Combination Chemotherapy in Treating Young Patients Who Are Undergoing Surgery and an Autologous Bone Marrow Transplant for Disseminated Neuroblastoma
Condition: Neuroblastoma
MeSH terms: Neuroblastoma
Study type: Interventional
Phase: Phase 3

Summary: 
      RATIONALE: Drugs used in chemotherapy 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 combination chemotherapy
      before surgery may make the tumor smaller and reduce the amount of normal tissue that needs
      to be removed. A bone marrow transplant, using bone marrow from the patient, may be able to
      replace blood-forming cells that were destroyed by chemotherapy. It is not yet know which
      combination chemotherapy schedule is more effective, when given before surgery and an
      autologous bone marrow transplant, in treating patients with disseminated neuroblastoma.

      PURPOSE: This randomized phase III trial is studying two different chemotherapy schedules to
      compare how well they work in treating young patients who are undergoing surgery and an
      autologous bone marrow transplant for disseminated neuroblastoma.
    

Detailed description: 
      OBJECTIVES:

        -  Compare the response rates (bone marrow and primary tumor) in young patients with
           disseminated neuroblastoma treated with two different combination chemotherapy schedules
           comprising vincristine, cyclophosphamide, cisplatin, etoposide, and carboplatin followed
           by surgery and autologous stem cell transplantation.

        -  Compare the event-free survival of patients treated with these regimens.

        -  Compare the prognostic factors of patients treated with these regimens.

        -  Compare the toxicity of these regimens in these patients.

      OUTLINE: This is a randomized, multicenter study. Patients are randomized to 1 of 2 treatment
      arms.

        -  Arm I (OPEC/OJEC): Patients receive OPEC combination chemotherapy comprising vincristine
           IV, cyclophosphamide IV, cisplatin IV continuously over 24 hours, and etoposide IV over
           4 hours on day 1 of course 1. Patients then receive OJEC combination chemotherapy
           comprising vincristine IV, cyclophosphamide IV, etoposide IV over 4 hours, and
           carboplatin IV over 1 hour on day 1 of course 2. OPEC and OJEC regimens alternate so
           that patients receive 4 courses of OPEC and 3 courses of OJEC over 18 weeks in the
           absence of disease progression or unacceptable toxicity.

        -  Arm II (Rapid COJEC): Patients receive vincristine IV and carboplatin IV over 1 hour on
           day 1 and etoposide IV over 4 hours on days 1 and 2 (regimen 1). Ten days later,
           patients receive vincristine IV followed by cisplatin IV continuously over 24 hours on
           day 1 (regimen 2). Ten days later, patients receive vincristine IV on day 1 and
           etoposide IV over 4 hours and cyclophosphamide IV on days 1 and 2 (regimen 3). Treatment
           continues for 10 weeks (with a 10-day interval between regimens in this order: regimen
           2, regimen 1, regimen 2, regimen 3, and regimen 2) in the absence of disease progression
           or unacceptable toxicity.

      Patients who achieve bone marrow complete remission then undergo surgery. Patients achieving
      bone marrow partial remission or less are removed from study.

      After surgery, patients receive cyclophosphamide IV on day -7 and undergo bone marrow harvest
      on day 1. Patients then receive high-dose melphalan IV on day 1. Autologous bone marrow cells
      are reinfused on day 3.

      After completion of study treatment, patients are followed periodically.

      PROJECTED ACCRUAL: A total of 190 patients will be accrued for this study.
    

Intervention name(s): carboplatin; cisplatin; cyclophosphamide; etoposide; melphalan; vincristine sulfate; autologous bone marrow transplantation; conventional surgery
Intervention type(s): Drug; Drug; Drug; Drug; Drug; Drug; Procedure; Procedure
Intervention MeSH terms: Cyclophosphamide; Melphalan; Carboplatin; Etoposide; Vincristine
Allocation: Randomized
Primary purpose: Treatment
Keywords: disseminated neuroblastoma