NCT04221035

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

• Status: Recruiting
• Phase: Phase 3
• Study type: Interventional
• Enrollment: 800 (estimated)
• Sponsor: Gustave Roussy, Cancer Campus, Grand Paris · Academic / Other
• Sex: All
• Age: 21 Years
• Healthy volunteers: Not accepted

Summary

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.

Detailed description

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. The first randomization (R-I) will compare the efficacy of two induction chemotherapies (RAPID COJEC and GPOH regimens) in a phase III setting. The primary endpoint will be the 3-year EFS from date of randomization . The R-I randomization will be stratified on age, stage, MYCN status and countries. The second randomization (R-HDC) will compare the efficacy of single HDC with Bu-Mel versus tandem HDC with Thiotepa followed by Bu-Mel. The primary endpoint is 3-year EFS calculated from the date of the R-HDC randomization. The R-HDC randomization will be stratified on the age, stage, MYCN status, induction chemotherapy regimen, response to induction phase and countries. The impact of local treatment in this phase III setting will be assessed, according to the presence or not of a macroscopic residual disease after surgery and HDC. In case of macroscopic residual disease, 21.6 Gy radiotherapy to the preoperative tumor bed will be randomized (R-RTx) versus the same treatment plus a sequential boost of additional 14.4 Gy to the residual tumor. The primary endpoint of R-RTx is 3-year EFS from the date of the R-RTx randomization. The R-RTx randomization will be stratified on age, stage, MYCN status, induction chemotherapy regimen, HDC regimen and countries. In case of no macroscopic residual disease, 21.6 Gy radiotherapy will be delivered to the preoperative tumor bed.

Conditions

• High-Risk Neuroblastoma
• Patient With Insufficient Response Chemoimmunotherapy

Interventions

Type	Name	Description
DRUG	Vincristine	1.5 mg/m2 (max dose 2 mg)
DRUG	Carboplatin	750 mg/m2
DRUG	Etoposide	175 mg/m2
DRUG	Vindesine	3 mg/m2/day (max dose 6 mg)
DRUG	Dacarbazine	200 mg/m2/day
DRUG	Ifosfamide	1500 mg/m2/day
DRUG	Doxorubicin	30 mg/m2/dose
DRUG	Busulfan	\< 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
DRUG	Melphalan	140 mg/m2/dose IV short infusion (15'), at least 24 h after the last busulfan dose
DRUG	Thiotepa	300 mg/m2/day over 2 hours
RADIATION	Radiotherapy	21.6 Gy 21.6 Gy + boost de 14.4 Gy
DRUG	Dinutuximab Beta	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
DRUG	Cisplatin	80 mg/m2/24h
DRUG	Temozolomide 100 MG	100 mg/m²/Day
DRUG	Irinotecan	50 mg/m²/jour de J0 à J4
DRUG	Cyclophosphamid	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.

Timeline

• Start date: 2019-11-05
• Primary completion: 2026-11-01
• Completion: 2032-11-01
• First posted: 2020-01-09
• Last updated: 2025-06-26

Locations

142 sites across 20 countries: Australia, Austria, Belgium, Czechia, Denmark, Finland, France, Germany, Greece, Israel, Italy, Lithuania, Netherlands, Norway, Slovakia, Slovenia, Spain, Sweden, Switzerland, United Kingdom