Trial Information

A Pilot Study Evaluating the Feasibility of an Intercontinental Phase III Chemotherapy Study for Patients With Choroid Plexus Tumors

Tumors of the choroid plexus epithelium are rare. Participants in this study will have
surgery to remove as much of the brain tumor as possible. Taking as much of the tumor out
during surgery is generally believed to have the best result for this disease. Some
participants may even have a second surgery to remove more tumor if thought necessary.

After the tumor surgery, exact treatment for each participant in this study will depend on
how much of the tumor is removed during surgery and the way the tumor tissue looks under a
microscope. Some participants will not require additional treatment because most or all of
the tumor has been taken out. Those participants will still be on study, but they will only
have observation and not receive additional treatment. Those that require additional
treatment will be randomly assigned (as in the toss of a coin) to one of 2 treatment groups
with an equal chance of being assigned to either group.

Chemotherapy (treatment with anti-cancer drugs) will be given as part of treatment for
participants whose tumors are not completely removed surgically. Participants in one group
will receive carboplatin plus etoposide, vincristine, and radiation therapy . Participants
in the other group will receive cyclophosphamide plus etoposide, vincristine, and radiation
therapy. Among all the known drugs for cancer, etoposide, vincristine, cyclophosphamide, and
platinum drugs are the most effective against brain tumors. Carboplatin will be used because
fewer side effects related to hearing should occur later on. This study also uses radiation
therapy after surgery for children younger than 3 years old. Normally, chemotherapy has
been used to delay radiation therapy until the child was older because of concerns about
side effects. This change has been made because of the poor results achieved when
chemotherapy was used to delay radiation therapy.

Chemotherapy is the one and only additional treatment that participants under 3 years of age
can receive in this study. After the first 2 cycles, response will be evaluated, including
all exams done at screening before you continue on treatment, if needed. Further surgery
will be considered after these exams. If both you and your doctor choose to consider further
surgery and agree for the procedure to be the next appropriate step, you may undergo a
second surgery to remove anymore remaining tumor. After the second surgery, the chemotherapy
will be again continued on the same schedule for 4 more cycles. If you did not require
further surgery, you will continue on with the chemotherapy as previously planned.

For participants older than 3 years of age, radiation therapy will be a part of the
treatment. It will be given after the second cycle of chemotherapy. Participants will
receive radiation once per day, five days per week, over a period of about 6 weeks. Most
of the participants do not need to stay in the hospital during this time. This will be
followed by 6 more cycles of chemotherapy. After 6 cycles of chemotherapy, further surgery
will again be considered. While on radiation treatment, you will have blood (about 2
teaspoons) drawn for routine tests 2 times a week. Before and after the finish of radiation,
another blood test (2-3 teaspoons) will be taken to monitor the kidney and liver function,
as well as to measure levels of hormones. You will have a physical exam, and blood (about 2
teaspoons) will be drawn for routine tests before each cycle of treatment.

Participants in the carboplatin group will receive etoposide over 1 hour on Days 1-5,
carboplatin over 2 hours on Days 2 and 3, and vincristine over 15 minutes on Day 5. This
will be repeated every 4 weeks for 24 weeks. Each period of 4 weeks is considered 1 cycle
of treatment.

Participants in the cyclophosphamide group will receive etoposide over 1 hour on Days 1-5,
cyclophosphamide over 1 hour on Days 2 and 3, and vincristine over 15 minutes on Day 5.
This will be repeated every 4 weeks for 6 cycles (24 weeks) of treatment. Mesna, a drug to
protect the bladder from the effects of cyclophosphamide, will be given 15 minutes before
each dose of cyclophosphamide.

The chemotherapy given in this study can cause your white blood cell count to be too low.
White blood cells are infection-fighting cells. If the white blood cell count is low for
too long, participants in both groups may be given a drug called G-CSF (filgrastim).
Filgrastim is a growth factor naturally produced in the body to increase the production of
white blood cells. Filgrastim will be given as a shot under the skin starting at Day 9
after starting the chemotherapy.

The total length of treatment that you can receive will be 7 months, if you are able to
complete all the cycles of the additional treatment. You will be taken off study if the
disease gets worse or intolerable side effects occur, and your doctor will discuss other
treatment options with you.

After completing treatment, there will be follow-up visits every 3 months for the first
year. Every 6 months there will still be visits with the doctor until 4 years after
completing treatment. You will continue to have follow-up visits every year after that to
monitor for any signs of the disease coming back, or for as long as you would agree to allow
follow-up visits. At each visit, you will have routine blood tests (about 2-3 teaspoons),
checking of hormone levels, measurement of growth, and a hearing test. The effects of
radiation/chemotherapy on your brain function, your ability to learn, and your quality of
life will be measured. You will have a MRI of the brain, all known metastatic sites, and of
the spine. Your body height and body weight will be measured. About 2 teaspoons of blood
will be drawn for routine tests. Your urine will be tested for the presence of blood. You
will have a spinal tap to look for cancer cells in the spinal fluid. Your hormone levels
will also be taken to see if there are any signs of metabolic disorder and growth
deficiency. This will be done with the other blood test and will not require any more extra
blood samples from you.

This is an investigational study. All of the drugs used in this study are FDA approved and
are commercially available. Their use together in this study is experimental. A total of up
to 100 patients will take part in this multicenter study. Up to 5 will be enrolled here at
M. D. Anderson.