High-Risk Neuroblastoma Study 2 of SIOP-Europa-Neuroblastoma (SIOPEN)
Trial statusRecruiting
Trial phasePhase 3
Trial typeInterventional
Biological sexAll
AgeUp to 21
SponsorGustave Roussy, Cancer Campus, Grand Paris
About this trial
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.
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
at diagnosis before the beginning of chemotherapy or
up to 21 days after one course of Carboplatin-Etoposide for patients with localized neuroblastoma or infants with metastatic neuroblastoma with MYCN amplification or patients with metastatic neuroblastoma treated in emergency or
up to 21 days after one course of the current protocol for R-I randomisation (RAPID COJEC/GPOH) low/intermediate risk neuroblastoma in Germany/Netherlands for patients with localized neuroblastoma or infants with metastatic neuroblastoma with MYCN amplification
Stage M neuroblastoma above 365 days of age at diagnosis (no upper age limit) and Ms neuroblastoma 12-18 months old, any MYCN status or
Disqualifiers
- Stage M neuroblastoma above 365 days of age at diagnosis, any MYCN status, EXCEPT patients with stage M or Ms 12-18 months old with numerical chromosomal alterations only, and in complete metastatic response at the end of induction: in this case, patients will have surgery and no further treatment.
Age < 21 years at the time of randomization
Bone disease: mIBG uptake completely resolved or SIOPEN score ≤ 3 and at least 50% reduction in mIBG score (or ≤ 3 bone lesions and at least 50% reduction in number of FDG- PET-avid bone lesions for mIBG-nonavid tumours).
Bone marrow disease: CR and/or minimal disease (MD) according to International Neuroblastoma Response Criteria
Trial design
Design model
Sequential
Treatments tested in this trial
Vincristine
Drug1.5 mg/m2 (max dose 2 mg)
Carboplatin
Drug750 mg/m2
Etoposide
Drug175 mg/m2
Vindesine
Drug3 mg/m2/day (max dose 6 mg)
Dacarbazine
Drug200 mg/m2/day
Ifosfamide
Drug1500 mg/m2/day
Doxorubicin
Drug30 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
Drug140 mg/m2/dose IV short infusion (15'), at least 24 h after the last busulfan dose
Thiotepa
Drug300 mg/m2/day over 2 hours
Radiotherapy
Radiation21.6 Gy 21.6 Gy + boost de 14.4 Gy
Dinutuximab Beta
DrugPatients \>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
Drug80 mg/m2/24h
Temozolomide 100 MG
Drug100 mg/m²/Day
Irinotecan
Drug50 mg/m²/jour de J0 à J4
Cyclophosphamid
DrugCyclophosphamide 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.
Treatment groups
800 Participants
are divided into 3 treatment groupsGroup A: phase induction-R-IExperimental treatment 12 interventions
Group B: Phase high dose chemotherapy consolidationExperimental treatment 3 interventions
Group C: Phase of radiotherapyExperimental treatment 2 interventions
Trial outcomes
Primary outcomes
1
Event free survival (EFS)
Event free survival
Time frame
Assessed at each end of randomization sequences up to one yearSponsors and contacts
Click on the lead sponsor to view all of their trials.
Source ClinicalTrials.gov