Cancer Center Green Bay
    • Green Bay, Wisconsin, United States, 54303
      • Saint Vincent Hospital Cancer Center at Saint Mary's
    • Kenosha, Wisconsin, United States, 53142
      • Aurora Cancer Care-Kenosha South
    • La Crosse, Wisconsin, United States, 54601
      • Gundersen Lutheran Medical Center
    • Ladysmith, Wisconsin, United States, 54848
      • Marshfield Clinic - Ladysmith Center
    • Manitowoc, Wisconsin, United States, 54221
      • Holy Family Memorial Hospital
    • Marinette, Wisconsin, United States, 54143
      • Aurora Bay Area Medical Group-Marinette
    • Marinette, Wisconsin, United States, 54143
      • Saint Vincent Hospital Cancer Center at Marinette
    • Marshfield, Wisconsin, United States, 54449
      • Marshfield Medical Center-Marshfield
    • Milwaukee, Wisconsin, United States, 53209
      • Aurora Cancer Care-Milwaukee
    • Milwaukee, Wisconsin, United States, 53215
      • Aurora Saint Luke's Medical Center
    • Milwaukee, Wisconsin, United States, 53233
      • Aurora Sinai Medical Center
    • Minocqua, Wisconsin, United States, 54548
      • Marshfield Clinic-Minocqua Center
    • New Richmond, Wisconsin, United States, 54017
      • Cancer Center of Western Wisconsin
    • Oconto Falls, Wisconsin, United States, 54154
      • Saint Vincent Hospital Cancer Center at Oconto Falls
    • Oshkosh, Wisconsin, United States, 54904
      • Vince Lombardi Cancer Clinic - Oshkosh
    • Racine, Wisconsin, United States, 53406
      • Aurora Cancer Care-Racine
    • Rice Lake, Wisconsin, United States, 54868
      • Marshfield Medical Center-Rice Lake
    • Sheboygan, Wisconsin, United States, 53081
      • Vince Lombardi Cancer Clinic-Sheboygan
    • Stevens Point, Wisconsin, United States, 54482
      • Marshfield Clinic Stevens Point Center
    • Sturgeon Bay, Wisconsin, United States, 54235-1495
      • Saint Vincent Hospital Cancer Center at Sturgeon Bay
    • Summit, Wisconsin, United States, 53066
      • Aurora Medical Center in Summit
    • Two Rivers, Wisconsin, United States, 54241
      • Vince Lombardi Cancer Clinic-Two Rivers
    • Wausau, Wisconsin, United States, 54401
      • Marshfield Clinic-Wausau Center
    • Wauwatosa, Wisconsin, United States, 53226
      • Aurora Cancer Care-Milwaukee West
    • West Allis, Wisconsin, United States, 53227
      • Aurora West Allis Medical Center
    • Weston, Wisconsin, United States, 54476
      • Marshfield Medical Center - Weston
    • Wisconsin Rapids, Wisconsin, United States, 54494
      • Marshfield Clinic - Wisconsin Rapids Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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 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.

Exclusion Criteria:

• 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.
• Patients with a resting heart rate less than 55 beats per minute, seizure disorder or peptic ulcer disease (PUD).
• History of congenital long QT syndrome or torsades de pointes.
• Screening QTc of > 460 milliseconds will make the patient ineligible.
• Pregnant women are excluded from this study. Following informed consent, women of child-bearing potential will be screened with a serum or urine pregnancy test within 10 days of enrollment. 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.
• On another intervention study involving medication at the time of enrollment or during participation in this study. (Exception: Patients will remain eligible for this study if they are also enrolled on the Alliance for Clinical Trials in Oncology study (NCT02927249): Aspirin in Preventing Recurrence of Cancer in Patients with HER2 Negative Stage II-III Breast Cancer After Chemotherapy, Surgery, and/or Radiation Therapy. Studies that involve only blood draws or questionnaires are also permitted.)
• Use of investigational drugs likely to affect cognition within 30 days prior to pre-screening visit.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Donepezil; 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; 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.; Other Names: Aricept
Placebo Comparator: Placebo; 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; 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.; Other Names: Sugar Pill

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
Digit Symbol Coding Results	The digit symbol coding (DSC) test measures processing speed, working memory, visuospatial processing, and attention. The DSC test measures processing speed. It requires respondents to transcribe symbols (e.g., >) associated with a number (0-9) into empty boxes beneath a series of randomly ordered numbers. Total score is number of correctly transcribed symbols in 2 minutes. Scores range from 0 to 100, with higher scores indicating higher cognitive function.	Baseline, Weeks 12, 24, 36
PROMIS 7-item Fatigue Scale Converted to T-scale Results	This self-report scale assesses fatigue. Scale ranges from 7 to 35 converted to T-scale ranging 29.4 to 83.2 Higher scores representing more fatigue.	Baseline, Weeks 12, 24, 36
FACT-Cognition (Version 3): Perceived Cognitive Impairment	The FACT-Cog is a patient-reported outcome (PRO) that includes subscales to measure Perceived Cognitive Impairment (PCI, n = 20 items, score range 0-80). Higher FACT-Cog PCI scores are better and indicate less cognitive impairment.	Baseline, Weeks 12, 24, 36
Controlled Oral Word Association Test (COWA) Results	The Controlled Oral Word Association Test from the Halstead-Reitan Neuropsychological Battery is a verbal fluency test in which participants are asked to say as many words as possible from a given category and in a specified timeframe (typically 60 seconds). Scores are the sum of all acceptable words. Minimum is 0 with no specified maximum; higher values represent better verbal fluency.	Baseline, Weeks 12, 24, 36
Trail Making Test, Parts A & B (TMT-A, TMT-B) Results	TMT Part A consists of 25 circles on a piece of paper with the numbers 1 to 25 written randomly in each. For Part A, the person is tasked with drawing a line from one circle to the next in ascending numerical order, from 1 to 25, as quickly as possible. The lines between the circles are referred to as the "trail." Range 1-300 in seconds. Lower values indicate completing task faster with less difficulty. It is a measure of executive functioning with lower values being better. TMT Part B also consists of 25 circles on a piece of paper, But, rather than all of the circles containing numbers, they contain numbers (1 to 12) and letters (A through L). For Part B, the person is tasked with connecting the circles in ascending order, alternating back and forth from numbers to letters. In other words, the "trail" would be connected like this:1-A-2-B-3-C-4-D-5-E-6-F-7-G-8-H-9-I-10-J-11-K-12-L-13. The range 1-300 seconds. Higher values indicate worse executive functioning.	Baseline, Weeks 12, 24, 36
Digit Span Test-Backwards (DST-B)	The Digit Span Task (Backwards-Only Version) measures working memory. On each question the participant repeats the numbers in reverse order of that presented aloud by the examiner (e.g., If the examiner says "5-6", the correct response would be "6-5"; If the examiner says "5-1-7-4-2-3-8", the correct response would be "8-3-2-4-7-1-5"). Score is 0 to 16 with higher scores representing better working memory.	Baseline, Weeks 12, 24, 36

Collaborators and Investigators

• Sponsor: Wake Forest University Health Sciences
• Collaborators: National Cancer Institute (NCI)
• Investigators: Principal Investigator: Stephen R Rapp, PhD, Wake Forest University Health Sciences

Study record dates

Study Major Dates

• Study Start (Actual): May 30, 2017
• Primary Completion (Actual): July 29, 2022
• Study Completion (Actual): July 29, 2022

Study Registration Dates

• First Submitted: June 30, 2016
• First Submitted That Met QC Criteria: June 30, 2016
• First Posted (Estimated): July 4, 2016

Study Record Updates

• Last Update Posted (Actual): September 13, 2023
• Last Update Submitted That Met QC Criteria: August 17, 2023
• Last Verified: July 1, 2023

More Information

Terms related to this study

• Keywords: Breast Cancer; Cognition; Donepezil
• Additional Relevant MeSH Terms: Mental Disorders; Neurocognitive Disorders; Cognition Disorders; Cognitive Dysfunction; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Cholinergic Agents; Enzyme Inhibitors; Nootropic Agents; Cholinesterase Inhibitors; Donepezil
• Other Study ID Numbers: IRB00041707 (Other Identifier: Wake Forest IRB ID); 3UG1CA189824-04S1 (U.S. NIH Grant/Contract); WF-97116 (Other Identifier: NCI); NCI-2016-01050 (Registry Identifier: NCI CTRP)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Wake Forest National Cancer Institute Community Oncology Research Program (NCORP) Research Base is committed to following the NIH Statement on Sharing Research Data. As of July 2018, the Wake Forest (WF) NCORP Research Base (RB) signed an agreement with NCI to contribute de-identified data and data dictionaries from clinical trials conducted through our RB to the NCI National Clinical Trials Network (NCTN)/NCORP data archive within 6 months of primary and non-primary publications of phase II/III and phase III trials. This will become the primary means for sharing raw data, and we will adhere to the guidelines spelled out in the NCTN/NCORP Data Archive Usage Guide.
• IPD Sharing Time Frame: See NIH Policy
• IPD Sharing Access Criteria: request using link below

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No