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

Sarcoma Clinical Trial

Official title:

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

Clinical Trial Details — Status: Withdrawn

Administrative data

• NCT number: NCT00334867
• Other study ID #: AEWS0531
• Secondary ID: COG-AEWS0531CDR0
• Status: Withdrawn
• Phase: Phase 3
• First received: June 7, 2006
• Last updated: June 27, 2013
• Start date: December 2005

Study information

• Verified date: June 2013
• Source: Children's Oncology Group
• Contact: n/a
• Is FDA regulated: No
• Health authority: Unspecified
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Withdrawn
• Enrollment: 0
• Est. primary completion date: January 2006
• Accepts healthy volunteers: No
• Gender: Both
• Age group: N/A to 50 Years

Eligibility

DISEASE CHARACTERISTICS:

• Histologically and cytologically confirmed extracranial Ewing's sarcoma or primitive neuroectodermal tumor (PNET) of bone or soft tissue

• Chest wall tumors with ipsilateral pleural effusions, ipsilateral positive pleural fluid cytology, or ipsilateral pleural-based secondary tumor nodules allowed

• Contralateral pleural effusions or pleural nodules are not eligible

• Tumor arising in the bony skull (extradural) are eligible

• Tumors arising in the intradural soft tissue are not eligible

• Newly diagnosed disease

• Only have had a biopsy of the primary tumor without an attempt at complete or partial resection

• Prior attempted or accomplished unplanned excision allowed provided adequate imaging was obtained prior to surgery AND resection considered incomplete and further local control required

• No evidence of metastatic disease, defined as lesions discontinuous from the primary tumor, are not regional lymph nodes, and do not share a body cavity with the primary tumor

• No evidence of metastatic lung disease by CT scan

• One pulmonary nodule > 1 cm in diameter OR > 1 nodule > 0.5 cm in diameter are considered evidence of pulmonary metastasis

• Solitary nodules 0.5-1.0 cm or multiple nodules 0.3-0.5 cm must be confirmed negative by biopsy

• Solitary nodules < 0.5 cm or multiple nodules < 0.3 cm not considered clear evidence of lung disease

• No distant nodule disease

• No esthesioneuroblastoma

PATIENT CHARACTERISTICS:

• Performance status (PS) 0-2 (Karnofsky PS 50-100% for patients = 16 years of age or Lansky PS 50-100% for patients < 16 years of age)

• Creatinine clearance or radioisotope glomerular filtration rate (GFR) = 70 mL/min

• Bilirubin = 1.5 times upper limit of normal (ULN)

• AST or ALT < 2.5 times ULN

• Shortening fraction = 27% by EKG

• Ejection fraction = 50% by radionuclide angiogram

• Not pregnant or nursing

• Negative pregnancy test

• Fertile patients must use effective contraception

PRIOR CONCURRENT THERAPY:

• See Disease Characteristics

• No prior radiotherapy

• No prior chemotherapy

Study Design

Allocation: Randomized, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Sarcoma
• Sarcoma, Ewing

Intervention

Drug:
• cyclophosphamide
Given IV
• dexrazoxane hydrochloride
Given IV
• doxorubicin hydrochloride
Given IV
• etoposide
Given IV
• ifosfamide
Given IV
• topotecan hydrochloride
Given IV
• vincristine sulfate
Given IV

Procedure:
• conventional surgery
Patients undergo surgery in week 18
• radiation therapy
Patients undergo radiation therapy in week 19

Locations

Country	Name	City	State
n/a

Sponsors (2)

Lead Sponsor	Collaborator
Children's Oncology Group	National Cancer Institute (NCI)

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Event-free survival			No
Secondary	Survival form study enrollment			No