Lisinopril or Coreg CR® in Reducing Side Effects in Women With Breast Cancer Receiving Trastuzumab - Full Text View

Purpose

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.

Condition	Intervention	Phase
Breast Cancer Cardiac Toxicity	Drug: Coreg CR® Drug: lisinopril Other: placebo	Phase 2


Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Parallel Assignment Masking: Double Blind (Subject, Investigator) Primary Purpose: Supportive Care
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®)

Resource links provided by NLM:

Genetics Home Reference related topics: breast cancer

MedlinePlus related topics: Breast Cancer Cancer

Drug Information available for: Carvedilol Lisinopril Trastuzumab Carvedilol hydrochloride

Genetic and Rare Diseases Information Center resources: Breast Cancer, Male

U.S. FDA Resources

Further study details as provided by University of South Florida:

Primary Outcome Measures:

Reduction in incidence of trastuzumab-induced cardiotoxicity after 52 weeks of treatment as measured by preservation of LVEF [ Time Frame: 2 years ] [ Designated as safety issue: No ]
Comparison of the LVEF of each treatment group with the placebo arm [ Time Frame: 2 years ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

Number of trastuzumab courses completed without interruption [ Time Frame: 2 years ] [ Designated as safety issue: No ]
Quality-of-life changes as assessed by EORTC-QLQ-C30 questionnaire at baseline and at the end of treatment [ Time Frame: 2 years ] [ Designated as safety issue: No ]
Long-term effects of study drugs as assessed at 18 and 24 months (or 6 and 12 months after completion of trastuzumab therapy) [ Time Frame: 2 years ] [ Designated as safety issue: No ]


Estimated Enrollment:	468
Study Start Date:	March 2010
Estimated Primary Completion Date:	July 2017 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: Arm I lisinopril Patients receive oral lisinopril once daily.	Drug: lisinopril Given orally Other Name: Registered Trade names: Prinivil, Tensopril, Zestril, Hipril
Experimental: Arm II Coreg CR® Patients receive oral Coreg CR® once daily.	Drug: Coreg CR® Given orally Other Name: carvedilol phosphate extended-release
Placebo Comparator: Arm III placebo Patients receive oral placebo once daily.	Other: placebo Given orally

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


Ages Eligible for Study:	18 Years and older (Adult, Senior)
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

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.

Contacts and Locations

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01009918

Show 174 Study Locations

Sponsors and Collaborators

University of South Florida

National Cancer Institute (NCI)

Investigators


Study Chair:	Maya Guglin, MD, PhD	University of South Florida
Study Chair:	Pamela N. Munster, MD	University of California, San Francisco

More Information


Responsible Party:	University of South Florida
ClinicalTrials.gov Identifier:	NCT01009918 History of Changes
Other Study ID Numbers:	SCUSF 0806 SCUSF-0806 5U10CA081920-11
Study First Received:	November 6, 2009
Last Updated:	September 16, 2016
Health Authority:	United States: Data and Safety Monitoring Board United States: Federal Government United States: Food and Drug Administration United States: Institutional Review Board

Keywords provided by University of South Florida:


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

Additional relevant MeSH terms:


Breast Neoplasms Cardiotoxicity Neoplasms by Site Neoplasms Breast Diseases Skin Diseases Pathologic Processes Drug-Related Side Effects and Adverse Reactions Chemically-Induced Disorders Radiation Injuries Wounds and Injuries Trastuzumab Carvedilol Lisinopril Antineoplastic Agents	Adrenergic beta-Antagonists Adrenergic Antagonists Adrenergic Agents Neurotransmitter Agents Molecular Mechanisms of Pharmacological Action Physiological Effects of Drugs Antihypertensive Agents Vasodilator Agents Adrenergic alpha-1 Receptor Antagonists Adrenergic alpha-Antagonists Angiotensin-Converting Enzyme Inhibitors Protease Inhibitors Enzyme Inhibitors Cardiotonic Agents Protective Agents

ClinicalTrials.gov processed this record on September 30, 2016