Trial Information

Detection of Cardiac Dysfunction in Patients Treated With Trastuzumab for HER-2 Positive Breast Cancer. The CADY Study

OBJECTIVES:

Primary

- To prospectively evaluate whether an increase in cardiac biomarker levels can predict
cardiac dysfunction in women with HER2/neu-positive breast cancer treated with
trastuzumab as curative intent.

Secondary

- To develop a predictive model for use in this patient population based on the most
accurate and sensitive combination of biomarkers.

This is an observational study with all patients having

- Blood tests for BNP, Nt-pro BNP, CRP and Troponin-T every 42 days (6 weeks) whilst on
treatment with chemotherapy and/or Trastuzumab.

- Echocardiograph or MUGA before treatment, after completion of anthracycline therapy
where applicable, and every twelve weeks whilst on Trastuzumab. Assessment of ejection
fraction may be carried out at any time for symptoms. All Echocardiographs and MUGAs
will be carried out locally. 2-D Echocardiograph is the preferred method for assessment
of LVEF. Where possible, the same cardiac imaging facility should be used for all LVEF
assessments. A sample study from each participating institution will be reviewed by the
principal investigating cardiologist. Results of left ventricular function assessment
will be used to make treatment decisions as normal. Managing clinicians will not be
made aware of the results of biomarker assessments, thus this study is blinded.

- Cardiorespiratory symptom assessment, ECOG score, vitals, weight and NYHA (if
applicable) prior to each dose of anthracyclines and every 6 weeks whilst on
Paclitaxel-trastuzumab and on single agent Trastuzumab.

Patients on BETH :

The LVEF monitoring sequence required by CADY will be altered to parallel that required by
BETH. Thus, echocardiograph or MUGA will be carried out according to the BETH cardiac safety
monitoring protocol. This altered schedule applies only to patients enrolled in both
studies. Of note, for patients on the BETH study, all LVEF assessments must be performed by
the same method used at baseline.

Patients on ALTTO:

It is possible that a patient who is enrolled on both CADY and ALLTO may not eventually
receive Trastuzumab. Nonetheless, as Lapatinib is also associated with a risk of
cardiotoxicity, such patients should remain on study whilst receiving single agent
Lapatinib. The schedule of on study assessments will be identical to that of patients
receiving Trastuzumab.

For patients enrolled in both studies, the LVEF monitoring sequence required by CADY will be
altered to parallel that required by ALLTO. Thus, echocardiograph or MUGA will be carried
out according to the ALLTO cardiac safety monitoring protocol Of note, for patients on the
ALLTO study, all LVEF assessments must be performed by the same method used at baseline.