Clinical trial NCT00858039: Cardiotoxicity of Adjuvant Trastuzumab
Official title: Prediction of Cardiotoxicity Using Serum N-terminal Pro-B-type Natriuretic Peptide in Breast Cancer Patients Receiving Adjuvant Trastuzumab
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Breast Neoplasms
Heart Failure
Lead sponsor: Royal Prince Alfred Hospital, Sydney, Australia
Sponsor class: OTHER
First posted: 2009-03-09
Enrollment: 220
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Patients presenting to tertiary referral medical oncology clinics

Brief summary: Trastuzumab (Herceptin®) increases the chances of cure in patients with Her-2 overexpressing early breast cancer. Unfortunately, both the chemotherapy drugs used in this setting (anthracyclines) and trastuzumab are known to cause cardiac dysfunction in a proportion of patients. Patients who develop heart problems when taking trastuzumab might have to stop this treatment, which could jeopardise their chances of cure. N-terminal pro-B-type natriuretic peptide (NT pro-BNP) is a cardiac biomarker that is measured in the blood, the levels of which have been shown to indicate the presence of heart failure. Some early research has suggested that there may be a correlation between elevated NT pro-BNP and heart damage due to cancer chemotherapy and also trastuzumab. Troponin is another substance measured in the blood that can indicate heart damage. Finally, certain variations in an individual's genetic makeup (called polymorphisms) could put them at increased risk of heart damage from trastuzumab. Here we are studying whether any of these factors (NT pro-BNP levels, troponin levels, or certain genetic polymorphisms) can accurately predict who is at highest risk of trastuzumab-related cardiotoxicity.

The principal aim of this study is to evaluate the utility of NT pro-BNP as a predictive biomarker for the development of trastuzumab related cardiotoxicity (TRC). The investigators will also examine if single nucleotide polymorphisms in the HER2 gene or Fc-gamma-receptor genes predict for TRC.


Eligibility criteria: Inclusion Criteria:

* Female 18 years or older
* Histologically confirmed, completely excised invasive breast cancer with Her-2 overexpression
* Primary surgery less than twelve weeks prior to registration
* LVEF\>50% as assessed by transthoracic echocardiogram or gated heart pool scan
* Eastern Cooperative Oncology Group Performance Status 0-2
* Adjuvant systemic treatment plan comprises at least three cycles of anthracycline chemotherapy AND 52 weeks of trastuzumab
* Before patient registration, informed consent must be given according to local regulations.

Exclusion Criteria:

* Pregnancy
* Distant metastases from breast cancer
* Any systemic chemotherapy prior to study entry

Primary outcomes:
measure: Cardiotoxicity (Cardiac death; grade 3/4 arrhythmia or ischaemia; NYHA Class 3 or 4 heart failure decline in LVEF by >10% to a level <55%; decline in LVEF by >5% to a level <50%)
timeFrame: Until 6 months after completing trastuzumab
Secondary outcomes:
Other outcomes:
Locations:
city: Sydney
country: Australia
facility: Royal Prince Alfred Hospital
state: New South Wales
city: Sydney
country: Australia
facility: Royal North Shore Private Hospital
state: New South Wales
city: Sydney
country: Australia
facility: Sydney Haematology Oncology Clinic
state: New South Wales
city: Sydney
country: Australia
facility: Concord Hospital
state: New South Wales
city: Sydney
country: Australia
facility: Liverpool Hospital
state: New South Wales
city: Sydney
country: Australia
facility: Bankstown Hospital
state: New South Wales
city: Sydney
country: Australia
facility: St George Private Hospital
state: New South Wales
city: Sydney
country: Australia
facility: Sutherland Hospital
state: New South Wales
city: Sydney
country: Australia
facility: Macarthur Cancer Therapy Centre
state: New South Wales
city: Sydney
country: Australia
facility: Nepean Cancer Care Centre
state: New South Wales
city: Tweed Heads
country: Australia
facility: Tweed Hospital
state: New South Wales
city: Brisbane
country: Australia
facility: Royal Brisbane Hospital
state: Queensland
city: Geelong
country: Australia
facility: Andrew Love Cancer Centre
state: Victoria
city: Warnambool
country: Australia
facility: Warnambool Hospital
state: Victoria
city: Perth
country: Australia
facility: The Mount Hospital
state: Western Australia
Study officials:
affiliation: Sydney South West Area Health Service (Royal Prince Alfred Hospital)
name: Jane Beith, MBBS FRACP PhD
role: STUDY_DIRECTOR
References:
citation: Goel S, Liu J, Guo H, Barry W, Bell R, Murray B, Lynch J, Bastick P, Chantrill L, Kiely BE, Abdi E, Rutovitz J, Asghari R, Sullivan A, Harrison M, Kohonen-Corish M, Beith J. Decline in Left Ventricular Ejection Fraction Following Anthracyclines Predicts Trastuzumab Cardiotoxicity. JACC Heart Fail. 2019 Sep;7(9):795-804. doi: 10.1016/j.jchf.2019.04.014. Epub 2019 Aug 7.