Comparison of Combination Chemotherapy Regimens in Treating Patients With Ewing's Sarcoma or Neuroectodermal Tumor
Condition: Sarcoma
MeSH terms: Sarcoma; Sarcoma, Ewing; Neuroectodermal Tumors
Study type: Interventional
Phase: Phase 3

Summary: 
      RATIONALE: Drugs used in chemotherapy work in different ways to stop tumor cells from
      dividing so they stop growing or die. Radiation therapy uses high-energy x-rays to damage
      tumor cells. It is not yet known which chemotherapy regimen combined with radiation therapy
      and/or surgery is more effective in treating Ewing's sarcoma or primitive neuroectodermal
      tumor.

      PURPOSE: Randomized phase III trial to compare the effectiveness of different chemotherapy
      regimens combined with radiation therapy and/or surgery in treating patients who have Ewing's
      sarcoma or primitive neuroectodermal tumor.
    

Detailed description: 
      OBJECTIVES:

        -  Compare the effect of interval-compressed vs standard chemotherapy in terms of
           event-free survival and overall survival in patients with newly diagnosed, localized
           Ewing's sarcoma or peripheral primitive neuroectodermal tumor.

      OUTLINE: This is a randomized, multicenter study. Patients are stratified according to age
      (under 18 years vs 18 years and over) and location of primary disease (pelvic vs nonpelvic).
      Patients are randomized to 1 of 2 treatment arms for induction and continuation therapy.

        -  Induction therapy (weeks 1-12):

             -  Arm I: Patients receive alternating courses of chemotherapy consisting of
                vincristine IV on day 1, doxorubicin IV continuously over 48 hours on days 1 and 2,
                and cyclophosphamide IV over 1 hour on day 1 for courses 1 and 3 and ifosfamide IV
                over 1 hour and etoposide IV over 1-2 hours on days 1-5 for courses 2 and 4.
                Beginning 24 hours after the last dose of chemotherapy for each course, patients
                receive filgrastim (G-CSF) subcutaneously (SC) daily until blood counts recover.
                Treatment continues every 3 weeks for 4 courses.

             -  Arm II: Patients receive alternating courses of chemotherapy consisting of
                vincristine, doxorubicin, and cyclophosphamide as in arm I for courses 1, 3, and 5
                and ifosfamide and etoposide as in arm I for courses 2, 4, and 6. Patients also
                receive G-CSF as in arm I. Treatment continues every 2 weeks for 6 courses.

      After completion of induction therapy, patients in both arms receive local control treatment
      to the primary tumor. Patients receive continuation chemotherapy after surgery or
      concurrently with radiotherapy.

        -  Continuation therapy:

             -  Arm I (weeks 13-42): Patients receive additional alternating courses of
                chemotherapy as in arm I of induction therapy with the exception of vincristine and
                cyclophosphamide alone for courses 7 and/or 11 and/or 13. Patients also receive
                G-CSF as in induction therapy. Treatment continues every 3 weeks for 10 courses.

             -  Arm II (weeks 13-29): Patients receive additional alternating courses of
                chemotherapy as in arm II of induction therapy with the exception of vincristine
                and cyclophosphamide alone for courses 9 and/or 11 and/or 13. Patients also receive
                G-CSF as in induction therapy. Treatment continues every 2 weeks for 8 courses.

      Patients are followed every 3 months for 4 years and then every 6 months for 1 year.

      PROJECTED ACCRUAL: Approximately 528 patients will be accrued for this study within 4-5
      years.
    

Intervention name(s): filgrastim; cyclophosphamide; doxorubicin hydrochloride; etoposide; ifosfamide; vincristine sulfate; adjuvant therapy; conventional surgery; neoadjuvant therapy; brachytherapy; radiation therapy
Intervention type(s): Biological; Drug; Drug; Drug; Drug; Drug; Procedure; Procedure; Procedure; Radiation; Radiation
Intervention description(s): Given IV; Given IV; Given IV; Given IV; Given IV; Given IV
Other intervention name(s): GRANULOCYTE COLONY-STIMULATING FACTOR; r-metHuG-CSF; G-CSF; Neupogen; NSC 614629; CTX; Cytoxan; NSC #026271; Adriamycin; NSC #123127; IND #7038; VP-16; VePesid; Etopophos; NSC #141540; Ifex; NSC #109724; Oncovin; NSC #067574
Intervention MeSH terms: Cyclophosphamide; Ifosfamide; Doxorubicin; Liposomal doxorubicin; Etoposide; Vincristine; Lenograstim
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: localized Ewing sarcoma/peripheral primitive neuroectodermal tumor