Clinical trial NCT00025649: Combination Chemotherapy Followed by Surgery and Peripheral Stem Cell or Bone Marrow Transplantation in Treating Infants With Newly Diagnosed Neuroblastoma
Official title: European Infant Neuroblastoma Study - Stage 2, 3, 4, and 4S; MYCN Amplified Tumors
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Neuroblastoma
Keywords: localized resectable neuroblastoma
regional neuroblastoma
disseminated neuroblastoma
stage 4S neuroblastoma
localized unresectable neuroblastoma
Lead sponsor: National Cancer Institute (NCI)
Sponsor class: NIH
First posted: 2003-01-27
Sex: ALL
Maximum age (years): 1
Standard ages: CHILD
Accepts healthy volunteers: no
Primary purpose: TREATMENT

Brief summary: RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Combining chemotherapy with peripheral stem cell or bone marrow transplantation may allow the doctor to give higher doses of chemotherapy drugs and kill more tumor cells.

PURPOSE: Phase II trial to study the effectiveness of combination chemotherapy given before surgery followed by peripheral stem cell or bone marrow transplantation in treating infants who have newly diagnosed neuroblastoma.

Detailed description: OBJECTIVES:

* Determine the survival of infants with newly diagnosed stage II, III, IV, or IVS neuroblastoma with MYCN amplification treated with etoposide, carboplatin, cyclophosphamide, doxorubicin, and vincristine followed by surgery and busulfan and melphalan with autologous peripheral blood stem cell or bone marrow transplantation.
* Determine whether there are 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 then 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.

Patients receive filgrastim (G-CSF) subcutaneously daily for 5 days. Patients undergo leukapheresis to collect peripheral blood stem cells (PBSC). Patients who do not mobilize sufficient cells undergo bone marrow harvest.

Patients eligible for surgery undergo surgical resection. Patients with stage IV disease with less than complete response of metastatic disease after initial chemotherapy are removed from the study.

Beginning within 2 weeks after surgery, patients receive 1 additional course of VP-CARBO chemotherapy followed by 1 additional course of CADO chemotherapy.

After at least 3 weeks, patients receive high-dose chemotherapy comprising busulfan IV over 24 hours on days -7 to -3 and melphalan IV on day -2. PBSC or bone marrow are reinfused on day 0.

At least 2 months after the completion of high-dose chemotherapy and bone marrow or PBSC transplantation, patients undergo radiotherapy to the primary site, according to preoperative imaging studies. Patients are treated with oral tretinoin after megatherapy.

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

PROJECTED ACCRUAL: A total of 40 patients will be accrued for this study within 4 years.

Eligibility criteria: DISEASE CHARACTERISTICS:

* Histologically confirmed newly diagnosed stage II, III, IV, or IVS neuroblastoma or ganglioneuroblastoma
* MYCN amplification (i.e., at least 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

Primary outcomes:
Secondary outcomes:
Other outcomes:
Locations:
city: Vienna
country: Austria
facility: St. Anna Children's Hospital
city: Ghent
country: Belgium
facility: Universitair Ziekenhuis Gent
city: Copenhagen
country: Denmark
facility: Rigshospitalet
city: Toulouse
country: France
facility: Centre Hospitalier Regional de Purpan
city: Genoa
country: Italy
facility: Istituto Giannina Gaslini
city: Oslo
country: Norway
facility: Rikshospitalet University Hospital
city: Lisboa
country: Portugal
facility: Instituto Portugues de Oncologia de Francisco Gentil - Centro Regional de Oncologia de Lisboa, S.A.
city: Valencia
country: Spain
facility: Hospital Universitario LA FE
city: Gothenburg
country: Sweden
facility: Ostra Sjukhuset
city: Lausanne
country: Switzerland
facility: Centre Hospitalier Universitaire Vaudois
city: Bristol
country: United Kingdom
facility: Bristol Royal Hospital for Children
state: England
Study officials:
affiliation: Hospital Universitario La Fe
name: Adela Canete, MD, PhD
role: STUDY_CHAIR
References:
citation: Canete A, Gerrard M, Rubie H, Castel V, Di Cataldo A, Munzer C, Ladenstein R, Brichard B, Bermudez JD, Couturier J, de Bernardi B, Pearson AJ, Michon J. Poor survival for infants with MYCN-amplified metastatic neuroblastoma despite intensified treatment: the International Society of Paediatric Oncology European Neuroblastoma Experience. J Clin Oncol. 2009 Mar 1;27(7):1014-9. doi: 10.1200/JCO.2007.14.5839. Epub 2009 Jan 26.