Study: NCT02265770

Intervention type: DRUG
Group type: EXPERIMENTAL
Intervention: 16 weeks of VEC + CDDP
Description: Days 1-36-71-106: Vincristine: 1.5 mg/m² (maximal dose 2 mg) i.v.; Days 1-3-36-38-71-73-106-108: Etoposide: 100 mg/m² infused over 60 minutes; Days 1-36-71-106: Cyclophosphamide: 3000 mg/m² in 3 divided infusions (1000 mg/m²/infusion) infused over 60 minutes; Days 22-57-92: Cisplatin: 80 mg/m² over 4 hours + Vincristine:1.5 mg/m² (maximal dose 2 mg) i.v.

Intervention type: DRUG
Group type: EXPERIMENTAL
Intervention: VEC + HD-MTX
Description: Days 1-22-43: Vincristine: 1.5 mg/m² (maximal dose 2 mg) i.v.; Days 1-3-22-24-43-45: Etoposide: 100 mg/m² infused over 60 minutes; Days 1-22-43: Cyclophosphamide: 3000 mg/m² in 3 divided infusions (1000 mg/m²/infusion) infused over 60 minutes; Days 15-36-57: Administer methotrexate at 8000 mg/m² as a 24 hour IV infusion on days 15-36-57. 10% of the dose should be given over the first hour and 90% over the remaining 23 hours. The infusion must finish at 24 hours even if it has not been completed.

Intervention type: DRUG
Group type: EXPERIMENTAL
Intervention: Chemotherapy + Valproate
Description: Days 1-57-113-169-225-281-337: Vincristine and Carboplatin; Days 15-71-127-183-239-295-351: Vincristine and Methotrexate; Days 29-85-141-197-253-309-365: Vincristine and Cyclophosphamide; Days 43-44-99-100-154-155-211-212-267-268-323-324-379-380: Cisplatin 2-day continuous infusion.~Valproate: initial dose 30 mg/kg/day for two weeks in 2 divided doses (BID 15 mg/kg). Increasing weekly up to 40 - 50 - 60 mg/kg/day in 2 divided doses.

Intervention type: RADIATION
Group type: EXPERIMENTAL
Intervention: Conformal radiotherapy
Description: Conformal radiotherapy: 59.4Gy (children \<18 months or with risk factors: 54Gy). Daily fraction 1.8 Gy, 5 fractions / week.

Intervention type: RADIATION
Group type: ACTIVE_COMPARATOR
Intervention: Conformal radiotherapy
Description: Conformal radiotherapy: 59.4Gy (children \<18 months or with risk factors: 54Gy). Daily fraction 1.8 Gy, 5 fractions / week.

Intervention type: DRUG
Group type: ACTIVE_COMPARATOR
Intervention: VEC
Description: D1: Vincristine: 1.5 mg/m² (maximal dose 2 mg) i.v.; D1-D3: Etoposide: 100 mg/m² infused over 60 minutes; D1: Cyclophosphamide: 3000 mg/m² in 3 divided infusions (1000 mg/m²/infusion) infused over 60 minutes; D22: Vincristine: 1.5 mg/m² (maximal dose 2 mg) i.v.; D22-D24: Etoposide: 100 mg/m² infused over 60 minutes; D22: Cyclophosphamide: 3000 mg/m² in 3 divided infusions (1000 mg/m²/infusion) infused over 60 minutes; D43: Vincristine: 1.5 mg/m² (maximal dose 2 mg) i.v.; D43-D45: Etoposide: 100 mg/m² infused over 60 minutes; D43: Cyclophosphamide: 3000 mg/m² in 3 divided infusions (1000 mg/m²/infusion) infused over 60 minutes

Intervention type: DRUG
Group type: ACTIVE_COMPARATOR
Intervention: Chemotherapy
Description: Days 1-57-113-169-225-281-337: Vincristine and Carboplatin; Days 15-71-127-183-239-295-351: Vincristine and Methotrexate; Days 29-85-141-197-253-309-365: Vincristine and Cyclophosphamide; Days 43-44-99-100-154-155-211-212-267-268-323-324-379-380: Cisplatin 2-day continuous infusion.

Intervention type: RADIATION
Group type: EXPERIMENTAL
Intervention: conformal radiotherapy +/- boost
Description: Conformal radiotherapy: 59.4Gy (children \<18 months or with risk factors: 54Gy). Daily fraction 1.8 Gy, 5 fractions / week.~In case of persistent residue : Boost of radiation 8 Gy in 2 equivalent fractions

Intervention type: RADIATION
Group type: ACTIVE_COMPARATOR
Intervention: conformal radiotherapy +/- boost
Description: Conformal radiotherapy: 59.4Gy (children \<18 months or with risk factors: 54Gy). Daily fraction 1.8 Gy, 5 fractions / week.~In case of persistent residue : Boost of radiation 8 Gy in 2 equivalent fractions