NCT01009918

Brief Summary

RATIONALE: Lisinopril or Coreg CR®, may help reduce side effects caused by trastuzumab. It is not yet known whether lisinopril or Coreg CR® are more effective than a placebo in reducing side effects caused by trastuzumab. PURPOSE: This phase II trial is studying lisinopril and Coreg CR® to see how well they work compared with a placebo in reducing side effects in patients with HER2-positive breast cancer receiving trastuzumab.

Trial Health

87
On Track

Trial Health Score

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

Enrollment
468

participants targeted

Target at P75+ for phase_2 breast-cancer

Timeline
Completed

Started Mar 2010

Longer than P75 for phase_2 breast-cancer

Geographic Reach
1 country

174 active sites

Status
completed

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

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

November 6, 2009

Completed
3 days until next milestone

First Posted

Study publicly available on registry

November 9, 2009

Completed
4 months until next milestone

Study Start

First participant enrolled

March 1, 2010

Completed
7.4 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

August 1, 2017

Completed
1.3 years until next milestone

Study Completion

Last participant's last visit for all outcomes

November 1, 2018

Completed
2.4 years until next milestone

Results Posted

Study results publicly available

March 30, 2021

Completed
Last Updated

March 30, 2021

Status Verified

April 1, 2019

Enrollment Period

7.4 years

First QC Date

November 6, 2009

Results QC Date

January 12, 2021

Last Update Submit

March 29, 2021

Conditions

Keywords

cardiac toxicityHER2-positive breast cancerrecurrent breast cancerstage IA breast cancerstage IB breast cancerstage II breast cancerstage IIIA breast cancerstage IIIB breast cancerstage IIIC breast cancermale breast cancer

Outcome Measures

Primary Outcomes (2)

  • Number of Participants With Trastuzumab-Induced Cardiotoxicity After 52 Weeks of Treatment

    Reduction in incidence of trastuzumab-induced cardiotoxicity after 52 weeks of treatment as measured by preservation of Left Ventricular Ejection Fraction (LVEF). Number of Patients who experienced a cardiotoxicity.

    2 years

  • Number of Participants With LVEF Decrease to <50%

    Number of Participants with Left Ventricular Ejection Fraction (LVEF) drop to \<50%

    2 years

Secondary Outcomes (3)

  • Number of Patients With Trastuzumab Course Interruption

    2 years

  • Quality-of-life Changes Between Baseline and 52-weeks

    52 weeks

  • Number of Participants With Cardiotoxicity-free Survival at 750 Days From Baseline

    2 years

Study Arms (3)

Arm I lisinopril

EXPERIMENTAL

Patients receive oral lisinopril once daily.

Drug: lisinopril

Arm II Coreg CR®

EXPERIMENTAL

Patients receive oral Coreg CR® once daily.

Drug: Coreg CR®

Arm III placebo

PLACEBO COMPARATOR

Patients receive oral placebo once daily.

Other: placebo

Interventions

Given orally

Also known as: carvedilol phosphate extended-release
Arm II Coreg CR®

Given orally

Also known as: Registered Trade names: Prinivil, Tensopril, Zestril, Hipril
Arm I lisinopril
placeboOTHER

Given orally

Arm III placebo

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • Males and Females ≥ 18 years old diagnosed with HER2 positive breast cancer
  • Scheduled to receive neoadjuvant or adjuvant trastuzumab (Herceptin®) therapy (anthracycline-containing regimens are permitted). Patients receiving Herceptin® with their chemotherapy are permitted for eligibility work-up. Taxanes are permitted. Trastuzumab (Herceptin®) therapy may be given with or after primary chemotherapy. Pertuzumab may be used in conjunction with trastuzumab.
  • Left Ventricular Ejection Fraction (LVEF) ≥ 50% by MUGA scan or echocardiogram
  • Adequate renal function for administration of trastuzumab-containing chemotherapy regimen.
  • Sitting systolic blood pressure of \> 90 mm Hg
  • Pulse ≥ 60 beats/minute
  • Not pregnant or breastfeeding
  • Female patients of childbearing potential, who are sexually active, must have a negative pregnancy test before starting the study
  • Both men and women must be willing to use effective contraception during the study. Teratogenicity is documented for both active study agents
  • Able to swallow capsules

You may not qualify if:

  • Patients with metastatic disease
  • Prior treatment with trastuzumab or anthracyclines prior to this chemotherapy regimen
  • Current treatment with angiotensin converting enzyme (ACE) inhibitors, angiotensin receptor blockers (ARBs), such as losartan, β-blockers or digoxin
  • Known cardiac history: heart failure, myocardial infarction, radiation-induced cardiac dysfunction
  • Known allergy to either ACE inhibitors or β-blockers
  • History of bronchial asthma or related bronchospastic conditions
  • Hereditary or idiopathic angioedema
  • History of severe hypersensitivity reactions to drugs or other causes, i.e. bee stings
  • This protocol does not exclude patients who are participating on other investigational studies. Refer to the local IRB guidelines.

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (174)

Todd Cancer Institute at Long Beach Memorial Medical Center

Long Beach, California, 90806, United States

Location

Olive View - UCLA Medical Center Foundation

Sylmar, California, 91342, United States

Location

Aurora Presbyterian Hospital

Aurora, Colorado, 80012, United States

Location

Boulder Community Hospital

Boulder, Colorado, 80301-9019, United States

Location

Penrose Cancer Center at Penrose Hospital

Colorado Springs, Colorado, 80933, United States

Location

St. Anthony Central Hospital

Denver, Colorado, 80204, United States

Location

Porter Adventist Hospital

Denver, Colorado, 80210, United States

Location

Presbyterian - St. Luke's Medical Center

Denver, Colorado, 80218, United States

Location

St. Joseph Hospital

Denver, Colorado, 80218, United States

Location

Rose Medical Center

Denver, Colorado, 80220, United States

Location

CCOP - Colorado Cancer Research Program

Denver, Colorado, 80222, United States

Location

Swedish Medical Center

Englewood, Colorado, 80110, United States

Location

North Colorado Medical Center

Greeley, Colorado, 80631, United States

Location

Littleton Adventist Hospital

Littleton, Colorado, 80122, United States

Location

Sky Ridge Medical Center

Lone Tree, Colorado, 80124, United States

Location

Hope Cancer Care Center at Longmont United Hospital

Longmont, Colorado, 80501, United States

Location

McKee Medical Center

Loveland, Colorado, 80539, United States

Location

Parker Adventist Hospital

Parker, Colorado, 80138, United States

Location

St. Mary - Corwin Regional Medical Center

Pueblo, Colorado, 81004, United States

Location

Exempla Lutheran Medical Center

Wheat Ridge, Colorado, 80033, United States

Location

Ella Milbank Foshay Cancer Center at Jupiter Medical Center

Jupiter, Florida, 33458, United States

Location

Lakeland Regional Cancer Center at Lakeland Regional Medical Center

Lakeland, Florida, 33805, United States

Location

CCOP - Mount Sinai Medical Center

Miami Beach, Florida, 33140, United States

Location

MBCCOP - Medical College of Georgia Cancer Center

Augusta, Georgia, 30912, United States

Location

Nancy N. and J. C. Lewis Cancer and Research Pavilion at St. Joseph's/Candler

Savannah, Georgia, 31405, United States

Location

Illinois CancerCare - Bloomington

Bloomington, Illinois, 61701, United States

Location

Illinois CancerCare - Canton

Canton, Illinois, 61520, United States

Location

Illinois CancerCare - Carthage

Carthage, Illinois, 62321, United States

Location

Resurrection Medical Center

Chicago, Illinois, 60631, United States

Location

Louis A. Weiss Memorial Hospital

Chicago, Illinois, 60640, United States

Location

Decatur Memorial Hospital Cancer Care Institute

Decatur, Illinois, 62526, United States

Location

Illinois CancerCare - Eureka

Eureka, Illinois, 61530, United States

Location

Galesburg Clinic, PC

Galesburg, Illinois, 61401, United States

Location

Illinois CancerCare - Havana

Havana, Illinois, 62644, United States

Location

Illinois CancerCare - Kewanee Clinic

Kewanee, Illinois, 61443, United States

Location

La Grange Memorial Hospital

La Grange, Illinois, 60525, United States

Location

Illinois CancerCare - Macomb

Macomb, Illinois, 61455, United States

Location

Illinois CancerCare - Monmouth

Monmouth, Illinois, 61462, United States

Location

Good Samaritan Regional Health Center

Mount Vernon, Illinois, 62864, United States

Location

Illinois CancerCare - Community Cancer Center

Normal, Illinois, 61761, United States

Location

Advocate Christ Medical Center

Oak Lawn, Illinois, 60453-2699, United States

Location

Oncology Hematology Associates of Central Illinois, PC - Ottawa

Ottawa, Illinois, 61350, United States

Location

Illinois CancerCare - Pekin

Pekin, Illinois, 61603, United States

Location

CCOP - Illinois Oncology Research Association

Peoria, Illinois, 61615, United States

Location

Illinois CancerCare - Peru

Peru, Illinois, 61354, United States

Location

Illinois CancerCare - Princeton

Princeton, Illinois, 61356, United States

Location

West Suburban Center for Cancer Care

River Forest, Illinois, 60305, United States

Location

Regional Cancer Center at Memorial Medical Center

Springfield, Illinois, 62781-0001, United States

Location

Bloomington Hospital Regional Cancer Institute

Bloomington, Indiana, 47403, United States

Location

Elkhart Clinic, LLC

Elkhart, Indiana, 46514-2098, United States

Location

Michiana Hematology-Oncology, PC - Elkhart

Elkhart, Indiana, 46514, United States

Location

Elkhart General Hospital

Elkhart, Indiana, 46515, United States

Location

St. Francis Hospital Cancer Care Services

Indianapolis, Indiana, 46237, United States

Location

Howard Community Hospital

Kokomo, Indiana, 46904, United States

Location

Center for Cancer Therapy at LaPorte Hospital and Health Services

La Porte, Indiana, 46350, United States

Location

Michiana Hematology-Oncology, PC - South Bend

Mishawaka, Indiana, 46545-1470, United States

Location

Saint Joseph Regional Medical Center

Mishawaka, Indiana, 46545-1470, United States

Location

Michiana Hematology Oncology PC - Plymouth

Plymouth, Indiana, 46563, United States

Location

Reid Hospital & Health Care Services

Richmond, Indiana, 47374, United States

Location

CCOP - Northern Indiana CR Consortium

South Bend, Indiana, 46601, United States

Location

Memorial Hospital of South Bend

South Bend, Indiana, 46601, United States

Location

Michiana Hematology Oncology PC - La Porte

Westville, Indiana, 46391, United States

Location

Cedar Rapids Oncology Associates

Cedar Rapids, Iowa, 52403, United States

Location

Medical Oncology and Hematology Associates - West Des Moines

Clive, Iowa, 50325, United States

Location

CCOP - Iowa Oncology Research Association

Des Moines, Iowa, 50309, United States

Location

Medical Oncology and Hematology Associates at John Stoddard Cancer Center

Des Moines, Iowa, 50309, United States

Location

Medical Oncology and Hematology Associates at Mercy Cancer Center

Des Moines, Iowa, 50314, United States

Location

Covenant Cancer Treatment Center

Waterloo, Iowa, 50702, United States

Location

Lucille P. Markey Cancer Center at University of Kentucky

Lexington, Kentucky, 40536-0093, United States

Location

MBCCOP - LSU Health Sciences Center

New Orleans, Louisiana, 70112, United States

Location

Mercy Hospital

Portland, Maine, 04101, United States

Location

Mercy Medical Center

Baltimore, Maryland, 21202, United States

Location

Alvin and Lois Lapidus Cancer Institute at Sinai Hospital

Baltimore, Maryland, 21215, United States

Location

Suburban Hospital

Bethesda, Maryland, 20814, United States

Location

Jordan Hospital Club Cancer Center

Plymouth, Massachusetts, 02360, United States

Location

Battle Creek Health System Cancer Care Center

Battle Creek, Michigan, 49017, United States

Location

Bay Regional Medical Center

Bay City, Michigan, 48708, United States

Location

Mecosta County Medical Center

Big Rapids, Michigan, 49307, United States

Location

Barbara Ann Karmanos Cancer Institute

Detroit, Michigan, 48201-1379, United States

Location

Singh and Arora Hematology Oncology, PC

Flint, Michigan, 48532, United States

Location

Butterworth Hospital at Spectrum Health

Grand Rapids, Michigan, 49503, United States

Location

Lacks Cancer Center at Saint Mary's Health Care

Grand Rapids, Michigan, 49503, United States

Location

West Michigan Cancer Center

Kalamazoo, Michigan, 49007-3731, United States

Location

Great Lakes Cancer Institute - Lapeer Campus

Lapeer, Michigan, 48446, United States

Location

Clemens Regional Medical Center

Mount Clemens, Michigan, 48043, United States

Location

Mercy General Health Partners

Muskegon, Michigan, 49444, United States

Location

Northern Michigan Hospital

Petoskey, Michigan, 49770, United States

Location

Lakeland Regional Cancer Care Center - St. Joseph

Saint Joseph, Michigan, 49085, United States

Location

Lakeside Cancer Specialists, PLLC

Saint Joseph, Michigan, 49085, United States

Location

Providence Cancer Institute at Providence Hospital - Southfield Campus

Southfield, Michigan, 48075, United States

Location

Munson Medical Center

Traverse City, Michigan, 49684, United States

Location

Fairview Ridges Hospital

Burnsville, Minnesota, 55337, United States

Location

Mercy and Unity Cancer Center at Mercy Hospital

Coon Rapids, Minnesota, 55433, United States

Location

Fairview Southdale Hospital

Edina, Minnesota, 55435, United States

Location

Mercy and Unity Cancer Center at Unity Hospital

Fridley, Minnesota, 55432, United States

Location

Hutchinson Area Health Care

Hutchinson, Minnesota, 55350, United States

Location

HealthEast Cancer Care at St. John's Hospital

Maplewood, Minnesota, 55109, United States

Location

Virginia Piper Cancer Institute at Abbott - Northwestern Hospital

Minneapolis, Minnesota, 55407, United States

Location

Hennepin County Medical Center - Minneapolis

Minneapolis, Minnesota, 55415, United States

Location

Humphrey Cancer Center at North Memorial Outpatient Center

Robbinsdale, Minnesota, 55422-2900, United States

Location

CCOP - Metro-Minnesota

Saint Louis Park, Minnesota, 55416, United States

Location

Park Nicollet Cancer Center

Saint Louis Park, Minnesota, 55416, United States

Location

Regions Hospital Cancer Care Center

Saint Paul, Minnesota, 55101, United States

Location

United Hospital

Saint Paul, Minnesota, 55102, United States

Location

St. Francis Cancer Center at St. Francis Medical Center

Shakopee, Minnesota, 55379, United States

Location

Lakeview Hospital

Stillwater, Minnesota, 55082, United States

Location

Ridgeview Medical Center

Waconia, Minnesota, 55387, United States

Location

Willmar Cancer Center at Rice Memorial Hospital

Willmar, Minnesota, 56201, United States

Location

Minnesota Oncology - Woodbury

Woodbury, Minnesota, 55125, United States

Location

Central Care Cancer Center

Bolivar, Missouri, 65613, United States

Location

Southeast Cancer Center

Cape Girardeau, Missouri, 63703, United States

Location

Saint Luke's Hospital

Chesterfield, Missouri, 63017, United States

Location

Goldschmidt Cancer Center

Jefferson City, Missouri, 65109, United States

Location

Freeman Cancer Institute

Joplin, Missouri, 64804, United States

Location

Missouri Baptist Cancer Center

St Louis, Missouri, 63131, United States

Location

Mercy Hospital St. Louis

St Louis, Missouri, 63141, United States

Location

CCOP - Montana Cancer Consortium

Billings, Montana, 59101, United States

Location

Hematology-Oncology Centers of the Northern Rockies - Billings

Billings, Montana, 59102, United States

Location

Billings Clinic - Downtown

Billings, Montana, 59107-7000, United States

Location

Bozeman Deaconess Cancer Center

Bozeman, Montana, 59715, United States

Location

Big Sky Oncology

Great Falls, Montana, 59405-5309, United States

Location

Sletten Cancer Institute at Benefis Healthcare

Great Falls, Montana, 59405, United States

Location

Kalispell Regional Medical Center

Kalispell, Montana, 59901, United States

Location

Montana Cancer Specialists at Montana Cancer Center

Missoula, Montana, 59807-7877, United States

Location

Good Samaritan Cancer Center at Good Samaritan Hospital

Kearney, Nebraska, 68848-1990, United States

Location

Norris Cotton Cancer Center at Dartmouth-Hitchcock Medical Center

Lebanon, New Hampshire, 03756-0002, United States

Location

Foundation Medical Partners

Nashua, New Hampshire, 03060, United States

Location

Oncology Center at St. Joseph Hospital

Nashua, New Hampshire, 03060, United States

Location

Dizzy Gillespie Cancer Institute at Englewood Hospital and Medical Center

Englewood, New Jersey, 07631, United States

Location

Monmouth Medical Center

Long Branch, New Jersey, 07740-6395, United States

Location

UMDNJ University Hospital

Newark, New Jersey, 07103, United States

Location

Franklin & Edith Scarpa Regional Cancer Center at South Jersey Healthcare

Vineland, New Jersey, 08360, United States

Location

Lovelace Medical Center - Downtown

Albuquerque, New Mexico, 87102, United States

Location

Presbyterian Cancer Treatment Center at Presbyterian Kaseman Hospital

Albuquerque, New Mexico, 87110, United States

Location

University of New Mexico Cancer Center

Albuquerque, New Mexico, 87131-5636, United States

Location

Bassett Healthcare Regional Cancer Program at Mary Imogene Bassett Hospital

Cooperstown, New York, 13326, United States

Location

Charles R. Wood Cancer Center at Glens Falls Hospital

Glens Falls, New York, 12801, United States

Location

Nalitt Cancer Institute at Staten Island University Hospital

Staten Island, New York, 10305, United States

Location

Park Ridge Health

Henderson, North Carolina, 28792, United States

Location

McDowell Cancer Center at Akron General Medical Center

Akron, Ohio, 44307, United States

Location

Summa Center for Cancer Care at Akron City Hospital

Akron, Ohio, 44309-2090, United States

Location

Aultman Cancer Center at Aultman Hospital

Canton, Ohio, 44710-1799, United States

Location

David L. Rike Cancer Center at Miami Valley Hospital

Dayton, Ohio, 45409, United States

Location

Samaritan North Cancer Care Center

Dayton, Ohio, 45415, United States

Location

CCOP - Dayton

Dayton, Ohio, 45420, United States

Location

Blanchard Valley Medical Associates

Findlay, Ohio, 45840, United States

Location

Middletown Regional Hospital

Franklin, Ohio, 45005-1066, United States

Location

Wayne Hospital

Greenville, Ohio, 45331, United States

Location

Charles F. Kettering Memorial Hospital

Kettering, Ohio, 45429, United States

Location

UVMC Cancer Care Center at Upper Valley Medical Center

Troy, Ohio, 45373-1300, United States

Location

United States Air Force Medical Center - Wright-Patterson

Wright-Patterson Air Force Base, Ohio, 45433-5529, United States

Location

Ruth G. McMillan Cancer Center at Greene Memorial Hospital

Xenia, Ohio, 45385, United States

Location

Cancer Care Associates - Norman

Norman, Oklahoma, 73071, United States

Location

Cancer Care Associates - Mercy Campus

Oklahoma City, Oklahoma, 73120, United States

Location

Natalie Warren Bryant Cancer Center at St. Francis Hospital

Tulsa, Oklahoma, 74136, United States

Location

Geisinger Cancer Institute at Geisinger Health

Danville, Pennsylvania, 17822-0001, United States

Location

Geisinger Hazleton Cancer Center

Hazleton, Pennsylvania, 18201, United States

Location

Joan Karnell Cancer Center at Pennsylvania Hospital

Philadelphia, Pennsylvania, 19107, United States

Location

Cancer Center at Phoenixville Hospital

Phoenixville, Pennsylvania, 19460, United States

Location

Guthrie Cancer Center at Guthrie Clinic Sayre

Sayre, Pennsylvania, 18840, United States

Location

Geisinger Medical Group - Scenery Park

State College, Pennsylvania, 16801, United States

Location

Frank M. and Dorothea Henry Cancer Center at Geisinger Wyoming Valley Medical Center

Wilkes-Barre, Pennsylvania, 18711, United States

Location

Keyserling Cancer Center at Beaufort Memorial Hospital

Beaufort, South Carolina, 29902, United States

Location

St. Francis Hospital

Greenville, South Carolina, 29601, United States

Location

Gibbs Cancer Center - Pelham

Greer, South Carolina, 29651, United States

Location

Rapid City Regional Hospital

Rapid City, South Dakota, 57701, United States

Location

Martha Jefferson Hospital Cancer Care Center

Charlottesville, Virginia, 22901, United States

Location

Green Bay Oncology, Limited at St. Vincent Hospital Regional Cancer Center

Green Bay, Wisconsin, 54301-3526, United States

Location

Green Bay Oncology, Limited at St. Mary's Hospital

Green Bay, Wisconsin, 54303, United States

Location

Mercy Regional Cancer Center

Janesville, Wisconsin, 53547, United States

Location

Gundersen Lutheran Center for Cancer and Blood

La Crosse, Wisconsin, 54601, United States

Location

D.N. Greenwald Center

Mukwonago, Wisconsin, 53149, United States

Location

Regional Cancer Center at Oconomowoc Memorial Hospital

Oconomowoc, Wisconsin, 53066, United States

Location

Waukesha Memorial Hospital Regional Cancer Center

Waukesha, Wisconsin, 53188, United States

Location

Related Publications (1)

  • Guglin M, Krischer J, Tamura R, Fink A, Bello-Matricaria L, McCaskill-Stevens W, Munster PN. Randomized Trial of Lisinopril Versus Carvedilol to Prevent Trastuzumab Cardiotoxicity in Patients With Breast Cancer. J Am Coll Cardiol. 2019 Jun 11;73(22):2859-2868. doi: 10.1016/j.jacc.2019.03.495.

MeSH Terms

Conditions

Breast NeoplasmsCardiotoxicityBreast Neoplasms, Male

Interventions

CarvedilolLisinopril

Condition Hierarchy (Ancestors)

Neoplasms by SiteNeoplasmsBreast DiseasesSkin DiseasesSkin and Connective Tissue DiseasesHeart DiseasesCardiovascular DiseasesPathologic ProcessesPathological Conditions, Signs and SymptomsDrug-Related Side Effects and Adverse ReactionsChemically-Induced DisordersRadiation InjuriesWounds and Injuries

Intervention Hierarchy (Ancestors)

PropanolaminesAmino AlcoholsAlcoholsOrganic ChemicalsPropanolsAminesCarbazolesIndolesHeterocyclic Compounds, 2-RingHeterocyclic Compounds, Fused-RingHeterocyclic CompoundsHeterocyclic Compounds, 3-RingDipeptidesOligopeptidesPeptidesAmino Acids, Peptides, and Proteins

Results Point of Contact

Title
Maya Guglin, MD, PhD
Organization
University of South Florida

Study Officials

  • Maya Guglin, MD, PhD

    University of South Florida

    STUDY CHAIR
  • Pamela N. Munster, MD

    University of California, San Francisco

    STUDY CHAIR

Publication Agreements

PI is Sponsor Employee
No
Restrictive Agreement
No

Study Design

Study Type
interventional
Phase
phase 2
Allocation
RANDOMIZED
Masking
DOUBLE
Who Masked
PARTICIPANT, INVESTIGATOR
Purpose
SUPPORTIVE CARE
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

November 6, 2009

First Posted

November 9, 2009

Study Start

March 1, 2010

Primary Completion

August 1, 2017

Study Completion

November 1, 2018

Last Updated

March 30, 2021

Results First Posted

March 30, 2021

Record last verified: 2019-04

Locations