Metastatic High Risk Neuroblastoma MedDRA version: 20.0 Level: PT Classification code 10029260 Term: Neuroblastoma System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Conditions
Interventions
Product Name: Topotecan
Pharmaceutical Form: Powder for concentrate for solution for infusion
INN or Proposed INN: Topotecan
CAS Number: 123948-87-8
Concentration unit: mg milligram(s)
Concentration t
Sponsors
Gustave Roussy
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Metastatic neuroblastoma (NBL) 2. Previously treated within the SIOPEN High Risk Neuroblastoma study or treated with the current standard treatment for very high risk neuroblastoma off-trial (Rapid COJEC induction chemotherapy) 3. 131I-mIBG scintigraphy positive at diagnosis and after induction chemotherapy (pre BuMel evaluation). 4. Metastatic response after induction chemotherapy lower than the SIOPEN High Risk Neuroblastoma 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. Acceptable contraception is listed in Appendix 12. Female patients who are lactating must agree to stop breast-feeding. 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. 7. Patient affiliated to a social security regimen or beneficiary of the same according to local requirements. 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 0
Exclusion criteria
Exclusion criteria: 1. Parenchymal brain metastasis(es) (even one) 2. Progressive disease at study entry 3. Previous high-dose therapy and ASCR 4. Performance status (Karnofsky or Lansky) 2 ULN o Creatinine clearance and/or GFR < 60 ml/min/1.73m2 and serum creatinine = 1.5 mg/dl 7. Any uncontrolled inter-current 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: The primary objective is to evaluate how well two different therapy regimens treat Very High Risk-NeuroBLastoma (VHR-NBL) by investigating the patients disease over time ("event-free survival") Each experimental treatment will be first evaluated to see how well the treatment works, then, if the treatments seem to treat the cancer successfully, the results of the different treatments will be compared. ;Secondary Objective: a - To investigate if the treatments prolong life ("overall survival") and to compare the life expectancy following the two treatments b - To investigate the side effects of the two treatments c - To investigate the disease response after the two study treatments and after the end of all treatment (i.e. after BuMel therapy) d - To investigate the differences in quality of life changes over time, following the two treatments. e - To evaluate the feasibility and document the logistical issues raised by 131I-mIBG and topotecan therapy given by multiple centres f - To evaluate the response to the two treatments over the time since the start of the treatments ("event free survival") g - To evaluate the response to the two treatments over the time since the diagnosis of disease ("event free survival") ;Primary end point(s): The primary endpoint is the 3 years Event-Free Survival from the date of randomisation into the VERITAS trial, considering as events: -disease progression or relapse -death from any cause -secondary malignancy. Patients without event are censored at the date of their last follow up evaluation. ;Timepoint(s) of evaluation of this end point: 3 years from the date of randomisation | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): a - Overall survival, defined as the time from randomisation to death from any cause. b - Adverse events, evaluated using NCI-CTCAE v5.0 toxicity grading system, reported by treatment phase and overall over the whole treatment duration (maximum grade). The stopping rule for toxicity will be based on the occurrence of adverse events leading to ventilation in an ICU and treatment-related deaths. These events will be specifically monitored over the first 6 months after randomisation. c - Disease response after BuMel and at the end of treatment d - For the Q-TWiST analysis: time spent with severe toxicity after randomisation 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. e - Logistical issues raised by 131I-mIBG and topotecan or thiotepa therapy in a multicentre setting f - Event-Free Survival from the date of start of the consolidation phase g - Event-Free Survival from the date of the neuroblastoma diagnosis ;Timepoint(s) of evaluation of this end point: a- Time from randomisation to death b- Duration of treatment c- after BuMel and at end of treatment d- time with toxicity following randomisation; time from progression until death f and g - time to Event | — |
Countries
Austria, France, Germany, Italy, Netherlands, Spain, United Kingdom
Contacts
Public ContactJennifer Laidler
The University of Birmingham
Outcome results
None listed