Actively Recruiting

Phase 3
Age: 0 - 21Years
All Genders
ID04221035

High-Risk Neuroblastoma Study 2 of SIOP-Europa-Neuroblastoma (SIOPEN)

Led by Gustave Roussy, Cancer Campus, Grand Paris · Updated on 2025-06-26

800

Participants Needed

142

Research Sites

313 weeks

Total Duration

On this page

AI-Summary

What this Trial Is About

Researchers are conducting an international, open-label, randomized phase III trial to evaluate the effectiveness of chemotherapy and radiotherapy treatments for patients with high-risk neuroblastoma. The study includes three sequential randomizations to compare different induction chemotherapy regimens, consolidation high-dose chemotherapy (HDC) approaches, and radiotherapy strategies. The goal is to improve event-free survival (EFS) over three years among children and young adults diagnosed with this aggressive cancer. The first randomization compares two induction chemotherapy regimens: RAPID COJEC versus GPOH. The second randomization assesses single HDC with Busulfan-Melphalan (Bu-Mel) versus tandem HDC with Thiotepa followed by Bu-Mel. For patients with macroscopic residual disease after surgery and HDC, the third randomization compares standard radiotherapy (21.6 Gy) to the tumor bed versus the same radiotherapy plus an additional boost (14.4 Gy). Patients without residual disease receive standard radiotherapy to the tumor bed. Treatments include various chemotherapy drugs, immunotherapy with dinutuximab beta, and radiotherapy delivered according to the assigned groups. Participants will undergo multiple assessments including disease evaluation after induction chemotherapy and surgery, blood tests, and monitoring of organ function. Researchers will measure event-free survival at one year after each randomization sequence. Patients are followed through the different phases of induction, consolidation, and radiotherapy, with adherence to protocol visits and procedures required. Safety and treatment responses are closely monitored throughout the study, which continues until the end date in November 2032.

CONDITIONS

Brief Title

High-Risk Neuroblastoma Study 2 of SIOP-Europa-Neuroblastoma (SIOPEN)

Who Can Participate

Age: 0 - 21Years
All Genders

Eligibility Criteria

Eligible

You may qualify if you...

  • Diagnosis of high-risk neuroblastoma according to SIOPEN-modified INRG criteria
  • Age up to 21 years at time of randomization
  • No previous chemotherapy or up to 21 days after one cycle of Carboplatin-Etoposide
  • Negative pregnancy test for females of childbearing potential
  • Use of acceptable contraception during and for one year after study treatment
  • Written informed consent from patient or legal guardian, with assent when appropriate
  • Affiliation to a social security or equivalent system
  • Ability and willingness to comply with study visits and procedures
  • Specific inclusion criteria for each randomization phase as per protocol
Not Eligible

You will not qualify if you...

  • Failure to meet any inclusion criteria
  • Patient under guardianship or deprived of liberty
  • Participation in another clinical trial with investigational medicinal product during study treatment
  • Chronic inflammatory bowel disease or bowel obstruction
  • Pregnant or breastfeeding women
  • Known allergy to study drugs or excipients
  • Use of medications that may interact with study drugs, including herbal supplements like St John's Wort
  • Specific exclusions for R-I randomization such as severe urinary tract obstruction, heart failure, neuropathy, hearing impairment, or contraindications to hyperhydration
  • Abnormal liver or kidney function exceeding defined limits
  • Dyspnea at rest or low oxygen saturation (for certain randomization phases)
  • Uncontrolled illness or infection
  • Allergy to peanut or soya
  • Concurrent use of live vaccines including yellow fever vaccine

AI-Screening

AI-Powered Screening

Complete this quick 3-step screening to check your eligibility

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Your Study Journey

Screening

Duration - 2 to 4 weeks

Participants are screened for eligibility to participate in the trial.

1 visit (in-person)

Induction Treatment

Duration - Several weeks (varies with regimen)

Participants receive one of two induction chemotherapy regimens (RAPID COJEC or GPOH) to treat high-risk neuroblastoma.

Multiple visits during induction chemotherapy cycles

High Dose Chemotherapy Consolidation

Duration - Several weeks (varies by regimen)

Participants receive high dose chemotherapy with either single Bu-Mel or tandem Thiotepa followed by Bu-Mel to consolidate treatment effects.

Multiple visits for chemotherapy administration and monitoring

Radiotherapy

Duration - Approximately 3 to 4 weeks

Participants with residual tumor receive radiotherapy to the tumor bed, either standard dose or with an additional boost depending on residual disease.

Daily visits for radiotherapy sessions during treatment period

Trial Site Locations

Total: 142 locations

1

Sydney children Hospital

Sydney, Randwick, Australia, NSW, 2031

Actively Recruiting

2

Children's Cancer Centre, Monash Children's Hospital

Clayton, Australia, VIC 3168

Actively Recruiting

3

Oncology/Haematology Department, Perth Children's Hospital

Nedlands, Australia, WA, 6009

Suspended

4

Children's Cancer & Haematology Services, John Hunter Children's Hospital

New Lambton Heights, Australia, NSW, 2305

Actively Recruiting

5

Australian and New Zealand Children's Hematology/oncology Group

Sydney, Australia, NSW, 2031

Active, Not Recruiting

6

sydney children Hospital

Sydney, Australia, NSW, 2031

Actively Recruiting

7

Cancer Centre for Children, The Children's Hospital

Westmead, Australia, NSW, 2145,

Suspended

8

Medical University Graz

Graz, Austria

Actively Recruiting

9

Landeskrankenhaus-Universitätsklinikum Innsbruck

Innsbruck, Austria

Actively Recruiting

10

Kepler Universitatsklinikum Linz

Linz, Austria

Actively Recruiting

11

Universitastsklinikum Salzburg

Salzburg, Austria

Actively Recruiting

12

St Anna'S Children Hospital

Vienna, Austria, A-1090

Actively Recruiting

13

Hôpital Universitaire des Enfants Reine Fabiola (ULB)

Brussels, Belgium, 1020

Actively Recruiting

14

Cliniques Universitaires Saint-Luc (UCL)

Brussels, Belgium, 1200

Actively Recruiting

15

University Hospital Gent

Ghent, Belgium, 9000

Actively Recruiting

16

University Hospitals Leuven

Leuven, Belgium, 3000

Actively Recruiting

17

CHR Citadelle

Liège, Belgium, 4000

Actively Recruiting

18

University Hospital Motol

Prague, Prague, Czechia, 15006

Actively Recruiting

19

Klinika dětské onkologie FN Brno

Brno, Czechia, 662 63

Not Yet Recruiting

20

Aarhus University Hospital

Aarhus, Denmark, DK-8200

Actively Recruiting

21

Department of Paediatrics and Adolescent Medicine, Rigshospitalet

Copenhagen, Denmark, DK-2100

Actively Recruiting

22

The Hans Christian Andersen Children's Hospital, University of Southern Denmark

Odense, Denmark, DK-5000

Actively Recruiting

23

New Children's Hospital, Helsinki University Hospital, Helsinki and Uusimaa Hospital District

Helsinki, Finland, 00029

Not Yet Recruiting

24

Kuopio University Hospital

Kuopio, Finland

Not Yet Recruiting

25

Oulu University Hospital

Oulu, Finland

Not Yet Recruiting

26

Tampere University Hospital

Tampere, Finland

Not Yet Recruiting

27

Turku University Hospital

Turku, Finland

Not Yet Recruiting

28

Gustave Roussy

Villejuif, Val De Marne, France, 94800

Actively Recruiting

29

CHU d'AMIENS

Amiens, France, 80054

Actively Recruiting

30

CHU angers

Angers, France

Actively Recruiting

31

CHU-Pôle Médico-Chirurgical de l'Enfant et l'Adolescant

Besançon, France

Actively Recruiting

32

CHU Bordeaux

Bordeaux, France, 33600

Actively Recruiting

33

Groupe Hospitalier Pellegrin - Chu - Bordeaux

Bordeaux, France

Actively Recruiting

34

CHU Brest

Brest, France, 29609

Actively Recruiting

35

CHU Brest - Hôpital du Morvan

Brest, France

Actively Recruiting

36

Centre François Baclesse

Caen, France

Active, Not Recruiting

37

CHU de Caen

Caen, France

Actively Recruiting

38

CHU Estaing

Clermont-Ferrand, France

Actively Recruiting

39

Centre Georges-François Leclerc

Dijon, France

Active, Not Recruiting

40

Hopital d'enfants Marechal de lattre

Dijon, France

Actively Recruiting

41

Hôpital Couple-Enfant CHU de Grenoble

Grenoble, France

Actively Recruiting

42

Chu de La Reunion - St Denis

La Réunion, France

Actively Recruiting

43

centre Oscar lambert

Lille, France

Actively Recruiting

44

Hôpital de la Mère et de l'Enfant - CHU Limoges

Limoges, France

Actively Recruiting

45

Centre Léon Berard

Lyon, France

Actively Recruiting

46

hopital la Timone

Marseille, France

Actively Recruiting

47

CHRU Nancy-Hôpital Brabois Enfant

Nancy, France

Actively Recruiting

48

Institut de cancérologie de Loraine

Nancy, France

Active, Not Recruiting

49

Centre Antoine Lacassagne

Nice, France

Active, Not Recruiting

50

CHU Nice-Hôpital d'Archet

Nice, France

Actively Recruiting

51

Hôpital Armand Trousseau

Paris, France

Actively Recruiting

52

institut Curie

Paris, France

Actively Recruiting

53

CHU Poitiers

Poitiers, France

Actively Recruiting

54

Hôpital Américain -CHU Reims

Reims, France

Actively Recruiting

55

Centre Eugène Marquis

Rennes, France

Active, Not Recruiting

56

CHU Rennes

Rennes, France

Actively Recruiting

57

Hôpital des Enfants - CHU Rouen

Rouen, France

Actively Recruiting

58

CHU Saint Etienne

Saint-Etienne, France

Actively Recruiting

59

Institut de cancérologie de l'Ouest - Sité René Gauducheau

Saint-Herblain, France

Active, Not Recruiting

60

CHU Haute Pierre

Strasbourg, France

Actively Recruiting

61

Institut de Cancérologie Strasbourg

Strasbourg, France

Active, Not Recruiting

62

Hopital des enfants-CHU Toulouse

Toulouse, France

Actively Recruiting

63

IUCT Oncopole

Toulouse, France

Active, Not Recruiting

64

CHU Tours Hôpital Clocheville

Tours, France

Actively Recruiting

65

charite universitatsmedizin Berlin

Berlin, Germany, 13353

Actively Recruiting

66

Uniklinik Köln, Klinik und Poliklinik für Kinder und Jugendmedizin

Cologne, Germany, 50937

Not Yet Recruiting

67

Children's General Hospital "I AGHIA SOFIA"

Athens, Greece, 11527

Actively Recruiting

68

Children's General Hospital "P. & A. KYRIAKOU"

Athens, Greece, 11527

Actively Recruiting

69

"MITERA" Private, General, Obstetrics - Gynaecology, Paediatric Clinic S.A.

Athens, Greece, 15123

Actively Recruiting

70

Children's General Hospital "AGHIA SOFIA"

Athens, Greece

Actively Recruiting

71

University General Hospital of Heraklion (UnGHH)

Heraklion, Greece, 71500

Actively Recruiting

72

University General Hospital of Thessaloniki "AHEPA"

Thessaloniki, Greece, 54621

Actively Recruiting

73

General Hospital of Thessaloniki "IPPOKRATIO"

Thessaloniki, Greece, 54642

Actively Recruiting

74

RAMBAM Medical Center

Haifa, Israel

Actively Recruiting

75

A.O.U Policlinico di Bari

Bari, Italy, 70124

Actively Recruiting

76

Spedali civili Ospedale Dei Bambini Oncoematologia pediatrica e TMO

Brescia, Italy, 3995041

Actively Recruiting

77

policlinico rodolico San marco

Catania, Italy, 95123

Actively Recruiting

78

Azienda ospedaliero universtaria Anna Meyer

Florence, Italy, 50139

Actively Recruiting

79

instituto Giannina Gaslini genova

Genova, Italy, 16147

Actively Recruiting

80

IRCCS "Istituto Giannina Gaslini"

Genova, Italy, 16147

Actively Recruiting

81

Azienda Policlinico di Modena

Modena, Italy, 41100

Actively Recruiting

82

Azienda ospedaliero universitaria di Parma

Parma, Italy, 43126

Actively Recruiting

83

Policlino San matteo di Pavia

Pavia, Italy, 27100

Actively Recruiting

84

U.O Pediatria, SS Oncoematologia pediatrica

Rimini, Italy, 47900

Actively Recruiting

85

IRCCS Burlo Garoflo oncoematologia

Trieste, Italy, 34137

Actively Recruiting

86

U.O.C oncoematologia pediatrica ospedale Donna Bambino

Verona, Italy, 37126

Actively Recruiting

87

Vilnius University Hospital Santaros Klinikos

Vilnius, Lithuania, 08406

Not Yet Recruiting

88

National Cancer Institute

Vilnius, Lithuania, 08660

Not Yet Recruiting

89

Universitair Medisch Centrum Groningen

Groningen, Netherlands, 9700

Active, Not Recruiting

90

Princess Maxima center

Utrecht, Netherlands, 3584CS

Actively Recruiting

91

Haukeland University Hospital

Haukeland, Norway

Actively Recruiting

92

Oslo University Hospital

Oslo, Norway, 0424

Actively Recruiting

93

University Hospital Northern Norway, Tromsoe

Tromsø, Norway

Not Yet Recruiting

94

St Olavs Hospital,

Trondheim, Norway

Not Yet Recruiting

95

Children's University Hospital Banská Bystrica

Banská Bystrica, Slovakia, 974 09

Not Yet Recruiting

96

NÚDCH- National Institute of Children's Diseases,

Bratislava, Slovakia, 833 40

Not Yet Recruiting

97

Children's University Hospital Košice

Košice, Slovakia, 040 11

Not Yet Recruiting

98

University medical center Ljubljana, University Children's Hospital Ljubljana, Slovenia

Ljubljana, Slovenia, 1000

Actively Recruiting

99

Hospital Universitario Son Espases

Balea, Spain, 07010

Actively Recruiting

100

Hospital Universitario Vall D´Hebron

Barcelona, Spain, 08035

Actively Recruiting

101

Hospital Universitario Cruces

Cruces, Spain, 48903

Actively Recruiting

102

Hospital Clínico Universitario Virgen de la Arrixaca

El Palmar, Spain, 30120

Actively Recruiting

103

Hospital Universitario Infantil Niño Jesús

Madrid, Spain, 28009

Actively Recruiting

104

Hospital Universitario La Paz

Madrid, Spain, 28046

Actively Recruiting

105

Hospital Regional Universitario de Málaga

Málaga, Spain, 29010

Actively Recruiting

106

Hospital Universitario Donostia

San Sebastián, Spain, 20014

Actively Recruiting

107

Hospital Clínico Universitario de Santiago

Santiago de Compostela, Spain, 15706

Actively Recruiting

108

Hospital Universitario Virgen del Rocío

Seville, Spain, 41013

Actively Recruiting

109

Hospital Universitario Politécnico de La FE

Valencia, Spain

Actively Recruiting

110

Sahlgrenska University Hospital

Gothenburg, Sweden

Not Yet Recruiting

111

Linköping University Hospital

Linköping, Sweden

Not Yet Recruiting

112

Skåne University Hospital

Lund, Sweden

Not Yet Recruiting

113

Karolinska University Hospital, Stockholm

Stockholm, Sweden

Not Yet Recruiting

114

Norrland University Hospital

Umeå, Sweden

Not Yet Recruiting

115

Uppsala University Hospital

Uppsala, Sweden

Not Yet Recruiting

116

Kantonsspital Aarau AG Klinik für Kinder und Jugendliche

Aarau, Switzerland, CH-5001

Actively Recruiting

117

Universitäts-Kinderspital beider Basel (UKBB)

Basel, Switzerland, CH-4031

Actively Recruiting

118

Ospedale San Giovanni Pediatria, Emato-oncologia pediatrica

Bellinzona, Switzerland, CH-6500

Actively Recruiting

119

Inselspital, Universitätsklinik für Kinderheilkunde

Bern, Switzerland, CH-3010

Actively Recruiting

120

HUG Hôpitaux Universitaires de Genève Unité d'Hémato-Oncologie Pédiatrique

Geneva, Switzerland, CH-1205

Actively Recruiting

121

CHUV - Centre Hospitalier Universitaire Vaudois

Lausanne, Switzerland, CH-1011

Actively Recruiting

122

Luzerner Kantonsspital, Kinderspital pädiatrische Hämatologie/Onkologie

Lucerne, Switzerland, CH-6000

Actively Recruiting

123

Ostschweizer Kinderspital Hämatologie/Onkologie Claudiusstrasse 6

Sankt Gallen, Switzerland, CH-9006

Actively Recruiting

124

Division of Pediatric Oncology Universitäts-Kinderspital Zürich

Zurich, Switzerland, CH-8032

Actively Recruiting

125

Royal Aberdeen Children's Hospital

Aberdeen, United Kingdom

Actively Recruiting

126

Royal Belfast Hospital for Sick Children

Belfast, United Kingdom

Not Yet Recruiting

127

Birmingham children's Hospital

Birmingham, United Kingdom, B46NH

Actively Recruiting

128

University Hospitals Birmingham Queen Elisabeth Hospital(UHB)

Birmingham, United Kingdom, B46NH

Active, Not Recruiting

129

University Hospitals Bristol and Weston NHS Foundation Trust

Bristol, United Kingdom, BS1 3NU

Actively Recruiting

130

Addenbrookes Hospital, Cambridge

Cambridge, United Kingdom

Actively Recruiting

131

Noah's Ark Children's Hospital for Wales - Cardiff

Cardiff, United Kingdom

Not Yet Recruiting

132

Royal Hospital for Sick Children - Edinburgh

Edinburgh, United Kingdom

Not Yet Recruiting

133

Royal Hospital for Children Glasgow

Glasgow, United Kingdom, G34

Actively Recruiting

134

Leeds General Infirmary

Leeds, United Kingdom

Actively Recruiting

135

Alder Hey Children's Hospital - Liverpool

Liverpool, United Kingdom

Actively Recruiting

136

Great Ormond Street Hospital - London

London, United Kingdom

Actively Recruiting

137

Royal Manchester Children's Hospital

Manchester, United Kingdom

Actively Recruiting

138

Royal Victoria Infirmary, Newcastle

Newcastle, United Kingdom

Actively Recruiting

139

Nottingham Children's Hospital

Nottingham, United Kingdom

Actively Recruiting

140

Sheffield Children's Hospital

Sheffield, United Kingdom, S102TH

Actively Recruiting

141

Southampton General Hospital

Southampton, United Kingdom

Actively Recruiting

142

Royal Marsden Hospital

Sutton, United Kingdom, SM2 5PT

Actively Recruiting

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Research Team

C

Claudia Pasqualini, MD PhD

H

Habiba Attalah, PhD

How is the study designed?

Study Type

INTERVENTIONAL

Masking

NONE

Allocation

RANDOMIZED

Model

SEQUENTIAL

Primary Purpose

TREATMENT

Number of Arms

3

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