Dettagli per singolo studio

DEC-NET Serial number FR382

Published online	04/04/2005 12.09.00
Last updated	09/09/2005 16.28.34

Other protocol ID number	Euro -INF-NB 1999
Current trial status	Complete(closed to recruitment of participants: follow-up complete)
Major Disease (ICD9 class)	MALIGNANT NEOPLASM OF ADRENAL GLAND
Experimental drug
Vincristine Treatment regimen (dosage and duration) 1/The "Cyclophosphamide- Vincristine" Cure are given to 14 days of interval Vincristine: 0.05 mg/kg IVDL First day. 2/The cure CADO (Cyclophosphamide, doxorubicine and vincristine) is given to 21 days of interval. Vincristine: 0.05 mg/kg IV injection at D1 and D5.
CARBOPLATIN Treatment regimen (dosage and duration) The Cure of VP-CARBO is given every 21 days. The two products are given of D1 with D3 of each cure. Carboplatine:6,6 mg/kg in 5% of glucose solution over 1 hour (3 times per day).
Cyclophosphamide Treatment regimen (dosage and duration) 1/The CO (Cyclophosphamide-vincristine) Cure is given to 14 days of interval. Cyclophosphamide:5 mg/kg IV or IM injection, 5 times per day. 2/The cure CADO (Cyclophosphamide, doxorubicine and vincristine) is given to 21 days of interval. Cyclophosphamide: 10 mg/kg in 5% of glucose solution over 1 hour, 5 times per day.
Etoposide (VP16) Treatment regimen (dosage and duration) The Cure of VP-CARBO is given every 21 days. The two products are given of D1 with D3 of each cure. Etoposide (VP16):5 mg/kg in saline solution over 2 hour 3 times per day.
Doxorubicine Treatment regimen (dosage and duration) The cure CADO (Cyclophosphamide, doxorubicine and vincristine) is given to 21 days of interval. A central route is essential to administer Adriamycine (Doxo) over 6 hours. Doxorubicine : 1 mg/kg in saline solution over 6 hours at D4 and D5.
Busulfan Treatment regimen (dosage and duration) This treatment is used only for the infants whose tumour with N-myc amplification, after they had a chemotherapy by 6 cures of VPCARBO-CADO and a surgery. Busulfan :120 mg/m2/day (30 mg/m2 per dose) at D-7 until D-3
Melphalan Treatment regimen (dosage and duration) This treatment is used only for the infants whose tumour with N-myc amplification, after they had a chemotherapy by 6 cures of VPCARBO-CADO and a surgery. Melphalan :140 mg/m2 IV over 15 minutes at D-2
Gender	Both
Age (range)	< 12 months
Eligibility criteria
Inclusion criteria
Commun criterias for all groups. - Neuroblastoma or ganglioneuroblastoma confirmed histologically (INSS criteria), not previously treated. - Informed and signed parental consent Additional criterias to enter th subgroups: NB 99:1 -Histologically or cytologically confirmed newly diagnosed stage 2 or 3 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. 2/NB 99.2 - Histologically confirmed newly diagnosed stage 4 or 4S neuroblastoma or ganglioneuroblastoma - Metastases confined to marrow, skin, nodes, or liver - No bone metastases (radiologic bone lesions in skeleton), CNS, pleura, or lung - No MYCN amplification (i.e., fewer than 10 copies). 3/ NB 99.3 - Histologically confirmed newly diagnosed stage 4 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). 4/ NB 99.4 - Histologically confirmed newly diagnosed stage 2, 3, 4, or 4S neuroblastoma or ganglioneuroblastoma. - MYCN amplification (> 10 copies)
Exclusion criteria
For all the study: - Will only be included in the test the patients for whom all the elligibility criteria, in particular the biological results, are registered in the international data base within 6 weeks of diagnosis. - The infants with a neuroblastoma or a ganglioneuroblastoma who are not eligible to one of the tests (nor in Test LNESG), because of unknown or unevaluated N-Myc result, or who are not recorded in a test group within 6 weeks of diagnosis, will be followed with a minimum of data, and will be analyzed separately. 1/Test NB 99.1: - metastatic Infiltration of bone marrow. - Fixing MIBG (or Technetium) or radiological lesions on the level of the skeleton. - Specific hepatic Attack (with sonography). - N-Myc Amplification (³ 10 copies). 2/Test NB 99.2: - radiological osseous Lesions. - N-Myc Amplification (³ 10 copies). 3/Test NB 99.3 - N-Myc Amplification (³ 10 copies). 4/Test NB 99.4 - Stage 1 with amplified N-Myc.
Trial design/methodology
Phase	2
Kind of study	Efficacy
Design
Purpose of study
Major Objective : 1/ To determine the evolution of neuroblastoma in infants according to the type of tumor and the various treatments. 2/ To adopt identical therapeutic strategies in the different groups of patients in order to : - To determine the survival and morbidity rate of infants with newly diagnosed stage 2 or 3 unresectable neuroblastoma without MYCN amplification treated with vincristine and cyclophosphamide, etoposide and carboplatin, and cyclophosphamide, doxorubicin, and vincristine followed by surgery. The objective is to obtain a survival rate higher than 90% to 3 years. - To confirm that the evolution of the infantsn with a stage 4S and without N-Myc amplification is not compromised by adopting a therapeutic approach based on cures of semi-intensive chemotherapy only given to the infants having life-threatening symptoms (Test NB 99.2). The objective is to obtain a survival rate higher than 85% to 2 years. - To confirm that the management of infants with newly diagnosed stage 4 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 (test NB 99.3). The objective is to obtain a survival rate higher than 70% to 2 years. - To determine the survival of infants with newly diagnosed stage 2, 3, 4, or 4S 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 (Test NB 99.4). The objective is to obtain a survival rate higher than 50% to 2 years.




Summary of study design, objectives, and ongoing research findings
The present trial aims : - To follow a standardized therapeutic protocol troughout Europe to treat infants with newly diagnosed neuroblastoma. - To determine the survival and morbidity rate according to different subgroups defined by: localised tumor, with or without MYCN, presence or not of metastases amplification