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.

Condition	Treatment or Intervention	Phase
localized unresectable neuroblastoma	Drug: carboplatin  Drug: cyclophosphamide  Drug: doxorubicin  Drug: etoposide  Drug: vincristine  Procedure: chemotherapy  Procedure: conventional surgery  Procedure: surgery	Phase II

Further Study Details: 

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.

Ages Eligible for Study:  up to  1 Year,  Genders Eligible for Study:  Both

Criteria

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

Austria
      St. Anna Children's Hospital, Vienna,  A-1090,  Austria; Recruiting
Belgium
      Universitair Ziekenhuis Gent, Ghent,  B-9000,  Belgium; Recruiting
Denmark
      Rigshospitalet, Copenhagen,  2100,  Denmark; Recruiting
France
      Centre Hospitalier Regional de Purpan, Toulouse,  31026,  France; Recruiting
Italy
      Istituto Giannina Gaslini, Genoa,  16148,  Italy; Recruiting
Norway
      Rikshospitalet University Hospital, Oslo,  0027,  Norway; Recruiting
Portugal
      Instituto Portugues de Oncologia de Francisco Gentil - Centro Regional de Oncologia de Lisboa, S.A., Lisboa,  1099-023 Codex,  Portugal; Recruiting
Spain
      Hospital Universitario LA FE, Valencia,  46009,  Spain; Recruiting
Sweden
      Ostra Sjukhuset, GOTHENBURG,  41685,  Sweden; Recruiting
Switzerland
      Centre Hospitalier Universitaire Vaudois, Lausanne,  CH-1011,  Switzerland; Recruiting
United Kingdom, England
      Bristol Royal Hospital for Children, Bristol,  England,  BS2 8BJ,  United Kingdom; Recruiting

Study chairs or principal investigators

Herve Rubie, MD,  Study Chair,  Centre Hospitalier Regional de Purpan   

Study ID Numbers:  CDR0000068977; EURO-INF-NB-STUDY-1999-99.1; EU-20125A; NCT00025597
Record last reviewed:  October 2001
Last Updated:  January 6, 2005
Record first received:  October 11, 2001
ClinicalTrials.gov Identifier:  NCT00025597
Health Authority: United States: Federal Government
ClinicalTrials.gov processed this record on 2005-04-08