Trial Information

Protocol for Infants With Neuroblastoma Diagnosed Under the Age of One Year

OBJECTIVES:

- Register all children < 12 months of age diagnosed with neuroblastoma.

- Evaluate possible prognostic factors in these patients with particular reference to the
collection of biological material.

- Correlate outcome with factors other than stage in these patients.

- Determine criteria to modify treatment for some children with advanced disease without
impairing survival.

OUTLINE: This is a nonrandomized, multicenter study. Patients are assigned to 1 of 4
treatment groups according to disease stage.

- Group 1 (stage 1, 2A, or 2B disease): Patients undergo surgical resection of the tumor.
Patients with paraspinal tumors may receive chemotherapy* to shrink the tumor before
undergoing surgery. Patients with local recurrence after surgery proceed to treatment
as in group 3. Patients with metastatic recurrence after surgery proceed to treatment
as in group 4.

- Group 2 (stage 4S disease): Patients undergo observation only. Patients with
hepatomegaly or progressive disease may receive chemotherapy*. Patients who do not
respond to chemotherapy may undergo up to 4 courses of radiotherapy.

- Group 3 (stage 3 disease): Patients receive OPEC chemotherapy comprising vincristine IV
and cyclophosphamide IV on day 1, cisplatin IV continuously over 24 hours on day 1, and
etoposide IV over 4 hours on day 3 during courses 1, 3, and 5. Patients receive OJEC
chemotherapy comprising vincristine IV, cyclophosphamide IV, etoposide IV over 4 hours,
and carboplatin IV over 1 hour on day 1 during courses 2, 4, and 6. Courses repeat
every 3 weeks with alternating OPEC and OJEC chemotherapy for 6 courses. Patients with
residual disease then receive 4 additional courses of alternating OPEC and OJEC
chemotherapy. Patients whose tumor becomes resectable after either 6 or 10 courses of
chemotherapy undergo surgery. Patients with residual disease after 10 courses of
chemotherapy are assessed by regular scans. Patients with disease progression on scans
undergo radiotherapy. Patients with ganglioneuroma or total necrosis only with no
evidence of neuroblastoma after either 6 or 10 courses of chemotherapy receive no
further treatment.

- Group 4 (stage 4 disease): Patients receive alternating courses of OPEC and OJEC for 6
courses as in group 3. Patients who do not achieve metastatic complete response (CR)
receive 4 additional courses of alternating OPEC and OJEC chemotherapy. Patients
achieving metastatic CR after either 6 or 10 courses of chemotherapy undergo surgery to
remove the tumor. Patients with macroscopic residual disease on resected specimen
receive 4 additional courses of alternating OPEC and OJEC chemotherapy and then undergo
biopsy. Patients with residual disease on biopsy are assessed by regular scans.
Patients with disease progression on scans undergo radiotherapy. Patients with
ganglioneuroma or total necrosis only after surgery with or without the 4 additional
courses of chemotherapy receive no further treatment.

NOTE: * OJEC chemotherapy with a lower dose of carboplatin

After completion of study treatment, patients are followed periodically.

PROJECTED ACCRUAL: A total of 120 patients will be accrued for this study.