Trial Information

Trial of Chemotherapy Intensification Through Compression in Ewing's Sarcoma and Related Tumors

OBJECTIVES:

- Compare the effect of interval-compressed vs standard chemotherapy in terms of
event-free survival and overall survival in patients with newly diagnosed, localized
Ewing's sarcoma or peripheral primitive neuroectodermal tumor.

OUTLINE: This is a randomized, multicenter study. Patients are stratified according to age
(under 18 years vs 18 years and over) and location of primary disease (pelvic vs nonpelvic).
Patients are randomized to 1 of 2 treatment arms for induction and continuation therapy.

- Induction therapy (weeks 1-12):

- Arm I: Patients receive alternating courses of chemotherapy consisting of
vincristine IV on day 1, doxorubicin IV continuously over 48 hours on days 1 and
2, and cyclophosphamide IV over 1 hour on day 1 for courses 1 and 3 and ifosfamide
IV over 1 hour and etoposide IV over 1-2 hours on days 1-5 for courses 2 and 4.
Beginning 24 hours after the last dose of chemotherapy for each course, patients
receive filgrastim (G-CSF) subcutaneously (SC) daily until blood counts recover.
Treatment continues every 3 weeks for 4 courses.

- Arm II: Patients receive alternating courses of chemotherapy consisting of
vincristine, doxorubicin, and cyclophosphamide as in arm I for courses 1, 3, and 5
and ifosfamide and etoposide as in arm I for courses 2, 4, and 6. Patients also
receive G-CSF as in arm I. Treatment continues every 2 weeks for 6 courses.

After completion of induction therapy, patients in both arms receive local control treatment
to the primary tumor. Patients receive continuation chemotherapy after surgery or
concurrently with radiotherapy.

- Continuation therapy:

- Arm I (weeks 13-42): Patients receive additional alternating courses of
chemotherapy as in arm I of induction therapy with the exception of vincristine
and cyclophosphamide alone for courses 7 and/or 11 and/or 13. Patients also
receive G-CSF as in induction therapy. Treatment continues every 3 weeks for 10
courses.

- Arm II (weeks 13-29): Patients receive additional alternating courses of
chemotherapy as in arm II of induction therapy with the exception of vincristine
and cyclophosphamide alone for courses 9 and/or 11 and/or 13. Patients also
receive G-CSF as in induction therapy. Treatment continues every 2 weeks for 8
courses.

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

PROJECTED ACCRUAL: Approximately 528 patients will be accrued for this study within 4-5
years.