Tasigna Neoadjuvant Gastrointestinal Stromal Tumor (GIST)

GIST is a rare cancer known as a soft-tissue sarcoma that forms in the gastrointestinal (GI)
tract and may spread to other parts of the body. However, sometimes GIST stays in the GI
tract where it may possibly be removed by surgery. While some chemotherapy drugs, such as
imatinib mesylate, are effective in shrinking or controlling GIST, some types of GIST tumors
do not respond to imatinib. Researchers want to find out if nilotinib (a drug similar to
imatinib) causes GIST cells to die, so that the tumors shrink enough to be removed by
surgery.

The Study Drugs:

Nilotinib is designed to prevent cells from multiplying by causing tumor cells to shrink
and/or die. This may prevent the cancer from growing.

Study Arms and Study Drug Administration:

If you are found to be eligible to take part in this study, a surgeon from M. D. Anderson
will check your imaging scans to decide if the tumor can be surgically removed.

Participants in this research study will be assigned to either Arm 1 or Arm 2, based on
whether the tumor is able to be removed by surgery at this point.

Arm 1:

If the surgeon thinks the tumor is able to be removed during surgery, you will be assigned
to Arm 1. You will receive nilotinib pills by mouth 2 times a day for 7 days. You will
receive a pill diary and will be shown how to record the date and time for each dose
received.

After the week of nilotinib therapy, you will be scheduled to have the GIST removed during
surgery. Tumor tissue that is removed during surgery will be used for research testing.
Some of these tests will help researchers learn how effectively nilotinib kills tumor cells.
Your DNA and RNA (the genetic material in your cells) will also be collected from these
tissue samples and used to help researchers understand how these tumor cells survive,
divide, and die as a result of nilotinib.

After 4-6 weeks of recovery time after surgery, you will receive standard of care treatment
off-study.

An assigned research nurse will see you at each clinic visit and will serve as the first
contact for any questions or concerns. During the course of this study, you will be asked
to report any serious problems or concerns at each study visit. If you have concerns or
questions between each study visits, you may contact your study nurse through the Sarcoma
Center at M. D. Anderson.

Arm 1 Study Visits:

Participants in Arm 1 will have the following tests and procedures performed:

On Day -7, you will begin taking nilotinib.

On Day -1:

- You will have a dynamic CT scan within 36 hours before surgery to check the status of
the disease.

- Blood (about 2-3 teaspoons) will be drawn for routine tests.

- You will have an ECG.

On Day 0, you will have surgery to remove the GIST.

On Day 56:

- You will be asked about your health, any drugs you may be taking, and any side effects
you may have experienced.

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

- Your performance status will be recorded.

- You will have a chest x-ray.

- You will have a standard CT scan or an MRI scan to check the status of the disease.

- Blood (about 2-3 teaspoons) will be drawn for routine tests.

Every 3 months:

- You will be asked about your health, any drugs you may be taking, and any side
effects you may have experienced.

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

- Your performance status will be recorded.

- You will have a standard CT scan or an MRI scan to check the status of the disease.

- Blood (about 2-3 teaspoons) will be drawn for routine tests.

Arm 2:

If the surgeon thinks the tumor is not able to be surgically removed at this time, or that
the tumor needs to shrink before it can be removed during surgery, you will be assigned to
Arm 2. You will receive nilotinib pills by mouth 2 times a day for 7 days. You will
receive a pill diary and will be shown how to record the date and time for each dose
received.

After the week of nilotinib therapy, you will be scheduled to have a biopsy on what is
counted as Day 0 on your pill diary. After 7 days of recovery from the biopsy, you will
continue receiving nilotinib on the same schedule (2 times a day by mouth).

After 8 weeks of nilotinib therapy, you will have more scans performed to measure the size
of the tumor. These scans will include a CT scan of your abdomen or pelvis. You may have a
magnetic resonance imaging (MRI) scan instead, if you have chronic kidney disease.

If the scans show that the tumor has gotten smaller, you will meet with the surgeon to
discuss surgery to remove the tumor. If you are scheduled to have surgery, you will stop
taking nilotinib 1 day before your surgery date. If the tumor has gotten bigger, you will
be taken off study treatment, and other treatment options will be discussed with you. If the
scan shows that the tumor is unchanged, you will continue to receive nilotinib until the
tumor either shrinks (and you are able to have surgery) or gets bigger (and you are taken
off study treatment).

Tumor tissue that is removed during your scheduled biopsy or during surgery will also be
used for biological and genetic testing.

After you have surgery, you will receive standard of care treatment off-study, depending on
the results of the surgery.

Your doctor may recommend that you begin taking imatinib mesylate after surgery (or if the
disease has gotten worse and you are not able to have surgery). In many cases, imatinib
mesylate is given on a daily basis for 1-2 years to lower the risk of the disease coming
back. During the time after the surgery, information will be collected about your overall
health.

If the disease gets worse while you are on study, and you agree, you will be asked to have a
tumor biopsy of an easily accessible area. If this happens, this procedure will be
described to you in more detail, and you will sign a separate consent.

An assigned research nurse will see you at each clinic visit and will serve as the first
contact for any questions or concerns. During the course of this study, you will be asked
to report any serious problems or concerns at each study visit. If you have concerns or
questions between each study visits, you may contact your study nurse through the Sarcoma
Center at M.D. Anderson.

Arm 2 Study Visits:

Participants in Arm 2 will have the following tests and procedures performed:

On Day -7, you will begin taking nilotinib.

On Day -1:

- You will have a a dynamic CT scan within 36 hours before your biopsy to check the
status of the disease.

- Blood (about 2-3 teaspoons) will be drawn for routine tests.

- You will have an ECG.

On Day 0:

-You will have a tumor tissue biopsy performed. To collect a tumor tissue biopsy, the skin
above and around the tumor area is numbed with anesthetic, and a sample of tumor tissue is
withdrawn through a large needle.

On Day 56:

- You will be asked about your health, any drugs you may be taking, and any side effects
you may have experienced.

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

- Your performance status will be recorded.

- You will have a chest x-ray.

- You will have a standard CT scan or an MRI scan to check the status of the disease.

- Blood (about 2-3 teaspoons) will be drawn for routine tests.

Depending on the results of the tests at Day 56 you will either have surgery, continue
nilotinib, or be taken off study and switched to another therapy.

Every 3 months:

- You will be asked about your health, any drugs you may be taking, and any side
effects you may have experienced.

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

- Your performance status will be measured.

- You will have a standard CT scan or an MRI scan to check the status of the disease.

- Blood (about 2-3 teaspoons) will be drawn for routine tests.

Additional Testing for Both Groups:

You will have blood (about 1 teaspoon each time) drawn for pharmacokinetic (PK) testing. PK
testing measures the amount of study drug in the body at different time points. These PK
samples will be drawn after the first 6 days of nilotinib (Day -1) and either at the
end-of-treatment visit or at any point that the disease gets worse.

When/if your treatment is interrupted for any reason and/or your dose is changed in any way,
you will also have ECGs performed. You will have an additional ECG 7 days after this.

End-of-Treatment 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 performance status will be recorded.

- You will be asked about your health, any drugs you may be taking, and any side effects
you may have experienced.

- Blood (about 1 tablespoon) will be drawn for routine tests.

- You will have an ECG.

- You will have a CT or MRI scan to check the status of the disease.

Length of Study:

You may continue taking the study drug for 1 week (Arm 1) before you have surgery. You may
continue taking the study drug for as long as your doctor thinks it is in your best
interest, or until you are able to have surgery (Arm 2). You will no longer be able to take
the study drug if the disease gets worse or intolerable side effects occur.

Follow-up Testing:

You will be asked to return to the clinic every 3 months for standard follow-up testing,
including routine blood tests and CT scans.

This is an investigational study. Nilotinib is FDA approved and commercially available for
the treatment of certain types of chronic myeloid leukemia. Its use in patients with GIST
is investigational.

Up to 24 patients will take part in this study. All will be enrolled at M. D. Anderson.