High-Risk Neuroblastoma Study 2 of SIOP-Europa-Neuroblastoma (SIOPEN) (HR-NBL2)
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|ClinicalTrials.gov Identifier: NCT04221035|
Recruitment Status : Recruiting
First Posted : January 9, 2020
Last Update Posted : January 9, 2020
|Condition or disease||Intervention/treatment||Phase|
|High-Risk Neuroblastoma||Drug: Vincristine Drug: Carboplatin Drug: Etoposide Drug: Cyclophosphamide Drug: Vindesine Drug: Dacarbazine Drug: Ifosfamide Drug: Doxorubicin Drug: Busulfan Drug: Melphalan Drug: Thiotepa Radiation: Radiotherapy Drug: Dinutuximab Beta Drug: Cisplatin||Phase 3|
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.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||800 participants|
|Intervention Model:||Sequential Assignment|
|Masking:||None (Open Label)|
|Official Title:||High-Risk Neuroblastoma Study 2 of SIOP-Europa-Neuroblastoma (SIOPEN)|
|Actual Study Start Date :||November 5, 2019|
|Estimated Primary Completion Date :||November 2026|
|Estimated Study Completion Date :||November 2032|
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.
1.5 mg/m2 (max dose 2 mg)
3 mg/m2/day (max dose 6 mg)
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%).
< 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
140 mg/m2/dose IV short infusion (15'), at least24 h after the last busulfan dose
300 mg/m2/day over 2 hours
R-RTx: 21.6 Gy radiotherapy vs 21.6 Gy + 14.4 Gy boost in patients with macroscopic residual disease
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/m2/day Patients ≤ 12 kg are dosed according to their body weight: 0.33 mg/kg/day
- Event free survival (EFS) [ Time Frame: Assessed at each end of randomization sequences up to one year ]
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04221035
|Contact: Dominique Valteau, MD||0142114211 ext +firstname.lastname@example.org|
|Contact: Benhamou Jessica||0142114211 ext +email@example.com|