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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT01728155


Additional trial details provided through ANZCTR are available at the end of this record.


Registration number
NCT01728155
Ethics application status
Date submitted
13/11/2012
Date registered
16/11/2012

Titles & IDs
Public title
European Low and Intermediate Risk Neuroblastoma Protocol
Scientific title
European Low and Intermediate Risk Neuroblastoma Protocol
Secondary ID [1] 0 0
LINES
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
LOW AND INTERMEDIATE PAEDIATRIC NEUROBLASTOMA AND NEONATAL SUPRARENAL MASSES 0 0
Condition category
Condition code
Cancer 0 0 0 0
Neuroendocrine tumour (NET)
Cancer 0 0 0 0
Children's - Other

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
No intervention: Group1 - initial observation (chemotherapy is only given if there is subsequent progression)

Active comparator: Group 1: chemotherapy - chemotherapy and surgery

Experimental: Group 2 - chemotherapy and surgery

Experimental: Group 3 - chemotherapy and surgery

No intervention: Group 4 - Observation

Experimental: Group 5 - chemotherapy

Experimental: Group 6 - chemotherapy and surgery

Experimental: Group 7 - chemotherapy and surgery

Experimental: Group 8 - chemotherapy, surgery, radiotherapy and 13 cis-retinoic acid

Experimental: Group 9 - chemotherapy, surgery, radiotherapy and 13 cis-retinoic acid

Experimental: Group 10 - chemotherapy, surgery,

Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Primary aim for Low Risk Neuroblastoma
Timepoint [1] 0 0
2 years
Primary outcome [2] 0 0
Primary aim for Intermediate Risk Neuroblastoma
Timepoint [2] 0 0
2 years
Primary outcome [3] 0 0
Primary Aim for Neonatal Suprarenal Masses
Timepoint [3] 0 0
3 year
Secondary outcome [1] 0 0
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)
Timepoint [1] 0 0
2 year
Secondary outcome [2] 0 0
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)
Timepoint [2] 0 0
2 year
Secondary outcome [3] 0 0
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)
Timepoint [3] 0 0
2 year
Secondary outcome [4] 0 0
To evaluate adherence to the protocol recommendations regarding LTS
Timepoint [4] 0 0
5 years
Secondary outcome [5] 0 0
To reduce surgical morbidity by promoting strict adherence to Image Defined-Risk Factors (IDRFs) to determine surgical resectability
Timepoint [5] 0 0
5 year
Secondary outcome [6] 0 0
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).
Timepoint [6] 0 0
5 year
Secondary outcome [7] 0 0
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).
Timepoint [7] 0 0
3 year
Secondary outcome [8] 0 0
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)
Timepoint [8] 0 0
3 year
Secondary outcome [9] 0 0
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).
Timepoint [9] 0 0
3 year
Secondary outcome [10] 0 0
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).
Timepoint [10] 0 0
5 years
Secondary outcome [11] 0 0
To manage infants with suprarenal masses discovered ante or neonatally with a uniform approach in Europe in a multicentre setting.
Timepoint [11] 0 0
5 years
Secondary outcome [12] 0 0
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.
Timepoint [12] 0 0
3 years
Secondary outcome [13] 0 0
To determine the 3-year surgery-free survival in infants with suprarenal masses discovered ante or neonatally and managed conservatively (non initial surgery).
Timepoint [13] 0 0
3 years
Secondary outcome [14] 0 0
To find out the natural history of perinatal suprarenal masses, according to the definitions set up for the study.
Timepoint [14] 0 0
5 years
Secondary outcome [15] 0 0
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).
Timepoint [15] 0 0
5 years
Secondary outcome [16] 0 0
To collect tissue from those suprarenal masses excised in order to perform standard and investigational pathological and biological studies (INPC, MYCN, 1p, 11).
Timepoint [16] 0 0
5 years
Secondary outcome [17] 0 0
To collect frozen plasma from all patients included in the study in order to perform research.
Timepoint [17] 0 0
5 years

Eligibility
Key inclusion criteria
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
Minimum age
90 Days
Maximum age
18 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
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; group assignment completed within 6 weeks from diagnosis; 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.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
Recruitment hospital [1] 0 0
Monash Children's Hospital - Clayton
Recruitment hospital [2] 0 0
Perth Children's Hospital - Nedlands
Recruitment hospital [3] 0 0
Sydney Children's Hospital - Sydney
Recruitment postcode(s) [1] 0 0
- Clayton
Recruitment postcode(s) [2] 0 0
- Nedlands
Recruitment postcode(s) [3] 0 0
- Sydney
Recruitment outside Australia
Country [1] 0 0
Austria
State/province [1] 0 0
Graz
Country [2] 0 0
Austria
State/province [2] 0 0
Innsbruck
Country [3] 0 0
Austria
State/province [3] 0 0
Linz
Country [4] 0 0
Austria
State/province [4] 0 0
Wien
Country [5] 0 0
Belgium
State/province [5] 0 0
Antwerpen
Country [6] 0 0
Belgium
State/province [6] 0 0
Bruxelles
Country [7] 0 0
Belgium
State/province [7] 0 0
Gent
Country [8] 0 0
Belgium
State/province [8] 0 0
Leuven
Country [9] 0 0
Belgium
State/province [9] 0 0
Liège
Country [10] 0 0
Denmark
State/province [10] 0 0
Aarhus
Country [11] 0 0
Denmark
State/province [11] 0 0
Copenhagen
Country [12] 0 0
Denmark
State/province [12] 0 0
Odense
Country [13] 0 0
Israel
State/province [13] 0 0
Beersheba
Country [14] 0 0
Israel
State/province [14] 0 0
Haifa
Country [15] 0 0
Israel
State/province [15] 0 0
Petah Tikva
Country [16] 0 0
Israel
State/province [16] 0 0
Tel aviv
Country [17] 0 0
Italy
State/province [17] 0 0
Ancona
Country [18] 0 0
Italy
State/province [18] 0 0
Bari
Country [19] 0 0
Italy
State/province [19] 0 0
Bergamo
Country [20] 0 0
Italy
State/province [20] 0 0
Bologna
Country [21] 0 0
Italy
State/province [21] 0 0
Brescia
Country [22] 0 0
Italy
State/province [22] 0 0
Cagliari
Country [23] 0 0
Italy
State/province [23] 0 0
Catania
Country [24] 0 0
Italy
State/province [24] 0 0
Ferrara
Country [25] 0 0
Italy
State/province [25] 0 0
Firenze
Country [26] 0 0
Italy
State/province [26] 0 0
Genova
Country [27] 0 0
Italy
State/province [27] 0 0
Milano
Country [28] 0 0
Italy
State/province [28] 0 0
Modena
Country [29] 0 0
Italy
State/province [29] 0 0
Napoli
Country [30] 0 0
Italy
State/province [30] 0 0
Padova
Country [31] 0 0
Italy
State/province [31] 0 0
Palermo
Country [32] 0 0
Italy
State/province [32] 0 0
Parma
Country [33] 0 0
Italy
State/province [33] 0 0
Pavia
Country [34] 0 0
Italy
State/province [34] 0 0
Pescara
Country [35] 0 0
Italy
State/province [35] 0 0
Rimini
Country [36] 0 0
Italy
State/province [36] 0 0
Roma
Country [37] 0 0
Italy
State/province [37] 0 0
San Giovanni Rotondo
Country [38] 0 0
Italy
State/province [38] 0 0
Siena
Country [39] 0 0
Italy
State/province [39] 0 0
Torino
Country [40] 0 0
Italy
State/province [40] 0 0
Tricase
Country [41] 0 0
Italy
State/province [41] 0 0
Trieste
Country [42] 0 0
Italy
State/province [42] 0 0
Verona
Country [43] 0 0
Norway
State/province [43] 0 0
Bergen
Country [44] 0 0
Norway
State/province [44] 0 0
Oslo
Country [45] 0 0
Norway
State/province [45] 0 0
Tromsø
Country [46] 0 0
Norway
State/province [46] 0 0
Trondheim
Country [47] 0 0
Spain
State/province [47] 0 0
Barcelona
Country [48] 0 0
Spain
State/province [48] 0 0
Madrid
Country [49] 0 0
Spain
State/province [49] 0 0
Tenerife
Country [50] 0 0
Spain
State/province [50] 0 0
Albacete
Country [51] 0 0
Spain
State/province [51] 0 0
Alicante
Country [52] 0 0
Spain
State/province [52] 0 0
Almería
Country [53] 0 0
Spain
State/province [53] 0 0
Badajoz
Country [54] 0 0
Spain
State/province [54] 0 0
Bilbao
Country [55] 0 0
Spain
State/province [55] 0 0
Córdoba
Country [56] 0 0
Spain
State/province [56] 0 0
Granada
Country [57] 0 0
Spain
State/province [57] 0 0
Jaén
Country [58] 0 0
Spain
State/province [58] 0 0
Murcia
Country [59] 0 0
Spain
State/province [59] 0 0
Málaga
Country [60] 0 0
Spain
State/province [60] 0 0
Oviedo
Country [61] 0 0
Spain
State/province [61] 0 0
Pamplona
Country [62] 0 0
Spain
State/province [62] 0 0
San Sebastián
Country [63] 0 0
Spain
State/province [63] 0 0
Santiago de Compostela
Country [64] 0 0
Spain
State/province [64] 0 0
Sevilla
Country [65] 0 0
Spain
State/province [65] 0 0
Valencia
Country [66] 0 0
Spain
State/province [66] 0 0
València
Country [67] 0 0
Spain
State/province [67] 0 0
Zaragoza
Country [68] 0 0
Sweden
State/province [68] 0 0
Göteborg
Country [69] 0 0
Sweden
State/province [69] 0 0
Linköping
Country [70] 0 0
Sweden
State/province [70] 0 0
Lund
Country [71] 0 0
Sweden
State/province [71] 0 0
Stockholm
Country [72] 0 0
Sweden
State/province [72] 0 0
Umeå
Country [73] 0 0
Sweden
State/province [73] 0 0
Uppsala
Country [74] 0 0
Switzerland
State/province [74] 0 0
Aarau
Country [75] 0 0
Switzerland
State/province [75] 0 0
Basel
Country [76] 0 0
Switzerland
State/province [76] 0 0
Bellinzona
Country [77] 0 0
Switzerland
State/province [77] 0 0
Bern
Country [78] 0 0
Switzerland
State/province [78] 0 0
Genève
Country [79] 0 0
Switzerland
State/province [79] 0 0
Lausanne
Country [80] 0 0
Switzerland
State/province [80] 0 0
Lucerne
Country [81] 0 0
Switzerland
State/province [81] 0 0
St. Gallen
Country [82] 0 0
Switzerland
State/province [82] 0 0
Zürich

Funding & Sponsors
Primary sponsor type
Other
Name
Instituto de Investigacion Sanitaria La Fe
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Adela Cañete, MD, PhD
Address 0 0
Hospital Universitari i Politècnic La Fe, Valencia, Spain
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

No documents have been uploaded by study researchers.



Additional trial details provided through ANZCTR
Accrual to date
Recruitment state(s)
Funding & Sponsors
Primary sponsor
Primary sponsor name
Primary sponsor address
Primary sponsor country
Secondary sponsor category [1] 26
Other Collaborative groups
Name [1] 26
ANZCHOG
Address [1] 26
27-31 Wright Street, Clayton VIC 3168
Country [1] 26
Australia
Ethics approval
Ethics application status
 
Public notes
Monash Children's Hospital
Sydney Children's Hospital

Contacts
Principal investigator
Title 133 0
Dr
Name 133 0
Toby Trahair
Address 133 0
High Street Randwick NSW
Country 133 0
Australia
Phone 133 0
+612 9382 2970
Fax 133 0
Email 133 0
Contact person for public queries
Title 134 0
Mrs
Name 134 0
Robyn Strong
Address 134 0
27-31 Wright Street, Clayton VIC 3168
Country 134 0
Australia
Phone 134 0
+613 8572 2684
Fax 134 0
+613 9902 4810
Email 134 0
Contact person for scientific queries
Title 135 0
Dr
Name 135 0
Toby Trahair
Address 135 0
High Street Randwick NSW
Country 135 0
Phone 135 0
+612 9382 2970
Fax 135 0
Email 135 0