Trial of Fulvestrant, MK-0646, and Dasatinib for Metastatic Hormone Receptor-Positive HER2-Negative Breast Cancer

The Study Drugs:

Fulvestrant is designed to block estrogen from helping breast cancer tumor cells grow. By
blocking estrogen, it may stop tumor growth.

Dasatinib is designed to change the function of genes. By changing the function of these
genes, it may prevent cancer from growing and spreading.

MK-0646 is designed to block proteins that help breast cancer cells grow. By blocking these
proteins, it may cause the cancer cells to die.

Study Procedures:

You will have a fine needle aspiration or core needle biopsy before you start the study
treatment and after 2 weeks. These biopsies are to study genes and proteins, and to see how
they change with treatment.

Study Groups:

If you are found to be eligible to take part in this study: you will be enrolled in Phase I
or Phase II of the study, depending on when you join the study.

If you are in Phase I, you will be assigned to either Group 1, 2, 3, or 4. If you are in
Phase II, (based on the result of the screening biopsy) you will be randomly assigned (as in
a roll of dice) to either Group 1, 2, 3, or 4:

- Group 1 will receive fulvestrant only.

- Group 2 will receive fulvestrant and MK-0646.

- Group 3 will receive fulvestrant and dasatinib.

- Group 4 will receive fulvestrant, MK-0646, and dasatinib.

All participants will receive the same dose level of fulvestrant.

If you are in Groups 2, 3, or 4, the dose of MK-0646 and/or dasatinib you receive will
depend on when you joined this study. The first set of participants in each group will
receive the lowest dose level of MK-0646 and/or dasatinib. Each new set will receive a
higher dose of MK-0646 and/or dasatinib than the set before it, if no intolerable side
effects were seen. This will continue until the highest tolerable dose of MK-0646 and/or
dasatinib is found. This is called the Phase I portion of the study.

If you are enrolled in the Phase II portion of the study, you will receive MK-0646 and/or
dasatinib at the dose that was tolerated in the Phase I portion.

Study Drug Administration:

Every 28 days makes up 1 study cycle.

You will receive fulvestrant through a needle into your muscle on Days 1 and 15 of Cycle 1
and on Day 1 of Cycles 2 and beyond. Except for Day 1 of Cycle 1, you will have 1 injection
each time. On Day 1 of Cycle 1, you will have injections into 2 different muscles.

If you are in Group 2 or Group 4, you will receive MK-0646 through a needle in your vein
weekly.

If you are in Group 3 or Group 4, you will take capsules of dasatinib by mouth every day
while you are on study. You should take the drug at about the same time each day with a cup
(8 ounces) of water. The study staff will give you a card on which you must record every
time that you take dasatinib.

Study Visits:

On Day 1 of every cycle, the following tests and procedures will be performed:

- You will have a physical exam, including measurement of your weight.

- You will be asked about any other drugs you may be taking and about any side effects
you may be having.

- Your performance status will be recorded.

- Blood (about 1 tablespoon) will be drawn for routine tests and to see how your immune
system may be responding to the study drug.

- If you are in Group 2 or 4, you will have a hearing test.

On Day 1 of Cycle 1, your vital signs will be measured.

On Days 8 and 22 of Cycle 1, your vital signs and weight will be measured. You will have an
ECG.

On Day 15 of Cycle 1, the following tests and procedures will be performed:

- Blood (about 1 tablespoon) will be drawn to see how your immune system may be
responding to the study drug.

- Your vital signs and weight will be measured.

- You will have an ECG.

- You will have a PET scan

- You will have a core needle biopsy (which removes more tissue) and/or a fine needle
aspiration (which has a smaller needle).

On Days 1, 8, 15, and 22 of Cycles 2 and beyond, your weight will be measured. Your vital
signs will also be measured if you are in Group 2 or 4.

On Day 1 of Cycle 4 and every 3 cycles after that, you will have CT scans of the chest,
abdomen and/or pelvis, to check the status of the disease. If the disease has spread, you
may also have a bone scan and/or x-rays of the bones.

If you are taking warfarin to prevent abnormal blood clotting, blood (about 1-2 teaspoons)
will be drawn to check your blood clotting function at least 1 time a week until your blood
clotting function becomes stable. After that, blood (about 1-2 teaspoons) will continue
being drawn to check your blood clotting function as often as the doctor decides is needed.

Length of Study:

You may receive the study therapy until either you experience intolerable side effects or if
the disease gets worse; then you will be taken off study.

End-of-Study Visit:

After you are off study, you will have an end-of-study visit. At this visit, the following
tests and procedures will be performed:

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

- You will be asked about any other drugs you may be taking and about any side effects
you may be having.

- Your performance status will be recorded.

- Blood (about 2 teaspoons) will be collected for routine tests.

- You will have a hearing test if you received MK-0646.

Four (4), 8, and 12 weeks after the last dose of study drug, blood (about 1 tablespoon) will
be drawn to see how your immune system may have responded to the study drug.

This is an investigational study. MK-0646 is not FDA-approved or commercially available.
At this time, MK-0646 is only being used in research. Fulvestrant is currently FDA
-approved and commercially available for the treatment of metastatic breast cancer in
post-menopausal women. Dasatinib is FDA-approved and commercially available to treat
chronic myeloid leukemia. At this time, the use of dasatinib in breast cancer patients is
investigational.

Up to 100 patients will take part in this multicenter study. Up to 100 may be enrolled at
M. D. Anderson.