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

A

Azienda Ospedaliero-Universitaria Careggi

Status and phase

Unknown
Phase 3

Conditions

Cardiotoxicity
Breast Cancer

Treatments

Drug: Ramipril
Drug: Bisoprolol
Drug: Placebo

Study type

Interventional

Funder types

Other

Identifiers

NCT02236806
SAFE2014

Details and patient eligibility

About

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.

Full 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.

Enrollment

262 patients

Sex

Female

Ages

18+ years old

Volunteers

No Healthy Volunteers

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)

Trial design

Primary purpose

Prevention

Allocation

Randomized

Interventional model

Parallel Assignment

Masking

Double Blind

262 participants in 4 patient groups, including a placebo group

Arm 1
Experimental group
Description:
bisoprolol plus ramipril
Treatment:
Drug: Ramipril
Drug: Bisoprolol
Arm 2
Active Comparator group
Description:
Bisoprolol plus placebo
Treatment:
Drug: Placebo
Drug: Bisoprolol
Arm 3
Active Comparator group
Description:
Ramipril plus placebo
Treatment:
Drug: Ramipril
Drug: Placebo
Arm 4
Placebo Comparator group
Description:
Placebo
Treatment:
Drug: Placebo

Trial contacts and locations

1

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Data sourced from clinicaltrials.gov

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