Trial Information

A Phase I Study of a Novel Chemotherapeutic Regimen: Topotecan, Ifosfamide and Carboplatin (TIC) in Children and Young Adults With Solid Tumors-- A Limited Multi-Institution Study

All of the chemotherapy drugs used in this study are FDA approved and commercially available
drugs designed to kill cancer cells.

Before you can start treatment on this study, you will have what are called "screening
tests". These tests will help the doctor decide if you are eligible to take part in the
study. You will have a physical exam and routine blood (about 2 teaspoons) and urine tests.
You will have electrocardiogram (ECG - test to measure the electrical activity of the
heart). You will have a chest x-ray and other scans (such as CT, MRI, Bone, Ultrasound or
radionucleotide scans ). You physician will decide which scans are appropriate based on the
disease and clinical situation. You will also have a bone marrow aspirate. To collect a
bone marrow aspirate, an area of the hip or chest bone is numbed with anesthetic and a small
amount of bone marrow is withdrawn through a large needle. Women who are able to have
children must have a negative pregnancy test before starting treatment.

If you are found to be eligible to take part in this study, you will be assigned to a
specific dose of topotecan. The first group of participants will receive a smaller dose of
topotecan. If patients in that group are able to recover a sufficient number of platelets by
Day 22 and no severe side effects are experienced, the next group of participants will be
treated with a larger dose topotecan. The dose will continue to be increased for each new
group of participants until all the participants in a dose group are unable to recover a
sufficient number of platelets by Day 22, or until severe side effects are experienced.
There will be 3 patients in each group. The doses of all the other drugs used on this study
will be the same for every participants.

Topotecan, ifosfamide, and carboplatin will be given for the first three days of each
course. Ifosfamide and carboplatin will be given into a vein for one hour each day along
with the drug mesna. Mesna is not an anti-cancer drug but a drug to help protect the bladder
from the potential damaging effects of ifosfamide. After the first dose of mesna,
participants will receive 3 more doses (one every three hours) over 15-30 minutes .
Topotecan is given directly into a vein for one-half hour beginning one hour after treatment
with ifosfamide, carboplatin, and the first dose of mesna is completed. Participants who
are 22 years or older will only receive Day 1 and 2 of carboplatin.

Starting on the fourth day of each course, you will be given a daily injection of the drug
Filgrastim. Filgrastim is a growth factor naturally produced in the body to stimulate the
production of white blood cells (infection fighting cells). Filgrastim can now be produced
in the laboratory and given to patients at higher doses than the body makes. Filgrastim
should help the body recover from treatment. Filgrastim will be given as an injection under
the skin once a day until an acceptable number of white blood cells are detected in the
bloodstream.

A second course of chemotherapy will begin as soon as 21 days after the start of treatment
as long as you have recovered enough white blood cells and platelets. If the white blood
cells and platelets have not recovered by 21 days, you will begin the next course when they
do recover.

After each of the first three courses, you will have a re-evaluation of the disease.
Re-evaluation will require the same scans to be performed as were done at study entry. If
the tumor shows a complete or partial response to the treatment after the second course,
then continuation on the study will be at the discretion of the treating physician. If the
disease is stable, meaning there is no change in the size or degree of the tumor, then
treatment can continue for a total of 3 courses overall.

If the disease gets worse or intolerable side effects occur, you will be taken off study and
other treatment options will be discussed with you.

You may need to be hospitalized during the first three days of each chemotherapy course and
will require visits as an outpatient at other times during treatment to receive laboratory
follow-up and evaluation. Participants may also require hospitalization because of side
effects.

During treatment, you will have a physical exam and routine blood (about 2 teaspoons) and
urine tests. You will also have an ECG, a chest x-ray, and other scans as thought
necessary. The physical exam will be done once a week for Courses 1 - 3. The blood tests
will be done on Days 1, 3, 5; then twice weekly and on Day 22 of each course. Urine tests
will be done on Day 1 of each course and at the end of Course 2. The scans and ECG will be
performed at the end of each course or sooner if it is suspected that the disease has
gotten worse.

This is an investigational study. The drugs on this study are FDA approved and commercially
available. However, their use together in this study is experimental. Up to 78 patients will
take part in this study. About 15 patients will be enrolled at UTMDACC.