Lisinopril or Coreg CR® in Reducing Side Effects in Women With Breast Cancer Receiving Trastuzumab
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| ClinicalTrials.gov Identifier: NCT01009918 |
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Recruitment Status :
Active, not recruiting
First Posted : November 9, 2009
Last Update Posted : September 19, 2016
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Sponsor:
University of South Florida
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
University of South Florida
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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 |
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 : | Interventional (Clinical Trial) |
| Estimated 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 |
| Estimated Primary Completion Date : | July 2017 |
Resource links provided by the National Library of Medicine
Genetics Home Reference related topics:
Breast cancer
MedlinePlus related topics:
Breast Cancer
| Arm | Intervention/treatment |
|---|---|
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Experimental: Arm I lisinopril
Patients receive oral lisinopril once daily.
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Drug: lisinopril
Given orally
Other Name: Registered Trade names: Prinivil, Tensopril, Zestril, Hipril |
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Experimental: Arm II Coreg CR®
Patients receive oral Coreg CR® once daily.
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Drug: Coreg CR®
Given orally
Other Name: carvedilol phosphate extended-release |
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Placebo Comparator: Arm III placebo
Patients receive oral placebo once daily.
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Other: placebo
Given orally |
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 ]
- Comparison of the LVEF of each treatment group with the placebo arm [ Time Frame: 2 years ]
Secondary Outcome Measures :
- 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 ]
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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.
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
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 |
| Responsible Party: | University of South Florida |
| ClinicalTrials.gov Identifier: | NCT01009918 History of Changes |
| 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: | September 19, 2016 |
| Last Verified: | September 2016 |
Keywords provided by University of South Florida:
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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 Trastuzumab Lisinopril Carvedilol Antineoplastic Agents |
Angiotensin-Converting Enzyme Inhibitors Protease Inhibitors Enzyme Inhibitors Molecular Mechanisms of Pharmacological Action Antihypertensive 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 |