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Cardiotoxicity Prevention in Breast Cancer Patients Treated With Anthracyclines and/or Trastuzumab (SAFE)

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ClinicalTrials.gov Identifier: NCT02236806
Recruitment Status : Recruiting
First Posted : September 11, 2014
Last Update Posted : January 11, 2018
Sponsor:
Information provided by (Responsible Party):
Lorenzo Livi, Azienda Ospedaliero-Universitaria Careggi

Tracking Information
First Submitted Date  ICMJE September 9, 2014
First Posted Date  ICMJE September 11, 2014
Last Update Posted Date January 11, 2018
Actual Study Start Date  ICMJE July 2015
Estimated Primary Completion Date July 2019   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: September 9, 2014)
Left ventricular ejection fraction (LVEF) [ Time Frame: at months 6,9,12,24 ]
Maximum change in LVEF
Original Primary Outcome Measures  ICMJE Same as current
Change History Complete list of historical versions of study NCT02236806 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE Not Provided
Original Secondary Outcome Measures  ICMJE Not Provided
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Cardiotoxicity Prevention in Breast Cancer Patients Treated With Anthracyclines and/or Trastuzumab
Official Title  ICMJE Role of ACE Inhibitors and Beta Blockers as Cardiotoxicity Prevention in Breast Cancer Patients Treated With (Neo)Adjuvant Anthracyclines and/or Trastuzumab: a Four Arm, Placebo Control, Randomized Trial
Brief Summary The aim of the study is to analyze the protective impact on the cardiac damage of beta blockers and ACE inhibitors for breast cancer patients treated with anthracyclines-based chemotherapy with or without trastuzumab.
Detailed Description

Over the years, due to the use of new generation therapeutic regimens, as well as the use of advanced radiation techniques, the curability of breast cancer reached an overall 10-year survival rate of approximately 80%.

Anthracyclines have a key role in the treatment of breast cancer. Many published studies showed a benefit of disease-free survival in patients with positive lymph nodes treated with anthracyclines-based regimens. Many anthracyclines and taxanes-based regimens are currently used in clinical practice in the treatment of breast cancer. Numerous randomized trials have confirmed the benefit of the addition of taxanes to anthracyclines.

Trastuzumab is a recombinant humanized monoclonal antibody with specificity for the extracellular domain of human epidermal growth factor receptor 2 (HER2). The use of trastuzumab administered sequentially or concurrently with adjuvant chemotherapy compared to chemotherapy in patients with HER2 positive was evaluated in several randomized trials. Many data concerning the incidence of adverse cardiovascular events acute, subacute and late are now available. The cardiac toxicity of anthracyclines may be acute, subacute and chronic. The acute toxicity occurs during or shortly after the infusion of the drug with arrhythmias, which in some cases leads to heart failure, pericarditis-myocarditis and electrocardiographic abnormalities. The acute toxicity is usually reversible in a dose-dependent manner. The acute and subacute toxicity are rare (1-4%). Data are available concerning clinically relevant cardiac toxicity with a chronic progressive deterioration of ventricular function up to heart failure.

Beside the cumulative dose risk factor, other unfavourable features such as advanced age, female sex, and the combination of anthracyclines and trastuzumab should be evaluated. In most cases, the late toxicity occurs within the first year following completion of chemotherapy but nevertheless the clinical manifestations can occur even after 10-20 years. This fact suggests that in women treated in (neo)adjuvant setting is strongly necessary an echocardiographic monitoring even after a longer time.

The aim of the study is to analyze the protective impact on the cardiac damage of beta blockers and ACE inhibitors for breast cancer patients treated with anthracyclines-based chemotherapy with or without trastuzumab, using myocardial strain imaging monitoring.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single (Participant)
Primary Purpose: Prevention
Condition  ICMJE
  • Breast Cancer
  • Cardiotoxicity
Intervention  ICMJE
  • Drug: Bisoprolol
    5 mg daily
  • Drug: Ramipril
    5 mg daily
  • Drug: Placebo
    1 capsule daily
Study Arms  ICMJE
  • Experimental: Arm 1
    bisoprolol plus ramipril
    Interventions:
    • Drug: Bisoprolol
    • Drug: Ramipril
  • Active Comparator: Arm 2
    Bisoprolol plus placebo
    Interventions:
    • Drug: Bisoprolol
    • Drug: Placebo
  • Active Comparator: Arm 3
    Ramipril plus placebo
    Interventions:
    • Drug: Ramipril
    • Drug: Placebo
  • Placebo Comparator: Arm 4
    Placebo
    Intervention: Drug: Placebo
Publications * Meattini I, Curigliano G, Terziani F, Becherini C, Airoldi M, Allegrini G, Amoroso D, Barni S, Bengala C, Guarneri V, Marchetti P, Martella F, Piovano P, Vannini A, Desideri I, Tarquini R, Galanti G, Barletta G, Livi L. SAFE trial: an ongoing randomized clinical study to assess the role of cardiotoxicity prevention in breast cancer patients treated with anthracyclines with or without trastuzumab. Med Oncol. 2017 May;34(5):75. doi: 10.1007/s12032-017-0938-x. Epub 2017 Mar 31. Review.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: September 9, 2014)
480
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE July 2019
Estimated Primary Completion Date July 2019   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Female
  • Age >18 years
  • Non-metastatic histologically confirmed primary invasive breast cancer
  • Scheduled to receive neoadjuvant and/or adjuvant anthracyclines with or without anti-HER2 therapy
  • Provided informed consent
  • Able to swallow capsules
  • LVEF > 50%

Exclusion Criteria:

  • Pregnant or lactating women
  • Treatment with ACE-inhibitors or beta blockers at diagnosis
  • History of NCI Common Toxicity Criteria for Adverse Effects (CTCAE) (version 4.0) Grade >2 symptomatic congestive heart failure (CHF), previous myocardial infarction, significant symptoms (Grade>2) relating to LVEF dysfunction, valvular disease, cardiac arrhythmia (Grade>3)
Sex/Gender  ICMJE
Sexes Eligible for Study: Female
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Lorenzo Livi, Full Prof +39 055 7947264 lorenzo.livi@unifi.it
Listed Location Countries  ICMJE Italy
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02236806
Other Study ID Numbers  ICMJE SAFE2014
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE
Plan to Share IPD: Undecided
Responsible Party Lorenzo Livi, Azienda Ospedaliero-Universitaria Careggi
Study Sponsor  ICMJE Azienda Ospedaliero-Universitaria Careggi
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Lorenzo Livi, Full Prof Radiation Oncology Unit, Azienda Ospedaliero-Universitaria Careggi, University of Florence, Florence, Italy
PRS Account Azienda Ospedaliero-Universitaria Careggi
Verification Date January 2018

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP