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®)”

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 women with HER2-positive breast cancer receiving trastuzumab.

Study Type: Interventional

Study Design: Supportive Care, Randomized, Double-Blind, Placebo Control

Study Primary Completion Date: March 2013

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 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.

OUTLINE: This is a multicenter study. 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.

Intervention(s) in this Clinical Trial

• Drug: carvedilol phosphate extended-release
  • Given orally
• Drug: lisinopril
  • Given orally
• Other: placebo
  • Given orally

Arms, Groups and Cohorts in this Clinical Trial

• Experimental: Arm I
  • Patients receive oral lisinopril once daily.
• Experimental: Arm II
  • Patients receive oral carvedilol phosphate extended-release once daily.
• Placebo Comparator: Arm III
  • Patients receive oral placebo once daily.

Primary Measures

• Reduction in incidence of trastuzumab-induced cardiotoxicity after 52 weeks of treatment as measured by preservation of LVEF
  • Safety Issue?: No

Secondary Measures

• Number of trastuzumab courses completed without interruption
  • Safety Issue?: No
• Quality-of-life changes as assessed by EORTC-QLQ-C30 questionnaire at baseline and at the end of treatment
  • 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)
  • Safety Issue?: No

DISEASE CHARACTERISTICS:

• Diagnosis of HER2-positive breast cancer
• Scheduled to receive adjuvant or neoadjuvant trastuzumab therapy
• Anthracycline-containing regimens allowed
• 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
• 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
• No other concurrent angiotensin-converting enzyme (ACE) inhibitors, β-blockers, or digoxin
• Concurrent participation in other investigational studies allowed

Gender Eligibility for this Clinical Trial: Female

Minimum Age for this Clinical Trial: 18 Years

Maximum Age for this Clinical Trial: N/A

Are Healthy Volunteers Accepted for this Clinical Trial?: No

Lead Sponsor: H. Lee Moffitt Cancer Center and Research Institute

Overall Clinical Trial Officials and Contacts

Maya Guglin, MD, PhD Study Chair H. Lee Moffitt Cancer Center and Research Institute  

Information obtained from ClinicalTrials.gov on February 08, 2010

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT01009918

Study ID Number: CDR0000654123

ClinicalTrials.gov Identifier: NCT01009918

Health Authority: Unspecified

Clinical trial summary from the National Cancer Institute's PDQ® database