Lisinopril or Coreg CR® in Reducing Side Effects in Women With Breast Cancer Receiving Trastuzumab
This study is currently recruiting participants.
Verified January 2013 by University of South Florida
Sponsor:
University of South Florida
Collaborator:
Information provided by (Responsible Party):
University of South Florida
ClinicalTrials.gov Identifier:
NCT01009918
First received: November 6, 2009
Last updated: May 20, 2013
Last verified: January 2013
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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
Please refer to this study by its ClinicalTrials.gov identifier: NCT01009918
Show 167 Study Locations
Show 167 Study LocationsSponsors 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: | May 20, 2013 |
| 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 Carvedilol Lisinopril Trastuzumab Adrenergic beta-Antagonists Adrenergic Antagonists Adrenergic Agents Neurotransmitter Agents Molecular Mechanisms of Pharmacological Action Pharmacologic Actions |
Physiological Effects of Drugs Antihypertensive Agents Cardiovascular Agents Therapeutic Uses Vasodilator Agents Adrenergic alpha-1 Receptor Antagonists Adrenergic alpha-Antagonists Angiotensin-Converting Enzyme Inhibitors Protease Inhibitors Enzyme Inhibitors Cardiotonic Agents Protective Agents Antineoplastic Agents |
ClinicalTrials.gov processed this record on June 18, 2013