Clinical trial NCT01009918: Lisinopril or Coreg CR® in Reducing Side Effects in Women With Breast Cancer Receiving Trastuzumab
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®)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Breast Cancer
Cardiac Toxicity
Keywords: cardiac toxicity
HER2-positive breast cancer
recurrent breast cancer
stage IA breast cancer
stage IB breast cancer
stage II breast cancer
stage IIIA breast cancer
stage IIIB breast cancer
stage IIIC breast cancer
male breast cancer
Lead sponsor: University of South Florida
Sponsor class: OTHER
Collaborators: name: National Cancer Institute (NCI)
First posted: 2009-11-09
Enrollment: 468
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: SUPPORTIVE_CARE

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.

Detailed 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.

Eligibility criteria: 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, 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.

Primary outcomes:
measure: Number of Participants With Trastuzumab-Induced Cardiotoxicity After 52 Weeks of Treatment
timeFrame: 2 years
measure: Number of Participants With LVEF Decrease to <50%
timeFrame: 2 years
Secondary outcomes:
measure: Number of Patients With Trastuzumab Course Interruption
timeFrame: 2 years
measure: Quality-of-life Changes Between Baseline and 52-weeks
timeFrame: 52 weeks
measure: Number of Participants With Cardiotoxicity-free Survival at 750 Days From Baseline
timeFrame: 2 years
Other outcomes:
Locations:
city: Long Beach
country: United States
facility: Todd Cancer Institute at Long Beach Memorial Medical Center
state: California
city: Sylmar
country: United States
facility: Olive View - UCLA Medical Center Foundation
state: California
city: Aurora
country: United States
facility: Aurora Presbyterian Hospital
state: Colorado
city: Boulder
country: United States
facility: Boulder Community Hospital
state: Colorado
city: Colorado Springs
country: United States
facility: Penrose Cancer Center at Penrose Hospital
state: Colorado
city: Denver
country: United States
facility: St. Anthony Central Hospital
state: Colorado
city: Denver
country: United States
facility: Porter Adventist Hospital
state: Colorado
city: Denver
country: United States
facility: Presbyterian - St. Luke's Medical Center
state: Colorado
city: Denver
country: United States
facility: St. Joseph Hospital
state: Colorado
city: Denver
country: United States
facility: Rose Medical Center
state: Colorado
city: Denver
country: United States
facility: CCOP - Colorado Cancer Research Program
state: Colorado
city: Englewood
country: United States
facility: Swedish Medical Center
state: Colorado
city: Greeley
country: United States
facility: North Colorado Medical Center
state: Colorado
city: Littleton
country: United States
facility: Littleton Adventist Hospital
state: Colorado
city: Lone Tree
country: United States
facility: Sky Ridge Medical Center
state: Colorado
city: Longmont
country: United States
facility: Hope Cancer Care Center at Longmont United Hospital
state: Colorado
city: Loveland
country: United States
facility: McKee Medical Center
state: Colorado
city: Parker
country: United States
facility: Parker Adventist Hospital
state: Colorado
city: Pueblo
country: United States
facility: St. Mary - Corwin Regional Medical Center
state: Colorado
city: Wheat Ridge
country: United States
facility: Exempla Lutheran Medical Center
state: Colorado
city: Jupiter
country: United States
facility: Ella Milbank Foshay Cancer Center at Jupiter Medical Center
state: Florida
city: Lakeland
country: United States
facility: Lakeland Regional Cancer Center at Lakeland Regional Medical Center
state: Florida
city: Miami Beach
country: United States
facility: CCOP - Mount Sinai Medical Center
state: Florida
city: Augusta
country: United States
facility: MBCCOP - Medical College of Georgia Cancer Center
state: Georgia
city: Savannah
country: United States
facility: Nancy N. and J. C. Lewis Cancer and Research Pavilion at St. Joseph's/Candler
state: Georgia
city: Bloomington
country: United States
facility: Illinois CancerCare - Bloomington
state: Illinois
city: Canton
country: United States
facility: Illinois CancerCare - Canton
state: Illinois
city: Carthage
country: United States
facility: Illinois CancerCare - Carthage
state: Illinois
city: Chicago
country: United States
facility: Resurrection Medical Center
state: Illinois
city: Chicago
country: United States
facility: Louis A. Weiss Memorial Hospital
state: Illinois
city: Decatur
country: United States
facility: Decatur Memorial Hospital Cancer Care Institute
state: Illinois
city: Eureka
country: United States
facility: Illinois CancerCare - Eureka
state: Illinois
city: Galesburg
country: United States
facility: Galesburg Clinic, PC
state: Illinois
city: Havana
country: United States
facility: Illinois CancerCare - Havana
state: Illinois
city: Kewanee
country: United States
facility: Illinois CancerCare - Kewanee Clinic
state: Illinois
city: La Grange
country: United States
facility: La Grange Memorial Hospital
state: Illinois
city: Macomb
country: United States
facility: Illinois CancerCare - Macomb
state: Illinois
city: Monmouth
country: United States
facility: Illinois CancerCare - Monmouth
state: Illinois
city: Mount Vernon
country: United States
facility: Good Samaritan Regional Health Center
state: Illinois
city: Normal
country: United States
facility: Illinois CancerCare - Community Cancer Center
state: Illinois
city: Oak Lawn
country: United States
facility: Advocate Christ Medical Center
state: Illinois
city: Ottawa
country: United States
facility: Oncology Hematology Associates of Central Illinois, PC - Ottawa
state: Illinois
city: Pekin
country: United States
facility: Illinois CancerCare - Pekin
state: Illinois
city: Peoria
country: United States
facility: CCOP - Illinois Oncology Research Association
state: Illinois
city: Peru
country: United States
facility: Illinois CancerCare - Peru
state: Illinois
city: Princeton
country: United States
facility: Illinois CancerCare - Princeton
state: Illinois
city: River Forest
country: United States
facility: West Suburban Center for Cancer Care
state: Illinois
city: Springfield
country: United States
facility: Regional Cancer Center at Memorial Medical Center
state: Illinois
city: Bloomington
country: United States
facility: Bloomington Hospital Regional Cancer Institute
state: Indiana
city: Elkhart
country: United States
facility: Elkhart Clinic, LLC
state: Indiana
city: Elkhart
country: United States
facility: Michiana Hematology-Oncology, PC - Elkhart
state: Indiana
city: Elkhart
country: United States
facility: Elkhart General Hospital
state: Indiana
city: Indianapolis
country: United States
facility: St. Francis Hospital Cancer Care Services
state: Indiana
city: Kokomo
country: United States
facility: Howard Community Hospital
state: Indiana
city: La Porte
country: United States
facility: Center for Cancer Therapy at LaPorte Hospital and Health Services
state: Indiana
city: Mishawaka
country: United States
facility: Michiana Hematology-Oncology, PC - South Bend
state: Indiana
city: Mishawaka
country: United States
facility: Saint Joseph Regional Medical Center
state: Indiana
city: Plymouth
country: United States
facility: Michiana Hematology Oncology PC - Plymouth
state: Indiana
city: Richmond
country: United States
facility: Reid Hospital & Health Care Services
state: Indiana
city: South Bend
country: United States
facility: CCOP - Northern Indiana CR Consortium
state: Indiana
city: South Bend
country: United States
facility: Memorial Hospital of South Bend
state: Indiana
city: Westville
country: United States
facility: Michiana Hematology Oncology PC - La Porte
state: Indiana
city: Cedar Rapids
country: United States
facility: Cedar Rapids Oncology Associates
state: Iowa
city: Clive
country: United States
facility: Medical Oncology and Hematology Associates - West Des Moines
state: Iowa
city: Des Moines
country: United States
facility: CCOP - Iowa Oncology Research Association
state: Iowa
city: Des Moines
country: United States
facility: Medical Oncology and Hematology Associates at John Stoddard Cancer Center
state: Iowa
city: Des Moines
country: United States
facility: Medical Oncology and Hematology Associates at Mercy Cancer Center
state: Iowa
city: Waterloo
country: United States
facility: Covenant Cancer Treatment Center
state: Iowa
city: Lexington
country: United States
facility: Lucille P. Markey Cancer Center at University of Kentucky
state: Kentucky
city: New Orleans
country: United States
facility: MBCCOP - LSU Health Sciences Center
state: Louisiana
city: Portland
country: United States
facility: Mercy Hospital
state: Maine
city: Baltimore
country: United States
facility: Mercy Medical Center
state: Maryland
city: Baltimore
country: United States
facility: Alvin and Lois Lapidus Cancer Institute at Sinai Hospital
state: Maryland
city: Bethesda
country: United States
facility: Suburban Hospital
state: Maryland
city: Plymouth
country: United States
facility: Jordan Hospital Club Cancer Center
state: Massachusetts
city: Battle Creek
country: United States
facility: Battle Creek Health System Cancer Care Center
state: Michigan
city: Bay City
country: United States
facility: Bay Regional Medical Center
state: Michigan
city: Big Rapids
country: United States
facility: Mecosta County Medical Center
state: Michigan
city: Detroit
country: United States
facility: Barbara Ann Karmanos Cancer Institute
state: Michigan
city: Flint
country: United States
facility: Singh and Arora Hematology Oncology, PC
state: Michigan
city: Grand Rapids
country: United States
facility: Butterworth Hospital at Spectrum Health
state: Michigan
city: Grand Rapids
country: United States
facility: Lacks Cancer Center at Saint Mary's Health Care
state: Michigan
city: Kalamazoo
country: United States
facility: West Michigan Cancer Center
state: Michigan
city: Lapeer
country: United States
facility: Great Lakes Cancer Institute - Lapeer Campus
state: Michigan
city: Mount Clemens
country: United States
facility: Clemens Regional Medical Center
state: Michigan
city: Muskegon
country: United States
facility: Mercy General Health Partners
state: Michigan
city: Petoskey
country: United States
facility: Northern Michigan Hospital
state: Michigan
city: Saint Joseph
country: United States
facility: Lakeland Regional Cancer Care Center - St. Joseph
state: Michigan
city: Saint Joseph
country: United States
facility: Lakeside Cancer Specialists, PLLC
state: Michigan
city: Southfield
country: United States
facility: Providence Cancer Institute at Providence Hospital - Southfield Campus
state: Michigan
city: Traverse City
country: United States
facility: Munson Medical Center
state: Michigan
city: Burnsville
country: United States
facility: Fairview Ridges Hospital
state: Minnesota
city: Coon Rapids
country: United States
facility: Mercy and Unity Cancer Center at Mercy Hospital
state: Minnesota
city: Edina
country: United States
facility: Fairview Southdale Hospital
state: Minnesota
city: Fridley
country: United States
facility: Mercy and Unity Cancer Center at Unity Hospital
state: Minnesota
city: Hutchinson
country: United States
facility: Hutchinson Area Health Care
state: Minnesota
city: Maplewood
country: United States
facility: HealthEast Cancer Care at St. John's Hospital
state: Minnesota
city: Minneapolis
country: United States
facility: Virginia Piper Cancer Institute at Abbott - Northwestern Hospital
state: Minnesota
city: Minneapolis
country: United States
facility: Hennepin County Medical Center - Minneapolis
state: Minnesota
city: Robbinsdale
country: United States
facility: Humphrey Cancer Center at North Memorial Outpatient Center
state: Minnesota
city: Saint Louis Park
country: United States
facility: CCOP - Metro-Minnesota
state: Minnesota
city: Saint Louis Park
country: United States
facility: Park Nicollet Cancer Center
state: Minnesota
city: Saint Paul
country: United States
facility: Regions Hospital Cancer Care Center
state: Minnesota
city: Saint Paul
country: United States
facility: United Hospital
state: Minnesota
city: Shakopee
country: United States
facility: St. Francis Cancer Center at St. Francis Medical Center
state: Minnesota
city: Stillwater
country: United States
facility: Lakeview Hospital
state: Minnesota
city: Waconia
country: United States
facility: Ridgeview Medical Center
state: Minnesota
city: Willmar
country: United States
facility: Willmar Cancer Center at Rice Memorial Hospital
state: Minnesota
city: Woodbury
country: United States
facility: Minnesota Oncology - Woodbury
state: Minnesota
city: Bolivar
country: United States
facility: Central Care Cancer Center
state: Missouri
city: Cape Girardeau
country: United States
facility: Southeast Cancer Center
state: Missouri
city: Chesterfield
country: United States
facility: Saint Luke's Hospital
state: Missouri
city: Jefferson City
country: United States
facility: Goldschmidt Cancer Center
state: Missouri
city: Joplin
country: United States
facility: Freeman Cancer Institute
state: Missouri
city: Saint Louis
country: United States
facility: Missouri Baptist Cancer Center
state: Missouri
city: Saint Louis
country: United States
facility: Mercy Hospital St. Louis
state: Missouri
city: Billings
country: United States
facility: CCOP - Montana Cancer Consortium
state: Montana
city: Billings
country: United States
facility: Hematology-Oncology Centers of the Northern Rockies - Billings
state: Montana
city: Billings
country: United States
facility: Billings Clinic - Downtown
state: Montana
city: Bozeman
country: United States
facility: Bozeman Deaconess Cancer Center
state: Montana
city: Great Falls
country: United States
facility: Big Sky Oncology
state: Montana
city: Great Falls
country: United States
facility: Sletten Cancer Institute at Benefis Healthcare
state: Montana
city: Kalispell
country: United States
facility: Kalispell Regional Medical Center
state: Montana
city: Missoula
country: United States
facility: Montana Cancer Specialists at Montana Cancer Center
state: Montana
city: Kearney
country: United States
facility: Good Samaritan Cancer Center at Good Samaritan Hospital
state: Nebraska
city: Lebanon
country: United States
facility: Norris Cotton Cancer Center at Dartmouth-Hitchcock Medical Center
state: New Hampshire
city: Nashua
country: United States
facility: Foundation Medical Partners
state: New Hampshire
city: Nashua
country: United States
facility: Oncology Center at St. Joseph Hospital
state: New Hampshire
city: Englewood
country: United States
facility: Dizzy Gillespie Cancer Institute at Englewood Hospital and Medical Center
state: New Jersey
city: Long Branch
country: United States
facility: Monmouth Medical Center
state: New Jersey
city: Newark
country: United States
facility: UMDNJ University Hospital
state: New Jersey
city: Vineland
country: United States
facility: Franklin & Edith Scarpa Regional Cancer Center at South Jersey Healthcare
state: New Jersey
city: Albuquerque
country: United States
facility: Lovelace Medical Center - Downtown
state: New Mexico
city: Albuquerque
country: United States
facility: Presbyterian Cancer Treatment Center at Presbyterian Kaseman Hospital
state: New Mexico
city: Albuquerque
country: United States
facility: University of New Mexico Cancer Center
state: New Mexico
city: Cooperstown
country: United States
facility: Bassett Healthcare Regional Cancer Program at Mary Imogene Bassett Hospital
state: New York
city: Glens Falls
country: United States
facility: Charles R. Wood Cancer Center at Glens Falls Hospital
state: New York
city: Staten Island
country: United States
facility: Nalitt Cancer Institute at Staten Island University Hospital
state: New York
city: Henderson
country: United States
facility: Park Ridge Health
state: North Carolina
city: Akron
country: United States
facility: McDowell Cancer Center at Akron General Medical Center
state: Ohio
city: Akron
country: United States
facility: Summa Center for Cancer Care at Akron City Hospital
state: Ohio
city: Canton
country: United States
facility: Aultman Cancer Center at Aultman Hospital
state: Ohio
city: Dayton
country: United States
facility: David L. Rike Cancer Center at Miami Valley Hospital
state: Ohio
city: Dayton
country: United States
facility: Samaritan North Cancer Care Center
state: Ohio
city: Dayton
country: United States
facility: CCOP - Dayton
state: Ohio
city: Findlay
country: United States
facility: Blanchard Valley Medical Associates
state: Ohio
city: Franklin
country: United States
facility: Middletown Regional Hospital
state: Ohio
city: Greenville
country: United States
facility: Wayne Hospital
state: Ohio
city: Kettering
country: United States
facility: Charles F. Kettering Memorial Hospital
state: Ohio
city: Troy
country: United States
facility: UVMC Cancer Care Center at Upper Valley Medical Center
state: Ohio
city: Wright-Patterson Air Force Base
country: United States
facility: United States Air Force Medical Center - Wright-Patterson
state: Ohio
city: Xenia
country: United States
facility: Ruth G. McMillan Cancer Center at Greene Memorial Hospital
state: Ohio
city: Norman
country: United States
facility: Cancer Care Associates - Norman
state: Oklahoma
city: Oklahoma City
country: United States
facility: Cancer Care Associates - Mercy Campus
state: Oklahoma
city: Tulsa
country: United States
facility: Natalie Warren Bryant Cancer Center at St. Francis Hospital
state: Oklahoma
city: Danville
country: United States
facility: Geisinger Cancer Institute at Geisinger Health
state: Pennsylvania
city: Hazleton
country: United States
facility: Geisinger Hazleton Cancer Center
state: Pennsylvania
city: Philadelphia
country: United States
facility: Joan Karnell Cancer Center at Pennsylvania Hospital
state: Pennsylvania
city: Phoenixville
country: United States
facility: Cancer Center at Phoenixville Hospital
state: Pennsylvania
city: Sayre
country: United States
facility: Guthrie Cancer Center at Guthrie Clinic Sayre
state: Pennsylvania
city: State College
country: United States
facility: Geisinger Medical Group - Scenery Park
state: Pennsylvania
city: Wilkes-Barre
country: United States
facility: Frank M. and Dorothea Henry Cancer Center at Geisinger Wyoming Valley Medical Center
state: Pennsylvania
city: Beaufort
country: United States
facility: Keyserling Cancer Center at Beaufort Memorial Hospital
state: South Carolina
city: Greenville
country: United States
facility: St. Francis Hospital
state: South Carolina
city: Greer
country: United States
facility: Gibbs Cancer Center - Pelham
state: South Carolina
city: Rapid City
country: United States
facility: Rapid City Regional Hospital
state: South Dakota
city: Charlottesville
country: United States
facility: Martha Jefferson Hospital Cancer Care Center
state: Virginia
city: Green Bay
country: United States
facility: Green Bay Oncology, Limited at St. Vincent Hospital Regional Cancer Center
state: Wisconsin
city: Green Bay
country: United States
facility: Green Bay Oncology, Limited at St. Mary's Hospital
state: Wisconsin
city: Janesville
country: United States
facility: Mercy Regional Cancer Center
state: Wisconsin
city: La Crosse
country: United States
facility: Gundersen Lutheran Center for Cancer and Blood
state: Wisconsin
city: Mukwonago
country: United States
facility: D.N. Greenwald Center
state: Wisconsin
city: Oconomowoc
country: United States
facility: Regional Cancer Center at Oconomowoc Memorial Hospital
state: Wisconsin
city: Waukesha
country: United States
facility: Waukesha Memorial Hospital Regional Cancer Center
state: Wisconsin
Study officials:
affiliation: University of South Florida
name: Maya Guglin, MD, PhD
role: STUDY_CHAIR
affiliation: University of California, San Francisco
name: Pamela N. Munster, MD
role: STUDY_CHAIR
References:
citation: 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.