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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT01009918
Recruitment Status : Completed
First Posted : November 9, 2009
Last Update Posted : April 26, 2019
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
University of South Florida

Study Description
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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.


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

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.

Study Design
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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 468 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, 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®)
Study Start Date : March 2010
Actual Primary Completion Date : August 2017
Actual Study Completion Date : November 2018

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Breast Cancer

Arms and Interventions
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Arm Intervention/treatment
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


Outcome Measures
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Primary Outcome Measures :
  1. Reduction in incidence of trastuzumab-induced cardiotoxicity after 52 weeks of treatment as measured by preservation of LVEF [ Time Frame: 2 years ]
  2. Comparison of the LVEF of each treatment group with the placebo arm [ Time Frame: 2 years ]

Secondary Outcome Measures :
  1. Number of trastuzumab courses completed without interruption [ Time Frame: 2 years ]
  2. Quality-of-life changes as assessed by EORTC-QLQ-C30 questionnaire at baseline and at the end of treatment [ Time Frame: 2 years ]
  3. 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 ]

Eligibility Criteria
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Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
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
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01009918


Locations
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Sponsors and Collaborators
University of South Florida
National Cancer Institute (NCI)
Investigators
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Study Chair: Maya Guglin, MD, PhD University of South Florida
Study Chair: Pamela N. Munster, MD University of California, San Francisco
More Information
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Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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Responsible Party: University of South Florida
ClinicalTrials.gov Identifier: NCT01009918    
Other Study ID Numbers: SCUSF 0806
SCUSF-0806 ( Other Identifier: SunCoast CCOP Research Base )
5U10CA081920-11 ( U.S. NIH Grant/Contract )
First Posted: November 9, 2009    Key Record Dates
Last Update Posted: April 26, 2019
Last Verified: April 2019
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:
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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
Carvedilol
Lisinopril
Adrenergic beta-Antagonists
Adrenergic Antagonists
 Adrenergic Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Physiological Effects of Drugs
Antihypertensive Agents
Antioxidants
Protective Agents
Calcium Channel Blockers
Membrane Transport Modulators
Calcium-Regulating Hormones and Agents
Vasodilator Agents
Adrenergic alpha-1 Receptor Antagonists
Adrenergic alpha-Antagonists
Angiotensin-Converting Enzyme Inhibitors
Protease Inhibitors