Trial Information

CHP-830 I-Metaiodobenzylguanidine (131 I-MIBG) Therapy for Refractory Neuroblastoma and Metastatic Pheochromocytoma (An Expanded Access Protocol)

General Description of the Medication Being Used on the Study:

Metaiodobenzylguanidine (MIBG) is a substance that is taken up by neuroblastoma or
pheochromocytoma tumor cells. MIBG is combined with radioactive iodine (131I) in the
laboratory to form the radioactive compound 131I-MIBG. The 131I-MIBG compound delivers
radiation specifically to the neuroblastoma cancer cells and causes them to die. 131I-MIBG
is experimental, but has been used in more than 100 children in the United States by itself
to treat relapsed neuroblastoma and metastatic pheochromocytoma. A recent study using
increasing doses of 131I-MIBG in both children and adults with relapsed neuroblastoma or
metastatic pheochromocytoma showed anti-cancer effects in some of these patients. The main
side effect of this treatment was a decrease in the number of normal blood-forming cells
(called stem cells) in the bone marrow, but a dose of 12 mCi/kg did not cause permanent
damage to the bone marrow in a small number of patients.

There are certain tests or procedures that will need to be done to confirm that the subject
is eligible for this therapy. These include lab work, physical exam and MIBG scan. A CT
scan, an MRI, a bone scan, Bone marrow aspirate and biopsy and urine tests will be done to
evaluate your disease status when clinically indicated. Your doctor will determine which
tests are required.

Before your child can begin treatment on this study, s/he will need to have an intravenous
catheter (tube) placed in a vein. We can use an existing central venous catheter to
administer the medicine.

Because your child's urine will be radioactive, a urinary catheter may be inserted through
your child's urethra into the bladder to ensure drainage of the urine, which will be
radioactive. The catheter will be removed 3-5 days following the treatment. General
anesthesia or sedation is typically given for the procedure of inserting the catheter.

1. Your child will be treated in a specially prepared room in the CHOP Pediatric Oncology
Unit. Upon admission, the nursing staff will instruct you on the care you will give
your child following the MIBG infusion. Because of the frequent exposure of the nursing
staff to radiation and the high level of radiation surrounding your child during
therapy, the nurses' contact will be limited to complex medical care, so that they are
available for your child in the event of an emergency. Adult family members will be
expected to be present at all times during the hospitalization to:

- Assist with hygiene

- Give oral medications

- Offer and empty bedpans

- Assist with meals

- Change diapers (if used)

- Change clothing and bed linens if soiled

- Entertain or distract individuals who become upset or restless due to the
isolation or procedures.

- Record Dosimeter readings.

2. Isolation: For 2-5 days your child will be placed in a single room with a bed
surrounded by lead shielding to prevent exposure of visitors and hospital personnel to
radioactivity. Family members may visit in the room, but must wear a radiation badge to
measure exposure. A single family member can sleep in the room, but no one is allowed
to go behind the shields or sleep in the bed with the child.

3. Your child will receive fluids through the central venous catheter. The fluids will
begin at least four hours before and continue at least 72 hours after the 131I-MIBG
treatment begins.

4. Your child will take a medicine by mouth, potassium iodide, to prevent thyroid damage
from the radioactive iodine contained in the 131I-MIBG. This medication will be taken
on the day of the treatment and will continue for a total of 6 weeks.

5. The 131I-MIBG will be given through an intravenous catheter over 1.0 - 2-hours.

6. During the administration of the drug, your child's blood pressure and heart rate will
be checked frequently.

7. Before and at regular intervals after treatment, your child will have routine blood
tests to check his/her blood counts, hormone, liver and kidney functions. Blood will be
checked at least weekly or more (if indicated) for approximately 6 weeks after the
treatment. Approximately 1 teaspoon of blood will be drawn weekly for 6 weeks to
perform the tests listed above.

8. A MIBG scan will be performed to see where the drug is concentrating in the body
following treatment. No injection of a radioactive marker will be required and this is
usually done on the day for discharge. It is identical to the pretherapy MIBG scan
except for not needing MIBG injection and it is usually shorter (15-30 minutes).

9. Six to eight weeks after treatment, an MIBG and other scans will be done to evaluate
the response of the tumor to the treatment.

10. If your child's tumor is responding or stable 6-7 weeks after each treatment, s/he may
be eligible for a second and third course of treatment, as long as his/her white blood
counts have recovered from the treatment and the patient has stem cells available if
needed. If another MIBG treatment is given, it will be at the same dose as the first
treatment, unless it is thought to be necessary for safety reasons (based on toxicity
information from the first infusion) to decrease the dose.

11. If your child's blood counts decrease following the therapy, we will start Filgrastim
(G-CSF) or Neulasta. G-CSF/neulasta is a medicine that helps increase the white blood
cells. This is given by a subcutaneous (under the skin) injection (like an insulin
shot). GCSF is given daily and Neulasta is given every 14 days instead of GCSF.
Neulasta works like GCSF to help increase the white blood counts but lasts longer in
your child's body.

This medicine will start if the ANC (absolute neutrophil count, a measure of the infection
fighting cells) goes below 750 and will continue until it rises above 5000.