RATIONALE: Drugs used in chemotherapy use different ways to stop tumor 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 different combination chemotherapy regimens in treating infants who have newly diagnosed neuroblastoma.

Condition	Treatment or Intervention	Phase
disseminated neuroblastoma stage 4S neuroblastoma	Drug: carboplatin  Drug: cyclophosphamide  Drug: doxorubicin  Drug: etoposide  Drug: vincristine  Procedure: chemotherapy	Phase II

Further Study Details: 

OBJECTIVES:

• Confirm that the outcome for infants with newly diagnosed stage IV or IVS neuroblastoma without MYCN amplification is not altered by treatment with etoposide and carboplatin followed by cyclophosphamide, doxorubicin, and vincristine.
• 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 age (under 1 month vs over 1 month).

Infants less than 1 month of age are further stratified according to Philadelphia score (less than 1 vs at least 1). Infants over 1 month of age are also further stratified according to Philadelphia score (less than 2 vs at least 2).

Infants under 1 month of age with Philadelphia score of less than 1 and infants over 1 month of age with Philadelphia score of less than 2 undergo observation only. Infants under 1 month of age with Philadelphia score of at least 1 and infants over 1 month of age with Philadelphia score of at least 2 receive VP-CARBO chemotherapy.

• VP-CARBO chemotherapy: Patients 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 with no response receive CADO chemotherapy.
• CADO chemotherapy: Patients 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 a maximum of 4 courses. Patients are followed within 6 months and then annually for 5 years.

PROJECTED ACCRUAL: A total of 130 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 confirmed newly diagnosed stage IV or IVS neuroblastoma or ganglioneuroblastoma
• Metastases confined to marrow, skin, nodes, or liver
• No metastases to bone (radiologic bone lesions in skeleton), CNS, pleura, or lung
• No MYCN amplification (i.e., fewer than 10 copies)

PATIENT CHARACTERISTICS: Age:

• Under 12 months at diagnosis

Performance status:

• Not specified

Life expectancy:

• Not specified

Hematopoietic:

• Not specified

Hepatic:

• Not specified

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
      Children's Hospital - Sheffield, Sheffield,  England,  S10 2TH,  United Kingdom; Recruiting

Study chairs or principal investigators

Mary P. Gerrard, BSc, MBChB, FRCP, FRCPCH,  Study Chair,  Children's Hospital - Sheffield   

Study ID Numbers:  CDR0000068979; EURO-INF-NB-STUDY-1999-99.2; EU-20125B; NCT00025610
Record last reviewed:  October 2001
Last Updated:  January 6, 2005
Record first received:  October 11, 2001
ClinicalTrials.gov Identifier:  NCT00025610
Health Authority: United States: Federal Government
ClinicalTrials.gov processed this record on 2005-04-08