Health conditions
(Data source: WHO)
High Risk Neuroblastoma;Therapeutic area: Diseases [C] - Cancer [C04]
Interventions (Data source: WHO)
Trade Name: Dinutuximab beta EUSA
Product Name: Dinutuximab beta EUSA
Pharmaceutical Form: Concentrate and solvent for solution for infusion
INN or Proposed INN: dinutuximab beta
Other descriptive name: ch14.18/CHO
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 4.5-
Inclusion/Exclusion Criteria
(Data source: WHO)
Gender:
Female: yes
Male: yes
Inclusion criteria:
- Established diagnosis of neuroblastoma according to the International Neuroblastoma Staging System (INSS)
- Age below 21 years.
- High-risk neuroblastoma, defined as either:
a) INSS stages 2, 3, 4 and 4s with MYCN amplification, or
b) INSS stage 4 without MYCN amplification aged = 12 months
- Patients who have received no previous chemotherapy except for 1 cycle of etoposide and carboplatin (Vp/Carbo). In this situation patients will receive Rapid COJEC induction and the first COJEC cycle may be replaced by the first cycle of Vp/Carbo.
- Written informed consent, including agreement of parents or legal guardian for minors, to enter a randomised study if the criteria for randomisation are met.
- Tumour cell material available for determination of biological prognostic factors.
- Registration of all eligibility criteria with the data centre within 6 weeks from diagnosis.
- Females of childbearing potential must have a negative pregnancy test. Patients of childbearing potential must agree to use an effective birth control method. Female patients who are lactating must agree to stop breast-feeding.
- Provisional follow up of 5 years.
- National and local ethical committee approval.
Are the trial subjects under 18? yes
Number of subjects for this age range: 3590
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 1115
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range
Exclusion criteria:
Any negative answer concerning the inclusion criteria of the study will render the patient ineligible for the corresponding therapy phase.
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Further information on trial
Date trial registered
Oct 5, 2006
Incorporation of the first participant
Nov 17, 2006
Recruitment status
Authorised-recruitment may be ongoing or finished
Academic title
(Data source: WHO)
High Risk Neuroblastoma Study 1 of SIOP-Europe (SIOPEN) - HR-NBL-1
Type of trial
(Data source: WHO)
Interventional clinical trial of medicinal product
Design of the trial
(Data source: WHO)
Controlled: yes Randomised: yes Open: yes Single blind: no Double blind: no Parallel group: no Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: yes Placebo: no Other: yes Other specify the comparator: Rapid Cojec Induction Number of treatment arms in the trial: 2
Phase
(Data source: WHO)
Human pharmacology (Phase I): noTherapeutic exploratory (Phase II): noTherapeutic confirmatory - (Phase III): yesTherapeutic use (Phase IV): no
Primary end point
(Data source: WHO)
Main Objective: With all substudies having randomisation question closed, the main objective of the HRNBL1 trial is to correlate clinical, therapeutic and molecular biological features with Event Free Survival (EFS).
Secondarily, the metastatic and primary tumour response and long-term Overall Survival (OS) and toxcicity or sequelae will be investigated.
;Secondary Objective: ?To test the molecular - biological profile of disseminating tumour cells (DTCs) obtained via liquid biopsies in comparison with molecular - biological profiles in BM and primary tumour at diagnosis and respective specified response and follow up time points to validate the value of liquid biopsies for future follow up and to correlate above parameters with EFS and OS.
?To evaluate BM response to Rapid COJEC (after the fourth and eight cycles with ICH-GD2, AIPF and QRT-PCR.
?To determine the effect of response of metastatic disease to induction therapy on EFS and overall survival (OS) with mIBG/SPECT SIOPEN stand scoring of skeletal response
?To investigate the relationship between complete surgical resection of the primary tumour on EFS and OS within the scope of established standard treatments.
;Primary end point(s): The primary endpoint is event free survival (EFS) calculated form the date of start of induction. Events are:
?disease progression or relapse
?death from any cause
?second neoplasm
Patients without event are censored at the date of last follow-up evaluation.
Sample Size : All randomised questions below have been closed by March 2018. Thereof no further sample size definition is set.
;Timepoint(s) of evaluation of this end point: The final analysis will be performed at End of trial
Secundary end point
(Data source: WHO)
Secondary end point(s): Secondary endpoints of the main trial
-Overall survival
Calculated from date of randomisation to death from any cause. Patients lost to follow-up without an event will be censored at the date of their last follow-up evaluation.
-Cumulative incidence of relapse/progression and deaths without relapse/progression
-The cumulative incidence of non-relapse mortality and of disease related mortality
-The cumulative incidence of secondary malignancies
-Response
Overall response (incl. primary tumour after induction), skeletal response on MIBG, BM-response,
-Toxicity
in particular comparison of the frequency of episodes of febrile neutropenia and grade 3-4 infections during induction (modified N7 vs. Rapid COJEC)
-Rate of patients that discontinued therapy
-Response rates, survival, EFS and the cumulative incidence of relapse/progressions will be related to potential prognostic factors including:
Biological factors (MYCN amplification, SCAs, expression signature) of neuroblastoma cells in the bone marrow and/or the primary tumour.
Serological factors (serum concentrations at diagnosis of LDH, ferritin, neuron specific enolase).
Urinary catecholamines at diagnosis (VMA, HVA, Dopamine)
;Timepoint(s) of evaluation of this end point: The final analysis will be performed at End of trial
Contact information
(Data source: WHO)
CCRI
Trial results
(Data source: WHO)
Results summary
High Risk Neuroblastoma Study 1 of SIOP-Europe (SIOPEN)
Link to the results in the primary register
no information available yet
Information on the availability of individual participant data
no information available yet
Trial sites
Countries
(Data source: WHO)
Australia, Austria, Belgium, China, Czechia, Denmark, Finland, France, Greece, Hong Kong, Hungary, Ireland, Israel, Italy, Norway, Poland, Portugal, Serbia, Slovakia, Slovenia, Spain, Sweden, Switzerland, United Kingdom
Contact for further information on the trial
Contact for general information
(Data source: WHO)
Ruth Ladenstein
Zimmermannplatz 10
St. Anna Kinderkrebsforschung GmbH
431404704750
ruth.ladenstein@ccri.at
Contact for scientific information
(Data source: WHO)
Ruth Ladenstein
Zimmermannplatz 10
St. Anna Kinderkrebsforschung GmbH
431404704750
ruth.ladenstein@ccri.at
Further trial identification numbers
Secondary ID (Data source: WHO)
SIOPENRNET003
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