European Low and Intermediate Risk Neuroblastoma Protocol
Condition: LOW AND INTERMEDIATE PAEDIATRIC NEUROBLASTOMA AND NEONATAL SUPRARENAL MASSES
MeSH terms: Neuroblastoma
Study type: Interventional
Phase: Phase 3

Summary: 
      The European study, LINES 2009 (Low and Intermediate Risk Neuroblastoma European Study),
      groups together in a single protocol the treatment of all patients with "non high risk"
      neuroblastoma (NB), with stratification into two groups: low risk and intermediate risk.
      These two separate cohorts are included in one single protocol to enable patient data from
      these two groups to be entered into a common database, as the current prognostic
      classifications determining treatment may evolve further with subsequent more detailed
      molecular analysis of the tumours.

      1. LOW RISK STUDY

      The Low Risk Study is proposed in order to:

        -  minimise the amount of treatment (chemotherapy and surgery) for all appropriate low risk
           patients, who in previous studies have been shown to have an excellent long-term outcome
           (as in the SIOPEN 99.1-2 infant neuroblastoma studies where the overall survival was
           greater than 97%(H. Rubie, JCO).

        -  improve the EFS and maintain the OS (overall survival) in L2 and Ms patients with a
           SCA(Segmental Cromosomal Aberration) genomic profile tumour (presence of any segmental
           chromosomal change (SCA)) by electively treating these patients with chemotherapy
           despite the absence of symptoms.

           2) INTERMEDIATE RISK STUDY

      The Intermediate Risk Study is proposed in order to:

        -  reduce the amount of chemotherapy for differentiating histology INRG (International
           Neuroblastoma Risk Group) stage L2 NB and ganglioneuroblastoma nodular patients who in
           previous SIOPEN study have been shown to have an excellent long-term outcome;

        -  increase the amount of treatment (radiotherapy and 13-cis-RA (13-cis-Retinoic Acid) for
           poorly differentiated or undifferentiated histology INRG stage L2 NB or
           ganglioneuroblastoma nodular patients in order to improve the EFS registered in the
           previous SIOPEN study;

        -  improve the EFS (Event Free Survival) of MYCN (V-Myc myelocytomatosis viral related
           oncogene, NB derived ,avian )amplified INSS (International NB Staging System) stage 1 NB
           patients with the introduction of adjuvant treatment;

        -  maintain the very good results obtained in previous SIOPEN study for INRG stage M
           infants with a moderate treatment.

      NEONATAL SUPRARENAL MASSES

      The incidence of suprarenal tumours/masses has increased in the last decade due to the
      expanded use of prenatal ultrasonography in routine obstetric care and in the neonatal and
      early infancy care. The differential diagnosis of these masses ranges from benign (adrenal
      haemorrhage) to malignant processes (neuroblastoma, adrenal carcinoma). Knowledge on
      perinatal suprarenal masses, although based on a relatively large literature, is scattered
      amongst studies on very few cases with no methodical approach and often short follow up.
      Therefore, the optimal management of these masses has not been clearly defined. Neuroblastoma
      at this age is an intriguing entity with a very good prognosis in most cases. The SIOPEN
      Group, based on their results in the first multicenter European Trial for infants with
      neuroblastoma (INES) and the world-wide experience provided in the literature, is launching
      this European surveillance study (Multi-centre, non-blinded, one armed prospective trial) for
      these masses. Treatment: Observation
    

Detailed description: 
      1. LOW RISK STUDY

      The low risk group of patients includes NB patients without MYCN amplification with or
      without life threatening symptoms in the following clinical situations:

        -  Children aged ≤ 18 months with localised neuroblastoma associated with image defined
           risk factors precluding upfront surgery (stage INRG L2).

        -  Children aged ≤ 12 months with disseminated neuroblastoma without bone, pleura, lung or
           CNS (Central Nervous System) disease (stage INRG Ms)

           2) INTERMEDIATE RISK STUDY

      The intermediate risk group of patients includes NB patients in the following clinical
      situations:

        -  Children aged >18 months with localised neuroblastoma without MYCN amplification,
           associated with image defined risk factors precluding upfront surgery (stage INRG L2).

        -  Children aged ≤12 months with disseminated neuroblastoma involving bone, pleura, lung
           and/or CNS (stage INRG M), without MYCN amplification.

        -  Children with localised resected NB (stage INSS I) with MYCN amplification. NEONATAL
           SUPRARENAL MASSES

      The incidence of suprarenal tumours/masses has increased in the last decade due to the
      expanded use of prenatal ultrasonography in routine obstetric care and in the neonatal and
      early infancy care. The differential diagnosis of these masses ranges from benign (adrenal
      haemorrhage) to malignant processes (neuroblastoma, adrenal carcinoma). Knowledge on
      perinatal suprarenal masses, although based on a relatively large literature, is scattered
      amongst studies on very few cases with no methodical approach and often short follow up.
      Therefore, the optimal management of these masses has not been clearly defined. Neuroblastoma
      at this age is an intriguing entity with a very good prognosis in most cases. The SIOPEN
      Group, based on their results in the first multicenter European Trial for infants with
      neuroblastoma (INES) and the world-wide experience provided in the literature, is launching
      this European surveillance study (Multi-centre, non-blinded, one armed prospective trial) for
      these masses. Treatment: Observation
    

Intervention name(s): chemotherapy
Intervention type(s): Drug
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: NEUROBLASTOMA, LOW RISK, INTERMEDIATE RISK