NCT00334867

Combination Chemotherapy With or Without Topotecan in Treating Patients With Newly Diagnosed Localized Ewing's Sarcoma

A Phase III Randomized Trial of Adding Vincristine-Topotecan-Cyclophosphamide to Standard Chemotherapy in Initial Treatment of Non-Metastatic Ewing Sarcoma

• Status: Withdrawn
• Phase: Phase 3
• Study type: Interventional
• Enrollment: 0 (actual)
• Sponsor: Children's Oncology Group · Network
• Sex: All
• Age: 50 Years
• Healthy volunteers: Not accepted

Summary

RATIONALE: Drugs used in chemotherapy, such as vincristine, doxorubicin, cyclophosphamide, ifosfamide, etoposide, and topotecan, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving more than one drug (combination chemotherapy) may kill more tumor cells. Giving chemotherapy before surgery may make the tumor smaller and reduce the amount of normal tissue that needs to be removed. Giving chemotherapy after surgery may kill any tumor cells that remain after surgery. It is not yet known which combination chemotherapy regimen is more effective in treating Ewing's sarcoma. PURPOSE: This randomized phase III trial is studying combination chemotherapy and topotecan to see how well they work compared with combination chemotherapy alone in treating patients with newly diagnosed localized Ewing's sarcoma.

Detailed description

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.

Conditions

• Sarcoma

Interventions

Type	Name	Description
DRUG	cyclophosphamide	Given IV
DRUG	dexrazoxane hydrochloride	Given IV
DRUG	doxorubicin hydrochloride	Given IV
DRUG	etoposide	Given IV
DRUG	ifosfamide	Given IV
DRUG	topotecan hydrochloride	Given IV
DRUG	vincristine sulfate	Given IV
PROCEDURE	conventional surgery	Patients undergo surgery in week 18
PROCEDURE	radiation therapy	Patients undergo radiation therapy in week 19

Timeline

• Start date: 2005-12-01
• Primary completion: 2006-01-01
• First posted: 2006-06-08
• Last updated: 2013-06-28