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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

Tracking Information
First Submitted Date  ICMJE November 6, 2009
First Posted Date  ICMJE November 9, 2009
Last Update Posted Date April 26, 2019
Study Start Date  ICMJE March 2010
Actual Primary Completion Date August 2017   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: May 20, 2013)
  • Reduction in incidence of trastuzumab-induced cardiotoxicity after 52 weeks of treatment as measured by preservation of LVEF [ Time Frame: 2 years ]
  • Comparison of the LVEF of each treatment group with the placebo arm [ Time Frame: 2 years ]
Original Primary Outcome Measures  ICMJE
 (submitted: November 6, 2009)
Reduction in incidence of trastuzumab-induced cardiotoxicity after 52 weeks of treatment as measured by preservation of LVEF
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: May 20, 2013)
  • Number of trastuzumab courses completed without interruption [ Time Frame: 2 years ]
  • Quality-of-life changes as assessed by EORTC-QLQ-C30 questionnaire at baseline and at the end of treatment [ Time Frame: 2 years ]
  • 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 ]
Original Secondary Outcome Measures  ICMJE
 (submitted: November 6, 2009)
  • Number of trastuzumab courses completed without interruption
  • Quality-of-life changes as assessed by EORTC-QLQ-C30 questionnaire at baseline and at the end of treatment
  • Long-term effects of study drugs as assessed at 18 and 24 months (or 6 and 12 months after completion of trastuzumab therapy)
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Lisinopril or Coreg CR® in Reducing Side Effects in Women With Breast Cancer Receiving Trastuzumab
Official Title  ICMJE 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®)
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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Supportive Care
Condition  ICMJE
  • Breast Cancer
  • Cardiac Toxicity
Intervention  ICMJE
  • Drug: Coreg CR®
    Given orally
    Other Name: carvedilol phosphate extended-release
  • Drug: lisinopril
    Given orally
    Other Name: Registered Trade names: Prinivil, Tensopril, Zestril, Hipril
  • Other: placebo
    Given orally
Study Arms  ICMJE
  • Experimental: Arm I lisinopril
    Patients receive oral lisinopril once daily.
    Intervention: Drug: lisinopril
  • Experimental: Arm II Coreg CR®
    Patients receive oral Coreg CR® once daily.
    Intervention: Drug: Coreg CR®
  • Placebo Comparator: Arm III placebo
    Patients receive oral placebo once daily.
    Intervention: Other: placebo
Publications * 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.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: November 6, 2009)
468
Original Estimated Enrollment  ICMJE Same as current
Actual Study Completion Date  ICMJE November 2018
Actual Primary Completion Date August 2017   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT01009918
Other Study ID Numbers  ICMJE SCUSF 0806
SCUSF-0806 ( Other Identifier: SunCoast CCOP Research Base )
5U10CA081920-11 ( U.S. NIH Grant/Contract )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party University of South Florida
Study Sponsor  ICMJE University of South Florida
Collaborators  ICMJE National Cancer Institute (NCI)
Investigators  ICMJE
Study Chair: Maya Guglin, MD, PhD University of South Florida
Study Chair: Pamela N. Munster, MD University of California, San Francisco
PRS Account University of South Florida
Verification Date April 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP