Combination Chemotherapy With or Without Radiation Therapy in Treating Patients With Newly Diagnosed Rhabdomyosarcoma

Study Overview
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Brief Summary
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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 whether chemotherapy is more effective with or without radiation therapy in treating patients who have rhabdomyosarcoma. PURPOSE: Phase III trial to compare the effectiveness of chemotherapy with or without radiation therapy in treating patients who have newly-diagnosed rhabdomyosarcoma.

Detailed Description
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OBJECTIVES: Determine the failure-free survival (FFS) rate in patients with newly diagnosed low-risk rhabdomyosarcoma of embryonal or botryoid subtype meeting criteria for group I after treatment with dactinomycin and vincristine with or without radiotherapy. Determine the FFS rate in these patients meeting criteria for group II after treatment with dactinomycin, vincristine, and cyclophosphamide with or without radiotherapy. Determine the FFS rate in patients with ectomesenchymomas containing rhabdomyosarcomatous elements (embryonal histiotype) who receive one of the above treatments. Determine new molecular markers specific to embryonal and botryoid tumor histologies which are of diagnostic and prognostic significance in patients treated with these regimens. OUTLINE: Patients are assigned to 1 of 2 groups, depending on histology and site of disease. Group I (favorable tumor site, negative lymph nodes, stage 1, clinical group I, IIA, or III (orbit only), node negative [N0] OR unfavorable tumor site, negative or unknown lymph nodes, stage 2, clinical group I): Patients receive vincristine IV over 1 minute weekly for 8 weeks and dactinomycin IV over 1 minute once every 3 weeks for 4 doses. Treatment repeats every 12 weeks for 4 courses. Radiotherapy is administered to patients with clinical group II or III disease on weeks 3-8. Group II (favorable tumor site, positive lymph nodes, stage 1, clinical group III (orbit only), node positive [N1] OR favorable tumor site except orbit, any lymph nodes, stage 1, clinical group III OR unfavorable tumor site, stage 2, clinical group II OR unfavorable tumor site, stage 3, clinical group I or II): Patients receive vincristine and dactinomycin as in group I. Patients also receive cyclophosphamide IV over 30-60 minutes and filgrastim (G-CSF) or sargramostim (GM-CSF) subcutaneously once daily beginning 24 hours after completion of chemotherapy and continuing for 10 days or until blood counts recover. Radiotherapy is administered on weeks 3-8, 12-17, or 28-33, if clinically indicated as in group I. Patients are followed every 3-4 months for 3 years (4 years after diagnosis), every 6 months for 1 year, and then annually thereafter. PROJECTED ACCRUAL: A total of 254 patients for group I will be accrued for this study within 6 years. Approximately 12 patients per year will be accrued for group II.

Official Title
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Actinomycin D and Vincristine With or Without Radiation Therapy, for Newly Diagnosed Patients With Low-Risk Rhabdomyosarcoma or Undifferentiated Sarcoma: IRS-V Protocol

Conditions
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Sarcoma

Intervention / Treatment
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* Biological: dactinomycin
* Biological: filgrastim
* Biological: sargramostim
* Drug: cyclophosphamide
* Drug: vincristine sulfate
* Radiation: radiation therapy


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Histologically confirmed embryonal (EMB) rhabdomyosarcoma (RMS) or botryoid or spindle cell variants of EMB RMS or embryonal ectomesenchymoma meeting 1 of the following criteria: Stage 1, no clinical group IV: Tumor in favorable site (orbit, head and neck [excluding parameningeal], genitourinary [not bladder/prostate], or biliary tract) and no metastatic disease Stage 2 or 3, clinical group I or II: Tumor in unfavorable site (bladder/prostate, extremity, cranial parameningeal, trunk, retroperitoneum, pelvis, perineal/perianal, intrathoracic, gastrointestinal, or liver), no gross residual disease after initial surgery, and no metastatic disease Must have ipsilateral lymph node dissection if age 10 or over with primary paratesticular cancer OR under age 10 with clinically positive regional lymph nodes Low risk of recurrence Previously untreated disease No alveolar RMS or undifferentiated sarcoma No intermediate-risk disease No metastatic disease at diagnosis PATIENT CHARACTERISTICS: Age: Under 50 Performance status: Not specified Hematopoietic: Not specified Hepatic: Bilirubin elevation secondary to biliary or hepatic primaries allowed Renal: Creatinine elevation secondary to tumor obstruction allowed Other: No uncontrolled infection Not pregnant or nursing Fertile patients must use effective contraception PRIOR CONCURRENT THERAPY: Biologic therapy Not specified Chemotherapy Not specified Endocrine therapy Not specified Radiotherapy Not specified Surgery Not specified

Ages Eligible for Study
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Maximum Age: 49 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
Masking: None (Open Label)


Arms and Interventions

| Intervention/Treatment |
| --- |
|Biological: dactinomycin|nan|
|Biological: filgrastim|nan|
|Biological: sargramostim|nan|
|Drug: cyclophosphamide|nan|
|Drug: vincristine sulfate|nan|
|Radiation: radiation therapy|nan|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Failure-free survival |  |  | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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embryonal childhood rhabdomyosarcoma, embryonal-botryoid childhood rhabdomyosarcoma, previously untreated childhood rhabdomyosarcoma, adult rhabdomyosarcoma, adult malignant mesenchymoma, childhood malignant mesenchymoma, nonmetastatic childhood soft tissue sarcoma, stage II adult soft tissue sarcoma, stage III adult soft tissue sarcoma, stage I adult soft tissue sarcoma