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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
1/01/2011
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
685
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.


Results not provided in https://clinicaltrials.gov/study/NCT01728155

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
toby.trahair@sesiahs.health.nsw.gov.au
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
Robyn.Strong@hudson.org.au
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
toby.trahair@sesiahs.health.nsw.gov.au