Trial Information

Pilot Trial of Intraperitoneal Paclitaxel and Carboplatin With IV Avastin Therapy in Treatment of Women With Newly Diagnosed, Optimally Cytoreduced Carcinoma of Mullerian Origin

The Study Drugs:

Carboplatin is designed to interfere with the growth of cancer cells by stopping cell
division, which may cause the cells to die.

Paclitaxel is designed to block the mechanisms of cell division in cancer cells, which may
cause them to die.

Avastin is designed to prevent or slow down the growth of cancer cells by blocking the
effects of VEGF, a blood-vessel stimulating agent that plays an important role in the growth
of both normal and abnormal blood vessels.

Intraperitoneal Port (IP) Placement:

If you are found eligible to take part in this study, you will need to have an IP port,
called an intraperitoneal catheter tube, placed into the abdomen. The catheter will be used
to give the paclitaxel and carboplatin directly into your abdomen. You may already have had
this catheter placed at a previous surgery. If not, you will have a minor surgical procedure
in the operating room to have it placed. You will be asked to sign a separate surgical
consent form describing this procedure, the risks involved, and the steps for taking care of
the catheter while it is in place.

Study Drug Administration:

You will receive up to 6 cycles of treatment with the study drugs. Each cycle is 21 days (3
weeks) long.

Cycle 1:

You will receive paclitaxel and carboplatin through a needle in your vein on Day 1.
Paclitaxel is given first followed by carboplatin. Both drugs are given over 1 hour. On
Days 8 and 15 you will only receive paclitaxel by vein. This infusion is also given over 1
hour.

Cycle 2:

On Day 1, about 2 cups of normal saline will be infused into your abdomen through the IP
catheter. This infusion takes 30-60 minutes. You will then receive paclitaxel through the IP
port in your abdomen. When the paclitaxel infusion is complete, you will receive carboplatin
through the IP port. Each infusion takes about 1 hour. After the chemotherapy infusions are
complete, another 2-4 cups of normal saline will be infused through the port. This is done
to help move the chemotherapy to all areas of your abdomen. You will be asked to change
position frequently.

On Day 8, about 2 cups of normal saline will be infused into your abdomen through the IP
catheter. You will then receive paclitaxel through the IP port in your abdomen over 1 hour.
While you are receiving paclitaxel through your IP port, you will also receive Avastin by
vein. The first dose of Avastin will be given over 90 minutes. If you tolerate the first
infusion well, the second infusion (given in Cycle 3) may be given over 60 minutes. If the
60-minute infusion is well-tolerated, all infusions after that may be given over 30 minutes.
After the paclitaxel infusion is complete, you will receive another 2-4 cups of normal
saline through the port. You will be asked to change position frequently.

On Day 15, about 2 cups of normal saline will be infused into your abdomen through the IP
catheter. You will then receive paclitaxel through the IP port in your abdomen. After the
paclitaxel infusion is complete, you will receive another 2-4 cups of normal saline through
the port. You will be asked to change position frequently.

Cycles 3-6:

On Day 1, about 2 cups of normal saline will be infused into your abdomen through the IP
catheter. You will receive paclitaxel through the IP catheter over 1 hour. After completing
paclitaxel, you will receive carboplatin through the IP catheter over 1 hour. After these
infusions are complete you will receive another 2-4 cups of normal saline through the port.
You will be asked to change position frequently. While undergoing IP therapy with paclitaxel
and carboplatin, you will also receive the second infusion of Avastin by vein. The length of
this infusion will depend how well you tolerated the drug the first time it was given in
Cycle 2.

On Days 8 and 15, about 2 cups of normal saline will be infused into your abdomen through
the IP catheter. You will then receive paclitaxel through the IP port in your abdomen over 1
hour. After the paclitaxel infusion is complete, you will receive another 2-4 cups of normal
saline through the port. You will be asked to change position frequently.

Before you receive paclitaxel and carboplatin, you will receive the drug dexamethasone by
vein to help decrease the risk of study drug side effects. You may also receive other drugs
(such as cimetidine and diphenhydramine) by vein to help with side effects, such as nausea
and allergic reaction. The choice of which drugs to use is up to your doctor.

Study Visits:

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

- Your medical history will be recorded, including a list of any drugs you are taking.

- You will be asked how well you are able to perform your normal daily activities
(performance status evaluation).

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

- You will be asked about any side effects you are experiencing.

- Blood (about 3 teaspoons) will be drawn for routine tests (this will be repeated on
Days 8 and 15 of each cycle as well).

Blood (about 1 teaspoon) will be drawn to check your CA125 level before treatment starts in
Cycle 1 and on Day 1 of Cycles 2, 4, and 6.

Before treatment starts in Cycle 1 and on Day 8 of Cycle 2 and Day 1 of Cycles 3-6, urine
will be collected for routine tests.

On Days 1, 8, and 15 of Cycles 1, 2, and 4, blood (1 teaspoon each time) will be drawn 12
different times each day for pharmacokinetic (PK) testing. PK testing measures the amount of
study drugs in the body at different time points. Blood (1 teaspoon each time) will also be
drawn 1 time on Days 2 and 3 of Cycles 1, 2, and 4.

On Day 8 of Cycle 2 and Day 1 of Cycles 3, 4, and 6 before paclitaxel starts, you will have
the levels of vascular endothelial growth factor (VEGF) in your abdominal fluid measured.
VEGF is a protein that causes fluid build-up (ascites) in the abdomen. About 2 cups of
normal saline will be infused through the IP port. You will be asked to change positions for
about 15 minutes. Then about 3-4 tablespoons of the fluid will be removed from the port with
a syringe. This shows how Avastin is affecting your abdominal fluid. You will also have
blood (about 1 teaspoon) drawn to check the levels of VEGF in your blood.

Length of Study:

You may remain on this study for up to 6 cycles. You will be taken off study early if the
disease gets worse or intolerable side effects occur.

End-of-Study Visit:

Once 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.

- You will have a computed tomography (CT) scan.

- Blood (about 1 teaspoon) will be drawn to check your CA125 level.

Long-Term Follow-Up:

After your last study visit, you will be contacted about every 3 months from then on to
check on how you are doing. You will return to the clinic (if you come to M. D. Anderson for
your regular care) or researchers will call you on the phone to ask you questions about how
you are doing. Your doctor will tell you if any standard tests and procedures need to be
performed.

This is an investigational study. Avastin, carboplatin, and paclitaxel are FDA approved and
commercially available for the treatment of many types of cancer. At this time, the addition
of Avastin to paclitaxel and carboplatin is being used to treat ovarian cancer in research
only.

Up to 46 patients will take part in this multicenter study. Up to 15 will be enrolled at M.
D. Anderson.