Lisinopril or Carvedilol Phosphate in Reducing Side Effects in Women With HER2-Positive Breast Cancer Receiving Trastuzumab - Full Text View

Purpose

RATIONALE: Lisinopril or carvedilol phosphate may help reduce side effects caused by trastuzumab. It is not yet known whether lisinopril or carvedilol phosphate are more effective than a placebo in reducing side effects caused by trastuzumab.

PURPOSE: This phase II trial is studying lisinopril and carvedilol phosphate 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: carvedilol phosphate extended-release capsule Drug: lisinopril Other: placebo	Phase 2

Study Type:	Interventional
Study Design:	Allocation: Randomized Masking: Double-Blind 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:

Genetics Home Reference related topics: breast cancer

MedlinePlus related topics: Breast Cancer Cancer

Drug Information available for: Carvedilol Lisinopril Trastuzumab Carvedilol phosphate

U.S. FDA Resources

Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:

Reduction in incidence of trastuzumab-induced cardiotoxicity after 52 weeks of treatment as measured by preservation of LVEF [ Designated as safety issue: No ]
Comparison of the LVEF of each treatment group with the placebo arm [ Designated as safety issue: No ]

Secondary Outcome Measures:

Number of trastuzumab courses completed without interruption [ Designated as safety issue: No ]
Quality-of-life changes as assessed by EORTC-QLQ-C30 questionnaire at baseline and at the end of treatment [ 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) [ Designated as safety issue: No ]

Estimated Enrollment:	468
Study Start Date:	March 2010
Estimated Primary Completion Date:	March 2013 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: Arm I Patients receive oral lisinopril once daily.	Drug: lisinopril Given orally
Experimental: Arm II Patients receive oral carvedilol phosphate extended-release once daily.	Drug: carvedilol phosphate extended-release capsule Given orally
Placebo Comparator: Arm III Patients receive oral placebo once daily.	Other: placebo Given orally

Detailed Description:

OBJECTIVES:

Primary

To determine if administration of lisinopril or carvedilol phosphate extended-release (compared to placebo) will reduce the incidence of trastuzumab-induced cardiotoxicity, as measured by LVEF, in women receiving adjuvant or neoadjuvant trastuzumab for HER2-positive breast cancer.

Secondary

To determine whether patients randomized to receive lisinopril or carvedilol phosphate extended-release have fewer interruptions in trastuzumab therapy due to cardiomyopathy.
To determine whether the treatment effect is consistent in anthracycline and nonanthracycline patient cohorts.
To determine changes in quality of life (QOL) in patients treated with these regimens.
To determine the long-term effects of lisinopril and/or carvedilol phosphate extended-release on the prevention of cardiomyopathy and their impact on QOL.
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 carvedilol phosphate extended-release 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

DISEASE CHARACTERISTICS:

Diagnosis of HER2-positive breast cancer
Scheduled to receive adjuvant or neoadjuvant trastuzumab therapy
- Anthracycline-containing regimens allowed
- Patients receive trastuzumab with their chemotherapy allowed for eligibility work-up
- Taxanes are allowed
- Trastuzumab therapy may be given with or after primary chemotherapy
- Pertuzumab may be used in conjunction with trastuzumab
No metastatic disease
Hormone receptor status not specified

PATIENT CHARACTERISTICS:

Menopausal status not specified
LVEF ≥ 50% by MUGA or ECHO
Creatinine ≤ 1.2 mg/dL
Sitting systolic BP > 90 mm Hg
Pulse ≥ 60 beats/minute
Not pregnant or nursing
Negative pregnancy test
Fertile patients must use effective contraception
Able to swallow capsules
Adequate renal function for administration of trastuzumab-containing chemotherapy regimen
No known cardiac history (i.e., heart failure, myocardial infarction, or radiation-induced cardiac dysfunction)
No known allergy to either ACE inhibitors or β-blockers
No history of bronchial asthma or related bronchospastic conditions
No hereditary or idiopathic angioedema
No history of severe hypersensitivity reactions to drugs or other causes (e.g., bee stings)

PRIOR CONCURRENT THERAPY:

See Disease Characteristics
No prior trastuzumab or anthracyclines prior to this chemotherapy regimen
No current treatment with other angiotensin-converting enzyme (ACE) inhibitors or angiotensin receptor blockers (ARBs), such as losartan, β-blockers, or digoxin
Concurrent participation in other investigational studies allowed

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT01009918

Show 167 Study Locations

Sponsors and Collaborators

University of South Florida

National Cancer Institute (NCI)

Investigators

Study Chair:	Maya Guglin, MD, PhD	H. Lee Moffitt Cancer Center and Research Institute
Investigator:	Pamela N. Munster, MD	University of California, San Francisco

More Information

Additional Information:

Clinical trial summary from the National Cancer Institute's PDQ® database This link exits the ClinicalTrials.gov site

No publications provided

Responsible Party:	Viki Huegel, SunCoast CCOP Research Base at the University of South Florida
ClinicalTrials.gov Identifier:	NCT01009918 History of Changes
Other Study ID Numbers:	CDR0000654123, SCUSF-0806, HLMCC-0806
Study First Received:	November 6, 2009
Last Updated:	January 22, 2013
Health Authority:	Unspecified

Keywords provided by National Cancer Institute (NCI):

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 May 16, 2013