Alternate Title
Basic Trial Information
Objectives
Entry Criteria
Expected Enrollment
Outcomes
Outline
Trial Contact Information
Registry Information

Alternate Title

Two Regimens of Combination Chemotherapy in Treating Younger Patients With Newly Diagnosed Localized Ewing Sarcoma Family of Tumors

Basic Trial Information

Phase	Type	Status	Age	Sponsor	Protocol IDs
No phase specified	Treatment	Temporarily closed	Under 31	NCI	COG-AEWS07P1 AEWS07P1, NCT00618813

Objectives

Primary

1. 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.

Secondary

1. To estimate the event-free survival in patients treated with this regimen.

Entry Criteria

Disease Characteristics:

• Diagnosis of extracranial Ewing sarcoma or peripheral primitive neuroectodermal tumor of bone or soft tissue
  • Newly diagnosed disease
  • Disease confirmed by biopsy only with no attempt at complete or partial resection
    • Unplanned excision allowed provided adequate imaging was obtained prior to surgery and incompletely resected disease is controlled by local therapy
  • No esthesioneuroblastoma



• Localized disease, including any of the following sites:
  • Chest wall tumors with ipsilateral pleural effusions, ipsilateral positive pleural fluid cytology, or ipsilateral pleural based secondary tumor nodules
    • No contralateral pleural effusions or pleural nodules
  • Regional lymph nodes that are clinically suspicious or confirmed by biopsy
    • No distant lymph node metastases
  • Extra-dural tumors arising in the bony skull
    • No tumors arising in the intra-dural soft tissue or the intra-dural region of the spine



• No evidence of metastatic disease, defined as any of the following:
  • Lesions that are discontinuous from the primary tumor
  • Lesions that are not regional lymph nodes
  • Lesions that do not share a body cavity with the primary tumor
  • No evidence by CT scan of metastatic lung disease, defined as any of the following:
    • One pulmonary nodule > 1 cm in diameter or more than one nodule > 0.5 cm diameter
      • Pulmonary nodules that are resected and are not found to be metastatic Ewing sarcoma are allowed
    • Biopsy proven solitary nodules measuring 0.5 to 1.0 cm or multiple nodules measuring 0.3 to 0.5 cm
      • Solitary nodules measuring < 0.5 cm or multiple nodules measuring < 0.3 cm are allowed unless biopsy proven to be metastatic (biopsy is not required)

Prior/Concurrent Therapy:

• See Disease Characteristics
• No prior chemotherapy or radiotherapy
• No concurrent pegfilgrastim (Neulasta®) or sargramostim (GM-CSF)
• No other concurrent cancer chemotherapy or immunomodulating agents, including steroids, unless used as an antiemetic

Patient Characteristics:

• Karnofsky performance status (PS) 0-2 (≥ 16 years old) OR Lansky PS 0-2 (< 16 years old)
• Creatinine clearance or radioisotope glomerular filtration rate ≥ 70 mL/min OR serum creatinine based on age/gender as follows:
  • 1 month to < 6 months old (males and females 0.4 mg/dL)
  • 6 months to < 1 year old (males and females 0.5 mg/dL)
  • 1 to < 2 years old (males and females 0.6 mg/dL)
  • 2 to < 6 years old (males and females 0.8 mg/dL)
  • 6 to < 10 years old (males and females 1.0 mg/dL)
  • 10 to < 13 years old (males and females 1.2 mg/dL)
  • 13 to < 16 years old (males 1.5 mg/dL and females 1.4 mg/dL)
  • ≥ 16 years old (males 1.7 mg/dL and females 1.4 mg/dL)
• Total bilirubin ≤ 1.5 times upper limit of normal (ULN) for age
• AST or ALT < 2.5 times ULN for age
• Shortening fraction of ≥ 27% by ECHO or ejection fraction of ≥ 50% by radionuclide angiogram (MUGA)
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception

Expected Enrollment

Outcomes

Incidence of death from complications during therapy or within one month of terminating therapy
Incidence rate of dose-limiting toxicity during therapy
Time from the start of therapy to the initiation of local control measures planned for week 13 of therapy
Evaluation of sustained compression
Estimation of event-free survival
Overall response

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 additional radiotherapy.



• 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.

Trial Contact Information

Trial Lead Organizations

Children's Oncology Group

Leo Mascarenhas, MD, Protocol chair		Ph: 323-669-2529

Registry Information
Official Title		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
Trial Start Date		2008-03-03
Trial Completion Date		2010-12-07 (estimated)
Registered in ClinicalTrials.gov		NCT00618813
Date Submitted to PDQ		2008-01-24
Information Last Verified		2009-05-13
NCI Grant/Contract Number		CA98543