Combination Chemotherapy in Treating Children With Metastatic Rhabdomyosarcoma or Other Malignant Mesenchymal Tumors
Condition: Ovarian Cancer; Sarcoma; Small Intestine Cancer
MeSH terms: Sarcoma; Rhabdomyosarcoma; Intestinal Neoplasms
Study type: Interventional
Phase: Phase 2

Summary: 
      RATIONALE: Drugs used in chemotherapy use different ways to stop cancer cells from dividing
      so they stop growing or die. Combining more than one drug may kill more tumor cells.

      PURPOSE: Phase II trial to study the effectiveness of combination chemotherapy in treating
      children with metastatic rhabdomyosarcoma or other malignant mesenchymal tumors.
    

Detailed description: 
      OBJECTIVES:

        -  Determine the overall survival of children with metastatic rhabdomyosarcoma or other
           malignant mesenchymal tumors treated with one of two different chemotherapy regimens
           based upon risk group.

        -  Determine the role of low-intensity maintenance chemotherapy after intensive
           conventional chemotherapy in standard-risk children.

        -  Determine the value of a therapeutic window in high-risk children.

        -  Determine the role of sequential high-dose chemotherapy with peripheral blood stem cell
           transplantation in achieving complete response in high-risk children.

        -  Determine the complete response, overall survival, and event-free survival in high-risk
           children.

      OUTLINE: This is a multicenter study. Patients are stratified according to risk group
      (standard vs high).

      Standard-risk patients:

        -  Initial chemotherapy: Patients receive vincristine IV on day 1 for weeks 1-7. Patients
           also receive dactinomycin IV on day 1 and ifosfamide IV over 1 hour on days 1-3 of week
           1. Patients then receive carboplatin IV over 1 hour and epirubicin IV over 6 hours on
           day 1 of week 4. Patients then receive ifosfamide IV over 1 hour and etoposide IV over 4
           hours on days 1-3 of week 7. Treatment repeats every 8 weeks for 3 courses in the
           absence of disease progression or unacceptable toxicity. After the second course,
           patients with less than 50% partial response (PR) are removed from study.

      Patients with parameningeal disease undergo radiotherapy 5 days a week for about 8 weeks
      beginning at week 9.

        -  Maintenance chemotherapy: Patients receive cyclophosphamide IV over 1 hour, vincristine
           IV, and dactinomycin IV on day 1. Treatment repeats every 3 weeks for 9 courses in the
           absence of disease progression or unacceptable toxicity.

      Patients who remain in PR at week 17 undergo radiotherapy for about 9 weeks beginning at week
      18.

      High-risk patients:

        -  Initial chemotherapy: Patients receive window study drug carboplatin IV over 1 hour or
           doxorubicin on day 1. Treatment repeats every 3 weeks for 2 courses.

      Patients receive high-dose cyclophosphamide IV over 1 hour on days 1-3 of week 7. Beginning
      on day 8, patients receive filgrastim (G-CSF) IV or subcutaneously (SC) daily until day 13.
      Patients may undergo peripheral blood stem cell (PBSC) collection.

      Patients receive high-dose etoposide IV over 24 hours on days 15-17. Beginning on day 22,
      patients receive G-CSF IV or SC daily until day 27.

      Patients receive high-dose cyclophosphamide IV over 1 hour on days 29-31. Beginning on day
      36, patients receive G-CSF IV or SC daily until day 42. Patients may undergo PBSC collection
      if not previously performed. Patients who achieve complete response (CR) are removed from
      study.

      Patients receive high-dose carboplatin IV over 1 hour on days 44-48. Patients undergo PBSC
      reinfusion on day 52. Beginning on day 55, patients receive G-CSF IV or SC daily until blood
      counts recover.

        -  Maintenance chemotherapy: Patients receive maintenance chemotherapy comprising
           cyclophosphamide, vincristine, and dactinomycin in the same manner as the standard-risk
           patients.

      Patients with parameningeal disease and those not achieving CR undergo radiotherapy beginning
      at week 17. Patients achieving CR, unless metastatic disease is resected, undergo
      radiotherapy beginning on week 15.

      Patients are followed every 2 months for 2 years, every 3 months for 1 year, every 6 months
      for 2 years, and then annually thereafter.

      PROJECTED ACCRUAL: A total of 8-30 standard-risk patients will be accrued for this study
      within 4 years. A total of 15-75 high-risk patients will be accrued for this study within 4-5
      years.
    

Intervention name(s): dactinomycin; filgrastim; carboplatin; cyclophosphamide; doxorubicin hydrochloride; epirubicin hydrochloride; etoposide; ifosfamide; vincristine sulfate; peripheral blood stem cell transplantation; radiation therapy
Intervention type(s): Biological; Biological; Drug; Drug; Drug; Drug; Drug; Drug; Drug; Procedure; Radiation
Intervention MeSH terms: Dactinomycin; Cyclophosphamide; Ifosfamide; Carboplatin; Doxorubicin; Liposomal doxorubicin; Etoposide; Vincristine; Epirubicin
Primary purpose: Treatment
Keywords: chondrosarcoma; small intestine leiomyosarcoma; fibrosarcomatous osteosarcoma; embryonal childhood rhabdomyosarcoma; alveolar childhood rhabdomyosarcoma; pleomorphic childhood rhabdomyosarcoma; mixed childhood rhabdomyosarcoma; embryonal-botryoid childhood rhabdomyosarcoma; metastatic childhood soft tissue sarcoma; extraosseous Ewing sarcoma/peripheral primitive neuroectodermal tumor; childhood fibrosarcoma; childhood synovial sarcoma; childhood malignant hemangiopericytoma; childhood liposarcoma; childhood alveolar soft-part sarcoma; childhood leiomyosarcoma; childhood angiosarcoma; childhood epithelioid sarcoma; childhood malignant mesenchymoma; stage IV uterine sarcoma; uterine leiomyosarcoma; ovarian sarcoma; previously untreated childhood rhabdomyosarcoma; childhood desmoplastic small round cell tumor