NCT02236806

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.

Trial Health

43
At Risk

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Trial has exceeded expected completion date
Enrollment
262

participants targeted

Target at P25-P50 for phase_3 breast-cancer

Timeline
Completed

Started Jul 2015

Typical duration for phase_3 breast-cancer

Geographic Reach
1 country

1 active site

Status
unknown

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

September 9, 2014

Completed
2 days until next milestone

First Posted

Study publicly available on registry

September 11, 2014

Completed
10 months until next milestone

Study Start

First participant enrolled

July 1, 2015

Completed
6.9 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

June 1, 2022

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

June 1, 2022

Completed
Last Updated

February 1, 2022

Status Verified

January 1, 2022

Enrollment Period

6.9 years

First QC Date

September 9, 2014

Last Update Submit

January 16, 2022

Conditions

Breast CancerCardiotoxicity

Keywords

Breast cancerAdjuvant chemotherapyNeoadjuvant chemotherapyCardioprotectionAnthracyclines

Outcome Measures

Primary Outcomes (2)

  • Left ventricular ejection fraction (LVEF)

    Change in LVEF (3-dimensional and 2-dimensional) at time-frame

    at months 6,9,12,24

  • Global longitudinal strain (GLS)

    Change in GLS at time-frame

    at months 6,9,12,24

Secondary Outcomes (2)

  • Indexed left ventricular end diastolic volume (EDVI)

    at months 6,9,12,24

  • Indexed left ventricular end systolic volume (ESVI)

    at months 6,9,12,24

Study Arms (4)

Arm 1

EXPERIMENTAL

bisoprolol plus ramipril

Drug: BisoprololDrug: Ramipril

Arm 2

ACTIVE COMPARATOR

Bisoprolol plus placebo

Drug: BisoprololDrug: Placebo

Arm 3

ACTIVE COMPARATOR

Ramipril plus placebo

Drug: RamiprilDrug: Placebo

Arm 4

PLACEBO COMPARATOR

Placebo

Drug: Placebo

Interventions

BisoprololDRUG

5 mg daily

Arm 1Arm 2
RamiprilDRUG

5 mg daily

Arm 1Arm 3
PlaceboDRUG

1 capsule daily

Arm 2Arm 3Arm 4

Eligibility Criteria

Age18 Years+
Sexfemale
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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%

You may not qualify if:

  • 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)

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Azienda Ospedaliero-Universitaria Careggi, Florence University

Florence, 50141, Italy

Location

Related Publications (4)

  • Francolini G, Desideri I, Meattini I, Becherini C, Terziani F, Olmetto E, Delli Paoli C, Pezzulla D, Loi M, Bonomo P, Greto D, Calusi S, Casati M, Pallotta S, Livi L. Assessment of a guideline-based heart substructures delineation in left-sided breast cancer patients undergoing adjuvant radiotherapy : Quality assessment within a randomized phase III trial testing a cardioprotective treatment strategy (SAFE-2014). Strahlenther Onkol. 2019 Jan;195(1):43-51. doi: 10.1007/s00066-018-1388-x. Epub 2018 Nov 7.

    PMID: 30406290BACKGROUND

  • 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.

    PMID: 28364270BACKGROUND

  • Livi L, Barletta G, Martella F, Saieva C, Desideri I, Bacci C, Del Bene MR, Airoldi M, Amoroso D, Coltelli L, Scotti V, Becherini C, Visani L, Salvestrini V, Mariotti M, Pedani F, Bernini M, Sanchez L, Orzalesi L, Nori J, Bianchi S, Olivotto I, Meattini I. Cardioprotective Strategy for Patients With Nonmetastatic Breast Cancer Who Are Receiving an Anthracycline-Based Chemotherapy: A Randomized Clinical Trial. JAMA Oncol. 2021 Oct 1;7(10):1544-1549. doi: 10.1001/jamaoncol.2021.3395.

    PMID: 34436523RESULT

  • Marrazzo L, Meattini I, Becherini C, Salvestrini V, Visani L, Barletta G, Saieva C, Del Bene MR, Pilato G, Desideri I, Arilli C, Paoletti L, Russo S, Scoccianti S, Martella F, Francolini G, Simontacchi G, Nori Cucchiari J, Pellegrini R, Livi L, Pallotta S. Subclinical cardiac damage monitoring in breast cancer patients treated with an anthracycline-based chemotherapy receiving left-sided breast radiation therapy: subgroup analysis from a phase 3 trial. Radiol Med. 2024 Dec;129(12):1926-1935. doi: 10.1007/s11547-024-01897-6. Epub 2024 Oct 22.

    PMID: 39436588DERIVED

MeSH Terms

Conditions

Breast NeoplasmsCardiotoxicity

Interventions

BisoprololRamipril

Condition Hierarchy (Ancestors)

Neoplasms by SiteNeoplasmsBreast DiseasesSkin DiseasesSkin and Connective Tissue DiseasesHeart DiseasesCardiovascular DiseasesPathologic ProcessesPathological Conditions, Signs and SymptomsDrug-Related Side Effects and Adverse ReactionsChemically-Induced DisordersRadiation InjuriesWounds and Injuries

Intervention Hierarchy (Ancestors)

PhenoxypropanolaminesPropanolaminesAmino AlcoholsAlcoholsOrganic ChemicalsPropanolsAminesHeterocyclic Compounds, 2-RingHeterocyclic Compounds, Fused-RingHeterocyclic Compounds

Study Officials

  • Lorenzo Livi, MD, Prof

    Azienda Ospedaliero-Universitaria Careggi

    STUDY CHAIR

  • Icro Meattini, MD, Prof

    University of Florence

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
interventional
Phase
phase 3
Allocation
RANDOMIZED
Masking
DOUBLE
Who Masked
PARTICIPANT, CARE PROVIDER
Masking Details
Both participants and Care Providers are not aware of intervention allocation.
Purpose
PREVENTION
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
PRINCIPAL INVESTIGATOR
PI Title
Full Professor

Study Record Dates

First Submitted

September 9, 2014

First Posted

September 11, 2014

Study Start

July 1, 2015

Primary Completion

June 1, 2022

Study Completion

June 1, 2022

Last Updated

February 1, 2022

Record last verified: 2022-01

Data Sharing

IPD Sharing
Will not share

Locations

IT(1)