Carvedilol for the Prevention of Anthracycline/Anti-HER2 Therapy Associated Cardiotoxicity Among Women With HER2-Positive Breast Cancer Using Myocardial Strain Imaging for Early Risk Stratification

This study is currently recruiting participants. (see Contacts and Locations)
Verified June 2014 by Memorial Sloan-Kettering Cancer Center
Sponsor:
Information provided by (Responsible Party):
Memorial Sloan-Kettering Cancer Center
ClinicalTrials.gov Identifier:
NCT02177175
First received: June 26, 2014
Last updated: NA
Last verified: June 2014
History: No changes posted
  Purpose

The purpose of this study is to find out the effects, good and/or bad, of a beta blocker (carvedilol) on heart function during treatment with anti-HER2 medication(s) including trastuzumab (Herceptin).


Condition Intervention Phase
Breast Cancer
Drug: Carvedilol
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: Prevention
Official Title: Carvedilol for the Prevention of Anthracycline/Anti-HER2 Therapy Associated Cardiotoxicity Among Women With HER2-Positive Breast Cancer Using Myocardial Strain Imaging for Early Risk Stratification

Resource links provided by NLM:


Further study details as provided by Memorial Sloan-Kettering Cancer Center:

Primary Outcome Measures:
  • maximum change in LVEF [ Time Frame: at months 3, 6, 9, and 12 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • incidence of abnormal LVEF [ Time Frame: at months 3, 6, 9, and 12 ] [ Designated as safety issue: No ]

Estimated Enrollment: 90
Study Start Date: June 2014
Estimated Primary Completion Date: June 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Carvedilol
Treatment in both carvedilol and placebo groups will be systematically up-titrated at weeks 3, 6, and 9 (+/- 1 week) after randomization to a goal dose of 25mg twice daily.
Drug: Carvedilol
Placebo Comparator: placebo
Treatment in both carvedilol and placebo groups will be systematically up-titrated at weeks 3, 6, and 9 (+/- 1 week) after randomization to a goal dose of 25mg twice daily.
Other: placebo

Detailed Description:

This phase II placebo-controlled study will evaluate the effect of carvedilol, compared to placebo, on anthracycline/anti-HER2 therapy induced left ventricular dysfunction in patients with HER2-positive breast cancer who are receiving adjuvant or neoadjuvant therapy. All patients will undergo routine cardiac surveillance with 2D echocardiograms per standard of care at multiple time points including pre-anthracycline (baseline), pre-anti-HER2 therapy, and 3, 6, 9, and 12 months (+/- 4 weeks) after initiation of anti-HER2 therapy. Additional speckle tracking strain analysis will be performed on these echocardiograms, and blood specimens will be drawn at several time points for biomarker analysis.

After completion of anthracycline treatment and prior to initiation of anti-HER2 therapy, 32 patients with abnormal myocardial strain, defined as global longitudinal strain < 19% or % change from baseline by > 11%, will be randomized in a 1:1 ratio to carvedilol versus placebo. Carvedilol will be administered twice daily for approximately 1 year OR until the end of anti-HER2 therapy, if it is discontinued prior to 1 year. Treatment in both carvedilol and placebo groups will be systematically up-titrated at weeks 3, 6, and 9 (+/- 1 week) after randomization to a goal dose of 25mg twice daily.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Female
  • Age ≥ 18 years
  • Non-metastatic histologically confirmed primary invasive breast carcinoma
  • Pathologically confirmed HER2-positive breast cancer
  • Scheduled to receive anthracycline chemotherapy followed by anti-HER2 therapy
  • Women of childbearing potential must be willing to use one highly effective form of contraception
  • Able and willing to provide informed consent
  • Willing and able to comply with the requirements of the protocol
  • Able to swallow capsules

For Aim 2, all patients must meet the following criteria:

  • Meet all inclusion criteria above

    • LVEF > 50%
  • Abnormal global longitudinal strain (<19%, or a % decrease of ≥ 11% from baseline) prior to initiation of planned anti-HER2 therapy
  • Heart rate ≥ 50 beats per minute
  • Sitting systolic blood pressure > 90 mmHg

Exclusion Criteria:

  • Pregnant or lactating women, or women of childbearing potential without a negative serum pregnancy test, within 2 weeks prior to study entry, regardless of the method of contraception used .
  • Patients are to be excluded from randomization for Aim 2 of this study if they meet any of the following criteria:
  • Current treatment with ACE-inhibitors or beta blockers
  • Allergies or inability to tolerate beta blockers previously due to bradycardia, hypotension, or AV block.
  • Known history of NCI CTCAE (Version 4.0) Grade ≥ 2 symptomatic CHF, myocardial infarction within 12 months prior to randomization, significant symptoms (Grade ≥ 3) relating to left ventricular dysfunction, significant (moderate or severe) valvular disease, or significant cardiac arrhythmia (Grade > 3)
  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: NCT02177175

Contacts
Contact: Anthony Yu, MD 212-639-7932
Contact: Chau Dang, MD 646-888-5426

Locations
United States, New York
Memorial Sloan Kettering Cancer Center Recruiting
New York, New York, United States, 10065
Contact: Anthony Yu, MD    212-639-7932      
Contact: Chau Dang, MD    646-888-5426      
Principal Investigator: Anthony Yu, MD         
Sponsors and Collaborators
Memorial Sloan-Kettering Cancer Center
Investigators
Principal Investigator: Anthony Yu, MD Memorial Sloan-Kettering Cancer Center
  More Information

Additional Information:
No publications provided

Responsible Party: Memorial Sloan-Kettering Cancer Center
ClinicalTrials.gov Identifier: NCT02177175     History of Changes
Other Study ID Numbers: 14-099
Study First Received: June 26, 2014
Last Updated: June 26, 2014
Health Authority: United States: Institutional Review Board

Keywords provided by Memorial Sloan-Kettering Cancer Center:
Carvedilol
Anthracycline
HER2
14-099

Additional relevant MeSH terms:
Breast Neoplasms
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Carvedilol
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

ClinicalTrials.gov processed this record on July 20, 2014