High-Risk Neuroblastoma Study 2 of SIOP-Europa-Neuroblastoma (SIOPEN)

Sponsor
Gustave Roussy, Cancer Campus, Grand Paris
Study ID
NCT04221035
Phase
PHASE3
Status
Recruiting
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Conditions

Eligibility Criteria

Sex
ALL
Age
N/A - 21 Years
Healthy Volunteers
Not accepted

Interventions

  • Vincristine — DRUG
    1.5 mg/m2 (max dose 2 mg)
  • Carboplatin — DRUG
    750 mg/m2
  • Etoposide — DRUG
    175 mg/m2
  • Vindesine — DRUG
    3 mg/m2/day (max dose 6 mg)
  • Dacarbazine — DRUG
    200 mg/m2/day
  • Ifosfamide — DRUG
    1500 mg/m2/day
  • Doxorubicin — DRUG
    30 mg/m2/dose
  • Busulfan — DRUG
    \< 9kg: 1.0 mg/kg/dose 9 kg to \< 16 kg : 1.2 mg/kg/dose 16 kg to 23 kg : 1.1 mg/kg/dose \>23 kg to 34 kg: 0.95 mg/kg/dose \>34 kg: 0.8 mg/kg/dose Infusion IV over 2 hours Administration every 6 hours for a total of 16 doses
  • Melphalan — DRUG
    140 mg/m2/dose IV short infusion (15'), at least 24 h after the last busulfan dose
  • Thiotepa — DRUG
    300 mg/m2/day over 2 hours
  • Radiotherapy — RADIATION
    21.6 Gy 21.6 Gy + boost de 14.4 Gy
  • Dinutuximab Beta — DRUG
    Patients \>12 kg are dosed based on the BSA: 10 mg/m\^2/day Patients ≤ 12 kg are dosed according to their body weight: 0.33 mg/kg/day
  • Cisplatin — DRUG
    80 mg/m2/24h
  • Temozolomide 100 MG — DRUG
    100 mg/m²/Day
  • Irinotecan — DRUG
    50 mg/m²/jour de J0 à J4
  • Cyclophosphamid — DRUG
    Cyclophosphamide has been demonstrated to have a cytostatic effect in many tumour types. The active metabolites of cyclophosphamide are alkylating agents which transfer alkyl groups to DNA during the process of cell division, thus preventing normal synthesis of DNA.

Study Details

This is an international multicenter, open-label, randomized phase III trial including three sequential randomizations to assess efficacy of induction and consolidation chemotherapies and radiotherapy for patients with high-risk neuroblastoma.

Key Dates

Start date
Nov 5, 2019
Status verified
Jun 2025
Primary completion
Nov 30, 2026
Completion
Nov 30, 2032

Study Design

Enrollment
800 participants (estimated)
Allocation
RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT

Arms

  • Experimental: phase induction-R-I
    R-I: induction regimens RAPID COJEC vs GPOH Assuming a baseline 3-year EFS of 40%, with a sample size of 686 patients (343 in each arm) and a two-sided alpha=5% this trial will have 90% power to demonstrate an improvement of 12% in 3-year EFS, within a recruitment period of 3 years and a minimum follow up of 1.5 years. Patients with insufficient metastatic response at the end of induction chemotherapy, defined as SIOPEN score \> 3 or less than 50% reduction in mIBG score (or \> 3 bone lesions or less 50% reduction in number of FDG-PET-avid bone lesions for mIBG-non avid tumours), have a poorer prognosis. Chemoimmunotherapy arm Metastatic response rate after 4 courses of irinotecan-temozolomide (TEMIRI) combined with dinutuximab beta (DB) in patients with insufficient metastatic response at the end of induction chemotherapy (TEMIRI/DB).
  • Experimental: Phase high dose chemotherapy consolidation
    R-HDC: consolidation regimen Bu-Mel vs Thiotepa + Bu-Mel The 3-year EFS in the Bu-Mel arm (with immunotherapy) is estimated to be 55%. This study aims to show an improvement of 12% for the Thiotepa + Bu-Mel arm (3-year EFS of 67%). With a recruitment of 448 patients (224 in each arm) over a period of 3 years and a minimum follow-up of 2 years, the power to show a 12% difference is 80% (two-sided logrank test and α=5%).
  • Experimental: Phase of radiotherapy
    R-RTx: 21.6 Gy radiotherapy vs 21.6 Gy + 14.4 Gy boost in patients with macroscopic residual disease

Primary Outcome Measure

Event free survival (EFS) [ Time Frame: Assessed at each end of randomization sequences up to one year ]

Central Contacts

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