S1501 Carvedilol in Preventing Cardiac Toxicity in Patients With Metastatic HER-2-Positive Breast Cancer

Cardiotoxicity Clinical Trial

Official title:

Prospective Evaluation of Carvedilol in Prevention of Cardiac Toxicity in Patients With Metastatic HER-2+ Breast Cancer, Phase III

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03418961
• Other study ID #: S1501
• Secondary ID: NCI-2016-01047S1
• Status: Recruiting
• Phase: Phase 3
• Start date: November 1, 2017
• Est. completion date: January 1, 2030

Study information

• Verified date: April 2024
• Source: SWOG Cancer Research Network
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This phase III trial studies how well carvedilol works in preventing cardiac toxicity in patients with human epidermal growth factor receptor (HER)-2-positive breast cancer that has spread to other places in the body. A beta-blocker, such as carvedilol, is used to treat heart failure and high blood pressure, and it may prevent the heart from side effects of chemotherapy.

Description:

PRIMARY OBJECTIVES:

I. To assess whether prophylactic beta blocker therapy with carvedilol compared with no intervention reduces the risk of subsequent cardiac dysfunction in patients with metastatic breast cancer receiving trastuzumab?based HER-2 targeted therapy.

SECONDARY OBJECTIVES:

I. To assess whether prophylactic beta blocker therapy with carvedilol compared with no intervention reduces the risk of predefined subsequent cardiac events in patients with metastatic breast cancer receiving trastuzumab?based HER-2 targeted therapy.

II. To evaluate if prophylactic carvedilol compared with no intervention results in a longer time to first interruption of trastuzumab?based HER-2 targeted therapy due to either cardiac dysfunction or events.

III. To assess whether prophylactic beta blocker therapy with carvedilol compared with no intervention reduces the risk of subsequent cardiac dysfunction OR events in this population.

IV. To establish and prospectively collect a predefined panel of baseline core cardiovascular measures and develop a predictive model of cardiac dysfunction.

V. To evaluate the rate of cardiac dysfunction in an observational arm consisting of individuals otherwise eligible for the study except for use of beta blockers, angiotensin receptor blocker (ARB), or angiotensin converting enzyme (ACE) inhibitors for other medical reasons.

TERTIARY OBJECTIVES:

I. To evaluate the isoleucine (lle) 655 valine (Val) and and alanine (Ala)ll70 proline (Pro) single nucleotide polymorphisms (SNPs) of the HER-2 gene as a predictive biomarker of study-defined cardiac dysfunction.

II. To evaluate plasma neuregulin-1 at baseline and over study time as a predictive biomarker of study-defined cardiac dysfunction.

III. To evaluate the feasibility of performing serial left ventricular strain in a National Clinical Trials Network (NCTN) group setting, with the goal of 75% of patients contributing both a baseline and at least one follow-up strain measurement.

IV. To bank blood for future translational medicine studies such as brain natriuretic peptide (BNP), additional SNPs, and high sensitivity troponin.

OUTLINE: Patients are randomized to 1 of 2 arms. Patients taking beta blocker, ARB, or ACE inhibitor at registration are assigned to Arm III.

ARM I: Patients not taking beta blocker, ARB, or ACE inhibitor at registration receive carvedilol orally (PO) twice daily (BID). Courses repeat every 12 weeks for 108 weeks in the absence of disease progression or unacceptable toxicity.

ARM II: Patients not taking beta blocker, ARB, or ACE inhibitor at registration receive no study intervention for up to 108 weeks.

ARM III: Patients undergo observation for up to 108 weeks.

After completion of study, patients are followed up for up to 108 weeks.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 817
• Est. completion date: January 1, 2030
• Est. primary completion date: January 1, 2030
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• STEP 1 REGISTRATION

• Patients must have metastatic breast cancer and be initiating within 7 days of step 1 registration or continuing trastuzumab?based HER-2 targeted therapy without concurrent anthracyclines in first or second line setting; patients may have brain metastasis; there is no limit for number of doses of HER-2 targeted therapy prior to registration; examples of eligible HER-2 targeted therapy:

• Trastuzumab

• Trastuzumab + chemotherapy or hormonal therapy

• Trastuzumab + other HER-2 targeted agent with or without chemotherapy (such as pertuzumab)

• Ado-trastuzumab (Kadcyla)

• NOTE: Patients on lapatinib without trastuzumab are not eligible; planned treatment with concurrent HER-2 targeted therapy and anthracyclines is not permitted

• Patients must be at increased risk for cardiotoxicity defined by at least one of the following:

• Previous anthracycline exposure, OR

• 1 or more of the following risk factors for heart disease:

• Left ventricular ejection fraction (LVEF) 50-54% by local echocardiography (ECHO) read

• Age >= 65

• Body mass index (BMI) >= 30 kg/m^2

• Current or prior anti-hypertensive therapy

• Diagnosis of coronary artery disease (CAD)

• Diabetes mellitus

• Atrial fibrillation/flutter

• Patients must not have taken within 21 days prior to step 1 registration, be currently taking at the time of step 1 registration, or planning to take once registered to step 1 a beta blocker, ARB, or ACE inhibitor in order to be randomized (Arms 1 and 2)

• Patients currently taking a beta blocker, ARB, or ACE inhibitor at the time of step 1 registration are eligible to register for the non-randomized observational cohort (Arm 3)

• Patients must not be currently taking or planning to take during study treatment the following medications:

• B2 agonists

• Bosutinib

• Ceritinib

• Floctafenine

• Methacholine

• Pazopanib

• Rivastigmine

• Vincristine

• Silodosin

• Patients must have a Zubrod Performance status of 0-2

• Patients must have a complete physical examination and medical history within 28 days prior to registration

• Patients must have LVEF >= 50% by 2-dimensional (D) echocardiogram within 28 days prior to registration; the echocardiogram must be obtained from a S1501 validated ECHO laboratory (lab) and submitted for central review by the S1501 ECHO core lab; ECHO should not be submitted for central read until patient has been otherwise deemed eligible

• Serum bilirubin < 3.0 x institutional upper limit of normal (IULN)

• Serum glutamic oxaloacetic transaminase (SGOT)/aspartate aminotransferase (AST) and serum glutamic pyruvic transaminase (SGPT)/alanine aminotransferase (ALT) < 5.0 x IULN

• Patients must have electrocardiogram with corrected QT (QTc) with correction within 28 days prior to registration

• Patients must have a systolic blood pressure >= 80 mm Hg within 14 days prior to registration

• Patients must not be dialysis dependent

• Patients must be able to swallow tablets

• Patients must not have uncontrolled asthma

• Patients must not co-enroll on other treatment trials

• No other prior malignancy is allowed except for the following: adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, prostate cancer on active surveillance, adequately treated stage I or II cancer from which the patient is currently in complete remission, or any other cancer from which the patient has been disease free for five years

• Patients must not be pregnant or nursing due to potential fetal or nursing infant harm; women/men of reproductive potential must have agreed to use an effective contraceptive method, a woman is considered to be of "reproductive potential" if she has had menses at any time in the preceding 12 consecutive months; in addition to routine contraceptive methods, "effective contraception" also includes heterosexual celibacy and surgery intended to prevent pregnancy (or with a side-effect of pregnancy prevention) defined as a hysterectomy, bilateral oophorectomy or bilateral tubal ligation; however, if at any point a previously celibate patient chooses to become heterosexually active during the time period for use of contraceptive measures outlined in the protocol, he/she is responsible for beginning contraceptive measures

• Patients must be willing to submit blood specimens

• Sites must seek additional patient consent for the future use of specimens

• Patients must be informed of the investigational nature of this study and must sign and give written informed consent in accordance with institutional and federal guidelines

• As a part of the OPEN registration process the treating institution's identity is provided in order to ensure that the current (within 365 days) date of institutional review board approval for this study has been entered in the system

• STEP 2 REGISTRATION (Randomization)

• Patients must not be registered to step 2 until receiving confirmation from the ECHO Core Lab that the patient?s LVEF by echocardiogram was >= 50% by central review; patients must be registered within 5 calendar days of receiving the e-mail notification

• Site must verify that there is no known change in the step 1 eligibility since initial registration

Related Conditions & MeSH terms

• Breast Neoplasms
• Cardiotoxicity
• HER2/Neu Positive
• Metastatic Malignant Neoplasm in the Brain
• Neoplasms
• Recurrent Breast Carcinoma
• Stage IV Breast Cancer AJCC v6 and v7

Intervention

Drug:
• Carvedilol
Given PO

Other:
• Laboratory Biomarker Analysis
Correlative studies
• Patient Observation
Undergo observation

Locations

Country	Name	City	State
Korea, Republic of	National Cancer Center-Korea	Goyang-si	Gyeonggi-do
Puerto Rico	Advance Oncology Center	Aguadilla
Puerto Rico	Doctor's Cancer Center-Arecibo	Arecibo
Puerto Rico	Cancer Center-Metro Medical Center Bayamon	Bayamon
Puerto Rico	Hematologia Oncologia San Pablo	Bayamon
Puerto Rico	HIMA San Pablo Oncologic Hospital	Caguas
Puerto Rico	Doctors Cancer Center	Manati
Puerto Rico	Instituto Oncologia Moderna Ponce	Ponce
Puerto Rico	Primary Care Physician Group	San Juan
Puerto Rico	San Juan City Hospital	San Juan
Puerto Rico	San Juan Community Oncology Group	San Juan
Puerto Rico	Centro de Hematologia y Oncologia del Sur	Santa Isabel
Saudi Arabia	King Faisal Specialist Hospital and Research Centre	Riyadh
United States	Pali Momi Medical Center	'Aiea	Hawaii
United States	Queen's Cancer Center - Pearlridge	'Aiea	Hawaii
United States	The Cancer Center of Hawaii-Pali Momi	'Aiea	Hawaii
United States	Providence Regional Cancer System-Aberdeen	Aberdeen	Washington
United States	Cleveland Clinic Akron General	Akron	Ohio
United States	University of New Mexico Cancer Center	Albuquerque	New Mexico
United States	Lehigh Valley Hospital-Cedar Crest	Allentown	Pennsylvania
United States	Community Hospital of Anaconda	Anaconda	Montana
United States	Alaska Breast Care and Surgery LLC	Anchorage	Alaska
United States	Alaska Oncology and Hematology LLC	Anchorage	Alaska
United States	Alaska Women's Cancer Care	Anchorage	Alaska
United States	Anchorage Associates in Radiation Medicine	Anchorage	Alaska
United States	Anchorage Oncology Centre	Anchorage	Alaska
United States	Katmai Oncology Group	Anchorage	Alaska
United States	Providence Alaska Medical Center	Anchorage	Alaska
United States	Saint Joseph Mercy Hospital	Ann Arbor	Michigan
United States	University of Michigan Comprehensive Cancer Center	Ann Arbor	Michigan
United States	Kaiser Permanente-Deer Valley Medical Center	Antioch	California
United States	Duluth Clinic Ashland	Ashland	Wisconsin
United States	Emory Saint Joseph's Hospital	Atlanta	Georgia
United States	Emory University Hospital Midtown	Atlanta	Georgia
United States	Emory University Hospital/Winship Cancer Institute	Atlanta	Georgia
United States	Northside Hospital	Atlanta	Georgia
United States	MultiCare Auburn Medical Center	Auburn	Washington
United States	Rush - Copley Medical Center	Aurora	Illinois
United States	Virginia Mason Bainbridge Island Medical Center	Bainbridge Island	Washington
United States	Saint Alphonsus Medical Center-Baker City	Baker City	Oregon
United States	Saint Louis Cancer and Breast Institute-Ballwin	Ballwin	Missouri
United States	Flaget Memorial Hospital	Bardstown	Kentucky
United States	Louisiana Hematology Oncology Associates	Baton Rouge	Louisiana
United States	Louisiana Hematology Oncology Associates LLC	Baton Rouge	Louisiana
United States	LSU Health Baton Rouge-North Clinic	Baton Rouge	Louisiana
United States	Mary Bird Perkins Cancer Center	Baton Rouge	Louisiana
United States	Medical Center of Baton Rouge	Baton Rouge	Louisiana
United States	Ochsner Health Center-Summa	Baton Rouge	Louisiana
United States	Our Lady of the Lake Medical Oncology	Baton Rouge	Louisiana
United States	Our Lady of the Lake Physicians Group - Medical Oncology	Baton Rouge	Louisiana
United States	Woman's Hospital	Baton Rouge	Louisiana
United States	Bronson Battle Creek	Battle Creek	Michigan
United States	McLaren Cancer Institute-Bay City	Bay City	Michigan
United States	UHHS-Chagrin Highlands Medical Center	Beachwood	Ohio
United States	Indu and Raj Soin Medical Center	Beavercreek	Ohio
United States	UM Upper Chesapeake Medical Center	Bel Air	Maryland
United States	Overlake Medical Center	Bellevue	Washington
United States	PeaceHealth Saint Joseph Medical Center	Bellingham	Washington
United States	Sanford Joe Lueken Cancer Center	Bemidji	Minnesota
United States	Saint Charles Health System	Bend	Oregon
United States	Lehigh Valley Hospital - Muhlenberg	Bethlehem	Pennsylvania
United States	Billings Clinic Cancer Center	Billings	Montana
United States	Sanford Bismarck Medical Center	Bismarck	North Dakota
United States	McLaren Cancer Institute-Bloomfield	Bloomfield	Michigan
United States	Illinois CancerCare-Bloomington	Bloomington	Illinois
United States	Prisma Health Cancer Institute - Spartanburg	Boiling Springs	South Carolina
United States	Saint Alphonsus Cancer Care Center-Boise	Boise	Idaho
United States	Saint Luke's Cancer Institute - Boise	Boise	Idaho
United States	Central Care Cancer Center - Bolivar	Bolivar	Missouri
United States	Parkland Health Center-Bonne Terre	Bonne Terre	Missouri
United States	Bozeman Deaconess Hospital	Bozeman	Montana
United States	Essentia Health Saint Joseph's Medical Center	Brainerd	Minnesota
United States	Cox Cancer Center Branson	Branson	Missouri
United States	Harrison HealthPartners Hematology and Oncology-Bremerton	Bremerton	Washington
United States	Harrison Medical Center	Bremerton	Washington
United States	Saint Joseph Mercy Brighton	Brighton	Michigan
United States	Trinity Health IHA Medical Group Hematology Oncology - Brighton	Brighton	Michigan
United States	Henry Ford Cancer Institute-Downriver	Brownstown	Michigan
United States	Saint Joseph Regional Cancer Center	Bryan	Texas
United States	Bryn Mawr Hospital	Bryn Mawr	Pennsylvania
United States	Providence Saint Joseph Medical Center/Disney Family Cancer Center	Burbank	California
United States	Highline Medical Center-Main Campus	Burien	Washington
United States	Lahey Hospital and Medical Center	Burlington	Massachusetts
United States	Fairview Ridges Hospital	Burnsville	Minnesota
United States	Saint Alphonsus Cancer Care Center-Caldwell	Caldwell	Idaho
United States	Aultman Health Foundation	Canton	Ohio
United States	Illinois CancerCare-Canton	Canton	Illinois
United States	Saint Joseph Mercy Canton	Canton	Michigan
United States	Trinity Health IHA Medical Group Hematology Oncology - Canton	Canton	Michigan
United States	Saint Francis Medical Center	Cape Girardeau	Missouri
United States	Southeast Cancer Center	Cape Girardeau	Missouri
United States	Memorial Hospital of Carbondale	Carbondale	Illinois
United States	Caro Cancer Center	Caro	Michigan
United States	SIH Cancer Institute	Carterville	Illinois
United States	Illinois CancerCare-Carthage	Carthage	Illinois
United States	Dayton Physicians LLC-Miami Valley South	Centerville	Ohio
United States	Miami Valley Hospital South	Centerville	Ohio
United States	Centralia Oncology Clinic	Centralia	Illinois
United States	Providence Regional Cancer System-Centralia	Centralia	Washington
United States	Christiana Care Health System-Concord Health Center	Chadds Ford	Pennsylvania
United States	Geauga Hospital	Chardon	Ohio
United States	Medical University of South Carolina	Charleston	South Carolina
United States	Memorial Hospital	Chattanooga	Tennessee
United States	Saint Joseph Mercy Chelsea	Chelsea	Michigan
United States	Trinity Health IHA Medical Group Hematology Oncology - Chelsea Hospital	Chelsea	Michigan
United States	John H Stroger Jr Hospital of Cook County	Chicago	Illinois
United States	University of Illinois	Chicago	Illinois
United States	Enloe Medical Center	Chico	California
United States	Bethesda North Hospital	Cincinnati	Ohio
United States	Good Samaritan Hospital - Cincinnati	Cincinnati	Ohio
United States	Oncology Hematology Care Inc-Kenwood	Cincinnati	Ohio
United States	The Christ Hospital	Cincinnati	Ohio
United States	TriHealth Cancer Institute-Anderson	Cincinnati	Ohio
United States	TriHealth Cancer Institute-Westside	Cincinnati	Ohio
United States	University of Cincinnati Cancer Center-UC Medical Center	Cincinnati	Ohio
United States	Clackamas Radiation Oncology Center	Clackamas	Oregon
United States	Providence Cancer Institute Clackamas Clinic	Clackamas	Oregon
United States	Hematology Oncology Consultants-Clarkston	Clarkston	Michigan
United States	McLaren Cancer Institute-Clarkston	Clarkston	Michigan
United States	Newland Medical Associates-Clarkston	Clarkston	Michigan
United States	Case Western Reserve University	Cleveland	Ohio
United States	Cleveland Clinic Cancer Center/Fairview Hospital	Cleveland	Ohio
United States	Cleveland Clinic Foundation	Cleveland	Ohio
United States	Prisma Health Cancer Institute - Laurens	Clinton	South Carolina
United States	Southeastern Medical Oncology Center-Clinton	Clinton	North Carolina
United States	Henry Ford Macomb Hospital-Clinton Township	Clinton Township	Michigan
United States	Medical Oncology and Hematology Associates-West Des Moines	Clive	Iowa
United States	Mercy Cancer Center-West Lakes	Clive	Iowa
United States	Billings Clinic-Cody	Cody	Wyoming
United States	Kootenai Health - Coeur d'Alene	Coeur d'Alene	Idaho
United States	Coffeyville Regional Medical Center	Coffeyville	Kansas
United States	Baptist Memorial Hospital and Cancer Center-Collierville	Collierville	Tennessee
United States	Penrose-Saint Francis Healthcare	Colorado Springs	Colorado
United States	Rocky Mountain Cancer Centers-Penrose	Colorado Springs	Colorado
United States	Baptist Memorial Hospital and Cancer Center-Golden Triangle	Columbus	Mississippi
United States	John B Amos Cancer Center	Columbus	Georgia
United States	Mercy Hospital	Coon Rapids	Minnesota
United States	Bay Area Hospital	Coos Bay	Oregon
United States	Commonwealth Cancer Center-Corbin	Corbin	Kentucky
United States	Alegent Health Mercy Hospital	Council Bluffs	Iowa
United States	Ochsner Hematology Oncology North Shore - Covington (West Region)	Covington	Louisiana
United States	Greater Regional Medical Center	Creston	Iowa
United States	Siteman Cancer Center at West County Hospital	Creve Coeur	Missouri
United States	UT Southwestern/Simmons Cancer Center-Dallas	Dallas	Texas
United States	Carle at The Riverfront	Danville	Illinois
United States	Dayton Physician LLC-Miami Valley Hospital North	Dayton	Ohio
United States	Good Samaritan Hospital - Dayton	Dayton	Ohio
United States	Miami Valley Hospital	Dayton	Ohio
United States	Miami Valley Hospital North	Dayton	Ohio
United States	Henry Ford Medical Center-Fairlane	Dearborn	Michigan
United States	Cancer Care Specialists of Illinois - Decatur	Decatur	Illinois
United States	Decatur Memorial Hospital	Decatur	Illinois
United States	Kaiser Permanente-Franklin	Denver	Colorado
United States	Porter Adventist Hospital	Denver	Colorado
United States	SCL Health Saint Joseph Hospital	Denver	Colorado
United States	Broadlawns Medical Center	Des Moines	Iowa
United States	Iowa Lutheran Hospital	Des Moines	Iowa
United States	Iowa Methodist Medical Center	Des Moines	Iowa
United States	Medical Oncology and Hematology Associates-Des Moines	Des Moines	Iowa
United States	Mercy Medical Center - Des Moines	Des Moines	Iowa
United States	Mission Cancer and Blood - Laurel	Des Moines	Iowa
United States	Ascension Saint John Hospital	Detroit	Michigan
United States	Henry Ford Hospital	Detroit	Michigan
United States	Wayne State University/Karmanos Cancer Institute	Detroit	Michigan
United States	Bayhealth Hospital Kent Campus	Dover	Delaware
United States	City of Hope Comprehensive Cancer Center	Duarte	California
United States	Epic Care-Dublin	Dublin	California
United States	Essentia Health Cancer Center	Duluth	Minnesota
United States	Essentia Health Saint Mary's Medical Center	Duluth	Minnesota
United States	Miller-Dwan Hospital	Duluth	Minnesota
United States	Mercy Medical Center	Durango	Colorado
United States	Southwest Oncology PC	Durango	Colorado
United States	Prisma Health Cancer Institute - Easley	Easley	South Carolina
United States	Great Lakes Cancer Management Specialists-Doctors Park	East China Township	Michigan
United States	Pocono Medical Center	East Stroudsburg	Pennsylvania
United States	Fairview Southdale Hospital	Edina	Minnesota
United States	Swedish Cancer Institute-Edmonds	Edmonds	Washington
United States	Carle Physician Group-Effingham	Effingham	Illinois
United States	Crossroads Cancer Center	Effingham	Illinois
United States	Mercy Cancer Center-Elyria	Elyria	Ohio
United States	Bay Area Breast Surgeons Inc	Emeryville	California
United States	Epic Care Partners in Cancer Care	Emeryville	California
United States	Walter Knox Memorial Hospital	Emmett	Idaho
United States	Saint Elizabeth Hospital	Enumclaw	Washington
United States	Illinois CancerCare-Eureka	Eureka	Illinois
United States	Providence Regional Cancer Partnership	Everett	Washington
United States	Fairbanks Memorial Hospital	Fairbanks	Alaska
United States	Essentia Health Cancer Center-South University Clinic	Fargo	North Dakota
United States	Sanford Broadway Medical Center	Fargo	North Dakota
United States	Sanford Roger Maris Cancer Center	Fargo	North Dakota
United States	Saint Francis Hospital	Federal Way	Washington
United States	Virginia Mason Federal Way Medical Center	Federal Way	Washington
United States	Lake Region Healthcare Corporation-Cancer Care	Fergus Falls	Minnesota
United States	Armes Family Cancer Center	Findlay	Ohio
United States	Blanchard Valley Hospital	Findlay	Ohio
United States	Orion Cancer Care	Findlay	Ohio
United States	Augusta Health Center for Cancer and Blood Disorders	Fishersville	Virginia
United States	Genesee Cancer and Blood Disease Treatment Center	Flint	Michigan
United States	Genesee Hematology Oncology PC	Flint	Michigan
United States	Genesys Hurley Cancer Institute	Flint	Michigan
United States	Hurley Medical Center	Flint	Michigan
United States	McLaren Cancer Institute-Flint	Flint	Michigan
United States	Singh and Arora Hematology Oncology PC	Flint	Michigan
United States	Broward Health Medical Center	Fort Lauderdale	Florida
United States	UT Southwestern/Simmons Cancer Center-Fort Worth	Fort Worth	Texas
United States	Beebe South Coastal Health Campus	Frankford	Delaware
United States	Atrium Medical Center-Middletown Regional Hospital	Franklin	Ohio
United States	Dayton Physicians LLC-Atrium	Franklin	Ohio
United States	Kaiser Permanente-Fremont	Fremont	California
United States	Fresno Cancer Center	Fresno	California
United States	Kaiser Permanente-Fresno	Fresno	California
United States	Unity Hospital	Fridley	Minnesota
United States	Saint Luke's Cancer Institute - Fruitland	Fruitland	Idaho
United States	Northeast Georgia Medical Center-Gainesville	Gainesville	Georgia
United States	Illinois CancerCare-Galesburg	Galesburg	Illinois
United States	Western Illinois Cancer Treatment Center	Galesburg	Illinois
United States	Central Care Cancer Center - Garden City	Garden City	Kansas
United States	Saint Catherine Hospital	Garden City	Kansas
United States	MultiCare Gig Harbor Medical Park	Gig Harbor	Washington
United States	Tacoma/Valley Radiation Oncology Centers-Gig Harbor	Gig Harbor	Washington
United States	Mountain Blue Cancer Care Center	Golden	Colorado
United States	Southeastern Medical Oncology Center-Goldsboro	Goldsboro	North Carolina
United States	Wayne Memorial Hospital	Goldsboro	North Carolina
United States	CHI Health Saint Francis	Grand Island	Nebraska
United States	Spectrum Health at Butterworth Campus	Grand Rapids	Michigan
United States	Trinity Health Grand Rapids Hospital	Grand Rapids	Michigan
United States	Central Care Cancer Center - Great Bend	Great Bend	Kansas
United States	Benefis Healthcare- Sletten Cancer Institute	Great Falls	Montana
United States	Great Falls Clinic	Great Falls	Montana
United States	Bellin Memorial Hospital	Green Bay	Wisconsin
United States	Dayton Physicians LLC-Wayne	Greenville	Ohio
United States	Prisma Health Cancer Institute - Butternut	Greenville	South Carolina
United States	Prisma Health Cancer Institute - Eastside	Greenville	South Carolina
United States	Prisma Health Cancer Institute - Faris	Greenville	South Carolina
United States	Prisma Health Greenville Memorial Hospital	Greenville	South Carolina
United States	Wayne Hospital	Greenville	Ohio
United States	Self Regional Healthcare	Greenwood	South Carolina
United States	Prisma Health Cancer Institute - Greer	Greer	South Carolina
United States	Baptist Cancer Center-Grenada	Grenada	Mississippi
United States	Academic Hematology Oncology Specialists	Grosse Pointe Woods	Michigan
United States	Great Lakes Cancer Management Specialists-Van Elslander Cancer Center	Grosse Pointe Woods	Michigan
United States	Michigan Breast Specialists-Grosse Pointe Woods	Grosse Pointe Woods	Michigan
United States	HaysMed University of Kansas Health System	Hays	Kansas
United States	Lehigh Valley Hospital-Hazleton	Hazleton	Pennsylvania
United States	Saint Peter's Community Hospital	Helena	Montana
United States	Penn State Milton S Hershey Medical Center	Hershey	Pennsylvania
United States	Essentia Health Hibbing Clinic	Hibbing	Minnesota
United States	Pulmonary Medicine Center of Chattanooga-Hixson	Hixson	Tennessee
United States	Hawaii Cancer Care Inc - Waterfront Plaza	Honolulu	Hawaii
United States	Hawaii Cancer Care Inc-Liliha	Honolulu	Hawaii
United States	Island Urology	Honolulu	Hawaii
United States	Kaiser Permanente Moanalua Medical Center	Honolulu	Hawaii
United States	Kapiolani Medical Center for Women and Children	Honolulu	Hawaii
United States	Kuakini Medical Center	Honolulu	Hawaii
United States	Queen's Cancer Cenrer - POB I	Honolulu	Hawaii
United States	Queen's Cancer Center - Kuakini	Honolulu	Hawaii
United States	Queen's Medical Center	Honolulu	Hawaii
United States	Straub Clinic and Hospital	Honolulu	Hawaii
United States	The Cancer Center of Hawaii-Liliha	Honolulu	Hawaii
United States	University of Hawaii Cancer Center	Honolulu	Hawaii
United States	CHI Saint Vincent Cancer Center Hot Springs	Hot Springs	Arkansas
United States	Centerpoint Medical Center LLC	Independence	Missouri
United States	Cleveland Clinic Cancer Center Independence	Independence	Ohio
United States	Franciscan Health Indianapolis	Indianapolis	Indiana
United States	Swedish Cancer Institute-Issaquah	Issaquah	Washington
United States	Allegiance Health	Jackson	Michigan
United States	University of Mississippi Medical Center	Jackson	Mississippi
United States	Onslow Memorial Hospital	Jacksonville	North Carolina
United States	Southeastern Medical Oncology Center-Jacksonville	Jacksonville	North Carolina
United States	Mercyhealth Hospital and Cancer Center - Janesville	Janesville	Wisconsin
United States	Capital Region Southwest Campus	Jefferson City	Missouri
United States	Freeman Health System	Joplin	Missouri
United States	Mercy Hospital Joplin	Joplin	Missouri
United States	Borgess Medical Center	Kalamazoo	Michigan
United States	Bronson Methodist Hospital	Kalamazoo	Michigan
United States	West Michigan Cancer Center	Kalamazoo	Michigan
United States	Kalispell Regional Medical Center	Kalispell	Montana
United States	Research Medical Center	Kansas City	Missouri
United States	Saint Luke's Hospital of Kansas City	Kansas City	Missouri
United States	Truman Medical Centers	Kansas City	Missouri
United States	University of Kansas Cancer Center	Kansas City	Kansas
United States	University of Kansas Cancer Center - North	Kansas City	Missouri
United States	University of Kansas Cancer Center-West	Kansas City	Kansas
United States	CHI Health Good Samaritan	Kearney	Nebraska
United States	Heartland Hematology and Oncology	Kearney	Nebraska
United States	Kadlec Clinic Hematology and Oncology	Kennewick	Washington
United States	Northwest Cancer Clinic	Kennewick	Washington
United States	First Dayton Cancer Care	Kettering	Ohio
United States	Greater Dayton Cancer Center	Kettering	Ohio
United States	Kettering Medical Center	Kettering	Ohio
United States	Illinois CancerCare-Kewanee Clinic	Kewanee	Illinois
United States	Providence Regional Cancer System-Lacey	Lacey	Washington
United States	Franciscan Saint Elizabeth Health - Lafayette East	Lafayette	Indiana
United States	Good Samaritan Medical Center	Lafayette	Colorado
United States	Kaiser Permanente-Rock Creek	Lafayette	Colorado
United States	Rocky Mountain Cancer Centers-Lakewood	Lakewood	Colorado
United States	Saint Anthony Hospital	Lakewood	Colorado
United States	Saint Clare Hospital	Lakewood	Washington
United States	Karmanos Cancer Institute at McLaren Greater Lansing	Lansing	Michigan
United States	Sparrow Hospital	Lansing	Michigan
United States	McLaren Cancer Institute-Lapeer Region	Lapeer	Michigan
United States	Saint Luke's East - Lee's Summit	Lee's Summit	Missouri
United States	University of Kansas Cancer Center - Lee's Summit	Lee's Summit	Missouri
United States	Kansas Institute of Medicine Cancer and Blood Center	Lenexa	Kansas
United States	Minimally Invasive Surgery Hospital	Lenexa	Kansas
United States	Beebe Medical Center	Lewes	Delaware
United States	Saint Joseph Hospital East	Lexington	Kentucky
United States	Saint Joseph Radiation Oncology Resource Center	Lexington	Kentucky
United States	Wilcox Memorial Hospital and Kauai Medical Clinic	Lihue	Hawaii
United States	Saint Elizabeth Regional Medical Center	Lincoln	Nebraska
United States	Littleton Adventist Hospital	Littleton	Colorado
United States	Hope Cancer Clinic	Livonia	Michigan
United States	Trinity Health Saint Mary Mercy Livonia Hospital	Livonia	Michigan
United States	Saint Joseph London	London	Kentucky
United States	Kaiser Permanente-Lone Tree	Lone Tree	Colorado
United States	Longmont United Hospital	Longmont	Colorado
United States	Rocky Mountain Cancer Centers-Longmont	Longmont	Colorado
United States	PeaceHealth Saint John Medical Center	Longview	Washington
United States	USC / Norris Comprehensive Cancer Center	Los Angeles	California
United States	Jewish Hospital	Louisville	Kentucky
United States	Saints Mary and Elizabeth Hospital	Louisville	Kentucky
United States	UofL Health Medical Center Northeast	Louisville	Kentucky
United States	UMC Cancer Center / UMC Health System	Lubbock	Texas
United States	Virginia Mason Lynnwood Medical Center	Lynnwood	Washington
United States	Great Lakes Cancer Management Specialists-Macomb Medical Campus	Macomb	Michigan
United States	Illinois CancerCare-Macomb	Macomb	Illinois
United States	Michigan Breast Specialists-Macomb Township	Macomb	Michigan
United States	Cleveland Clinic Cancer Center Mansfield	Mansfield	Ohio
United States	Fairview Clinics and Surgery Center Maple Grove	Maple Grove	Minnesota
United States	Minnesota Oncology Hematology PA-Maplewood	Maplewood	Minnesota
United States	Saint John's Hospital - Healtheast	Maplewood	Minnesota
United States	Saint Mary's Oncology/Hematology Associates of Marlette	Marlette	Michigan
United States	Contra Costa Regional Medical Center	Martinez	California
United States	WVUH-Berkely Medical Center	Martinsburg	West Virginia
United States	Carle Physician Group-Mattoon/Charleston	Mattoon	Illinois
United States	Hillcrest Hospital Cancer Center	Mayfield Heights	Ohio
United States	Loyola University Medical Center	Maywood	Illinois
United States	Riddle Memorial Hospital	Media	Pennsylvania
United States	Baptist Memorial Hospital and Cancer Center-Memphis	Memphis	Tennessee
United States	Baptist Memorial Hospital for Women	Memphis	Tennessee
United States	UH Seidman Cancer Center at Lake Health Mentor Campus	Mentor	Ohio
United States	Idaho Urologic Institute-Meridian	Meridian	Idaho
United States	Saint Luke's Cancer Institute - Meridian	Meridian	Idaho
United States	Mount Sinai Medical Center	Miami Beach	Florida
United States	UH Seidman Cancer Center at Southwest General Hospital	Middleburg Heights	Ohio
United States	Middlesex Hospital	Middletown	Connecticut
United States	Abbott-Northwestern Hospital	Minneapolis	Minnesota
United States	Health Partners Inc	Minneapolis	Minnesota
United States	Hennepin County Medical Center	Minneapolis	Minnesota
United States	City of Hope Mission Hills	Mission Hills	California
United States	Community Medical Hospital	Missoula	Montana
United States	Saint Patrick Hospital - Community Hospital	Missoula	Montana
United States	Kaiser Permanente-Modesto	Modesto	California
United States	Monticello Cancer Center	Monticello	Minnesota
United States	Franciscan Health Mooresville	Mooresville	Indiana
United States	West Virginia University Healthcare	Morgantown	West Virginia
United States	Morristown Medical Center	Morristown	New Jersey
United States	McLaren Cancer Institute-Macomb	Mount Clemens	Michigan
United States	Good Samaritan Regional Health Center	Mount Vernon	Illinois
United States	Trinity Health Muskegon Hospital	Muskegon	Michigan
United States	Saint Alphonsus Cancer Care Center-Nampa	Nampa	Idaho
United States	Saint Luke's Cancer Institute - Nampa	Nampa	Idaho
United States	Baptist Memorial Hospital and Cancer Center-Union County	New Albany	Mississippi
United States	Ochsner Medical Center Jefferson	New Orleans	Louisiana
United States	Cancer Center of Western Wisconsin	New Richmond	Wisconsin
United States	New Ulm Medical Center	New Ulm	Minnesota
United States	NYP/Columbia University Medical Center/Herbert Irving Comprehensive Cancer Center	New York	New York
United States	Christiana Care Health System-Christiana Hospital	Newark	Delaware
United States	Delaware Clinical and Laboratory Physicians PA	Newark	Delaware
United States	Helen F Graham Cancer Center	Newark	Delaware
United States	Medical Oncology Hematology Consultants PA	Newark	Delaware
United States	Providence Newberg Medical Center	Newberg	Oregon
United States	City of Hope Newport Beach	Newport Beach	California
United States	Newton Medical Center	Newton	New Jersey
United States	Lakeland Hospital Niles	Niles	Michigan
United States	University of Kansas Cancer Center at North Kansas City Hospital	North Kansas City	Missouri
United States	Ascension Providence Hospitals - Novi	Novi	Michigan
United States	Henry Ford Medical Center-Columbus	Novi	Michigan
United States	Nyack Hospital	Nyack	New York
United States	Cancer Care Center of O'Fallon	O'Fallon	Illinois
United States	Alta Bates Summit Medical Center - Summit Campus	Oakland	California
United States	Bay Area Tumor Institute	Oakland	California
United States	Kaiser Permanente Oakland-Broadway	Oakland	California
United States	Kaiser Permanente-Oakland	Oakland	California
United States	Mercy Hospital Oklahoma City	Oklahoma City	Oklahoma
United States	University of Oklahoma Health Sciences Center	Oklahoma City	Oklahoma
United States	Olathe Health Cancer Center	Olathe	Kansas
United States	Alegent Health Bergan Mercy Medical Center	Omaha	Nebraska
United States	Alegent Health Immanuel Medical Center	Omaha	Nebraska
United States	Alegent Health Lakeside Hospital	Omaha	Nebraska
United States	Creighton University Medical Center	Omaha	Nebraska
United States	Hematology and Oncology Consultants PC	Omaha	Nebraska
United States	Saint Alphonsus Medical Center-Ontario	Ontario	Oregon
United States	Memorial GYN Plus	Ooltewah	Tennessee
United States	Illinois CancerCare-Ottawa Clinic	Ottawa	Illinois
United States	Menorah Medical Center	Overland Park	Kansas
United States	Saint Luke's South Hospital	Overland Park	Kansas
United States	University of Kansas Cancer Center-Overland Park	Overland Park	Kansas
United States	University of Kansas Hospital-Indian Creek Campus	Overland Park	Kansas
United States	Baptist Memorial Hospital and Cancer Center-Oxford	Oxford	Mississippi
United States	Paoli Memorial Hospital	Paoli	Pennsylvania
United States	Midlands Community Hospital	Papillion	Nebraska
United States	Parker Adventist Hospital	Parker	Colorado
United States	Rocky Mountain Cancer Centers-Parker	Parker	Colorado
United States	Camden Clark Medical Center	Parkersburg	West Virginia
United States	Singing River Hospital	Pascagoula	Mississippi
United States	Illinois CancerCare-Pekin	Pekin	Illinois
United States	OSF Saint Francis Radiation Oncology at Pekin Cancer Treatment Center	Pekin	Illinois
United States	Illinois CancerCare-Peoria	Peoria	Illinois
United States	Methodist Medical Center of Illinois	Peoria	Illinois
United States	OSF Saint Francis Medical Center	Peoria	Illinois
United States	OSF Saint Francis Radiation Oncology at Peoria Cancer Center	Peoria	Illinois
United States	Illinois CancerCare-Peru	Peru	Illinois
United States	Valley Radiation Oncology	Peru	Illinois
United States	Phoenixville Hospital	Phoenixville	Pennsylvania
United States	Ascension Via Christi - Pittsburg	Pittsburg	Kansas
United States	21st Century Oncology-Pontiac	Pontiac	Michigan
United States	Hope Cancer Center	Pontiac	Michigan
United States	Newland Medical Associates-Pontiac	Pontiac	Michigan
United States	Saint Joseph Mercy Oakland	Pontiac	Michigan
United States	Jefferson Healthcare	Port Townsend	Washington
United States	Kaiser Permanente Northwest	Portland	Oregon
United States	Oregon Health and Science University	Portland	Oregon
United States	Providence Portland Medical Center	Portland	Oregon
United States	Providence Saint Vincent Medical Center	Portland	Oregon
United States	Kootenai Clinic Cancer Services - Post Falls	Post Falls	Idaho
United States	Harrison HealthPartners Hematology and Oncology-Poulsbo	Poulsbo	Washington
United States	Peninsula Cancer Center	Poulsbo	Washington
United States	Illinois CancerCare-Princeton	Princeton	Illinois
United States	Rocky Mountain Cancer Centers - Pueblo	Pueblo	Colorado
United States	Saint Mary Corwin Medical Center	Pueblo	Colorado
United States	MultiCare Good Samaritan Hospital	Puyallup	Washington
United States	Tacoma/Valley Radiation Oncology Centers-Puyallup	Puyallup	Washington
United States	Kaiser Permanente-Rancho Cordova Cancer Center	Rancho Cordova	California
United States	Saint Charles Health System-Redmond	Redmond	Oregon
United States	Kaiser Permanente-Redwood City	Redwood City	California
United States	Spectrum Health Reed City Hospital	Reed City	Michigan
United States	Beebe Health Campus	Rehoboth Beach	Delaware
United States	Valley Medical Center	Renton	Washington
United States	UT Southwestern Clinical Center at Richardson/Plano	Richardson	Texas
United States	Kaiser Permanente-Richmond	Richmond	California
United States	Reid Health	Richmond	Indiana
United States	North Memorial Medical Health Center	Robbinsdale	Minnesota
United States	Great Lakes Cancer Management Specialists-Rochester Hills	Rochester Hills	Michigan
United States	Rohnert Park Cancer Center	Rohnert Park	California
United States	Delbert Day Cancer Institute at PCRMC	Rolla	Missouri
United States	Mercy Clinic-Rolla-Cancer and Hematology	Rolla	Missouri
United States	Kaiser Permanente-Roseville	Roseville	California
United States	The Permanente Medical Group-Roseville Radiation Oncology	Roseville	California
United States	Kaiser Permanente - Sacramento	Sacramento	California
United States	Kaiser Permanente-South Sacramento	Sacramento	California
United States	South Sacramento Cancer Center	Sacramento	California
United States	University of California Davis Comprehensive Cancer Center	Sacramento	California
United States	Ascension Saint Mary's Hospital	Saginaw	Michigan
United States	Oncology Hematology Associates of Saginaw Valley PC	Saginaw	Michigan
United States	Heartland Regional Medical Center	Saint Joseph	Missouri
United States	Lakeland Medical Center Saint Joseph	Saint Joseph	Michigan
United States	Marie Yeager Cancer Center	Saint Joseph	Michigan
United States	Mercy Hospital Saint Louis	Saint Louis	Missouri
United States	Mercy Hospital South	Saint Louis	Missouri
United States	Missouri Baptist Medical Center	Saint Louis	Missouri
United States	Saint Louis Cancer and Breast Institute-South City	Saint Louis	Missouri
United States	Siteman Cancer Center at Christian Hospital	Saint Louis	Missouri
United States	Siteman Cancer Center-South County	Saint Louis	Missouri
United States	Washington University School of Medicine	Saint Louis	Missouri
United States	Park Nicollet Clinic - Saint Louis Park	Saint Louis Park	Minnesota
United States	Regions Hospital	Saint Paul	Minnesota
United States	United Hospital	Saint Paul	Minnesota
United States	Siteman Cancer Center at Saint Peters Hospital	Saint Peters	Missouri
United States	Sainte Genevieve County Memorial Hospital	Sainte Genevieve	Missouri
United States	Salina Regional Health Center	Salina	Kansas
United States	University Hospital	San Antonio	Texas
United States	University of Texas Health Science Center at San Antonio	San Antonio	Texas
United States	Kaiser Permanente-San Francisco	San Francisco	California
United States	Kaiser Permanente-Santa Teresa-San Jose	San Jose	California
United States	Kaiser Permanente San Leandro	San Leandro	California
United States	Kaiser Permanente-San Rafael	San Rafael	California
United States	Kaiser San Rafael-Gallinas	San Rafael	California
United States	Kootenai Cancer Clinic	Sandpoint	Idaho
United States	North Coast Cancer Care	Sandusky	Ohio
United States	Kaiser Permanente Medical Center - Santa Clara	Santa Clara	California
United States	Kaiser Permanente-Santa Rosa	Santa Rosa	California
United States	Lewis Cancer and Research Pavilion at Saint Joseph's/Candler	Savannah	Georgia
United States	Low Country Cancer Care	Savannah	Georgia
United States	Summit Cancer Care-Candler	Savannah	Georgia
United States	Guthrie Medical Group PC-Robert Packer Hospital	Sayre	Pennsylvania
United States	TidalHealth Nanticoke / Allen Cancer Center	Seaford	Delaware
United States	FHCC South Lake Union	Seattle	Washington
United States	Kaiser Permanente Washington	Seattle	Washington
United States	Pacific Gynecology Specialists	Seattle	Washington
United States	Swedish Medical Center-Ballard Campus	Seattle	Washington
United States	Swedish Medical Center-Cherry Hill	Seattle	Washington
United States	Swedish Medical Center-First Hill	Seattle	Washington
United States	University of Washington Medical Center - Montlake	Seattle	Washington
United States	Virginia Mason Medical Center	Seattle	Washington
United States	PeaceHealth United General Medical Center	Sedro-Woolley	Washington
United States	Prisma Health Cancer Institute - Seneca	Seneca	South Carolina
United States	Saint Francis Regional Medical Center	Shakopee	Minnesota
United States	Providence Regional Cancer System-Shelton	Shelton	Washington
United States	Jewish Hospital Medical Center South	Shepherdsville	Kentucky
United States	Welch Cancer Center	Sheridan	Wyoming
United States	LSU Health Sciences Center at Shreveport	Shreveport	Louisiana
United States	Sanford Cancer Center Oncology Clinic	Sioux Falls	South Dakota
United States	Sanford USD Medical Center - Sioux Falls	Sioux Falls	South Dakota
United States	Robert Wood Johnson University Hospital Somerset	Somerville	New Jersey
United States	City of Hope South Pasadena	South Pasadena	California
United States	Kaiser Permanente Cancer Treatment Center	South San Francisco	California
United States	Kaiser Permanente-South San Francisco	South San Francisco	California
United States	Ascension Providence Hospitals - Southfield	Southfield	Michigan
United States	Baptist Memorial Hospital and Cancer Center-Desoto	Southhaven	Mississippi
United States	MultiCare Deaconess Cancer and Blood Specialty Center - Downtown	Spokane	Washington
United States	MultiCare Deaconess Cancer and Blood Specialty Center - North	Spokane	Washington
United States	MultiCare Deaconess Cancer and Blood Specialty Center - Valley	Spokane Valley	Washington
United States	CoxHealth South Hospital	Springfield	Missouri
United States	Memorial Medical Center	Springfield	Illinois
United States	Mercy Hospital Springfield	Springfield	Missouri
United States	Southern Illinois University School of Medicine	Springfield	Illinois
United States	Springfield Clinic	Springfield	Illinois
United States	Springfield Regional Cancer Center	Springfield	Ohio
United States	Springfield Regional Medical Center	Springfield	Ohio
United States	Stamford Hospital/Bennett Cancer Center	Stamford	Connecticut
United States	Bhadresh Nayak MD PC-Sterling Heights	Sterling Heights	Michigan
United States	Lakeview Hospital	Stillwater	Minnesota
United States	Kaiser Permanente-Stockton	Stockton	California
United States	Stony Brook University Medical Center	Stony Brook	New York
United States	Cleveland Clinic Cancer Center Strongsville	Strongsville	Ohio
United States	Missouri Baptist Sullivan Hospital	Sullivan	Missouri
United States	Overlook Hospital	Summit	New Jersey
United States	Missouri Baptist Outpatient Center-Sunset Hills	Sunset Hills	Missouri
United States	Southwest Illinois Health Services LLP	Swansea	Illinois
United States	Franciscan Research Center-Northwest Medical Plaza	Tacoma	Washington
United States	MultiCare Tacoma General Hospital	Tacoma	Washington
United States	Northwest Medical Specialties PLLC	Tacoma	Washington
United States	Tacoma/Valley Radiation Oncology Centers-Jackson Hall	Tacoma	Washington
United States	Tacoma/Valley Radiation Oncology Centers-Saint Joe's	Tacoma	Washington
United States	Moffitt Cancer Center	Tampa	Florida
United States	Ascension Saint Joseph Hospital	Tawas City	Michigan
United States	Holy Name Hospital	Teaneck	New Jersey
United States	Union Hospital	Terre Haute	Indiana
United States	Lewis Hall Singletary Oncology Center	Thomasville	Georgia
United States	Rocky Mountain Cancer Centers-Thornton	Thornton	Colorado
United States	University of Kansas Health System Saint Francis Campus	Topeka	Kansas
United States	City of Hope South Bay	Torrance	California
United States	Munson Medical Center	Traverse City	Michigan
United States	Dayton Physicians LLC - Troy	Troy	Ohio
United States	Upper Valley Medical Center	Troy	Ohio
United States	Oklahoma Cancer Specialists and Research Institute-Tulsa	Tulsa	Oklahoma
United States	Saint Luke's Cancer Institute - Twin Falls	Twin Falls	Idaho
United States	City of Hope Upland	Upland	California
United States	Carle Cancer Center	Urbana	Illinois
United States	The Carle Foundation Hospital	Urbana	Illinois
United States	Kaiser Permanente Medical Center-Vacaville	Vacaville	California
United States	Kaiser Permanente-Vallejo	Vallejo	California
United States	PeaceHealth Southwest Medical Center	Vancouver	Washington
United States	Essentia Health Virginia Clinic	Virginia	Minnesota
United States	Ridgeview Medical Center	Waconia	Minnesota
United States	University Hospitals Sharon Health Center	Wadsworth	Ohio
United States	Providence Saint Mary Regional Cancer Center	Walla Walla	Washington
United States	Kaiser Permanente-Walnut Creek	Walnut Creek	California
United States	Advanced Breast Care Center PLLC	Warren	Michigan
United States	Great Lakes Cancer Management Specialists-Macomb Professional Building	Warren	Michigan
United States	Macomb Hematology Oncology PC	Warren	Michigan
United States	Michigan Breast Specialists-Warren	Warren	Michigan
United States	Saint John Macomb-Oakland Hospital	Warren	Michigan
United States	South Pointe Hospital	Warrensville Heights	Ohio
United States	Mercy Hospital Washington	Washington	Missouri
United States	Henry Ford West Bloomfield Hospital	West Bloomfield	Michigan
United States	Saint Mary's Oncology/Hematology Associates of West Branch	West Branch	Michigan
United States	University of Cincinnati Cancer Center-West Chester	West Chester	Ohio
United States	Mercy Medical Center-West Lakes	West Des Moines	Iowa
United States	Methodist West Hospital	West Des Moines	Iowa
United States	UH Seidman Cancer Center at Saint John Medical Center	Westlake	Ohio
United States	UHHS-Westlake Medical Center	Westlake	Ohio
United States	Cleveland Clinic-Weston	Weston	Florida
United States	University of Kansas Hospital-Westwood Cancer Center	Westwood	Kansas
United States	Wheeling Hospital/Schiffler Cancer Center	Wheeling	West Virginia
United States	Dickstein Cancer Treatment Center	White Plains	New York
United States	Rice Memorial Hospital	Willmar	Minnesota
United States	Christiana Care Health System-Wilmington Hospital	Wilmington	Delaware
United States	Winchester Hospital	Winchester	Massachusetts
United States	Minnesota Oncology Hematology PA-Woodbury	Woodbury	Minnesota
United States	Cleveland Clinic Wooster Family Health and Surgery Center	Wooster	Ohio
United States	Lankenau Medical Center	Wynnewood	Pennsylvania
United States	Fairview Lakes Medical Center	Wyoming	Minnesota
United States	University of Michigan Health - West	Wyoming	Michigan
United States	North Star Lodge Cancer Center at Yakima Valley Memorial Hospital	Yakima	Washington
United States	Providence Regional Cancer System-Yelm	Yelm	Washington
United States	Rush-Copley Healthcare Center	Yorkville	Illinois
United States	Huron Gastroenterology PC	Ypsilanti	Michigan
United States	Trinity Health IHA Medical Group Hematology Oncology Ann Arbor Campus	Ypsilanti	Michigan

Sponsors (2)

Lead Sponsor	Collaborator
SWOG Cancer Research Network	National Cancer Institute (NCI)

Countries where clinical trial is conducted

United States,  Korea, Republic of,  Puerto Rico,  Saudi Arabia, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Time to the first identification of cardiac dysfunction	Real-time, blinded, central echocardiography (ECHO) read as a decrease in the left ventricular ejection fraction (LVEF) of >= 10 percentage points from baseline to a value of < 50% OR decrease of LVEF by >= 5 percentage points from baseline to LVEF < 50% in those baselines having a baseline LVEF of 50-54%. The distributions of time to cardiac dysfunction will be described using cumulative incidence estimates, with the statistical significance of treatment arm differences assessed by Cox and Fine-Gray regression models with adjustment for stratification factors. Gray's test will also be applied	Up to 108 weeks
Secondary	Incidence of adverse events associated with beta blocker treatment	Adverse events associated with beta blocker treatment will be assessed.	Up to 108 weeks
Secondary	Rate of first interruption of trastuzumab	The distributions of time to interruption of trastuzumab-based therapy will be described using cumulative incidence estimates, with the statistical significance of treatment arm differences assessed by Cox and Fine-Gray regression models with adjustment for stratification factors. Gray?s test will also be applied to the primary endpoint to assess whether the results are sensitive to different model assumptions.	Up to 108 weeks
Secondary	Rate of death	Will compare rate of death from competing causes between treatment arms via Cox regression to evaluate whether those rates impact the primary analysis comparison.	Up to 108 weeks
Secondary	Time to first occurrence of cardiac event	any of the following treating physician documented events requiring hospitalization or medical treatment, and subsequent temporary or permanent discontinuation of trastuzumab- based HER-2 targeted therapy: arrhythmia, unstable angina, non-ST segment elevated myocardial infarction, myocardial infarction, or congestive heart failure.	Up to 108 weeks
Secondary	Drug adherence	Patients on the active arm will be asked to record study drug consumption on a monthly intake calendar. Amount of study drug taken among patients randomized to the active arm and study drug adoption among patients randomized to the no intervention arm (i.e., contamination) will be recorded by study site staff on a case report form at each follow-up visit to assess the sensitivity of the primary treatment effect to observed conditions.	Up to 108 weeks