Combination Chemotherapy Followed by Surgery in Treating Infants With Newly Diagnosed Neuroblastoma.

Study Overview
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Brief Summary
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RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Giving a chemotherapy drug before surgery may shrink the tumor so that it can be removed during surgery. PURPOSE: Phase II trial to study the effectiveness of combination chemotherapy followed by surgery in treating infants who have newly diagnosed neuroblastoma.

Detailed Description
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OBJECTIVES: Determine the survival and morbidity of infants with newly diagnosed stage II or III unresectable neuroblastoma without MYCN amplification treated with vincristine and cyclophosphamide, etoposide and carboplatin, and cyclophosphamide, doxorubicin, and vincristine followed by surgery. Determine whether deletion of chromosome 1p or diploidy/tetraploidy are prognostic factors in these patients. Determine whether there are other prognostic criteria that could be used in future therapeutic stratification of these patients. OUTLINE: This is a multicenter study. Patients are stratified according to symptomatic spinal cord involvement (yes vs no). Patients without evidence of symptomatic spinal cord compression receive vincristine IV on day 1 and cyclophosphamide IV on days 1-5. Treatment repeats every 14 days for 2 courses. Patients eligible for surgery undergo surgical resection and then are removed from the study. Patients ineligible for surgery after 2 courses of initial chemotherapy, but with at least 25% response to initial chemotherapy, receive 2 additional courses of vincristine and cyclophosphamide. Patients eligible for surgery undergo surgical resection and then are removed from the study. Patients ineligible for surgery after 2 additional courses of initial chemotherapy or with disease progression receive etoposide IV over 2 hours and carboplatin IV over 1 hour on days 1-3. Treatment repeats every 21 days for 2 courses. Patients eligible for surgery undergo surgical resection and then are removed from the study. Patients who remain ineligible for surgery or with disease progression after etoposide and carboplatin receive cyclophosphamide IV over 1 hour on days 1-5, doxorubicin IV over 6 hours on days 4 and 5, and vincristine IV on days 1 and 5. Treatment repeats every 21 days for 2 courses. Patients then undergo surgical resection or biopsy. Patients with symptomatic spinal cord compression receive initial treatment with etoposide and carboplatin as above. Patients with improved symptoms and resectable disease after initial chemotherapy undergo surgical resection or biopsy. Patients who remain ineligible for surgery or with no improvement in symptoms after initial chemotherapy receive cyclophosphamide, doxorubicin, and vincristine as above. Patients then undergo surgical resection or biopsy. Patients are followed within 6 months and then annually for 5 years. PROJECTED ACCRUAL: A total of 100 patients will be accrued for this study within 4 years.

Official Title
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European Infant Neuroblastoma Study - Unresectable Tumors (MYCN Not Amplified)

Conditions
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Neuroblastoma

Intervention / Treatment
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* Drug: carboplatin
* Drug: cyclophosphamide
* Drug: doxorubicin hydrochloride
* Drug: etoposide
* Drug: vincristine sulfate
* Procedure: conventional surgery


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Histologically or cytologically confirmed newly diagnosed stage II or III neuroblastoma or ganglioneuroblastoma Unresectable disease No MYCN amplification (i.e., fewer than 10 copies) No metastases to bone marrow No radiological bone lesions in skeleton PATIENT CHARACTERISTICS: Age: Under 12 months at diagnosis Performance status: Not specified Life expectancy: Not specified Hematopoietic: Not specified Hepatic: No evidence of liver disease by ultrasound Renal: Not specified 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: 1 Year

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 |
| --- |
|Drug: carboplatin|nan|
|Drug: cyclophosphamide|nan|
|Drug: doxorubicin hydrochloride|nan|
|Drug: etoposide|nan|
|Drug: vincristine sulfate|nan|
|Procedure: conventional surgery|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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localized unresectable neuroblastoma