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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT01704716




Registration number
NCT01704716
Ethics application status
Date submitted
5/10/2012
Date registered
11/10/2012
Date last updated
23/10/2020

Titles & IDs
Public title
High Risk Neuroblastoma Study 1.8 of SIOP-Europe (SIOPEN)
Scientific title
High Risk Neuroblastoma Study 1 of SIOP-Europe (SIOPEN)
Secondary ID [1] 0 0
HR-NBL-1.8 / SIOPEN
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Neuroblastoma 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
Treatment: Drugs - Vincristine
Treatment: Drugs - Aldesleukin
Treatment: Drugs - ch14.18/CHO
Treatment: Drugs - Carboplatin
Treatment: Drugs - Etoposide
Treatment: Drugs - Cisplatin
Treatment: Drugs - Cyclophosphamide
Treatment: Drugs - Doxorubicin
Treatment: Drugs - G-CSF
Treatment: Drugs - Busulfan
Treatment: Drugs - Melphalan

Experimental: R0: COJEC plus G-CSF - Patients randomised to G-CSF during induction treatment (Rapid COJEC) received a single daily subcutaneous injection of 5 microgram/kg/day G-CSF (filgrastim) beginning 24 hours after the last chemotherapy dose.

Active comparator: R0: COJEC - Induction treatment (COJEC) without filgrastim Patients randomised to Rapid COJEC alone will receive induction Treatment without G-CSF

Active comparator: R1: BuMel MAT - The BuMel MAT regimen consists of oral administration of busulphan and the short i.v. infusion of melphalan.

In July 2007 (amendment 3) oral busulfan was changed to i.v. Busulfan (Busilvex)

Experimental: R1: CEM MAT - The CEM MAT regimen uses three drugs: the dose of Carboplatin must be based on renal function with a target area under the concentration versus time curve (AUC) of 16.4 mg/ml.min, etoposide 350 mg/m2/course and melphalan 210 mg/m2/course

Active comparator: R2: ch14.18/CHO - ch14.18/CHO is given at a dose of 20 mg/m2/day over five days every four weeks for five courses

Experimental: R2: ch14.18/CHO plus Aldesleukin - Patients randomised to receive ch14.18/CHO plus Aldesleukin

Active comparator: R3: COJEC Induction - Rapid COJEC induction treatment is applied over ten weeks; three different courses are given every ten days:

Course A (given on days 0 and 40): vincristine, carboplatin, and etoposide Course B (given on days 10, 30, 50, and 70): vincristine and cisplatin Course C (given on days 20 and 60): vincristine, etoposide, and cyclophosphamide

Experimental: R3: Modified N7 - The modified N7 induction is a dose intense induction chemotherapy regimen including two putatively non cross-resistent drug combinations: high-dose cyclophosphamide plus doxorubicin/vincristine (CAV) and high-dose cisplatin/etoposide (P/E).

Active comparator: R4: cnt inf ch14.18/CHO - ch14.18/CHO is given as continuous Infusion over 10 days at a cumulative dose of 100mg/m2. Patients receive 5 cycles of ch14.18/CHO

Experimental: R4: cnt inf ch14.18/CHO plus Aldesleukin - ch14.18/CHO is given as continuous Infusion over 10 days at a cumulative dose of 100mg/m2. Patients receive 5 cycles of ch14.18/CHO.

In addition, Aldesleukin is given at a dose of 3 x 10e6 on days 1 to 5 and on days 9, 11, 13, 15, and 17 during ch14.18/CHO infusion


Treatment: Drugs: Vincristine
given during Rapid COJEC and modified N7 therapy

Treatment: Drugs: Aldesleukin
Aldesleukin is given during MRD Treatment for patients randomised to the arm with IL-2

Treatment: Drugs: ch14.18/CHO
ch14.18/CHO antibody is given during MRD treatment

Treatment: Drugs: Carboplatin
Carboplatin is given during induction Treatment (R3 randomisation: Rapid COJEC arm)

Treatment: Drugs: Etoposide
Etoposide is given during Induction Treatment (both R3 randomisation arms)

Treatment: Drugs: Cisplatin
Cisplatin is given during Induction Treatment (both R3 randomisation arms)

Treatment: Drugs: Cyclophosphamide
Cyclophosphamid is given during Induction Treatment (both R3 randomisation arms)

Treatment: Drugs: Doxorubicin
Doxorubicin is given during Induction Treatment (R3 arm modified N7)

Treatment: Drugs: G-CSF
G-CSF is given during Induction Treatment

Treatment: Drugs: Busulfan
In case i.v. busulfan is not available, the use of oral busulfan is permitted, although not recommended.

Treatment: Drugs: Melphalan
Melphalan is given during MAT treatment
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Event Free Survival (R1: MAT therapy)
Timepoint [1] 0 0
Up to three years
Primary outcome [2] 0 0
Event Free Survival (immunotherapy)
Timepoint [2] 0 0
Up to three years
Primary outcome [3] 0 0
Complete metastatic response (R3: Induction therapy)
Timepoint [3] 0 0
Up to 95 days
Primary outcome [4] 0 0
Event free survival (R3: Induction therapy)
Timepoint [4] 0 0
Up to three years

Eligibility
Key inclusion criteria
* • Established diagnosis of neuroblastoma according to the International Neuroblastoma Staging System (INSS).

* Age below 21 years.
* High risk neuroblastoma defined as either:

1. INSS stage 2, 3, 4, and 4s with MYCN amplification, or
2. INSS stage 4 without MYCN amplification aged > 12 months at diagnosis
* Patients who have received no previous chemotherapy except for one cycle of etoposide and carboplatin (VP16/Carbo). In this situation patients will receive Rapid COJEC induction and the first Rapid COJEC cycle may be replaced by the first cycle VP16/Carbo (etoposide / carboplatin).
* 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.
* 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.
* Registration of all eligibility criteria with the data centre within 6 weeks from diagnosis.
* Provisional follow up of 5 years.
* National and local ethical committee approval.
Minimum age
1 Month
Maximum age
21 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Any negative answer concerning the inclusion criteria of the study

-

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised 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
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
1/02/2002
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
1/09/2026
Actual
Sample size
Target
3300
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
Recruitment hospital [1] 0 0
Women and Children´s Hospital - Adelaide
Recruitment hospital [2] 0 0
Lady Cilento Children´s Hospital - Brisbane
Recruitment hospital [3] 0 0
John Hunter Children's Hospital - Newcastle
Recruitment hospital [4] 0 0
Royal Children's Hospital Melbourne - Parkville
Recruitment hospital [5] 0 0
Sydney Children's Hospital - Sydney
Recruitment hospital [6] 0 0
Children´s Hospital Westmead - Westmead
Recruitment postcode(s) [1] 0 0
- Adelaide
Recruitment postcode(s) [2] 0 0
- Brisbane
Recruitment postcode(s) [3] 0 0
- Newcastle
Recruitment postcode(s) [4] 0 0
- Parkville
Recruitment postcode(s) [5] 0 0
- Sydney
Recruitment postcode(s) [6] 0 0
- Westmead
Recruitment outside Australia
Country [1] 0 0
Austria
State/province [1] 0 0
Austra
Country [2] 0 0
Austria
State/province [2] 0 0
Graz
Country [3] 0 0
Austria
State/province [3] 0 0
Innsbruck
Country [4] 0 0
Austria
State/province [4] 0 0
Linz
Country [5] 0 0
Austria
State/province [5] 0 0
Salzburg
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Belgium
State/province [6] 0 0
Brussels
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Belgium
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Gent
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Belgium
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Leuven
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Belgium
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Lüttich
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Belgium
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Montegnee
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Czechia
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Prague
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Denmark
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Aarhus
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Denmark
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Copenhagen
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Denmark
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Odense
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Denmark
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Skejby
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France
State/province [16] 0 0
Dijon
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France
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Grenoble
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France
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Le Pellerin
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France
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Lille
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France
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Marseille
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France
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Nantes
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France
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Paris
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France
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Reims
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France
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Saint Etienne
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France
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Strasbourg
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France
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Toulouse
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France
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Villejuif
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Greece
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Athens
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Greece
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Heraklion
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Hungary
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Budapest
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Hungary
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Debrecen
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Hungary
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Pécs
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Hungary
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Szeged
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Ireland
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Dublin
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Israel
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Haifa
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Israel
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Petah Tiqwa
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Israel
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Tel Aviv
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Italy
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Ancona
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Italy
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Bari
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Italy
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Bergamo
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Italy
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Bologna
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Cagliari
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Italy
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Cosenza
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Italy
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Firenze
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Italy
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Genua
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Italy
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Milano
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Italy
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Modena
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Napoli
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Italy
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Padova
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Italy
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Palermo
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Italy
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Parma
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Italy
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Pavia
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Italy
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Pescara
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Italy
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Rimini
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Italy
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Roma
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Italy
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Rome
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Italy
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San Giovanni Rotondo
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Torino
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Italy
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Trieste
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Norway
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Bergen
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Norway
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Oslo
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Norway
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Tromso
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Bialystok
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Bydgoszcz
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Chorzów
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Gdansk
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Lublin
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Poznan
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Warschau
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Wroclaw
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Portugal
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Lissabon
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Slovakia
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Banská Bystrica
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Slovenia
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Ljubljana
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Alicante
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Barcelona
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Bilbao
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San Sebastián
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Santiago De Compostela
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Sevilla
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Valencia
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Zaragoza
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Göteburg
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Sweden
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Linkoping
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Switzerland
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Geneva
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Switzerland
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Lausanne
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United Kingdom
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Aberdeen
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Belfast
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Birmingham
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Bristol
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Cambridge
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Cardiff
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Edinburgh
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Glasgow
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Leeds
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Leicester
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United Kingdom
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Liverpool
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United Kingdom
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London
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United Kingdom
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Manchester
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United Kingdom
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Newcastle
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Nottingham
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United Kingdom
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Oxford
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United Kingdom
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Sheffield
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United Kingdom
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Southhampton
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United Kingdom
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Sutton

Funding & Sponsors
Primary sponsor type
Other
Name
St. Anna Kinderkrebsforschung
Address
Country

Ethics approval
Ethics application status

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

Contacts
Principal investigator
Name 0 0
Ruth L Ladenstein, MD, MBA, cPM
Address 0 0
St. Anna Kinderkrebsforschung
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Ruth L Ladenstein, MD, MBA, cPM
Address 0 0
Country 0 0
Phone 0 0
0043140470
Fax 0 0
Email 0 0
ruth.ladenstein@ccri.at
Contact person for scientific queries

No information has been provided regarding IPD availability


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents


Results not provided in https://clinicaltrials.gov/study/NCT01704716