Trial record 1 of 1 for:    scusf 0806
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Lisinopril or Coreg CR® in Reducing Side Effects in Women With Breast Cancer Receiving Trastuzumab

This study is currently recruiting participants. (see Contacts and Locations)
Verified August 2014 by University of South Florida
Sponsor:
Collaborator:
Information provided by (Responsible Party):
University of South Florida
ClinicalTrials.gov Identifier:
NCT01009918
First received: November 6, 2009
Last updated: August 20, 2014
Last verified: August 2014
  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:


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: March 2016 (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
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
Investigators
Study Chair: Maya Guglin, MD, PhD University of South Florida
Study Chair: Pamela N. Munster, MD University of California, San Francisco
  More Information

Additional Information:
No publications provided

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: August 20, 2014
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
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Trastuzumab
Lisinopril
Carvedilol
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Angiotensin-Converting Enzyme Inhibitors
Protease Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Antihypertensive Agents
Cardiovascular Agents
Cardiotonic Agents
Protective Agents
Physiological Effects of Drugs
Adrenergic beta-Antagonists
Adrenergic Antagonists
Adrenergic Agents
Neurotransmitter Agents
Vasodilator Agents
Adrenergic alpha-1 Receptor Antagonists
Adrenergic alpha-Antagonists

ClinicalTrials.gov processed this record on September 22, 2014