A Phase III Randomized Trial of Adding Vincristine-Topotecan-Cyclophosphamide to Standard Chemotherapy in Initial Treatment of Non-Metastatic Ewing Sarcoma
OBJECTIVES:
Primary
- Compare the event-free and overall survival of patients with newly diagnosed localized
Ewing's sarcoma treated with doxorubicin hydrochloride, cyclophosphamide, vincristine,
etoposide, and ifosfamide with vs without topotecan hydrochloride.
- Compare the side effects of these regimens in these patients.
Secondary
- Evaluate initial tumor size as a prognostic factor for event-free survival of these
patients.
- Evaluate histological response as a prognostic factor for event-free survival of these
patients.
- Continue evaluation of biologic markers both as related to prognosis and as eventual
therapeutic targets via encouraging concurrent enrollment on COG-AEWS02B1.
- Evaluate radiologic response by positron emission tomography as a prognostic factor for
event-free survival.
OUTLINE: This is a randomized, multicenter study. Patients are stratified according to age
(≤ 17 vs ≥ 18 years of age) and primary tumor site (pelvic vs nonpelvic [including
extra-osseous Ewing's sarcoma]). Patients are randomized to 1 of 2 treatment arms.
- Arm I: Patients receive vincristine IV over 1 minute once a week on day 1 in weeks 1-3,
7-9, and 13-15; doxorubicin hydrochloride IV over 15 minutes on days 1 and 2 in weeks
1, 7, and 13; cyclophosphamide IV over 1 hour on day 1 in weeks 1, 7, and 13; and
ifosfamide IV over 1 hour and etoposide IV over 1 hour on days 1-5 in weeks 4, 10, and
16. Patients undergo local therapy comprising surgical resection in approximately week
18 and/or radiotherapy beginning in approximately week 19. Patients then receive
vincristine as above in weeks 19-21, 28-30, 34-36, 40-42, and 46-51; dexrazoxane
hydrochloride IV over 15 minutes on days 1 and 2 and doxorubicin hydrochloride as above
in weeks 19 and 28; cyclophosphamide as above in weeks 19, 28, 34, 40, 46, and 49; and
ifosfamide and etoposide as above in weeks 22, 25, 31, 37, and 43.
- Arm II: Patients receive vincristine IV over 1 minute once a week on day 1 in weeks
1-3, 7-9, and 13-16; topotecan hydrochloride IV over 30 minutes on days 1-5 in weeks 1
and 13; cyclophosphamide IV over 30 minutes on days 1-5 in weeks 1 and 13 and IV over 1
hour on day 1 in weeks 7 and 16; ifosfamide IV over 1 hour and etoposide IV over 1 hour
on days 1-5 in weeks 4 and 10; and doxorubicin hydrochloride IV over 15 minutes on days
1 and 2 in weeks 7 and 16. Patients undergo local therapy comprising surgical resection
in approximately week 18 and/or radiotherapy beginning in approximately week 19.
Patients then receive vincristine as above in weeks 19-21, 28-33, 37-42, and 46-48;
topotecan hydrochloride as above in weeks 19, 31, and 40; cyclophosphamide IV over 30
minutes in weeks 19, 31, and 40 and IV over 1 hour in weeks 28, 37, and 46; ifosfamide
and etoposide as above in weeks 22, 25, 34, 43, and 49; dexrazoxane hydrochloride IV
over 15 minutes on days 1 and 2 in weeks 37 and 46; and doxorubicin hydrochloride as
above in weeks 28, 37, and 46.
After completion of study treatment, patients are followed periodically for 5 years.
PROJECTED ACCRUAL: A total of 528 patients will be accrued for this study.
Interventional
Allocation: Randomized, Primary Purpose: Treatment
Event-free survival
No
Mason Bond, MD
Study Chair
Children's & Women's Hospital of British Columbia
Unspecified
AEWS0531
NCT00334867
December 2005
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