The Cardio-Oncology Breast Cancer Study (COBC)

March 6, 2018 updated by: Elham Hedayati, Karolinska University Hospital

Effects of Identifying and Treating Early, Subclinical Cardiotoxicity on the Long-Term Incidence of Clinical Cardiotoxicity in Women With Breast Cancer, A Prospective Randomized Study: The Cardio-Oncology Breast Cancer Study (COBC)

The main objective of this randomized controlled trial is to test the association between standard cardiac risk factors, biomarkers and parameters of echocardiography, electrocardiography, and cardiac magnetic resonance imaging, (predictors) and subsequent occurrence, frequency and severity of clinical or subclinical cardiotoxicity (outcome) within and between-groups, before start of chemotherapy, during treatment and at 1, 5, and 10 years after the completion of the chemotherapy among women with early breast cancer.

Study Overview

Status

Unknown

Conditions

Intervention / Treatment

Detailed Description

Rationale for the study:

Breast cancer is the most common cancer among Swedish women, accounting for a third of all cancer cases among females. The breast cancer incidence has increased from 2596 to more than 8000 breast cancer diagnosis 2011. During the past 40 years, the age-adjusted incidence has doubled. Early adjuvant therapy reduces the risk of dying with about 50%. (Early adjuvant therapies; chemotherapy, antibodies, endocrine therapy, and radiotherapy). Treatment advances have improved survival rates, but treatment-related cardiotoxicity (CT) remains a substantial problem.

In general, earlier treatment of cardiotoxicity offers the best chances of preventing or ameliorating clinical cardiotoxicity. Risk factors should be modified or reduced by treating elevated blood pressure, normalizing lipids, encouraging weight reduction and smoking cessation. Patient-tailored therapy is now possible, especially given the availability of different chemotherapy regimens, safer anthracycline analogs such as liposomal doxorubicin, and cardioprotective medications such as angiotensin converting enzyme (ACE)-inhibitors, angiotensin receptor blockers, and b-blockers. It is now suggested that new cardiac biomarkers and ultrasound techniques can detect cardiotoxicity in its early, subclinical, stages. The investigators hypothesized that biomarkers can be used to detect subclinical cardiotoxicity and that detecting early signs of cardiotoxicity might reduce the number, time-to-onset, and severity of cardiotoxic events.

In present proposal the investigators aim in a randomized study to compare primary cardiac preventive measurements versus standard care.

Objectives of the trial:

  1. Primary objective In a randomized study to investigate the cumulative incidence of cardiotoxic events, per randomized arm, before start of chemotherapy, during treatment and at 1, 5, and 10 years after the completion of the chemotherapy.
  2. Secondary Objectives To compare the number, time-to-onset, and severity of cardiotoxic events in an experimental group assessed and treated for subclinical cardiotoxicity before start of chemotherapy, during treatment and at 1, 5, and 10 years after the completion of the chemotherapy and a control group receiving standard of care without early assessment for subclinical cardiotoxicity. Data on the same variables will be collected from both groups before start of chemotherapy, during treatment and at 1, 5, and 10 years. Data from the experimental group will be used in real time to guide therapy, but data from the control group will be not be analyzed until after the end of the study.

To assess subclinical cardiotoxicity with serum concentrations of biomarkers, tissue Doppler and strain echocardiography, electrocardiography, and magnetic resonance imaging, as well as with standard cardiac risk assessment based on standard risk factors: a history of heart disease, increasing age, obesity, hypertension, diabetes mellitus, hypercholesterolemia, smoking, parasternal radiotherapy, and the cumulative dose of anthracyclines and trastuzumab.

To assess the association between primary treatment of existing standard cardiac risk factors, biomarkers and parameters of echocardiography, electrocardiography, and cardiac magnetic resonance imaging, (predictors) and subsequent occurrence of clinical or subclinical cardiotoxicity of cardiotoxicity (outcome) within and between-groups, over time.

To examine how a diagnosis of breast cancer and the development of cardiotoxicity influences women's quality of life.

Study Type

Interventional

Enrollment (Anticipated)

320

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Sweden
      • Stockholm, Sweden, 171 76
        • Karolinska University Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

Female

Description

Inclusion Criteria:

  • Women with newly diagnosed breast cancer who are eligible to receive neo-adjuvant or adjuvant chemotherapy, with or without trastuzumab, according to the guidelines for breast cancer.
  • Written informed consent must be given.

Exclusion Criteria:

  • A history of heart disease; ischemic heart disease, arrhythmias, heart failure, and valve diseases.
  • Previously received oncological treatment for any malignancy.
  • Other disease or conditions that complicates or precludes the patient from following the study protocol.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Prevention
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
No Intervention: Observational arm
Participants randomized to observational arm will receive standard oncological followup and care.
Experimental: Intervention arm
Intervention arm receives standard oncological followup and care + subclinical cardiotoxicity surveillance and treatment.
Other: Subclinical cardiotoxicity surveillance and treatment
Intervention arm receives cardiology assessment and intervention.
Other Names:
  • Assessment and intervention of cardiac risk factors.
  • Assessment of biomarkers, echocardiography and ECG.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Event free survival
Time Frame: 1 year after the completion of the chemotherapy.
The cumulative incidence of clinical or subclinical cardiotoxicity, per randomized arm, in women with breast cancer at 1 year after treatment with neo- or adjuvant chemotherapy.
1 year after the completion of the chemotherapy.

Secondary Outcome Measures

Outcome Measure
Time Frame
Event free survival
Time Frame: 5 and 10 years after the completion of the chemotherapy.
5 and 10 years after the completion of the chemotherapy.
Overall survival
Time Frame: 1, 5 and 10 years after the completion of the chemotherapy.
1, 5 and 10 years after the completion of the chemotherapy.
The levels of serum biomarkers (hs-Troponin T (hs-TnT), B-type natriuretic peptide (BNP)).
Time Frame: 1, 5 and 10 years after the completion of the chemotherapy.
1, 5 and 10 years after the completion of the chemotherapy.
Echocardiographic global longitudinal strain
Time Frame: 1, 5 and 10 years after the completion of the chemotherapy.
1, 5 and 10 years after the completion of the chemotherapy.
The quality of life
Time Frame: 1, 5 and 10 years after the completion of the chemotherapy.
1, 5 and 10 years after the completion of the chemotherapy.

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Karolinska University Hospital

Investigators

  • Principal Investigator: Elham Hedayati, MD, PhD, Karolinska University Hospital
  • Principal Investigator: Laila Hubbert, MD, PhD, University Hospital, Linkoeping

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

July 1, 2014

Primary Completion (Anticipated)

February 1, 2020

Study Completion (Anticipated)

February 1, 2020

Study Registration Dates

First Submitted

September 20, 2015

First Submitted That Met QC Criteria

October 7, 2015

First Posted (Estimate)

October 8, 2015

Study Record Updates

Last Update Posted (Actual)

March 7, 2018

Last Update Submitted That Met QC Criteria

March 6, 2018

Last Verified

March 1, 2018

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • COBC

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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