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, and giving them 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
disseminated neuroblastoma	Drug: carboplatin  Drug: cyclophosphamide  Drug: doxorubicin  Drug: etoposide  Drug: vincristine  Procedure: chemotherapy  Procedure: conventional surgery  Procedure: surgery	Phase II

Further Study Details: 

OBJECTIVES:

• Confirm that the management of infants with newly diagnosed stage IV neuroblastoma without MYCN amplification treated with etoposide and carboplatin and cyclophosphamide, doxorubicin, and vincristine followed by surgery does not require intensive high-dose chemotherapy consolidation.
• 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 receive VP-CARBO chemotherapy comprising etoposide IV over 2 hours and carboplatin IV over 1 hour on days 1-3. Treatment repeats every 21 days for 2 courses.

Patients without disease progression receive 2 additional courses of VP-CARBO chemotherapy. Patients with metastatic complete response (CR) undergo surgical resection of primary disease.

Patients with disease progression after 2 or 4 courses of VP-CARBO chemotherapy receive CADO chemotherapy comprising 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.

After 2 courses of CADO chemotherapy, patients with metastatic CR undergo surgical resection of primary disease. Patients with residual disease receive 2 additional courses of CADO chemotherapy. Patients with residual disease after 4 courses of CADO chemotherapy are removed from the study. Patients with metastatic CR after additional CADO chemotherapy undergo surgical resection of primary disease.

Patients are followed within 6 months and then annually for 5 years.

PROJECTED ACCRUAL: A total of 60 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 neuroblastoma or ganglioneuroblastoma
• Metastases to bone, CNS, or pleura/lung by x-ray or CT scan
• 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

Study chairs or principal investigators

Bruno De Bernardi, MD,  Study Chair,  Istituto Giannina Gaslini   

Study ID Numbers:  CDR0000068980; EURO-INF-NB-STUDY-1999-99.3; EU-20125C; NCT00025623
Record last reviewed:  October 2001
Last Updated:  January 6, 2005
Record first received:  October 11, 2001
ClinicalTrials.gov Identifier:  NCT00025623
Health Authority: United States: Federal Government
ClinicalTrials.gov processed this record on 2005-04-08