MedPath

Phase 3 Randomized Placebo Controlled Clinical Trial of Donepezil

Phase 3
Completed
Conditions
Cognitive Dysfunction
Memory Impairment
Interventions
Registration Number
NCT02822573
Lead Sponsor
Wake Forest University Health Sciences
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.

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).

Recruitment & Eligibility

Status
COMPLETED
Sex
Female
Target Recruitment
276
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.
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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.
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Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
DonepezilDonepezil 5 mgParticipants 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.
PlaceboPlaceboParticipants 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.
Primary Outcome Measures
NameTimeMethod
Hopkins Verbal Learning Test-Revised (HVLT-R) - TotalBaseline, Weeks 12, 24, 36

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.

Secondary Outcome Measures
NameTimeMethod
Digit Symbol Coding ResultsBaseline, Weeks 12, 24, 36

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.

Digit Span Test-Backwards (DST-B)Baseline, Weeks 12, 24, 36

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.

PROMIS 7-item Fatigue Scale Converted to T-scale ResultsBaseline, Weeks 12, 24, 36

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.

FACT-Cognition (Version 3): Perceived Cognitive ImpairmentBaseline, Weeks 12, 24, 36

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.

Controlled Oral Word Association Test (COWA) ResultsBaseline, Weeks 12, 24, 36

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.

Trail Making Test, Parts A & B (TMT-A, TMT-B) ResultsBaseline, Weeks 12, 24, 36

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.

Trial Locations

Locations (278)

Illinois CancerCare-Peru

🇺🇸

Peru, Illinois, United States

Southeastern Medical Oncology Center-Jacksonville

🇺🇸

Jacksonville, North Carolina, United States

Kaiser Permanente West Los Angeles

🇺🇸

Los Angeles, California, United States

Kaiser San Rafael-Gallinas

🇺🇸

San Rafael, California, United States

Vince Lombardi Cancer Clinic - Oshkosh

🇺🇸

Oshkosh, Wisconsin, United States

Missouri Baptist Medical Center

🇺🇸

Saint Louis, Missouri, United States

Geisinger Medical Center

🇺🇸

Danville, Pennsylvania, United States

Christiana Care Health System-Christiana Hospital

🇺🇸

Newark, Delaware, United States

Saint Luke's Cancer Institute - Meridian

🇺🇸

Meridian, Idaho, United States

Saint Luke's Cancer Institute - Boise

🇺🇸

Boise, Idaho, United States

Saint Luke's Cancer Institute - Fruitland

🇺🇸

Fruitland, Idaho, United States

Saint Luke's Cancer Institute - Nampa

🇺🇸

Nampa, Idaho, United States

LSU Health Baton Rouge-North Clinic

🇺🇸

Baton Rouge, Louisiana, United States

Mary Bird Perkins Cancer Center

🇺🇸

Baton Rouge, Louisiana, United States

Mercy Hospital Springfield

🇺🇸

Springfield, Missouri, United States

Baptist Memorial Hospital and Cancer Center-Desoto

🇺🇸

Southhaven, Mississippi, United States

CHI Health Good Samaritan

🇺🇸

Kearney, Nebraska, United States

Prisma Health Cancer Institute - Eastside

🇺🇸

Greenville, South Carolina, United States

Sanford Cancer Center Oncology Clinic

🇺🇸

Sioux Falls, South Dakota, United States

Riverside Methodist Hospital

🇺🇸

Columbus, Ohio, United States

Marshfield Medical Center-Marshfield

🇺🇸

Marshfield, Wisconsin, United States

IHA Hematology Oncology Consultants-Chelsea

🇺🇸

Chelsea, Michigan, United States

Saint Joseph Mercy Chelsea

🇺🇸

Chelsea, Michigan, United States

Spectrum Health Reed City Hospital

🇺🇸

Reed City, Michigan, United States

Munson Medical Center

🇺🇸

Traverse City, Michigan, United States

Metro Health Hospital

🇺🇸

Wyoming, Michigan, United States

Unity Hospital

🇺🇸

Fridley, Minnesota, United States

Mercy Health Mercy Campus

🇺🇸

Muskegon, Michigan, United States

Saint Mary's Oncology/Hematology Associates of West Branch

🇺🇸

West Branch, Michigan, United States

Hematology Oncology Consultants-Clarkston

🇺🇸

Clarkston, Michigan, United States

Ascension Saint Mary's Hospital

🇺🇸

Saginaw, Michigan, United States

Genesys Hurley Cancer Institute

🇺🇸

Flint, Michigan, United States

William Beaumont Hospital-Royal Oak

🇺🇸

Royal Oak, Michigan, United States

Fairview Ridges Hospital

🇺🇸

Burnsville, Minnesota, United States

Minnesota Oncology Hematology PA-Woodbury

🇺🇸

Woodbury, Minnesota, United States

William Beaumont Hospital - Troy

🇺🇸

Troy, Michigan, United States

Rice Memorial Hospital

🇺🇸

Willmar, Minnesota, United States

Saint Joseph Mercy Canton

🇺🇸

Canton, Michigan, United States

Saint Mary Mercy Hospital

🇺🇸

Livonia, Michigan, United States

Newland Medical Associates-Pontiac

🇺🇸

Pontiac, Michigan, United States

Mercy Hospital

🇺🇸

Coon Rapids, Minnesota, United States

Regions Hospital

🇺🇸

Saint Paul, Minnesota, United States

Self Regional Healthcare

🇺🇸

Greenwood, South Carolina, United States

Geisinger Cancer Services-Pottsville

🇺🇸

Pottsville, Pennsylvania, United States

Gibbs Cancer Center-Gaffney

🇺🇸

Gaffney, South Carolina, United States

Baptist Memorial Hospital and Cancer Center-Memphis

🇺🇸

Memphis, Tennessee, United States

Prisma Health Cancer Institute - Easley

🇺🇸

Easley, South Carolina, United States

Aurora Cancer Care-Southern Lakes VLCC

🇺🇸

Burlington, Wisconsin, United States

Community Medical Center

🇺🇸

Scranton, Pennsylvania, United States

Sanford USD Medical Center - Sioux Falls

🇺🇸

Sioux Falls, South Dakota, United States

Tidelands Georgetown Memorial Hospital

🇺🇸

Georgetown, South Carolina, United States

Aurora Health Center-Fond du Lac

🇺🇸

Fond Du Lac, Wisconsin, United States

Spartanburg Medical Center

🇺🇸

Spartanburg, South Carolina, United States

Aurora Cancer Care-Grafton

🇺🇸

Grafton, Wisconsin, United States

Geisinger Medical Oncology-Selinsgrove

🇺🇸

Selinsgrove, Pennsylvania, United States

Aurora BayCare Medical Center

🇺🇸

Green Bay, Wisconsin, United States

Geisinger Wyoming Valley/Henry Cancer Center

🇺🇸

Wilkes-Barre, Pennsylvania, United States

Prisma Health Cancer Institute - Faris

🇺🇸

Greenville, South Carolina, United States

Gundersen Lutheran Medical Center

🇺🇸

La Crosse, Wisconsin, United States

AnMed Health Cancer Center

🇺🇸

Anderson, South Carolina, United States

Prisma Health Cancer Institute - Spartanburg

🇺🇸

Boiling Springs, South Carolina, United States

Gibbs Cancer Center-Pelham

🇺🇸

Greer, South Carolina, United States

Prisma Health Cancer Institute - Seneca

🇺🇸

Seneca, South Carolina, United States

Saint Vincent Hospital Cancer Center at Marinette

🇺🇸

Marinette, Wisconsin, United States

Aurora Bay Area Medical Group-Marinette

🇺🇸

Marinette, Wisconsin, United States

Saint Vincent Hospital Cancer Center at Saint Mary's

🇺🇸

Green Bay, Wisconsin, United States

Baptist Memorial Hospital for Women

🇺🇸

Memphis, Tennessee, United States

Aurora West Allis Medical Center

🇺🇸

West Allis, Wisconsin, United States

Prisma Health Cancer Institute - Butternut

🇺🇸

Greenville, South Carolina, United States

Prisma Health Cancer Institute - Greer

🇺🇸

Greer, South Carolina, United States

Holy Family Memorial Hospital

🇺🇸

Manitowoc, Wisconsin, United States

Marshfield Medical Center - Weston

🇺🇸

Weston, Wisconsin, United States

MGC Hematology Oncology-Union

🇺🇸

Union, South Carolina, United States

Saint Vincent Hospital Cancer Center Green Bay

🇺🇸

Green Bay, Wisconsin, United States

Good Samaritan Hospital - Cincinnati

🇺🇸

Cincinnati, Ohio, United States

Bethesda North Hospital

🇺🇸

Cincinnati, Ohio, United States

TriHealth Cancer Institute-Westside

🇺🇸

Cincinnati, Ohio, United States

TriHealth Cancer Institute-Anderson

🇺🇸

Cincinnati, Ohio, United States

Straub Clinic and Hospital

🇺🇸

Honolulu, Hawaii, United States

Hawaii Cancer Care Inc-Liliha

🇺🇸

Honolulu, Hawaii, United States

Queen's Cancer Center - Kuakini

🇺🇸

Honolulu, Hawaii, United States

Kaiser Permanente San Leandro

🇺🇸

San Leandro, California, United States

Meharry Medical College

🇺🇸

Nashville, Tennessee, United States

Sanford Bismarck Medical Center

🇺🇸

Bismarck, North Dakota, United States

Sanford Broadway Medical Center

🇺🇸

Fargo, North Dakota, United States

Cancer Center of Kansas - Salina

🇺🇸

Salina, Kansas, United States

Cancer Center of Kansas-Manhattan

🇺🇸

Manhattan, Kansas, United States

Pali Momi Medical Center

🇺🇸

'Aiea, Hawaii, United States

Cancer Center of Kansas-Kingman

🇺🇸

Kingman, Kansas, United States

Cancer Center of Kansas - Parsons

🇺🇸

Parsons, Kansas, United States

Cancer Center of Kansas - Wellington

🇺🇸

Wellington, Kansas, United States

Cancer Center of Kansas - McPherson

🇺🇸

McPherson, Kansas, United States

Cancer Center of Kansas - Fort Scott

🇺🇸

Fort Scott, Kansas, United States

Cancer Center of Kansas-Independence

🇺🇸

Independence, Kansas, United States

Sanford Roger Maris Cancer Center

🇺🇸

Fargo, North Dakota, United States

Cancer Center of Kansas - Chanute

🇺🇸

Chanute, Kansas, United States

Kaiser Permanente-Fontana

🇺🇸

Fontana, California, United States

Abbott-Northwestern Hospital

🇺🇸

Minneapolis, Minnesota, United States

Fairview Clinics and Surgery Center Maple Grove

🇺🇸

Maple Grove, Minnesota, United States

Minnesota Oncology Hematology PA-Maplewood

🇺🇸

Maplewood, Minnesota, United States

North Memorial Medical Health Center

🇺🇸

Robbinsdale, Minnesota, United States

Kaiser Permanente-Oakland

🇺🇸

Oakland, California, United States

Kaiser Permanente-Riverside

🇺🇸

Riverside, California, United States

Hennepin County Medical Center

🇺🇸

Minneapolis, Minnesota, United States

Illinois CancerCare-Galesburg

🇺🇸

Galesburg, Illinois, United States

Kaiser Permanente-South Sacramento

🇺🇸

Sacramento, California, United States

South Sacramento Cancer Center

🇺🇸

Sacramento, California, United States

Kaiser Permanente - Sacramento

🇺🇸

Sacramento, California, United States

Kaiser Permanente-Franklin

🇺🇸

Denver, Colorado, United States

Porter Adventist Hospital

🇺🇸

Denver, Colorado, United States

Saint Joseph Mercy Hospital

🇺🇸

Ann Arbor, Michigan, United States

Wake Forest University Health Sciences

🇺🇸

Winston-Salem, North Carolina, United States

Kaiser Permanente Northwest

🇺🇸

Portland, Oregon, United States

Aurora Sinai Medical Center

🇺🇸

Milwaukee, Wisconsin, United States

Aurora Cancer Care-Milwaukee

🇺🇸

Milwaukee, Wisconsin, United States

Aurora Saint Luke's Medical Center

🇺🇸

Milwaukee, Wisconsin, United States

IHA Hematology Oncology Consultants-Ann Arbor

🇺🇸

Ypsilanti, Michigan, United States

Saint John's Hospital - Healtheast

🇺🇸

Maplewood, Minnesota, United States

Kaiser Permanente-Deer Valley Medical Center

🇺🇸

Antioch, California, United States

Kaiser Permanente-Baldwin Park

🇺🇸

Baldwin Park, California, United States

Kaiser Permanente-Anaheim

🇺🇸

Anaheim, California, United States

Kaiser Permanente-Bellflower

🇺🇸

Bellflower, California, United States

Kaiser Permanente-Fremont

🇺🇸

Fremont, California, United States

Fresno Cancer Center

🇺🇸

Fresno, California, United States

Kaiser Permanente-Fresno

🇺🇸

Fresno, California, United States

Kaiser Permanente-Irvine

🇺🇸

Irvine, California, United States

Kaiser Permanente - Harbor City

🇺🇸

Harbor City, California, United States

Kaiser Permanente Los Angeles Medical Center

🇺🇸

Los Angeles, California, United States

Kaiser Permanente-Ontario

🇺🇸

Ontario, California, United States

Kaiser Permanente-Modesto

🇺🇸

Modesto, California, United States

Kaiser Permanente - Panorama City

🇺🇸

Panorama City, California, United States

Kaiser Permanente-Richmond

🇺🇸

Richmond, California, United States

Kaiser Permanente-Rancho Cordova Cancer Center

🇺🇸

Rancho Cordova, California, United States

Kaiser Permanente-Roseville

🇺🇸

Roseville, California, United States

The Permanente Medical Group-Roseville Radiation Oncology

🇺🇸

Roseville, California, United States

Kaiser Permanente Downtown Commons

🇺🇸

Sacramento, California, United States

Kaiser Permanente-Santa Teresa-San Jose

🇺🇸

San Jose, California, United States

Kaiser Permanente-San Diego Zion

🇺🇸

San Diego, California, United States

Kaiser Permanente-San Marcos

🇺🇸

San Marcos, California, United States

Kaiser Permanente-San Francisco

🇺🇸

San Francisco, California, United States

Kaiser Permanente-San Rafael

🇺🇸

San Rafael, California, United States

Kaiser Permanente-Stockton

🇺🇸

Stockton, California, United States

Kaiser Permanente-Santa Rosa

🇺🇸

Santa Rosa, California, United States

Kaiser Permanente Medical Center - Santa Clara

🇺🇸

Santa Clara, California, United States

Kaiser Permanente Medical Center-Vacaville

🇺🇸

Vacaville, California, United States

Kaiser Permanente-South San Francisco

🇺🇸

South San Francisco, California, United States

Kaiser Permanente-Vallejo

🇺🇸

Vallejo, California, United States

Penrose-Saint Francis Healthcare

🇺🇸

Colorado Springs, Colorado, United States

Kaiser Permanente-Walnut Creek

🇺🇸

Walnut Creek, California, United States

Rocky Mountain Cancer Centers-Penrose

🇺🇸

Colorado Springs, Colorado, United States

Kaiser Permanente-Woodland Hills

🇺🇸

Woodland Hills, California, United States

Kaiser Permanente-Rock Creek

🇺🇸

Lafayette, Colorado, United States

Littleton Adventist Hospital

🇺🇸

Littleton, Colorado, United States

Longmont United Hospital

🇺🇸

Longmont, Colorado, United States

Kaiser Permanente-Lone Tree

🇺🇸

Lone Tree, Colorado, United States

Helen F Graham Cancer Center

🇺🇸

Newark, Delaware, United States

Parker Adventist Hospital

🇺🇸

Parker, Colorado, United States

Medical Oncology Hematology Consultants PA

🇺🇸

Newark, Delaware, United States

Beebe Health Campus

🇺🇸

Rehoboth Beach, Delaware, United States

Holy Cross Hospital

🇺🇸

Fort Lauderdale, Florida, United States

TidalHealth Nanticoke / Allen Cancer Center

🇺🇸

Seaford, Delaware, United States

Saint Luke's Cancer Institute - Twin Falls

🇺🇸

Twin Falls, Idaho, United States

Illinois CancerCare-Canton

🇺🇸

Canton, Illinois, United States

Illinois CancerCare-Bloomington

🇺🇸

Bloomington, Illinois, United States

Centralia Oncology Clinic

🇺🇸

Centralia, Illinois, United States

Carle on Vermilion

🇺🇸

Danville, Illinois, United States

Cancer Care Specialists of Illinois - Decatur

🇺🇸

Decatur, Illinois, United States

Crossroads Cancer Center

🇺🇸

Effingham, Illinois, United States

Decatur Memorial Hospital

🇺🇸

Decatur, Illinois, United States

Carle Physician Group-Effingham

🇺🇸

Effingham, Illinois, United States

Illinois CancerCare-Kewanee Clinic

🇺🇸

Kewanee, Illinois, United States

Carle Physician Group-Mattoon/Charleston

🇺🇸

Mattoon, Illinois, United States

Illinois CancerCare-Pekin

🇺🇸

Pekin, Illinois, United States

Illinois CancerCare-Peoria

🇺🇸

Peoria, Illinois, United States

Illinois CancerCare-Ottawa Clinic

🇺🇸

Ottawa, Illinois, United States

Physicians' Clinic of Iowa PC

🇺🇸

Cedar Rapids, Iowa, United States

Carle Cancer Center

🇺🇸

Urbana, Illinois, United States

Methodist West Hospital

🇺🇸

West Des Moines, Iowa, United States

Cancer Center of Kansas - El Dorado

🇺🇸

El Dorado, Kansas, United States

Cancer Center of Kansas - Newton

🇺🇸

Newton, Kansas, United States

Cancer Center of Kansas - Winfield

🇺🇸

Winfield, Kansas, United States

Flaget Memorial Hospital

🇺🇸

Bardstown, Kentucky, United States

Christus Saint Frances Cabrini Hospital

🇺🇸

Alexandria, Louisiana, United States

Saint Joseph London

🇺🇸

London, Kentucky, United States

Louisiana Hematology Oncology Associates LLC

🇺🇸

Baton Rouge, Louisiana, United States

Our Lady of the Lake Physicians Group - Medical Oncology

🇺🇸

Baton Rouge, Louisiana, United States

CHRISTUS Highland Medical Center

🇺🇸

Shreveport, Louisiana, United States

IHA Hematology Oncology Consultants-Canton

🇺🇸

Canton, Michigan, United States

Saint Joseph Mercy Brighton

🇺🇸

Brighton, Michigan, United States

IHA Hematology Oncology Consultants-Brighton

🇺🇸

Brighton, Michigan, United States

Caro Cancer Center

🇺🇸

Caro, Michigan, United States

Beaumont Hospital - Dearborn

🇺🇸

Dearborn, Michigan, United States

Newland Medical Associates-Clarkston

🇺🇸

Clarkston, Michigan, United States

Beaumont Hospital - Farmington Hills

🇺🇸

Farmington Hills, Michigan, United States

Genesee Cancer and Blood Disease Treatment Center

🇺🇸

Flint, Michigan, United States

Genesee Hematology Oncology PC

🇺🇸

Flint, Michigan, United States

Green Bay Oncology - Escanaba

🇺🇸

Escanaba, Michigan, United States

Mercy Health Saint Mary's

🇺🇸

Grand Rapids, Michigan, United States

Spectrum Health at Butterworth Campus

🇺🇸

Grand Rapids, Michigan, United States

William Beaumont Hospital-Grosse Pointe

🇺🇸

Grosse Pointe, Michigan, United States

Saint Joseph Mercy Oakland

🇺🇸

Pontiac, Michigan, United States

Oncology Hematology Associates of Saginaw Valley PC

🇺🇸

Saginaw, Michigan, United States

Ascension Saint Joseph Hospital

🇺🇸

Tawas City, Michigan, United States

New Ulm Medical Center

🇺🇸

New Ulm, Minnesota, United States

Health Partners Inc

🇺🇸

Minneapolis, Minnesota, United States

United Hospital

🇺🇸

Saint Paul, Minnesota, United States

Park Nicollet Clinic - Saint Louis Park

🇺🇸

Saint Louis Park, Minnesota, United States

Saint Francis Regional Medical Center

🇺🇸

Shakopee, Minnesota, United States

Ridgeview Medical Center

🇺🇸

Waconia, Minnesota, United States

Lakeview Hospital

🇺🇸

Stillwater, Minnesota, United States

Fairview Lakes Medical Center

🇺🇸

Wyoming, Minnesota, United States

Baptist Memorial Hospital and Cancer Center-Union County

🇺🇸

New Albany, Mississippi, United States

Baptist Memorial Hospital and Cancer Center-Oxford

🇺🇸

Oxford, Mississippi, United States

Baptist Memorial Hospital and Cancer Center-Golden Triangle

🇺🇸

Columbus, Mississippi, United States

Capital Region Southwest Campus

🇺🇸

Jefferson City, Missouri, United States

Randolph Hospital

🇺🇸

Asheboro, North Carolina, United States

Mission Hospital

🇺🇸

Asheville, North Carolina, United States

AdventHealth Infusion Center Asheville

🇺🇸

Asheville, North Carolina, United States

Hope Women's Cancer Centers-Asheville

🇺🇸

Asheville, North Carolina, United States

Gaston Hematology and Oncology Associates-Belmont

🇺🇸

Belmont, North Carolina, United States

Wake Forest University at Clemmons

🇺🇸

Clemmons, North Carolina, United States

Southeastern Medical Oncology Center-Clinton

🇺🇸

Clinton, North Carolina, United States

Southeastern Medical Oncology Center-Goldsboro

🇺🇸

Goldsboro, North Carolina, United States

CaroMont Regional Medical Center

🇺🇸

Gastonia, North Carolina, United States

Gaston Hematology and Oncology Associates

🇺🇸

Gastonia, North Carolina, United States

Margaret R Pardee Memorial Hospital

🇺🇸

Hendersonville, North Carolina, United States

Cone Health Cancer Center

🇺🇸

Greensboro, North Carolina, United States

AdventHealth Hendersonville

🇺🇸

Hendersonville, North Carolina, United States

Strecker Cancer Center-Belpre

🇺🇸

Belpre, Ohio, United States

Columbus Oncology and Hematology Associates Inc

🇺🇸

Columbus, Ohio, United States

Armes Family Cancer Center

🇺🇸

Findlay, Ohio, United States

Marietta Memorial Hospital

🇺🇸

Marietta, Ohio, United States

Licking Memorial Hospital

🇺🇸

Newark, Ohio, United States

Geisinger Medical Center-Cancer Center Hazleton

🇺🇸

Hazleton, Pennsylvania, United States

Geisinger Medical Oncology-Lewisburg

🇺🇸

Lewisburg, Pennsylvania, United States

Family Cancer Center-Memphis

🇺🇸

Memphis, Tennessee, United States

Marshfield Clinic-Chippewa Center

🇺🇸

Chippewa Falls, Wisconsin, United States

Marshfield Medical Center-EC Cancer Center

🇺🇸

Eau Claire, Wisconsin, United States

Aurora Health Care Germantown Health Center

🇺🇸

Germantown, Wisconsin, United States

Aurora Cancer Care-Kenosha South

🇺🇸

Kenosha, Wisconsin, United States

Marshfield Clinic - Ladysmith Center

🇺🇸

Ladysmith, Wisconsin, United States

Cancer Center of Western Wisconsin

🇺🇸

New Richmond, Wisconsin, United States

Marshfield Clinic-Minocqua Center

🇺🇸

Minocqua, Wisconsin, United States

Marshfield Medical Center-Rice Lake

🇺🇸

Rice Lake, Wisconsin, United States

Saint Vincent Hospital Cancer Center at Oconto Falls

🇺🇸

Oconto Falls, Wisconsin, United States

Aurora Cancer Care-Racine

🇺🇸

Racine, Wisconsin, United States

Saint Vincent Hospital Cancer Center at Sturgeon Bay

🇺🇸

Sturgeon Bay, Wisconsin, United States

Marshfield Clinic Stevens Point Center

🇺🇸

Stevens Point, Wisconsin, United States

Vince Lombardi Cancer Clinic-Sheboygan

🇺🇸

Sheboygan, Wisconsin, United States

Vince Lombardi Cancer Clinic-Two Rivers

🇺🇸

Two Rivers, Wisconsin, United States

Aurora Medical Center in Summit

🇺🇸

Summit, Wisconsin, United States

Aurora Cancer Care-Milwaukee West

🇺🇸

Wauwatosa, Wisconsin, United States

Marshfield Clinic-Wausau Center

🇺🇸

Wausau, Wisconsin, United States

Marshfield Clinic - Wisconsin Rapids Center

🇺🇸

Wisconsin Rapids, Wisconsin, United States

Hurley Medical Center

🇺🇸

Flint, Michigan, United States

The Carle Foundation Hospital

🇺🇸

Urbana, Illinois, United States

UNC Lineberger Comprehensive Cancer Center

🇺🇸

Chapel Hill, North Carolina, United States

Louisiana State University Health Science Center

🇺🇸

New Orleans, Louisiana, United States

University Medical Center New Orleans

🇺🇸

New Orleans, Louisiana, United States

Ochsner Medical Center Jefferson

🇺🇸

New Orleans, Louisiana, United States

Hawaii Cancer Care Inc - Waterfront Plaza

🇺🇸

Honolulu, Hawaii, United States

Queen's Cancer Cenrer - POB I

🇺🇸

Honolulu, Hawaii, United States

Queen's Medical Center

🇺🇸

Honolulu, Hawaii, United States

University of Hawaii Cancer Center

🇺🇸

Honolulu, Hawaii, United States

Iowa Methodist Medical Center

🇺🇸

Des Moines, Iowa, United States

Medical Oncology and Hematology Associates-Des Moines

🇺🇸

Des Moines, Iowa, United States

Broadlawns Medical Center

🇺🇸

Des Moines, Iowa, United States

Mercy Medical Center - Des Moines

🇺🇸

Des Moines, Iowa, United States

Iowa Lutheran Hospital

🇺🇸

Des Moines, Iowa, United States

Saint Joseph Radiation Oncology Resource Center

🇺🇸

Lexington, Kentucky, United States

Saint Joseph Hospital East

🇺🇸

Lexington, Kentucky, United States

Kaiser Permanente Moanalua Medical Center

🇺🇸

Honolulu, Hawaii, United States

Kapiolani Medical Center for Women and Children

🇺🇸

Honolulu, Hawaii, United States

Associates In Womens Health

🇺🇸

Wichita, Kansas, United States

Cancer Center of Kansas-Wichita Medical Arts Tower

🇺🇸

Wichita, Kansas, United States

Ascension Via Christi Hospitals Wichita

🇺🇸

Wichita, Kansas, United States

Cancer Center of Kansas - Wichita

🇺🇸

Wichita, Kansas, United States

Fairview Southdale Hospital

🇺🇸

Edina, Minnesota, United States

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