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®)
Phase 2
18 Years
N/A
18 Years
N/A
Open (Enrolling)
Both
Breast Cancer, Cardiac Toxicity
Both
Breast Cancer, Cardiac Toxicity
Trial Information
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®)
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.
Inclusion 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.
Type of Study:
Interventional
Study Design:
Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Supportive Care
Outcome Measure:
Reduction in incidence of trastuzumab-induced cardiotoxicity after 52 weeks of treatment as measured by preservation of LVEF
Outcome Time Frame:
2 years
Safety Issue:
No
Principal Investigator
Maya Guglin, MD, PhD
Investigator Role:
Study Chair
Investigator Affiliation:
University of South Florida
Authority:
United States: Data and Safety Monitoring Board
Study ID:
SCUSF 0806
NCT ID:
NCT01009918
Start Date:
March 2010
Completion Date:
Related Keywords:
- Breast Cancer
- Cardiac Toxicity
- 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
- Breast Neoplasms
Name | Location |
|---|---|
| Suburban Hospital | Bethesda, Maryland 20814 |
| Barbara Ann Karmanos Cancer Institute | Detroit, Michigan 48201 |
| CCOP - Mount Sinai Medical Center | Miami Beach, Florida 33140 |
| CCOP - Illinois Oncology Research Association | Peoria, Illinois 61602 |
| CCOP - Iowa Oncology Research Association | Des Moines, Iowa 50309-1016 |
| CCOP - Metro-Minnesota | Saint Louis Park, Minnesota 55416 |
| Aurora Presbyterian Hospital | Aurora, Colorado 80012 |
| Boulder Community Hospital | Boulder, Colorado 80301-9019 |
| Penrose Cancer Center at Penrose Hospital | Colorado Springs, Colorado 80933 |
| CCOP - Colorado Cancer Research Program | Denver, Colorado 80224-2522 |
| Porter Adventist Hospital | Denver, Colorado 80210 |
| Presbyterian - St. Luke's Medical Center | Denver, Colorado 80218 |
| St. Joseph Hospital | Denver, Colorado 80218 |
| Rose Medical Center | Denver, Colorado 80220 |
| Swedish Medical Center | Englewood, Colorado 80110 |
| Sky Ridge Medical Center | Lone Tree, Colorado 80124 |
| Hope Cancer Care Center at Longmont United Hospital | Longmont, Colorado 80502 |
| St. Mary - Corwin Regional Medical Center | Pueblo, Colorado 81004 |
| Cedar Rapids Oncology Associates | Cedar Rapids, Iowa 52403 |
| West Michigan Cancer Center | Kalamazoo, Michigan 49007-3731 |
| Fairview Ridges Hospital | Burnsville, Minnesota 55337 |
| Mercy and Unity Cancer Center at Mercy Hospital | Coon Rapids, Minnesota 55433 |
| Fairview Southdale Hospital | Edina, Minnesota 55435 |
| Mercy and Unity Cancer Center at Unity Hospital | Fridley, Minnesota 55432 |
| Hutchinson Area Health Care | Hutchinson, Minnesota 55350 |
| HealthEast Cancer Care at St. John's Hospital | Maplewood, Minnesota 55109 |
| Hennepin County Medical Center - Minneapolis | Minneapolis, Minnesota 55415 |
| Virginia Piper Cancer Institute at Abbott - Northwestern Hospital | Minneapolis, Minnesota 55407 |
| St. Francis Cancer Center at St. Francis Medical Center | Shakopee, Minnesota 55379 |
| Park Nicollet Cancer Center | St. Louis Park, Minnesota 55416 |
| Regions Hospital Cancer Care Center | St. Paul, Minnesota 55101 |
| United Hospital | St. Paul, Minnesota 55102 |
| Ridgeview Medical Center | Waconia, Minnesota 55387 |
| Aultman Cancer Center at Aultman Hospital | Canton, Ohio 44710-1799 |
| Natalie Warren Bryant Cancer Center at St. Francis Hospital | Tulsa, Oklahoma 74136 |
| Geisinger Medical Group - Scenery Park | State College, Pennsylvania 16801 |
| Frank M. and Dorothea Henry Cancer Center at Geisinger Wyoming Valley Medical Center | Wilkes-Barre, Pennsylvania 18711 |
| Rapid City Regional Hospital | Rapid City, South Dakota 57709 |
| Memorial Hospital of South Bend | South Bend, Indiana 46601 |
| CCOP - Montana Cancer Consortium | Billings, Montana 59101 |
| CCOP - Dayton | Kettering, Ohio 45429 |
| CCOP - Northern Indiana CR Consortium | South Bend, Indiana 46601 |
| Saint Joseph Regional Medical Center | South Bend, Indiana 46617 |
| Norris Cotton Cancer Center at Dartmouth-Hitchcock Medical Center | Lebanon, New Hampshire 03756-0002 |
| MBCCOP - LSU Health Sciences Center | New Orleans, Louisiana 70112 |
| Monmouth Medical Center | Long Branch, New Jersey 07740-6395 |
| Louis A. Weiss Memorial Hospital | Chicago, Illinois 60640 |
| West Suburban Center for Cancer Care | River Forest, Illinois 60305 |
| UMDNJ University Hospital | Newark, New Jersey 07103 |
| McDowell Cancer Center at Akron General Medical Center | Akron, Ohio 44307 |
| Waukesha Memorial Hospital Regional Cancer Center | Waukesha, Wisconsin 53188 |
| Advocate Christ Medical Center | Oak Lawn, Illinois 60453 |
| Alvin and Lois Lapidus Cancer Institute at Sinai Hospital | Baltimore, Maryland 21215 |
| Green Bay Oncology, Limited at St. Vincent Hospital Regional Cancer Center | Green Bay, Wisconsin 54301-3526 |
| Green Bay Oncology, Limited at St. Mary's Hospital | Green Bay, Wisconsin 54303 |
| North Colorado Medical Center | Greeley, Colorado 80631 |
| McKee Medical Center | Loveland, Colorado 80539 |
| Battle Creek Health System Cancer Care Center | Battle Creek, Michigan 49017 |
| Northern Michigan Hospital | Petoskey, Michigan 49770 |
| Munson Medical Center | Traverse City, Michigan 49684 |
| Hematology-Oncology Centers of the Northern Rockies - Billings | Billings, Montana 59101 |
| Big Sky Oncology | Great Falls, Montana 59405 |
| Kalispell Regional Medical Center | Kalispell, Montana 59901 |
| Montana Cancer Specialists at Montana Cancer Center | Missoula, Montana 59802 |
| MBCCOP - Medical College of Georgia Cancer Center | Augusta, Georgia 30912-3730 |
| Lucille P. Markey Cancer Center at University of Kentucky | Lexington, Kentucky 40536-0093 |
| Butterworth Hospital at Spectrum Health | Grand Rapids, Michigan 49503-2560 |
| University of New Mexico Cancer Center | Albuquerque, New Mexico 87131-5636 |
| Geisinger Cancer Institute at Geisinger Health | Danville, Pennsylvania 17822-0001 |
| Gundersen Lutheran Center for Cancer and Blood | La Crosse, Wisconsin 54601 |
| Decatur Memorial Hospital Cancer Care Institute | Decatur, Illinois 62526 |
| Todd Cancer Institute at Long Beach Memorial Medical Center | Long Beach, California 90801 |
| Elkhart General Hospital | Elkhart, Indiana 46515 |
| Howard Community Hospital | Kokomo, Indiana 46904 |
| Lakeland Regional Cancer Care Center - St. Joseph | St. Joseph, Michigan 49085 |
| Lakeland Regional Cancer Center at Lakeland Regional Medical Center | Lakeland, Florida 33805 |
| Joan Karnell Cancer Center at Pennsylvania Hospital | Philadelphia, Pennsylvania 19107 |
| Ella Milbank Foshay Cancer Center at Jupiter Medical Center | Jupiter, Florida 33458 |
| Oncology Hematology Associates of Central Illinois, PC - Ottawa | Ottawa, Illinois 61350 |
| Center for Cancer Therapy at LaPorte Hospital and Health Services | La Porte, Indiana 46350 |
| Medical Oncology and Hematology Associates at John Stoddard Cancer Center | Des Moines, Iowa 50309 |
| Medical Oncology and Hematology Associates at Mercy Cancer Center | Des Moines, Iowa 50314 |
| Medical Oncology and Hematology Associates - West Des Moines | West Des Moines, Iowa 50266 |
| Bay Regional Medical Center | Bay City, Michigan 48708 |
| Mecosta County Medical Center | Big Rapids, Michigan 49307 |
| Providence Cancer Institute at Providence Hospital - Southfield Campus | Southfield, Michigan 48075 |
| Charles R. Wood Cancer Center at Glens Falls Hospital | Glens Falls, New York 12801 |
| Samaritan North Cancer Care Center | Dayton, Ohio 45415 |
| David L. Rike Cancer Center at Miami Valley Hospital | Dayton, Ohio 45409 |
| Blanchard Valley Medical Associates | Findlay, Ohio 45840 |
| Charles F. Kettering Memorial Hospital | Kettering, Ohio 45429 |
| Middletown Regional Hospital | Middletown, Ohio 45044 |
| UVMC Cancer Care Center at Upper Valley Medical Center | Troy, Ohio 45373-1300 |
| Ruth G. McMillan Cancer Center at Greene Memorial Hospital | Xenia, Ohio 45385 |
| St. Anthony Central Hospital | Denver, Colorado 80204-1335 |
| Exempla Lutheran Medical Center | Wheat Ridge, Colorado 80033 |
| Saint Luke's Hospital | Chesterfield, Missouri 63017 |
| Missouri Baptist Cancer Center | St. Louis, Missouri 63131 |
| Nancy N. and J. C. Lewis Cancer and Research Pavilion at St. Joseph's/Candler | Savannah, Georgia 31405 |
| Michiana Hematology-Oncology, PC - Elkhart | Elkhart, Indiana 46514 |
| Elkhart Clinic, LLC | Elkhart, Indiana 46514-2098 |
| Michiana Hematology Oncology PC - La Porte | La Porte, Indiana 46350 |
| Michiana Hematology-Oncology, PC - South Bend | Mishawaka, Indiana 46545-1470 |
| Michiana Hematology Oncology PC - Plymouth | Plymouth, Indiana 46563 |
| Reid Hospital & Health Care Services | Richmond, Indiana 47374 |
| Covenant Cancer Treatment Center | Waterloo, Iowa 50702 |
| Lakeside Cancer Specialists, PLLC | Saint Joseph, Michigan 49085 |
| Willmar Cancer Center at Rice Memorial Hospital | Willmar, Minnesota 56201 |
| Billings Clinic - Downtown | Billings, Montana 59107-7000 |
| Bozeman Deaconess Cancer Center | Bozeman, Montana 59715 |
| Sletten Cancer Institute at Benefis Healthcare | Great Falls, Montana 59405 |
| Summa Center for Cancer Care at Akron City Hospital | Akron, Ohio 44309-2090 |
| Wayne Hospital | Greenville, Ohio 45331 |
| Cancer Care Associates - Mercy Campus | Oklahoma City, Oklahoma 73120 |
| Geisinger Hazleton Cancer Center | Hazleton, Pennsylvania 18201 |
| Guthrie Cancer Center at Guthrie Clinic Sayre | Sayre, Pennsylvania 18840 |
| Regional Cancer Center at Memorial Medical Center | Springfield, Illinois 62781-0001 |
| Good Samaritan Cancer Center at Good Samaritan Hospital | Kearney, Nebraska 68848-1990 |
| Dizzy Gillespie Cancer Institute at Englewood Hospital and Medical Center | Englewood, New Jersey 07631 |
| Martha Jefferson Hospital Cancer Care Center | Charlottesville, Virginia 22901 |
| Regional Cancer Center at Oconomowoc Memorial Hospital | Oconomowoc, Wisconsin 53066 |
| Resurrection Medical Center | Chicago, Illinois 60631 |
| Jordan Hospital Club Cancer Center | Plymouth, Massachusetts 02360 |
| Nalitt Cancer Institute at Staten Island University Hospital | Staten Island, New York 10305 |
| La Grange Memorial Hospital | La Grange, Illinois 60525 |
| Lacks Cancer Center at Saint Mary's Health Care | Grand Rapids, Michigan 49503 |
| Franklin & Edith Scarpa Regional Cancer Center at South Jersey Healthcare | Vineland, New Jersey 08360 |
| Cancer Center at Phoenixville Hospital | Phoenixville, Pennsylvania 19460 |
| Galesburg Clinic, PC | Galesburg, Illinois 61401 |
| Illinois CancerCare - Bloomington | Bloomington%, Illinois 61701 |
| Illinois CancerCare - Canton | Canton, Illinois 61520 |
| Illinois CancerCare - Carthage | Carthage, Illinois 62321 |
| Illinois CancerCare - Eureka | Eureka, Illinois 61530 |
| Illinois CancerCare - Havana | Havana, Illinois 62644 |
| Illinois CancerCare - Kewanee Clinic | Kewanee, Illinois 61443 |
| Illinois CancerCare - Macomb | Macomb, Illinois 61455 |
| Illinois CancerCare - Monmouth | Monmouth, Illinois 61462 |
| Illinois CancerCare - Community Cancer Center | Normal, Illinois 61761 |
| Illinois CancerCare - Pekin | Pekin, Illinois 61603 |
| Illinois CancerCare - Peru | Peru, Illinois 61354 |
| Illinois CancerCare - Princeton | Princeton, Illinois 61356 |
| Mercy General Health Partners | Muskegon, Michigan 49443 |
| United States Air Force Medical Center - Wright-Patterson | Wright-Patterson AFB, Ohio 45433-5529 |
| Olive View - UCLA Medical Center Foundation | Sylmar, California 91342 |
| Oncology Center at St. Joseph Hospital | Nashua, New Hampshire 03060 |
| Lovelace Medical Center - Downtown | Albuquerque, New Mexico 87102 |
| Mercy Regional Cancer Center | Janesville, Wisconsin 53547 |
| Humphrey Cancer Center at North Memorial Outpatient Center | Robbinsdale, Minnesota 55422-2900 |
| Lakeview Hospital | Stillwater, Minnesota 55082 |
| Minnesota Oncology - Woodbury | Woodbury, Minnesota 55125 |
| Mercy Medical Center | Baltimore, Maryland 21202 |
| Bassett Healthcare Regional Cancer Program at Mary Imogene Bassett Hospital | Cooperstown, New York 13326 |
| Foundation Medical Partners | Nashua, New Hampshire 03060 |
| Keyserling Cancer Center at Beaufort Memorial Hospital | Beaufort, South Carolina 29902 |
| Clemens Regional Medical Center | Mount Clemens, Michigan 48043 |
| Southeast Cancer Center | Cape Girardeau, Missouri 63703 |
| Goldschmidt Cancer Center | Jefferson City, Missouri 65109 |
| Presbyterian Cancer Treatment Center at Presbyterian Kaseman Hospital | Albuquerque, New Mexico 87110 |
| Cancer Care Associates - Norman | Norman, Oklahoma 73071 |
| Littleton Adventist Hospital | Littleton, Colorado 80122 |
| Parker Adventist Hospital | Parker, Colorado 80138 |
| Mercy Hospital | Portland, Maine 04101 |
| Bloomington Hospital Regional Cancer Institute | Bloomington, Indiana 47403 |
| St. Francis Hospital Cancer Care Services | Indianapolis, Indiana 46237 |
| D.N. Greenwald Center | Mukwonago, Wisconsin 53149 |
| Singh and Arora Hematology Oncology, PC | Flint, Michigan 48532 |
| Great Lakes Cancer Institute - Lapeer Campus | Lapeer, Michigan 48446 |
