Trial Information

Early Detection of Cardiotoxicity During Sunitinib or Sorafenib Chemotherapy Using Cardiac Biomarkers

The Blood Tests:

Some chemotherapies are known to cause damage to heart muscle cells, resulting in heart
failure. Often, the damage is not detected until heart failure has already occurred. Some
studies have shown that the blood tests, troponin I and/or T, and BNP may be useful in
detecting heart damage earlier than other tests currently performed (such as echocardiogram
and electrocardiogram).

Several studies have shown that measuring BNP levels is useful in the diagnosis of heart
failure. BNP is produced by chambers in the heart in response to pressure and an overloaded
amount of blood, and it is connected to both abnormalities in patients treated with
doxorubicin. Short-term increases in BNP are seen after a patient is given a single dose of
anthracycline, but the patients with BNP levels that stay elevated appear to have the
greatest risk for developing heart-related side effects. BNP has also been shown to be
elevated before the development of a type of heart problem in patients undergoing high-dose
chemotherapy and stem cell transplantation.

Other biomarkers for early doxorubicin side effects, such as the levels of troponins I and T
in the blood, have recently been shown to be raised before changes in LVEF (Left Ventricular
Ejection Fraction: the percentage of blood emptied from the left ventricle of the heart
during contraction) and before the appearance of heart symptoms. There is no current
standard for these blood tests. The use of biomarkers (blood tests) to predict
heart-related side effects has not been fully tested and proven effective at this time.

Study Visits:

If you are found to be eligible to take part in this study, you will have 8 study visits,
including the baseline (screening) visit and the end-of-study visit. Visit 1 will be 2 weeks
after you begin chemotherapy. You will then have study visits about every 4-6 weeks (Visits
2-6).

At VISIT 1, the following tests and procedures will be performed:

- You will complete a questionnaire about any symptoms you may be experiencing.

- You will have a physical exam, including measurement of vital signs.

- Blood will be drawn for routine blood tests as a part of your standard-of-care. During
this standard-of-care blood draw, additional blood (about 1 teaspoon) will be drawn to
test troponin I and/or T and BNP levels.

At VISIT 2, the following tests and procedures will be performed:

- You will repeat the questionnaire about any symptoms you may be experiencing.

- You will have a physical exam, including measurement of vital signs.

- Blood will be drawn for routine blood tests as a part of your standard-of-care. During
this standard-of-care blood draw, additional blood (about 1 teaspoon) will be drawn to
test troponin I and/or T and BNP levels.

- If the study doctor thinks it is necessary, you will have an ECG.

- If the study doctor thinks it is necessary, you will have an echocardiogram.

At VISITS 3, 5, and 6, the following tests and procedures will be performed:

- If your study doctor thinks it is necessary, you will repeat the symptom questionnaire.

- You will have a physical exam, including measurement of vital signs.

- Blood will be drawn for routine blood tests as a part of your standard-of-care. During
this standard-of-care blood draw, additional blood (about 1 teaspoon) will be drawn to
test troponin I and/or T and BNP levels.

At VISIT 4, the following tests and procedures will be performed:

- You will repeat the symptom questionnaire.

- You will have a physical exam, including measurement of vital signs.

- Blood will be drawn for routine blood tests as a part of your standard-of-care. During
this standard-of-care blood draw, additional blood (about 1 teaspoon) will be drawn to
test troponin I and/or T and BNP levels.

- You will have an ECG.

- You will have an echocardiogram.

At any time during the study, if your doctor thinks it is necessary, you will have an ECG
and/or echocardiogram.

Length of Study:

This study will last about 6 months.

End-of-Study Visit:

About 6 months after you begin chemotherapy, you will have an end-of-study visit. At this
visit the following tests and procedures will be performed:

- You will fill repeat the symptom questionnaire.

- You will have a physical exam, including measurement of vital signs.

- Blood will be drawn for routine blood tests as a part of your standard-of-care. During
this standard-of-care blood draw, additional blood (about 1 teaspoon) will be drawn to
test troponin I and/or T and BNP levels.

- You will have an ECG.

- You will have an echocardiogram.

This is an investigational study. Up to 200 patients will take part in this study. All
will be enrolled at M. D. Anderson.