Lisinopril or Coreg CR® in Reducing Side Effects in Women With Breast Cancer Receiving Trastuzumab

Breast Cancer Clinical Trial

Official title:

Phase II Placebo-controlled Trial of Lisinopril and Coreg CR® to Reduce Cardiotoxicity in Patients With Breast Cancer Receiving (Neo)Adjuvant Chemotherapy With Trastuzumab (Herceptin®)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01009918
• Other study ID #: SCUSF 0806
• Secondary ID: SCUSF-08065U10CA
• Status: Completed
• Phase: Phase 2
• Start date: March 2010
• Est. completion date: November 2018

Study information

• Verified date: April 2019
• Source: University of South Florida
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Description:

OBJECTIVES:

Primary

• The primary objective of this study is to determine if administration of lisinopril or Coreg CR®, compared to placebo, will reduce the incidence of trastuzumab-induced cardiotoxicity, as measured by LVEF, in patients receiving adjuvant, or neoadjuvant,therapy for HER2 positive breast cancer.

Secondary

• To determine whether subjects randomized to active agent have fewer interruptions in trastuzumab therapy due to cardiomyopathy.

• To determine whether the treatment effect is consistent in anthracycline and nonanthracycline patient cohorts

• To compare changes in HRQL among the treatment groups during the study intervention

• To evaluate the long term effects on the prevention of cardiomyopathy and impact on HRQL for either or both study agents

• To compare the predictive value of troponin I and BNP in the identification of trastuzumab-induced cardiotoxicity

OUTLINE: This is a multicenter study. Patients are stratified according to chemotherapy comprising an anthracycline (yes vs no). Patients are randomized to 1 of 3 treatment arms.

• Arm I: Patients receive oral lisinopril once daily.

• Arm II: Patients receive oral Coreg CR® once daily.

• Arm III: Patients receive oral placebo once daily.

In all arms, study treatment begins with the first dose of trastuzumab and continues for up to 52 weeks or until the end of trastuzumab therapy.

Quality of life is assessed using the EORTC QLQ-C30 questionnaire at baseline, at 52 weeks (or at the end of trastuzumab therapy), and at 18 and 24 months (or 6 and 12 months after the completion of trastuzumab).

After completion of study treatment, patients are followed up at 3, 6, 9, and 12 months.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 468
• Est. completion date: November 2018
• Est. primary completion date: August 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

INCLUSION CRITERIA

• 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

EXCLUSION CRITERIA:

• 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, ß-blockers or digoxin

• Known cardiac history: heart failure, myocardial infarction, radiation-induced cardiac dysfunction

• Known allergy to either ACE inhibitors or ß-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.

Related Conditions & MeSH terms

• Breast Cancer
• Breast Neoplasms
• Cardiac Toxicity
• Cardiotoxicity

Intervention

Drug:
• Coreg CR®
Given orally
• lisinopril
Given orally

Other:
• placebo
Given orally

Locations

Country	Name	City	State
United States	McDowell Cancer Center at Akron General Medical Center	Akron	Ohio
United States	Summa Center for Cancer Care at Akron City Hospital	Akron	Ohio
United States	Lovelace Medical Center - Downtown	Albuquerque	New Mexico
United States	Presbyterian Cancer Treatment Center at Presbyterian Kaseman Hospital	Albuquerque	New Mexico
United States	University of New Mexico Cancer Center	Albuquerque	New Mexico
United States	MBCCOP - Medical College of Georgia Cancer Center	Augusta	Georgia
United States	Aurora Presbyterian Hospital	Aurora	Colorado
United States	Alvin and Lois Lapidus Cancer Institute at Sinai Hospital	Baltimore	Maryland
United States	Mercy Medical Center	Baltimore	Maryland
United States	Battle Creek Health System Cancer Care Center	Battle Creek	Michigan
United States	Bay Regional Medical Center	Bay City	Michigan
United States	Keyserling Cancer Center at Beaufort Memorial Hospital	Beaufort	South Carolina
United States	Suburban Hospital	Bethesda	Maryland
United States	Mecosta County Medical Center	Big Rapids	Michigan
United States	Billings Clinic - Downtown	Billings	Montana
United States	CCOP - Montana Cancer Consortium	Billings	Montana
United States	Hematology-Oncology Centers of the Northern Rockies - Billings	Billings	Montana
United States	Bloomington Hospital Regional Cancer Institute	Bloomington	Indiana
United States	Illinois CancerCare - Bloomington	Bloomington	Illinois
United States	Central Care Cancer Center	Bolivar	Missouri
United States	Boulder Community Hospital	Boulder	Colorado
United States	Bozeman Deaconess Cancer Center	Bozeman	Montana
United States	Fairview Ridges Hospital	Burnsville	Minnesota
United States	Aultman Cancer Center at Aultman Hospital	Canton	Ohio
United States	Illinois CancerCare - Canton	Canton	Illinois
United States	Southeast Cancer Center	Cape Girardeau	Missouri
United States	Illinois CancerCare - Carthage	Carthage	Illinois
United States	Cedar Rapids Oncology Associates	Cedar Rapids	Iowa
United States	Martha Jefferson Hospital Cancer Care Center	Charlottesville	Virginia
United States	Saint Luke's Hospital	Chesterfield	Missouri
United States	Louis A. Weiss Memorial Hospital	Chicago	Illinois
United States	Resurrection Medical Center	Chicago	Illinois
United States	Medical Oncology and Hematology Associates - West Des Moines	Clive	Iowa
United States	Penrose Cancer Center at Penrose Hospital	Colorado Springs	Colorado
United States	Mercy and Unity Cancer Center at Mercy Hospital	Coon Rapids	Minnesota
United States	Bassett Healthcare Regional Cancer Program at Mary Imogene Bassett Hospital	Cooperstown	New York
United States	Geisinger Cancer Institute at Geisinger Health	Danville	Pennsylvania
United States	CCOP - Dayton	Dayton	Ohio
United States	David L. Rike Cancer Center at Miami Valley Hospital	Dayton	Ohio
United States	Samaritan North Cancer Care Center	Dayton	Ohio
United States	Decatur Memorial Hospital Cancer Care Institute	Decatur	Illinois
United States	CCOP - Colorado Cancer Research Program	Denver	Colorado
United States	Porter Adventist Hospital	Denver	Colorado
United States	Presbyterian - St. Luke's Medical Center	Denver	Colorado
United States	Rose Medical Center	Denver	Colorado
United States	St. Anthony Central Hospital	Denver	Colorado
United States	St. Joseph Hospital	Denver	Colorado
United States	CCOP - Iowa Oncology Research Association	Des Moines	Iowa
United States	Medical Oncology and Hematology Associates at John Stoddard Cancer Center	Des Moines	Iowa
United States	Medical Oncology and Hematology Associates at Mercy Cancer Center	Des Moines	Iowa
United States	Barbara Ann Karmanos Cancer Institute	Detroit	Michigan
United States	Fairview Southdale Hospital	Edina	Minnesota
United States	Elkhart Clinic, LLC	Elkhart	Indiana
United States	Elkhart General Hospital	Elkhart	Indiana
United States	Michiana Hematology-Oncology, PC - Elkhart	Elkhart	Indiana
United States	Dizzy Gillespie Cancer Institute at Englewood Hospital and Medical Center	Englewood	New Jersey
United States	Swedish Medical Center	Englewood	Colorado
United States	Illinois CancerCare - Eureka	Eureka	Illinois
United States	Blanchard Valley Medical Associates	Findlay	Ohio
United States	Singh and Arora Hematology Oncology, PC	Flint	Michigan
United States	Middletown Regional Hospital	Franklin	Ohio
United States	Mercy and Unity Cancer Center at Unity Hospital	Fridley	Minnesota
United States	Galesburg Clinic, PC	Galesburg	Illinois
United States	Charles R. Wood Cancer Center at Glens Falls Hospital	Glens Falls	New York
United States	Butterworth Hospital at Spectrum Health	Grand Rapids	Michigan
United States	Lacks Cancer Center at Saint Mary's Health Care	Grand Rapids	Michigan
United States	Big Sky Oncology	Great Falls	Montana
United States	Sletten Cancer Institute at Benefis Healthcare	Great Falls	Montana
United States	North Colorado Medical Center	Greeley	Colorado
United States	Green Bay Oncology, Limited at St. Mary's Hospital	Green Bay	Wisconsin
United States	Green Bay Oncology, Limited at St. Vincent Hospital Regional Cancer Center	Green Bay	Wisconsin
United States	St. Francis Hospital	Greenville	South Carolina
United States	Wayne Hospital	Greenville	Ohio
United States	Gibbs Cancer Center - Pelham	Greer	South Carolina
United States	Illinois CancerCare - Havana	Havana	Illinois
United States	Geisinger Hazleton Cancer Center	Hazleton	Pennsylvania
United States	Park Ridge Health	Henderson	North Carolina
United States	Hutchinson Area Health Care	Hutchinson	Minnesota
United States	St. Francis Hospital Cancer Care Services	Indianapolis	Indiana
United States	Mercy Regional Cancer Center	Janesville	Wisconsin
United States	Goldschmidt Cancer Center	Jefferson City	Missouri
United States	Freeman Cancer Institute	Joplin	Missouri
United States	Ella Milbank Foshay Cancer Center at Jupiter Medical Center	Jupiter	Florida
United States	West Michigan Cancer Center	Kalamazoo	Michigan
United States	Kalispell Regional Medical Center	Kalispell	Montana
United States	Good Samaritan Cancer Center at Good Samaritan Hospital	Kearney	Nebraska
United States	Charles F. Kettering Memorial Hospital	Kettering	Ohio
United States	Illinois CancerCare - Kewanee Clinic	Kewanee	Illinois
United States	Howard Community Hospital	Kokomo	Indiana
United States	Gundersen Lutheran Center for Cancer and Blood	La Crosse	Wisconsin
United States	La Grange Memorial Hospital	La Grange	Illinois
United States	Center for Cancer Therapy at LaPorte Hospital and Health Services	La Porte	Indiana
United States	Lakeland Regional Cancer Center at Lakeland Regional Medical Center	Lakeland	Florida
United States	Great Lakes Cancer Institute - Lapeer Campus	Lapeer	Michigan
United States	Norris Cotton Cancer Center at Dartmouth-Hitchcock Medical Center	Lebanon	New Hampshire
United States	Lucille P. Markey Cancer Center at University of Kentucky	Lexington	Kentucky
United States	Littleton Adventist Hospital	Littleton	Colorado
United States	Sky Ridge Medical Center	Lone Tree	Colorado
United States	Todd Cancer Institute at Long Beach Memorial Medical Center	Long Beach	California
United States	Monmouth Medical Center	Long Branch	New Jersey
United States	Hope Cancer Care Center at Longmont United Hospital	Longmont	Colorado
United States	McKee Medical Center	Loveland	Colorado
United States	Illinois CancerCare - Macomb	Macomb	Illinois
United States	HealthEast Cancer Care at St. John's Hospital	Maplewood	Minnesota
United States	CCOP - Mount Sinai Medical Center	Miami Beach	Florida
United States	Hennepin County Medical Center - Minneapolis	Minneapolis	Minnesota
United States	Virginia Piper Cancer Institute at Abbott - Northwestern Hospital	Minneapolis	Minnesota
United States	Michiana Hematology-Oncology, PC - South Bend	Mishawaka	Indiana
United States	Saint Joseph Regional Medical Center	Mishawaka	Indiana
United States	Montana Cancer Specialists at Montana Cancer Center	Missoula	Montana
United States	Illinois CancerCare - Monmouth	Monmouth	Illinois
United States	Clemens Regional Medical Center	Mount Clemens	Michigan
United States	Good Samaritan Regional Health Center	Mount Vernon	Illinois
United States	D.N. Greenwald Center	Mukwonago	Wisconsin
United States	Mercy General Health Partners	Muskegon	Michigan
United States	Foundation Medical Partners	Nashua	New Hampshire
United States	Oncology Center at St. Joseph Hospital	Nashua	New Hampshire
United States	MBCCOP - LSU Health Sciences Center	New Orleans	Louisiana
United States	UMDNJ University Hospital	Newark	New Jersey
United States	Illinois CancerCare - Community Cancer Center	Normal	Illinois
United States	Cancer Care Associates - Norman	Norman	Oklahoma
United States	Advocate Christ Medical Center	Oak Lawn	Illinois
United States	Regional Cancer Center at Oconomowoc Memorial Hospital	Oconomowoc	Wisconsin
United States	Cancer Care Associates - Mercy Campus	Oklahoma City	Oklahoma
United States	Oncology Hematology Associates of Central Illinois, PC - Ottawa	Ottawa	Illinois
United States	Parker Adventist Hospital	Parker	Colorado
United States	Illinois CancerCare - Pekin	Pekin	Illinois
United States	CCOP - Illinois Oncology Research Association	Peoria	Illinois
United States	Illinois CancerCare - Peru	Peru	Illinois
United States	Northern Michigan Hospital	Petoskey	Michigan
United States	Joan Karnell Cancer Center at Pennsylvania Hospital	Philadelphia	Pennsylvania
United States	Cancer Center at Phoenixville Hospital	Phoenixville	Pennsylvania
United States	Jordan Hospital Club Cancer Center	Plymouth	Massachusetts
United States	Michiana Hematology Oncology PC - Plymouth	Plymouth	Indiana
United States	Mercy Hospital	Portland	Maine
United States	Illinois CancerCare - Princeton	Princeton	Illinois
United States	St. Mary - Corwin Regional Medical Center	Pueblo	Colorado
United States	Rapid City Regional Hospital	Rapid City	South Dakota
United States	Reid Hospital & Health Care Services	Richmond	Indiana
United States	West Suburban Center for Cancer Care	River Forest	Illinois
United States	Humphrey Cancer Center at North Memorial Outpatient Center	Robbinsdale	Minnesota
United States	Lakeland Regional Cancer Care Center - St. Joseph	Saint Joseph	Michigan
United States	Lakeside Cancer Specialists, PLLC	Saint Joseph	Michigan
United States	Mercy Hospital St. Louis	Saint Louis	Missouri
United States	Missouri Baptist Cancer Center	Saint Louis	Missouri
United States	CCOP - Metro-Minnesota	Saint Louis Park	Minnesota
United States	Park Nicollet Cancer Center	Saint Louis Park	Minnesota
United States	Regions Hospital Cancer Care Center	Saint Paul	Minnesota
United States	United Hospital	Saint Paul	Minnesota
United States	Nancy N. and J. C. Lewis Cancer and Research Pavilion at St. Joseph's/Candler	Savannah	Georgia
United States	Guthrie Cancer Center at Guthrie Clinic Sayre	Sayre	Pennsylvania
United States	St. Francis Cancer Center at St. Francis Medical Center	Shakopee	Minnesota
United States	CCOP - Northern Indiana CR Consortium	South Bend	Indiana
United States	Memorial Hospital of South Bend	South Bend	Indiana
United States	Providence Cancer Institute at Providence Hospital - Southfield Campus	Southfield	Michigan
United States	Regional Cancer Center at Memorial Medical Center	Springfield	Illinois
United States	Geisinger Medical Group - Scenery Park	State College	Pennsylvania
United States	Nalitt Cancer Institute at Staten Island University Hospital	Staten Island	New York
United States	Lakeview Hospital	Stillwater	Minnesota
United States	Olive View - UCLA Medical Center Foundation	Sylmar	California
United States	Munson Medical Center	Traverse City	Michigan
United States	UVMC Cancer Care Center at Upper Valley Medical Center	Troy	Ohio
United States	Natalie Warren Bryant Cancer Center at St. Francis Hospital	Tulsa	Oklahoma
United States	Franklin & Edith Scarpa Regional Cancer Center at South Jersey Healthcare	Vineland	New Jersey
United States	Ridgeview Medical Center	Waconia	Minnesota
United States	Covenant Cancer Treatment Center	Waterloo	Iowa
United States	Waukesha Memorial Hospital Regional Cancer Center	Waukesha	Wisconsin
United States	Michiana Hematology Oncology PC - La Porte	Westville	Indiana
United States	Exempla Lutheran Medical Center	Wheat Ridge	Colorado
United States	Frank M. and Dorothea Henry Cancer Center at Geisinger Wyoming Valley Medical Center	Wilkes-Barre	Pennsylvania
United States	Willmar Cancer Center at Rice Memorial Hospital	Willmar	Minnesota
United States	Minnesota Oncology - Woodbury	Woodbury	Minnesota
United States	United States Air Force Medical Center - Wright-Patterson	Wright-Patterson Air Force Base	Ohio
United States	Ruth G. McMillan Cancer Center at Greene Memorial Hospital	Xenia	Ohio

Sponsors (2)

Lead Sponsor	Collaborator
University of South Florida	National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	Number of Participants With LVEF Decrease to <50%	Number of Participants with Left Ventricular Ejection Fraction (LVEF) drop to <50%	2 years
Secondary	Number of Patients With Trastuzumab Course Interruption	Measure indicates the number of patients who had an interruption of trastuzumab for any reason	2 years
Secondary	Quality-of-life Changes Between Baseline and 52-weeks	Quality-of-life changes as assessed by North European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC-QLQ-C30), which measures the quality of life of cancer patients. Higher score indicates higher quality of life. Score range is 0-100. The questionnaire was administered at baseline and at 52 weeks.	52 weeks
Secondary	Number of Participants With Cardiotoxicity-free Survival at 750 Days From Baseline	Number of Participants with cardiotoxicity-free survival at 750 days from baseline	2 years