Trial Information

European Infant Neuroblastoma Study - Unresectable Tumors (MYCN Not Amplified)

OBJECTIVES:

- Determine the survival and morbidity of infants with newly diagnosed stage II or III
unresectable neuroblastoma without MYCN amplification treated with vincristine and
cyclophosphamide, etoposide and carboplatin, and cyclophosphamide, doxorubicin, and
vincristine followed by surgery.

- Determine whether deletion of chromosome 1p or diploidy/tetraploidy are prognostic
factors in these patients.

- Determine whether there are other prognostic criteria that could be used in future
therapeutic stratification of these patients.

OUTLINE: This is a multicenter study. Patients are stratified according to symptomatic
spinal cord involvement (yes vs no).

Patients without evidence of symptomatic spinal cord compression receive vincristine IV on
day 1 and cyclophosphamide IV on days 1-5. Treatment repeats every 14 days for 2 courses.
Patients eligible for surgery undergo surgical resection and then are removed from the
study.

Patients ineligible for surgery after 2 courses of initial chemotherapy, but with at least
25% response to initial chemotherapy, receive 2 additional courses of vincristine and
cyclophosphamide. Patients eligible for surgery undergo surgical resection and then are
removed from the study.

Patients ineligible for surgery after 2 additional courses of initial chemotherapy or with
disease progression receive etoposide IV over 2 hours and carboplatin IV over 1 hour on days
1-3. Treatment repeats every 21 days for 2 courses. Patients eligible for surgery undergo
surgical resection and then are removed from the study.

Patients who remain ineligible for surgery or with disease progression after etoposide and
carboplatin receive cyclophosphamide IV over 1 hour on days 1-5, doxorubicin IV over 6 hours
on days 4 and 5, and vincristine IV on days 1 and 5. Treatment repeats every 21 days for 2
courses. Patients then undergo surgical resection or biopsy.

Patients with symptomatic spinal cord compression receive initial treatment with etoposide
and carboplatin as above. Patients with improved symptoms and resectable disease after
initial chemotherapy undergo surgical resection or biopsy. Patients who remain ineligible
for surgery or with no improvement in symptoms after initial chemotherapy receive
cyclophosphamide, doxorubicin, and vincristine as above. Patients then undergo surgical
resection or biopsy.

Patients are followed within 6 months and then annually for 5 years.

PROJECTED ACCRUAL: A total of 100 patients will be accrued for this study within 4 years.