A Pilot Study of Chemotherapy Intensification by Adding Vincristine, Topotecan and Cyclophosphamide to Standard Chemotherapy Agents With an Interval Compression Schedule in Newly Diagnosed Patients With Localized Ewing Sarcoma Family of Tumors
I. To assess the feasibility and safety of adding interval-compressed vincristine, topotecan
hydrochloride, and cyclophosphamide to a treatment protocol utilizing interval compression
of vincristine, doxorubicin hydrochloride, cyclophosphamide, ifosfamide, and etoposide in
patients with localized Ewing sarcoma family of tumors.
I. To estimate the event-free survival in patients treated with this regimen.
OUTLINE: This is a multicenter study.
INDUCTION THERAPY (WEEKS 1-12): Patients receive vincristine IV on day 1 in weeks 1, 2, 5,
6, 9, 10, 11, and 12; topotecan hydrochloride IV over 30 minutes on days 1-5 in weeks 1 and
9; cyclophosphamide IV over 1 hour on days 1-5 in weeks 1 and 9 and on day 1 in weeks 5 and
11; ifosfamide IV over 1 hour on days 1-5 in weeks 3 and 7; etoposide IV over 1 hour on days
1-5 in weeks 3 and 7; and doxorubicin hydrochloride IV over 15 minutes on days 1 and 2 in
weeks 5 and 11. Patients also receive filgrastim (G-CSF) subcutaneously (SC) beginning 24-36
hours after the last dose of chemotherapy and continuing for at least 7 days or until blood
counts recover, whichever comes last. Filgrastim is discontinued at least 24 hours prior to
the next course of chemotherapy.
LOCAL CONTROL: Patients who respond to induction therapy may undergo surgery alone if the
lesion can be resected with negative margins and with a reasonable functional result
beginning in week 13. Following surgery, patients with unresectable lesions or inadequate
margins may receive radiotherapy during week 15. Patients with bulky lesions in surgically
difficult sites such as the spine, skull, and periacetabular pelvis; poor response to
induction chemotherapy; or those in whom surgery would result in unacceptable functional
results may receive radiotherapy alone in weeks 13-19. Patients with bulky lesions in
difficult sites and who do not have a good clinical and radiographic response to induction
therapy may receive radiotherapy to the primary site during weeks 13-19 followed by surgery
of the involved site during week 25 after recovery from course 11 of chemotherapy. Patients
with microscopic residual disease after planned pre-operative radiotherapy will receive
CONTINUATION THERAPY (WEEKS 15-36): Patients receive vincristine IV on day 1 in weeks 15,
16, 21-24, 27-30, 33, and 34; topotecan hydrochloride IV over 30 minutes on days 1-5 in
weeks 15, 21, and 29; cyclophosphamide IV over 1 hour on days 1-5 in weeks 15, 21 and 29 and
on day 1 in weeks 23, 27, and 33; ifosfamide IV over 1 hour on days 1-5 in weeks 17, 19, 25,
31, and 35; etoposide IV over 1 hour on days 1-5 in weeks 17, 19, 25, 31, and 35; and
doxorubicin hydrochloride IV over 15 minutes on days 1 and 2 of weeks 23, 27, and 33.
Patients also receive G-CSF SC as in induction therapy.
After completion of study treatment, patients are followed for 10 years.
Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Incidence of death from complications during therapy or within one month of terminating therapy
Up to 1 month
Children's Oncology Group
United States: Food and Drug Administration
|Children's Oncology Group||Arcadia, California 91006-3776|