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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

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.

Condition or disease Intervention/treatment Phase
Breast Cancer Cardiotoxicity Drug: Bisoprolol Drug: Ramipril Drug: Placebo Phase 3

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 : Interventional  (Clinical Trial)
Estimated Enrollment : 480 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single (Participant)
Primary Purpose: Prevention
Official Title: 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
Actual Study Start Date : July 2015
Estimated Primary Completion Date : July 2019
Estimated Study Completion Date : July 2019

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Breast Cancer
Drug Information available for: Trastuzumab

Arm Intervention/treatment
Experimental: Arm 1
bisoprolol plus ramipril
Drug: Bisoprolol
5 mg daily

Drug: Ramipril
5 mg daily

Active Comparator: Arm 2
Bisoprolol plus placebo
Drug: Bisoprolol
5 mg daily

Drug: Placebo
1 capsule daily

Active Comparator: Arm 3
Ramipril plus placebo
Drug: Ramipril
5 mg daily

Drug: Placebo
1 capsule daily

Placebo Comparator: Arm 4
Placebo
Drug: Placebo
1 capsule daily




Primary Outcome Measures :
  1. Left ventricular ejection fraction (LVEF) [ Time Frame: at months 6,9,12,24 ]
    Maximum change in LVEF



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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

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)

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): NCT02236806


Contacts
Contact: Lorenzo Livi, Full Prof +39 055 7947264 lorenzo.livi@unifi.it

Locations
Italy
Azienda Ospedaliero-Universitaria Careggi, Florence University Recruiting
Florence, Italy, 50141
Principal Investigator: Lorenzo Livi, Full Prof         
Sub-Investigator: Roberto Tarquini, MD         
Sub-Investigator: Icro Meattini, MD         
Sponsors and Collaborators
Azienda Ospedaliero-Universitaria Careggi
Investigators
Principal Investigator: Lorenzo Livi, Full Prof Radiation Oncology Unit, Azienda Ospedaliero-Universitaria Careggi, University of Florence, Florence, Italy

Additional Information:
Responsible Party: Lorenzo Livi, Full Professor, Azienda Ospedaliero-Universitaria Careggi
ClinicalTrials.gov Identifier: NCT02236806     History of Changes
Other Study ID Numbers: SAFE2014
First Posted: September 11, 2014    Key Record Dates
Last Update Posted: January 11, 2018
Last Verified: January 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

Keywords provided by Lorenzo Livi, Azienda Ospedaliero-Universitaria Careggi:
Breast cancer
Adjuvant chemotherapy
Neoadjuvant chemotherapy
Cardioprotection
Anthracyclines

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
Trastuzumab
Ramipril
Bisoprolol
Antineoplastic Agents
Angiotensin-Converting Enzyme Inhibitors
Protease Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Antihypertensive Agents
Sympatholytics
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Adrenergic beta-1 Receptor Antagonists
Adrenergic beta-Antagonists
Adrenergic Antagonists
Adrenergic Agents
Neurotransmitter Agents