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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 ongoing, but not recruiting participants.
Sponsor:
ClinicalTrials.gov Identifier:
NCT02177175
First Posted: June 27, 2014
Last Update Posted: May 30, 2017
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
Information provided by (Responsible Party):
Memorial Sloan Kettering Cancer Center
  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
Intervention Model: Parallel Assignment
Masking: Double (Participant, 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 ]

Secondary Outcome Measures:
  • incidence of abnormal LVEF [ Time Frame: at months 3, 6, 9, and 12 ]

Enrollment: 82
Actual Study Start Date: June 2014
Estimated Study Completion Date: June 2018
Estimated Primary Completion Date: June 2018 (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 which will align as closely as possible to the following: pre-anthracycline (baseline), pre-anti-HER2 therapy, and 3, 6, 9, and 12 months (+/- 4 weeks) after initiation of anti-HER2 therapy. In the case that standard of care echocardiograms are not done at these time points, either due to a delay in anti-cancer therapy or due to the patient's medical condition, the principal investigator will determine if the standard of care echocardiogram may be used in lieu of one of the time points listed. 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

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Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes 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 at MSKCC
  • 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:

  • 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)
  • Pre-menopausal women without a negative serum or urine pregnancy test within 4 weeks of starting treatment
  • Enrollment in a therapeutic intervention trial in the Breast Medicine service
  Contacts and Locations
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): NCT02177175


Locations
United States, New York
Memorial Sloan Kettering West Harrison
Harrison, New York, United States, 10604
Memorial Sloan Kettering Cancer Center
New York, New York, United States, 10065
Sponsors and Collaborators
Memorial Sloan Kettering Cancer Center
Investigators
Principal Investigator: Anthony Yu, MD Memorial Sloan Kettering Cancer Center
  More Information

Additional Information:
Responsible Party: Memorial Sloan Kettering Cancer Center
ClinicalTrials.gov Identifier: NCT02177175     History of Changes
Other Study ID Numbers: 14-099
First Submitted: June 26, 2014
First Posted: June 27, 2014
Last Update Posted: May 30, 2017
Last Verified: May 2017

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

Additional relevant MeSH terms:
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
Carvedilol
Trastuzumab
Adrenergic beta-Antagonists
Adrenergic Antagonists
Adrenergic Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Physiological Effects of Drugs
Antihypertensive Agents
Vasodilator Agents
Adrenergic alpha-1 Receptor Antagonists
Adrenergic alpha-Antagonists
Antineoplastic Agents