Very High Risk neuroblastoma MedDRA version: 20.0 Level: LLT Classification code 10008126 Term: Cerebral neuroblastoma System Organ Class: 100000004864
Conditions
Sponsors
Gustave Roussy
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1 - Metastatic neuroblastoma (NBL) 2 - Patient previously treated within the ongoing High Risk Neuroblastoma SIOPEN study or treated with the current standard treatment for very high risk neuroblastoma off-trial 3 - mIBG scintigraphy positive at diagnosis and after induction chemotherapy (pre BuMel evaluation). 4 - Metastatic response after induction chemotherapy lower than the ongoing High Risk Neuroblastoma SIOPEN trial criteria to be eligible for High Dose Chemotherapy (metastatic response worse than partial response ( 3) 5 - Females of childbearing potential must have a negative serum pregnancy test within 7 days prior to initiation of treatment. Sexually active patients must agree to use acceptable and appropriate contraception while on study drug and for one year after stopping the study drug. 6 -Written informed consent from parents/legal representative, patient, and age-appropriate assent before any study-specific screening procedures are conducted according to local, regional or national guidelines. Are the trial subjects under 18? yes Number of subjects for this age range: 150 F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 5 F.1.3 Elderly (>=65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: 1 - Parenchymal brain metastasis (even one) 2 - Progressive disease at study entry 3 - Previous high-dose therapy and Autologous Stem Cell Reinfusion 4 - Performance status (Karnofsky, Lansky) <70% 5 - Patient having received other therapy for cancer treatment than those allowed as per the ongoing High Risk Neuroblastoma SIOPEN trial or as defined in the future frontlines protocol (for HRNBL1 trial : after induction + 2 TVD) 6 - Impaired organ function (liver, kidney, heart, lungs) 7 - Any uncontrolled intercurrent illness or infection that in the investigator’s opinion would impair study participation 8 - Concomitant use with yellow fever vaccine and with live virus and bacterial vaccines 9 - Patient allergic to peanut or soya 10 - Chronic inflammatory bowel disease and/or bowel obstruction 11 - Pregnant or breastfeeding women 12 - Known hypersensitivity to the active substance or to any of the excipients of study drugs 13 - Known hypersensitivity to dacarbazine 14 - Concomitant use with St John's Wort
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To evaluate the efficacy of two intensified consolidation strategies in very-high risk neuroblastoma (VHR-NBL) patients in terms of event-free survival from randomisation date. This evaluation will follow a hierarchical testing procedure: each experimental treatment will be first evaluated as a single-arm phase 2 study, and in case of positive conclusion, the relative efficacy of both arms will then be evaluated comparatively.;Secondary Objective: •To estimate and compare the overall survival (OS) of patients treated in the two treatment strategies •To evaluate and compare the safety of the two treatment strategies in terms of toxic death and non-fatal toxicities rates. •To estimate and compare the disease response after BuMel and at the end of treatment of the two treatment strategies •To evaluate the between-treatment differences in Quality adjusted Time WIthout Symptoms and Toxicity (Q-TWiST approach) •To evaluate the feasibility and document the logistical issues raised by 131I-mIBG and topotecan therapy in a multicenter setting •To estimate and compare the Event-Free Survival of the two treatment strategies from the start of the intensified consolidation chemotherapy •To estimate and compare the Event-Free Survival of the two treatment strategies from the date of the neuroblastoma diagnosis;Primary end point(s): Event Free Survival (EFS) from the date of randomisation into the VERITAS trial;Timepoint(s) of evaluation of this end point: 3 years | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): •Overall survival •Adverse events, evaluated using NCI-CTCAE v5.0 toxicity grading system, reported by treatment phase and overall over the whole treatment duration (maximum grade). •Disease response after BuMel and at the end of treatment •For the Q-TWiST analysis: time spent with severe toxicity after randomization and before progression/relapse (duration of hospitalisation will be used as a surrogate of time with toxicity); time spent without progression/relapse and without toxicity; and time from progression until death. •Feasibility of each strategy of intensified consolidation chemotherapy •Event-Free Survival from the date of start of the consolidation phase •Event-Free Survival from the date of the neuroblastoma diagnosis;Timepoint(s) of evaluation of this end point: *By treatment phase and on the whole treatment duration *At disease progression / relapse *At death | — |
Countries
Austria, France, Germany, Israel, Italy, Netherlands, Spain, United Kingdom
Contacts
Public ContactSponsor CRA
Gustave Roussy
Outcome results
None listed