Trial Information

A Pilot Induction Regimen Incorporating Topotecan for Treatment of Newly Diagnosed High Risk Neuroblastoma

OBJECTIVES:

Primary

- Determine the toxicity and feasibility of adding cyclophosphamide and topotecan to
induction therapy in patients with newly diagnosed or progressive high-risk
neuroblastoma undergoing autologous peripheral blood stem cell (PBSC) transplantation.

- Determine the feasibility of PBSC mobilization and in vivo PBSC tumor purging in these
patients after treatment with this regimen.

Secondary

- Determine tumor response rate in patients treated with this regimen.

- Determine the pharmacokinetics of this regimen in these patients.

- Determine whether topotecan affects cyclophosphamide pharmacokinetics in these
patients.

- Correlate host DNA with toxicity and cyclophosphamide and topotecan pharmacokinetics in
patients treated with this regimen.

- Determine toxicity in patients treated with this regimen.

OUTLINE: This is a pilot, multicenter study. Patients are stratified according to diagnosis
(newly diagnosed vs initially stage 1, 2, or 4S that progressed to stage 4 without interval
chemotherapy).

- Induction therapy: Patients receive 6 courses of induction therapy.

- Courses 1 and 2: Patients receive cyclophosphamide IV over 30 minutes and
topotecan IV over 30 minutes on days 1-5 and filgrastim (G-CSF) subcutaneously
(SC) or IV beginning on day 6 and continuing until blood counts recover.

- Course 3: Patients receive etoposide IV over 2 hours on days 1-3, cisplatin IV
over 1 hour on days 1-4, and G-CSF SC or IV beginning on day 5 and continuing
until blood counts recover.

- Course 4: Patients receive cyclophosphamide IV over 6 hours on day 1 and
doxorubicin IV and vincristine IV continuously over 24 hours on days 1-3. Patients
also receive G-CSF SC or IV beginning on day 4 and continuing until blood counts
recover.

- Course 5: Patients receive etoposide, cisplatin, and G-CSF as in course 3.

- Course 6: Patients receive cyclophosphamide, doxorubicin, vincristine, and G-CSF
as in course 4.

Treatment repeats every 21 days for a total of 6 courses in the absence of disease
progression or unacceptable toxicity.

- Consolidation therapy: Within 4-6 weeks after completing induction therapy, patients
receive melphalan IV on days -7 to -5 and etoposide IV and carboplatin IV continuously
over 24 hours on days -7 to -4.

- Stem cell transplantation: Peripheral blood stem cells are collected after course 2 of
induction therapy and infused on day 0. Patients receive G-CSF IV beginning on day 0
and continuing until blood counts recover.

- Surgery: After course 5 of induction therapy, patients undergo surgery.

- Radiotherapy: Beginning 28-42 days after transplantation, patients receive 12 fractions
of local radiotherapy to all areas of residual soft tissue disease and the primary
tumor site, even if completely resected.

- Maintenance therapy: Beginning 66 days after transplantation, patients receive oral
isotretinoin twice daily on days 1-14. Treatment repeats every 28 days for a total of 6
courses.

Patients are followed every 3 months for 1 year, every 6 months for 4 years, and then
annually thereafter.

PROJECTED ACCRUAL: A total of 10-29 patients will be accrued for this study within 2 years.