European Ewing Tumour Working Initiative of National Groups Ewing Tumour Studies 1999 (EURO-E.W.I.N.G.99)

Trial Information

European Ewing Tumour Working Initiative of National Groups Ewing Tumour Studies 1999 (EURO-E.W.I.N.G.99)

OBJECTIVES:

Primary

- Compare the event-free and overall survival of patients with tumor of the Ewing's
family treated with standard induction chemotherapy comprising vincristine,
dactinomycin, ifosfamide and etoposide (VIDE) followed by consolidation chemotherapy
comprising vincristine, dactinomycin, and ifosfamide versus high-dose busulfan and
melphalan (Bu-Mel) followed by autologous peripheral blood stem cell (PBSC)
transplantation with or without radiotherapy and/or surgery.

Secondary

- Determine the prognostic significance of EWS-Flil transcript in these patients.

- Determine the frequency and prognostic value of minimal disease in bone marrow and
PBSC, as determined by the presence or absence of EWS-Flil transcript, in these
patients.

- Determine the feasibility and toxicity of VIDE induction chemotherapy in these
patients.

- Determine the response of these patients to VIDE induction chemotherapy.

- Determine the feasibility and toxicity of VAI consolodation chemotherapy in these
patients.

- Determine the feasibility and toxicity of Bu-Mel consolodation chemotherapy in these
patients.

- Determine event-free survival and overall survival of patients treated with these
regimens by prognostic group analysis.

OUTLINE: This is a randomized, multicenter study. Patients are stratified according to age
and local treatment of the primary tumor (yes vs no).

Patients receive induction chemotherapy comprising vincristine IV on day 1 and ifosfamide IV
over 3 hours, doxorubicin IV over 4 hours, and etoposide IV over 1 hour on days 1-3 (VIDE).
Treatment repeats every 21 days for 4 courses in the absence of unacceptable toxicity.
Peripheral blood stem cells (PBSC) are collected after course 3 and/or 4. Patients are
evaluated after course 4. Patients in need of early radiotherapy due to an axial tumor or
patients who require radiotherapy to the brain and/or spinal cord (at any time during study)
are assigned to group 1. Patients not needing early radiotherapy are assigned to group 2.

- Group 1: Patients receive 2 additional courses of VIDE induction chemotherapy (courses
5 and 6). Patients requiring radiotherapy to the axial tumor also undergo concurrent
radiotherapy 5 days a week. Some patients may then undergo surgical resection of the
tumor. All patients will then receive vincristine IV on day 1 and dactinomycin IV and
ifosfamide IV over 3 hours on days 1 and 2 (VAI). Treatment repeats every 21 days for 8
courses (courses 7-14). Patients requiring radiotherapy to the brain and/or spinal cord
also undergo concurrent radiotherapy.

- Group 2: Patients undergo 2 additional courses of VIDE induction chemotherapy (courses
5 and 6). Some patients may then undergo surgical resection of the tumor. All patients
receive VAI chemotherapy as in group 1 for 1 course. Patients are randomized to 1 of 2
consolidation therapy arms.

- Arm I: Patients receive 7 additional courses of VAI chemotherapy (courses 8-14).
Patients with unresectable, partially resected, or inadequately resected disease
undergo concurrent whole-lung radiotherapy for 6-12 days.

- Arm II: Patients receive high-dose chemotherapy comprising oral busulfan every 6
hours on days -6 to -3 and melphalan IV over 30 minutes on day -2. Patients
receive autologous PBSC IV on day 0. Patients with unresectable, partially
resected, or inadequately resected disease undergo concurrent radiotherapy 5 days
a week for at least 5 weeks.

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

Peer Reviewed and Funded or Endorsed by Cancer Research UK

PROJECTED ACCRUAL: Approximately 1,200 patients will be accrued for this study within
approximately 7 years.