Brief description of trial (Data source: BASEC)
Le neuroblastome (NB) est la tumeur solide extra-craniale la plus fréquente chez les enfants.
Ce cancer est caractérisé par une hétérogénéité de la présentation clinique et de comportement de la maladie. Dans le passé le traitement a été décidé surtout en fonction du stade tumoral défini par le système de classification Internationale des NB, de l’âge au diagnostic et de la génétique de n-myc.
La nouvelle classification internationale de ces tumeurs du Groupe International des Risques du NB tient compte de l'hétérogénéité clinique de la tumeur et fournit un outil plus élaboré pour la classification du traitement selon: l'âge au diagnostic, le comportement et l’histologie de la tumeur, la présence ou l'absence de facteurs de risques définis par imagerie permettant l’ablation chirurgicale d'une tumeur localisée, ainsi que les données génomiques du tissu tumoral.
L’étude LINES est basée sur cette classification et regroupe dans un protocole unique tous les patients avec un NB à risque bas et intermédiaire afin d’avoir une base de données commune qui pourrait encore faire évoluer la classification pronostique actuelle
Le but de cette étude est de confirmer la validité de classification des NB permettant d’adapter le traitement au risque réel du NB de chaque patient. Dans certains cas le traitement est réduit ou même remplacé par une surveillance, afin de minimiser pour les enfants le risque de possibles conséquences à long terme.
Health conditions investigated(Data source: BASEC)
Neuroblastomes à risques bas et intermédiaires
Health conditions
(Data source: WHO)
LOW AND INTERMEDIATE PAEDIATRIC NEUROBLASTOMA AND NEONATAL SUPRARENAL MASSES
Rare disease
(Data source: BASEC)
No
Intervention investigated (e.g. drug, therapy or campaign)
(Data source: BASEC)
Observation ou chimiothérapie avec radiothérapie et chirurgie si indiqué.
Interventions
(Data source: WHO)
Drug: chemotherapy
Criteria for participation in trial
(Data source: BASEC)
-Signature confirmant l’information éclairée écrite
-suivi garanti
-assignement à un groupe de traitement au plus tard 6 semaines après le diagnostic
-Pas de chimio- ou radiothérapie au préalable.
Exclusion criteria
(Data source: BASEC)
-Diagnostic de ganglioneurome ou ganglioneuroblastome intermixed (entité histologique spécifique)
Inclusion/Exclusion Criteria
(Data source: WHO)
1. LOW RISK STUDY
Inclusion criteria for the whole low risk group:
- informed consent and follow-up warranted; group assignment completed within 6
weeks from diagnosis; no prior chemotherapy or radiotherapy
- Biopsy proven neuroblastoma
- Tumour genomic profile obtained in a NRL according to guidelines
- MYCN non-amplified
Exclusion criteria for the whole low risk group:
* Diagnosis of ganglioneuroma or ganglioneuroblastoma intermixed INRG Stage L2
Inclusion criteria:
*age = 18 months
Exclusion criteria:
- any metastatic site
- MYCN amplification
- age > 18 months INRG Stage Ms
Inclusion criteria:
* age = 12 months
Exclusion criteria:
- bone, pleura/lung and/or CNS metastasis
- MYCN amplification
- age > 12 months
2. INTERMEDIATE RISK STUDY
Inclusion criteria for the whole intermediate risk group:
- informed consent and follow-up warranted; no prior chemotherapy or radiotherapy
- Tumour material available for biological studies according to guidelines
- Biopsy proven neuroblastoma confirmed in a National Reference Laboratory (NRL)
Exclusion criteria for the whole intermediate risk group:
* Diagnosis of ganglioneuroma or ganglioneuroblastoma intermixed
INRG Stage L1 and INSS stage 1:
Inclusion criteria:
* MYCN amplified
Exclusion criteria:
- MYCN non-amplified
- INSS stages 2, 3, 4, 4s
INRG Stage L2:
Inclusion criteria:
- Histology: differentiating, poorly differentiated, undifferentiated neuroblastoma
or ganglioneuroblastoma nodular
- MYCN non-amplified
- age >18 months
Exclusion criteria:
- neuroblastoma NOS
- MYCN amplification.
- age = 18 months
INRG Stage M:
Inclusion criteria:
- Any histology
- MYCN non-amplified
- age = 12 months
Exclusion criteria:
- MYCN amplification
- age > 12 months
3. NEONATAL SUPRARENAL MASSES
Inclusion criteria:
- Age less than or equal to 90 days when the suprarenal mass is discovered.
- Suprarenal mass detected by ultrasound and/or MRI. The suprarenal mass may be cystic
and/or solid, but IT CANNOT REACH THE MIDLINE AND should MEASURE = 5 CM AT THE LARGEST
DIAMETER.
- No regional involvement: MRI scan does not show evidence of positive
ipsi/contralateral lymph nodes or other spread outside the suprarenal gland.
- No metastatic involvement.
- Frozen plasma available.
- Informed consent.
- Availability to do the adequate follow-up
Exclusion criteria:
- Age older than 90 days.
- Suprarenal mass bigger than 5 cm.
- Regional involvement.
- Metastatic involvement.
- Inability to undertake mandatory diagnostic studies (biological markers, US, MRI,
MIBG).
- Follow-up not guaranteed by parents/guardians.
-
Further information on trial
Date trial registered
Nov 13, 2012
Incorporation of the first participant
Dec 1, 2011
Recruitment status
Recruiting
Academic title
(Data source: WHO)
European Low and Intermediate Risk Neuroblastoma Protocol
Type of trial
(Data source: WHO)
Interventional
Design of the trial
(Data source: WHO)
Allocation: Randomized. Intervention model: Parallel Assignment. Primary purpose: Treatment. Masking: None (Open Label).
Phase
(Data source: WHO)
Phase 3
Primary end point
(Data source: WHO)
Primary aim for Low Risk Neuroblastoma;Primary aim for Intermediate Risk Neuroblastoma;Primary Aim for Neonatal Suprarenal Masses
Secundary end point
(Data source: WHO)
To maintain a 2 year EFS of at least 90% and an OS of at least 95% in L2 patients with LTS without SCA (study group 2);To maintain the 2 year EFS of 85% and an OS of at least 98% in Ms patients without SCA (study groups 4 and 5);To improve the 2 year EFS to at least 90% and maintain the OS of close to 100% in L2 patients with SCA (Study Group 3) and improve the 2 year EFS to over 70% in Ms patients with SCA (study group 6);To evaluate adherence to the protocol recommendations regarding LTS;To reduce surgical morbidity by promoting strict adherence to Image Defined-Risk Factors (IDRFs) to determine surgical resectability;To define the long term follow-up and natural history of the Stage L2 non-resected masses that have remained IDRF positive at the end of treatment (study groups 1-3).;To confirm in a larger patient cohort the excellent OS of 95% in stage M neuroblastoma without MYCN amplification, less than 12 months of age, when treated with moderate therapy (study group 10).;Maintain the results of 3yr-EFS of 90% and 3yr-OS of 100% in stage L2 patients over the age of 18 months, with differentiating neuroblastoma or differentiating ganglioneuroblastoma nodular, despite a treatment reduction (group7);To improve the 3 year EFS to at least 50% and the 3 year OS to 80% in INSS stage I patients with MYCN amplified neuroblastoma by the addition of adjuvant treatment (study group 9).;To evaluate the impact of the tumour genomic profile on patient outcome, in order to consider its role in the treatment stratification of these intermediate risk patients (all study groups).;To manage infants with suprarenal masses discovered ante or neonatally with a uniform approach in Europe in a multicentre setting.;To maintain an excellent overall survival with a non-operative therapeutic approach (serial monitoring, surgery if warranted) in infants with a localised suprarenal mass discovered ante or neonatally.;To determine the 3-year surgery-free survival in infants with suprarenal masses discovered ante or neonatally and managed conservatively (non initial surgery).;To find out the natural history of perinatal suprarenal masses, according to the definitions set up for the study.;To study the kinetics of regression in those suspected suprarenal neuroblastomas in infants with suprarenal masses discovered ante or neonatally and managed conservatively (non initial surgery).;To collect tissue from those suprarenal masses excised in order to perform standard and investigational pathological and biological studies (INPC, MYCN, 1p, 11).;To collect frozen plasma from all patients included in the study in order to perform research.
Contact information
(Data source: WHO)
Please refer to primary and secondary sponsors
Trial results
(Data source: WHO)
Results summary
no information available yet
Link to the results in the primary register
no information available yet
Information on the availability of individual participant data
No
Trial sites
Trial sites in Switzerland
(Data source: BASEC)
Aarau, Basel, Bellinzona, Bern, Geneva, Lausanne, Luzern, St. Gallen, Zurich
Countries
(Data source: WHO)
Austria, Belgium, Denmark, Israel, Italy, Norway, Spain, Sweden, Switzerland
Contact for further information on the trial
Details of contact in Switzerland
(Data source: BASEC)
Prof. Dr. med. Maja Beck Popovic
+41 21 314 35 67
maja.beck-popovic@chuv.ch
Contact for general information
(Data source: WHO)
Adela Cañete, MD, PhD;Gudrun Schleiermacher;Kate Wheeler;Andrea di Cataldo;Vassilius Papadakis
Hospital Universitari i Politècnic La Fe, Valencia, Spain;Institut Curie;Oxford: John Radcliffe Hospital, UK;Policlinico Universitario, Italy;Aghia Sophia Children's Hospital, Athens
0034 96 124 49 04
canyete_ade@gva.es
Contact for scientific information
(Data source: WHO)
Adela Cañete, MD, PhD;Gudrun Schleiermacher;Kate Wheeler;Andrea di Cataldo;Vassilius Papadakis
Hospital Universitari i Politècnic La Fe, Valencia, Spain;Institut Curie;Oxford: John Radcliffe Hospital, UK;Policlinico Universitario, Italy;Aghia Sophia Children's Hospital, Athens
0034 96 124 49 04
canyete_ade@gva.es
Further trial identification numbers
Secondary ID (Data source: WHO)
LINES
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