Combination Chemotherapy in Treating Children With Metastatic Rhabdomyosarcoma or Other Malignant Mesenchymal Tumors

Study Overview
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Brief Summary
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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
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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.

Official Title
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MMT 98 Study For Metastatic Disease Rhabdomyosarcoma And Other Malignant Soft Tissue Sarcoma Of Childhood

Conditions
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Ovarian Cancer, Sarcoma, Small Intestine Cancer

Intervention / Treatment
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* Biological: dactinomycin
* Biological: filgrastim
* Drug: carboplatin
* Drug: cyclophosphamide
* Drug: doxorubicin hydrochloride
* Drug: epirubicin hydrochloride
* Drug: etoposide
* Drug: ifosfamide
* Drug: vincristine sulfate
* Procedure: peripheral blood stem cell transplantation
* Radiation: radiation therapy


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Histologically confirmed metastatic rhabdomyosarcoma or other malignant mesenchymal tumors Standard risk defined as: Less than 10 years of age No bone or bone marrow involvement High risk defined as: At least 10 years of age OR Bone or bone marrow involvement Diagnosed less than 8 weeks ago Previously untreated disease except for initial surgery within the past 8 weeks PATIENT CHARACTERISTICS: Age: 6 months to under 18 years Performance status: Not specified Life expectancy: Not specified Hematopoietic: Not specified Hepatic: Not specified Renal: Not specified PRIOR CONCURRENT THERAPY: Biologic therapy: No prior biologic therapy Chemotherapy: No prior chemotherapy Endocrine therapy: No prior endocrine therapy Radiotherapy: Concurrent radiotherapy allowed Surgery: See Disease Characteristics

Ages Eligible for Study
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Minimum Age: 6 Years
Maximum Age: 17 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment


Arms and Interventions

| Intervention/Treatment |
| --- |
|Biological: dactinomycin|nan|
|Biological: filgrastim|nan|
|Drug: carboplatin|nan|
|Drug: cyclophosphamide|nan|
|Drug: doxorubicin hydrochloride|nan|
|Drug: epirubicin hydrochloride|nan|
|Drug: etoposide|nan|
|Drug: ifosfamide|nan|
|Drug: vincristine sulfate|nan|
|Procedure: peripheral blood stem cell transplantation|nan|
|Radiation: radiation therapy|nan|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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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