Trial Information

Phase I Trial of Hepatic Arterial Infusion of Abraxane With a Pharmacokinetic Study in Advanced Solid Cancer Patients With Predominant Hepatic Metastases

The Study Drug:

Nab-paclitaxel is designed to block cancer cells from dividing, which may cause the cells to
die.

Giving nab-paclitaxel directly into the liver may allow a higher dose of the drug to be
given, while avoiding some of the side effects that occur when high doses of chemotherapy
are given other ways (for example, by vein into an arm).

Study Drug Dose Level:

If you are found to be eligible to take part in this study, you will be assigned to a study
group based on when you joined this study. Up to 9 groups of 6 participants will be
enrolled in Part 1 of the study, and up to 18 participants will be enrolled in Part 2. If
you are enrolled in Part 1, the dose of the study drug you receive will depend on when you
joined this study. The first group of participants will receive the lowest dose level of
the study drug. Each new group will receive a higher dose of the study drug than the group
before it, if no intolerable side effects were seen. This will continue until the highest
tolerable dose of the study drug is found. If you are enrolled in Part 2, you will receive
the study drug at the highest dose that was tolerated in the Part 1 portion.

Study Drug Administration:

The study drug will be given on Day 1 of "cycles" that are 21 days long. In Cycle 1 only,
some participants may receive the study drug through a vein in their arm. The infusion will
last 60 minutes. In Cycles 2 and later, you will receive the study drug through a catheter
(a thin plastic tube). Each time the catheter is placed, you will be admitted to the
hospital.

The doctor who performs the catheter placement procedure will explain it to you in more
detail, and you will be asked to sign a separate consent form that describes the procedure
and its risks in more detail.

You will be taken to the Interventional Radiology area, and the catheter will be placed in a
blood vessel in your groin area, on the right side of your body. The catheter will be
advanced to the liver. The catheter will be carefully taped in order to prevent it from
moving or coming out while you are receiving the study drug. You will be on bedrest for the
entire time that the catheter is in place.

After having the catheter inserted, you will be taken to the Nuclear Medicine area, and a
test called "flow study" will be performed in order to confirm that the catheter is in the
right place. The doctor who performs this test will explain it to you in more detail, and
you will be asked to sign a separate consent form that describes the procedure and its risks
in more detail.

After you return to your room, you will receive the study drug through the catheter over 60
minutes or 4 hours, depending on when you enroll. You will be asked to lie flat on your
back while receiving the study drug.

The catheter will be removed by someone experienced in the procedure. It will be removed
right after your study drug dose is complete. While the catheter is being removed, the
study staff will apply pressure to your groin area for 15 minutes in order to stop the
bleeding.

You will repeat this procedure once every 21 days. The catheter will be placed and removed
each time.

Study Procedures and Tests:

Once a week, including before each dose of the study drug, blood (about 2 teaspoons) will be
drawn for routine tests. These blood draws can be done at M. D. Anderson or somewhere else,
if there is a place that is more convenient for you.

Once during each cycle (on a day when you are already in clinic), you will have a physical
exam, including measurement of height, weight, and vital signs. Urine will be collected for
routine tests.

At the end of every 3 cycles, you will have scans performed (the same type of scans as at
screening) to check the status of the disease. If the study doctor feels it is appropriate,
you may have blood drawn (about 1 teaspoon) to look for tumor markers.

Blood Testing for Research Purposes:

In Cycles 1 and 2, additional blood will be drawn for pharmacokinetic (PK) testing. PK
testing measures the amount of study drug in the body at different time points. For
participants receiving the study drug over 60 minutes, this blood (about 1 teaspoon each
time) will be drawn on Day 1 (before you receive the study drug and at 5, 10, 20 and 40
minutes after the start of the dose, and then at 1, 1½, 2, 3, 4, and 6 hours after the start
of the dose). Blood will also be drawn on Day 2 (24 hours after the start of the dose).

For participants receiving the study drug over 4 hours, this blood (about 1 teaspoon each
time) will be drawn on Day 1 (before you receive the study drug and at 30 minutes after the
start of the dose, and then at 1, 2, 3, 4, 4 ½, 5, 6, 7, and 9 hours after the start of the
dose). Blood will also be drawn on Day 2 (24 hours after the start of the dose).

Length of Study Participation:

You will continue to receive the study drug once every 21 days. If the disease gets worse
or intolerable side effects occur, you will be taken off the study drug.

End-of-Study Visit:

After your last dose of the study drug, you will have an end-of-study visit. At this visit,
the following procedures will be performed:

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

- Blood (about 2 tablespoons) and urine will be collected for routine tests.

- To check the status of the disease, you will have scans performed (the same types of
scans that you had before).

- If the study doctor feels it is appropriate, you may have blood drawn (about 1
teaspoon) to look for tumor markers.

This is an investigational study. Nab-paclitaxel is commercially available and FDA approved
for use in breast cancer and for "systemic" use only. Systemic therapies affect the body as
a whole. It is investigational to give nab-paclitaxel directly into the liver and to give
it to patients with advanced cancer. At this time, giving it directly into the liver of
patients with advanced cancer is only being done in research.

Up to 56 patients will take part in this study. All will be enrolled at M. D. Anderson.