AzTrials
AzTrials

High-Risk NeuroblastomaPhase 3HR-NBL2NCT04221035

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

A Phase 3 study testing Vincristine, Carboplatin and Etoposide in people with High-Risk Neuroblastoma and Patient With Insufficient Response Chemoimmunotherapy, run by Gustave Roussy, Cancer Campus, Grand Paris at 142 sites in 20 countries.

Recruiting

Looking for participants now. Contact the study team or a site below to ask about taking part.

Sites and contacts
Official record
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Trial summary

This is an international multicenter, open-label, randomized phase III trial including three sequential randomizations to assess efficacy of induction and consolidation chemotherapies and radiotherapy for patients with high-risk neuroblastoma. Read more about this study

Who is it for?
Ages Up to 21 years
What is being tested?
Vincristine, Carboplatin and Etoposide
Could I receive a placebo?
No, everyone receives an active treatment
How many people
800 participants
Where
142 sitesin 20 countries
Study dates
5 Nov 2019to Nov 2032
Phase
Phase 3
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages Up to 21 years
  • All sexes
  • No healthy volunteers
  • Child, Adult

Who may be able to join

  • Enrollment in HR-NBL2 will be performed:
  • at diagnosis before the beginning of chemotherapy or
  • up to 21 days after one course of Carboplatin-Etoposide for patients with localized neuroblastoma or infants with metastatic neuroblastoma with MYCN amplification or patients with metastatic neuroblastoma treated in emergency or
  • up to 21 days after one course of the current protocol for R-I randomisation (RAPID COJEC/GPOH) low/intermediate risk neuroblastoma in Germany/Netherlands for patients with localized neuroblastoma or infants with metastatic neuroblastoma with MYCN amplification
  • HR-NBL2 eligibility criteria:
  • Established diagnosis of neuroblastoma according to the SIOPEN- modified International Neuroblastoma Risk Group (INRG) criteria, High-risk neuroblastoma defined as:
Show all 91Show fewer
  • Stage M neuroblastoma above 365 days of age at diagnosis (no upper age limit) and Ms neuroblastoma 12-18 months old, any MYCN status or
  • L2, M or Ms neuroblastoma any age with MYCN amplification, or focal high level MYC or MYCL amplification.
  • In Germany, patients aged less than 18 months with stage M and without MYCN amplification will not be enrolled in HR-NBL2 trial.
  • No previous chemotherapy or up to 21 days after one cycle of Carboplatin-Etoposide chemotherapy for patients with localized neuroblastoma or infants with metastatic neuroblastoma with MYCN amplification or patients with metastatic neuroblastoma treated in emergency or up to 21 days after one course of the current protocol for low/intermediate risk neuroblastoma in Germany/Netherlands for patients with localized neuroblastoma or infants with metastatic neuroblastoma with MYCN amplification
  • Females of childbearing potential must have a negative serum or urine pregnancy test within 7 days prior to initiation of treatment. Sexually active patients must agree to use acceptable and appropriate contraception while on HR-NBL2 study and for one year after stopping the study. Acceptable contraception is defined in CTFG Guidelines "Recommendations related to contraception and pregnancy testing in clinical trials" (Appendix 11). Female patients who are lactating must agree to stop breast-feeding.
  • Written informed consent to enter the HR-NBL2 protocol from patient or parents/legal representative, patient, and age-appropriate assent.
  • Patient affiliated to a social security regimen or beneficiary of the same according to local requirements.
  • Patients should be able and willing to comply with study visits and procedures as per protocol
  • R-I eligibility criteria:
  • Written informed consent to enter the R-I randomisation from patient or parents/legal representative, patient, and age- appropriate assent.
  • In case of parents'/patient's refusal to R-I, or Organ toxicity exclusion criteria at diagnosis, patients can still be enrolled in HR- NBL2 trial with parents'/patient's consent before or within 3 weeks from the beginning of chemotherapy
  • R-HDC randomisation (Single HDC Bu-Mel/ Tandem HDC Thiotepa+Bu-Mel) Etoposide or one course of the current protocol for low/intermediate risk neuroblastoma in Germany/Netherlands). Patients will be treated with the standard induction regimen per country (Rapid COJEC or GPOH) and will be potentially eligible for subsequent randomisations.
  • Randomisation for HDC strategy will be performed at the end of induction after the disease evaluation and after surgery of the primary tumour for those patients who will receive surgery before HDC.
  • R-HDC eligibility criteria:
  • - Stage M neuroblastoma above 365 days of age at diagnosis, any MYCN status, EXCEPT patients with stage M or Ms 12-18 months old with numerical chromosomal alterations only, and in complete metastatic response at the end of induction: in this case, patients will have surgery and no further treatment.
  • OR
  • L2, M or Ms neuroblastoma, any age, with MYCN amplification, or focal high level MYC or MYCL amplification
  • Age < 21 years at the time of randomization
  • Complete response (CR) or partial response (PR) at metastatic sites:
  • Bone disease: mIBG uptake completely resolved or SIOPEN score ≤ 3 and at least 50% reduction in mIBG score (or ≤ 3 bone lesions and at least 50% reduction in number of FDG- PET-avid bone lesions for mIBG-nonavid tumours).
  • Bone marrow disease: CR and/or minimal disease (MD) according to International Neuroblastoma Response Criteria
  • Other metastatic sites: CR. (after induction chemotherapy +/- surgery), except for distant lymph nodes for which PR is accepted with a possible secondary surgery
  • Acceptable organ function and performance status:
  • Performance status ≥ 50%.
  • Hematological status: ANC>0.5x109/L, platelets > 20x 109/L
  • Cardiac function: (< grade 2)
  • Normal chest X-Ray and oxygen saturation.
  • Absence of any toxicity ≥ grade 3. 4) Sufficient collected stem cells available; a total harvest of at least 6 x 106/kg CD34+ cells, to be stored in at least 4 separate bags to administer at least 3 x 106/kg CD34+ cells per rescue.
  • Written informed consent, including agreement of patient or parents/legal guardian for minors, to enter the R-HDC randomisation.
  • Patient affiliated to a social security regimen or beneficiary of the same according to local requirements.
  • Patients should be able and willing to comply with study visits and procedures as per protocol.
  • In case of parents'/patient's refusal, or insufficient stem cells, collection for tandem HDC but with a minimum of 3 x 106 CD34+ cells/kg body weight, or in case of patients older than 21 years, or organ toxicity, HDC will consist on the standard HD Bu-Mel and patients will be eligible for the subsequent randomisation.
  • R-RTx randomisation (Local Radiotherapy) Chemoimmunotherapy arm
  • R-RTx eligibility criteria:
  • An evaluation of the local disease will be performed after HDC/ASCR and surgery:
  • In case of no local macroscopic disease, all patients will receive 21,6-Gy radiotherapy to the pre-operative tumour bed
  • In case of local macroscopic residual disease, patients will be eligible to R-RTx if the following criteria are met:
  • No evidence of disease progression after HDC/ASCR.
  • Interval between the last ASCR and radiotherapy start between 60 and 90 days.
  • Performance status greater or equal 50%.
  • Hematological status: ANC >0.5x109/L, platelets > 20x109/L.
  • Written informed consent, including agreement of patient or parents/legal guardian for minors, to enter the R-RTx randomisation.
  • Patient affiliated to a social security regimen or beneficiary of the same according to local requirements.
  • Patients should be able and willing to comply with study visits and procedures as per protocol.
  • In case of parents'/patient's refusal of the randomisation, the patient will receive 21.6 Gy radiotherapy to the pre-operative tumour bed.
  • Chemoimmunotherapy arm eligibility criteria:
  • Insufficient metastatic response at the end of induction chemotherapy, defined as:
  • SIOPEN score > 3 or less than 50% reduction in mIBG score (or > 3 bone lesions or less 50% reduction in number of FDG-PET-avid bone lesions for mIBG-non avid tumours) OR
  • Bone marrow disease: SD according to International Neuroblastoma Response Criteria OR
  • Other metastatic sites: PR or SD. For distant lymph nodes: PR and not resectable or SD.
  • Performance status ≥ 50%.
  • Hematological status: ANC>0.75x109/L without G-CSF for at least 48 hours (or ANC ≥ 0.50 x 109 /L in case of bone marrow involvement), platelets > 50x 109/L and rising, without platelets transfusion for 72 hours.
  • AST or ALT ≤7.5 ULN and total bilirubin ≤1.5 ULN. In patients with liver metastases, total bilirubin ≤2.5 ULN is allowed.
  • No active infection;
  • No grade >2 gastrointestinal toxicity.
  • No grade ≥ 3 toxicity related to previous treatment.
  • Oxygen saturation > 94%
  • Non-inclusion criteria for HR-NBL2:
  • Any negative answer concerning the HR-NLB2 inclusion criteria
  • Patient under guardianship or deprived of his liberty by a judicial or administrative decision or incapable of giving his consent.
  • Participating in another clinical study with an IMP while on study treatment.
  • Chronic inflammatory bowel disease and/or bowel obstruction.
  • Pregnant or breastfeeding women.
  • Known hypersensitivity to the active substance or to any of the excipients of the study drugs
  • Concomitant self-medication medicine that in the investigator opinion could interact with study treatments, including herbal medicine (e.g. St John's Wort (Hypericum Perforatum).
  • Non-inclusion criteria specific to the R-I randomisation (RAPID COJEC/GPOH):
  • Urinary tract obstruction ≥ grade 3
  • Heart failure or myocarditis ≥ grade 2, any arrhythmia or myocardial infection
  • Peripheral motor or sensory neuropathy ≥ grade 3
  • Demyelinating form of Charcot-Marie-Tooth syndrome
  • Hearing impairment ≥ grade 2
  • Concurrent prophylactic use of phenytoin
  • Cardiorespiratory disease that contraindicates hyperhydration
  • Non-inclusion criteria common to all randomisations (R-I, R-HDC, and R-RTx):
  • Any negative answer concerning the inclusion criteria of R-I or R- HDC or R-RTx will render the patient ineligible for the corresponding therapy phase randomisation. However, these patients may remain on study and be considered to receive standard treatment of the respective therapy phase, and may be potentially eligible for subsequent randomisations.
  • Liver function: Alanine aminotransferase (ALT) > 3.0 x ULN and blood bilirubin > 1.5 x ULN (toxicity ≥ grade 2). In case of toxicity ≥ grade 2, call national principal investigator study coordinator to discuss the feasibility.
  • Renal function: Creatinine clearance and/or GFR < 60 ml/min/1.73m² (toxicity ≥ grade 2). If GFR < 60ml/min/1.73m², call national principal investigator study coordinator to discuss about the treatment.
  • Dyspnea at rest and/or pulse oximetry <95% in air (only for R-HDC, and R-RTx)
  • Any uncontrolled intercurrent illness or infection that in the investigator opinion would impair study participation.
  • Concomitant use with yellow fever vaccine and with live virus or bacterial vaccines.
  • Patient allergic to peanut or soya.
  • Non-inclusion criteria to R-HDC:
  • Any negative answer concerning the R-HDC inclusion criteria
  • Non-inclusion criteria to chemoimmunotherapy arm:
  • Any negative answer concerning the inclusion criteria of chemoimmunotherapy arm.

Who cannot join

None listed.

Trial locations and contacts

142 sites in 20 countries. Contact the study team or a site near you to ask about taking part.

Claudia Pasqualini, MD PhD contact

+33 (0)1 42 11 42 11

claudia.pasqualini@gustaveroussy.fr

Habiba Attalah, PhD contact

+33 (0)1 42 11 64 46

habiba.attalah@gustaveroussy.fr

142 sites in 20 countries

France37 sites, 29 recruiting

  • CHU d'AMIENS

    Amiens, 80054

    Leslie Andry, MD, andry.leslie@chu-amiens.fr

    Recruiting

  • CHU angers

    Angers

    Stéphanie Proust, MD, stproust@chu-angers.fr

    Recruiting

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

    Besançon

    Veronique LAITHIER, MD, vlaithier@chu-besancon.fr

    Recruiting

  • CHU Bordeaux

    Bordeaux, 33600

    Ayemeri Huchet, MD, ayemeri.huchet@chu-bordeaux.fr

    Recruiting

  • Groupe Hospitalier Pellegrin - Chu - Bordeaux

    Bordeaux

    Julie Tandonnet, MD, julie.tandonnet@chu-bordeaux.fr

    Recruiting

  • CHU Brest

    Brest, 29609

    Liana Carausu, MD, liana.carausu@chu-brest.fr

    Recruiting

  • CHU Brest - Hôpital du Morvan

    Brest

    Liana CARAUSU, MD, liana.carausu@chu-brest.fr

    Recruiting

  • Centre François Baclesse

    Caen

    Active, not recruiting

  • CHU de Caen

    Caen

    Damien Bodet, MD, bodet-d@chu-caen.fr

    Recruiting

  • CHU Estaing

    Clermont-Ferrand

    justyna KANOLD, MD, jkanold@chu-clermontferrand.fr

    Recruiting

  • Centre Georges-François Leclerc

    Dijon

    Active, not recruiting

  • Hopital d'enfants Marechal de lattre

    Dijon

    claire BRIANDET, MD, claire.briandet@chu-dijon.fr

    Recruiting

  • Hôpital Couple-Enfant CHU de Grenoble

    Grenoble

    Dominique Plantaz, MD, dplantaz@chu-grenoble.fr

    Recruiting

  • Chu de La Reunion - St Denis

    La Réunion

    Yves REGUERRE, MD, yves.reguerre@chu-reunion.fr

    Recruiting

  • centre Oscar lambert

    Lille

    Anne-Sophie DEFACHELLES, AS-Defachelles@o-lambret.fr

    Recruiting

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

    Limoges

    christophe PIGUET, MD, christophe.piguet@chu-limoges.fr

    Recruiting

  • Centre Léon Berard

    Lyon

    Benoit Dumond, MD, Benoit.DUMONT@ihope.fr

    Recruiting

  • hopital la Timone

    Marseille

    carole coze, MD, carole.coze@ap-hm.fr

    Recruiting

  • CHRU Nancy-Hôpital Brabois Enfant

    Nancy

    Ludovic Mansuy, MD, lu.mansuy@chru-nancy.fr

    Recruiting

  • Institut de cancérologie de Loraine

    Nancy

    Active, not recruiting

  • Centre Antoine Lacassagne

    Nice

    Active, not recruiting

  • CHU Nice-Hôpital d'Archet

    Nice

    Joy Benadiba, benadiba.j@chu-nice.fr

    Recruiting

  • Hôpital Armand Trousseau

    Paris

    Arnaud Petit, MD, arnaud.petit@aphp.fr

    Recruiting

  • institut Curie

    Paris

    Gudrun SCHLEIERMACHER, MD ;PhD, gudrun.schleiermacher@curie.fr

    Recruiting

  • CHU Poitiers

    Poitiers

    Frederic Millot, MD, Frederic.MILLOT@chu-poitiers.fr

    Recruiting

  • Hôpital Américain -CHU Reims

    Reims

    Claire PLUCHART, MD, cpluchart@chu-reims.fr

    Recruiting

  • Centre Eugène Marquis

    Rennes

    Active, not recruiting

  • CHU Rennes

    Rennes

    sophie taque, MD, sophie.taque@chu-rennes.fr

    Recruiting

  • Hôpital des Enfants - CHU Rouen

    Rouen

    cecile DUMESNIL DE MAURICOURT, MD, Cecile.Dumesnil@chu-rouen.fr

    Recruiting

  • CHU Saint Etienne

    Saint-Etienne

    sandrine THOUVENIN-DOULET, MD, sandrine.thouvenin@chu-st-etienne.fr

    Recruiting

  • Institut de cancérologie de l'Ouest - Sité René Gauducheau

    Saint-Herblain

    Active, not recruiting

  • CHU Haute Pierre

    Strasbourg

    catherine PAILLARD, MD, catherine.paillard@chru-strasbourg.fr

    Recruiting

  • Institut de Cancérologie Strasbourg

    Strasbourg

    Active, not recruiting

  • Hopital des enfants-CHU Toulouse

    Toulouse

    Marion Gambart, MD, gambart.m@chu-toulouse.fr

    Recruiting

  • IUCT Oncopole

    Toulouse

    Active, not recruiting

  • CHU Tours Hôpital Clocheville

    Tours

    Pascal Blouin, MD, p.blouin@chu-tours.fr

    Recruiting

  • Gustave Roussy

    Villejuif, Val De Marne, 94800

    Claudia Pasqualini, MD PhD, +33 (0)1 42 11 42 11, claudia.pasqualini@gustaveroussy.fr

    Attalah Habiba, PhD, +33 (0)1 42 11 64 46, habiba.attalah@gustaveroussy.fr

    Recruiting

Other trials in France

United Kingdom18 sites, 17 recruiting

  • Royal Aberdeen Children's Hospital

    Aberdeen

    Fiona HERD, MD, fiona.herd2@nhs.scot

    Recruiting

  • Royal Belfast Hospital for Sick Children

    Belfast

    Robert JOHNSTON, MD, Robert.johnston@belfasttrust.hscni.net

    Not yet recruiting

  • Birmingham children's Hospital

    Birmingham, B46NH

    David Hobin, MD, 01213338258, davidhobin@nhs.net

    Recruiting

  • University Hospitals Birmingham Queen Elisabeth Hospital(UHB)

    Birmingham, B46NH

    Active, not recruiting

  • University Hospitals Bristol and Weston NHS Foundation Trust

    Bristol, BS1 3NU

    Antony NG, MD, antony.ng@uhbristol.nhs.uk

    Recruiting

  • Addenbrookes Hospital, Cambridge

    Cambridge

    Matthew MURRAY, MD, matthew.murray1@nhs.net

    Recruiting

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

    Cardiff

    Cathy MORLEY-JACOB, MD, Charlotte.Chambers@wales.nhs.uk

    Not yet recruiting

  • Royal Hospital for Sick Children - Edinburgh

    Edinburgh

    Lesley SIMPSON, MD, Lesley.a.simpson@nhslothian.scot.nhs.uk

    Not yet recruiting

  • Royal Hospital for Children Glasgow

    Glasgow, G34

    Dermot Murphy, MD, Dermot.Murphy@ggc.scot.nhs.uk

    Recruiting

  • Leeds General Infirmary

    Leeds

    Martin ELLIOTT, MD, martin.elliott1@nhs.net

    Recruiting

  • Alder Hey Children's Hospital - Liverpool

    Liverpool

    Lisa HOWELL, MD, Lisa.Howell@alderhey.nhs.uk

    Recruiting

  • Great Ormond Street Hospital - London

    London

    Giuseppe BARONE, MD, giuseppe.barone@gosh.nhs.uk

    Recruiting

  • Royal Manchester Children's Hospital

    Manchester

    Recruiting

  • Royal Victoria Infirmary, Newcastle

    Newcastle

    Deborah Tweddle, MD, 0912082230, deborah.tweddle@newcastle.ac.uk

    Recruiting

  • Nottingham Children's Hospital

    Nottingham

    MADNI MADNI, MD, majid.madni@nuh.nhs.uk

    Recruiting

  • Sheffield Children's Hospital

    Sheffield, S102TH

    Dan Yeomanson, MD, 01142717366, danyeomanson@nhs.net

    Recruiting

  • Southampton General Hospital

    Southampton

    Ramya RAMANUJACHAR, MD, ramya.ramanujachar@uhs.nhs.uk

    Recruiting

  • Royal Marsden Hospital

    Sutton, SM2 5PT

    Sucheta vaidya, MD, 02086613635, sucheta.vaidya@icr.ac.uk

    Recruiting

Other trials in United Kingdom

Italy12 sites, 12 recruiting

  • A.O.U Policlinico di Bari

    Bari, 70124

    Nicola santoro, MD, 0805593363, nico.santoro1956@libero.it

    Recruiting

  • Spedali civili Ospedale Dei Bambini Oncoematologia pediatrica e TMO

    Brescia, 3995041

    Fulvio porta, 0303995711, fulvio.porta@asst-spedalicivili.it

    Recruiting

  • policlinico rodolico San marco

    Catania, 95123

    Andrea di cataldo, MD, 095/3782683, adicata@unict.it

    Recruiting

  • Azienda ospedaliero universtaria Anna Meyer

    Florence, 50139

    annalisa Tondo, MD, 055/56622739, annalisa.tondo@meyer.it

    Recruiting

  • instituto Giannina Gaslini genova

    Genova, 16147

    alberto garaventa, MD, 010/563662410, albertogaraventa@gaslini.org

    Recruiting

  • IRCCS "Istituto Giannina Gaslini"

    Genova, 16147

    Garaventa Alberto, MD, 01056362410, albertogaraventa@gaslini.org

    Recruiting

  • Azienda Policlinico di Modena

    Modena, 41100

    ssa Monica Cellini, MD, 059/4224485-2837, cellini.monica@policlinico.mo.it

    Recruiting

  • Azienda ospedaliero universitaria di Parma

    Parma, 43126

    patrizia Bertolini, MD, 0521/702831, pbertolini@ao.pr.it

    Recruiting

  • Policlino San matteo di Pavia

    Pavia, 27100

    frederico Bonetti, MD, 0382/502607, f.bonetti@smatteo.pv.it

    Recruiting

  • U.O Pediatria, SS Oncoematologia pediatrica

    Rimini, 47900

    Roberta Pericoli, MD, 0541/705034, roberta.pericoli@auslromagna.it

    Recruiting

  • IRCCS Burlo Garoflo oncoematologia

    Trieste, 34137

    marco Rabusin, 0403785563, marco.rabusin@burlo.triete.it

    Recruiting

  • U.O.C oncoematologia pediatrica ospedale Donna Bambino

    Verona, 37126

    simone cesaro, MD, 0458127874, simone.cesaro@ospedaleuniverona.it

    Recruiting

Other trials in Italy

Spain11 sites, 11 recruiting

  • Hospital Universitario Son Espases

    Balea, 07010

    samuel Navarro Noguera, MD, +34871205000, samuel.navarro@ssib.es

    Recruiting

  • Hospital Universitario Vall D´Hebron

    Barcelona, 08035

    Lucas Moreno Martin, MD, +34934893093, lucas.moreno@vallhebron.cat

    Recruiting

  • Hospital Universitario Cruces

    Cruces, 48903

    Ricardo Lopez Almaraz, MD, +34946006289, RICARDO.LOPEZALMARAZ@osakidetza.eus

    Recruiting

  • Hospital Clínico Universitario Virgen de la Arrixaca

    El Palmar, 30120

    Maria Del Mar Bermudez, MD, +34968929461, mariam.bermudez2@carm.es

    Recruiting

  • Hospital Universitario Infantil Niño Jesús

    Madrid, 28009

    Alba Rubio San Simon, MD, +34915035900, alba.rubio@salud.madrid.org

    Recruiting

  • Hospital Universitario La Paz

    Madrid, 28046

    Pedro rubio Aparicio, MD, +34912071116, pedro.rubio@salud.madrid.org

    Recruiting

  • Hospital Regional Universitario de Málaga

    Málaga, 29010

    Laura Garcia Hidalgo, MD, +34662244641, laura.garcia.hidalgo.sspa@juntadeandalucia.es

    Recruiting

  • Hospital Universitario Donostia

    San Sebastián, 20014

    Miriam Abos Garcia, MD, +34943007176, miriam.garciaabos@osakidetza.eus

    Recruiting

  • Hospital Clínico Universitario de Santiago

    Santiago de Compostela, 15706

    Manuel Fernández Sanmartín, MD, +34981951120, manuel.fernandez.sanmartin@sergas.es

    Recruiting

  • Hospital Universitario Virgen del Rocío

    Seville, 41013

    catalina Marquez Vega, MD, +34955012921, catalina.marquez.sspa@juntadeandalucia.es

    Recruiting

  • Hospital Universitario Politécnico de La FE

    Valencia

    Adela canete, MD, +34961244900, canyete_ade@gva.es

    Recruiting

Other trials in Spain

Switzerland9 sites, 9 recruiting

  • Kantonsspital Aarau AG Klinik für Kinder und Jugendliche

    Aarau, CH-5001

    Andreas Klein-Franke, MD, 41 62 838 92 45, Andreas.Klein-Franke@ksa.ch

    Recruiting

  • Universitäts-Kinderspital beider Basel (UKBB)

    Basel, CH-4031

    Nicolas von der Weid, Pr, 41 61 704 17 62, nicolas.vonderweid@ukbb.ch

    Recruiting

  • Ospedale San Giovanni Pediatria, Emato-oncologia pediatrica

    Bellinzona, CH-6500

    Pierluigi Brazzola, MD, 41 91 811 89 76, Pierluigi.Brazzola@eoc.ch

    Recruiting

  • Inselspital, Universitätsklinik für Kinderheilkunde

    Bern, CH-3010

    Jochen Rößler, MD, 41 31 632 94 95, jochen.roessler@insel.ch

    Recruiting

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

    Geneva, CH-1205

    Fabienne Gumy Pause, MD, 41 79 55 32 594, fabienne.gumypause@hcuge.ch

    Recruiting

  • CHUV - Centre Hospitalier Universitaire Vaudois

    Lausanne, CH-1011

    Maja Beck Popovic, Pr, 41 21 314 35 67, maja.beck-popovic@chuv.ch

    Recruiting

  • Luzerner Kantonsspital, Kinderspital pädiatrische Hämatologie/Onkologie

    Lucerne, CH-6000

    Freimut H. Schilling, MD, +41 41 205 32 10, freimut.schilling@luks.ch

    Recruiting

  • Ostschweizer Kinderspital Hämatologie/Onkologie Claudiusstrasse 6

    Sankt Gallen, CH-9006

    Cornelia Vetter, MD, +41 71 243 13 48, cornelia.vetter@kispisg.ch

    Recruiting

  • Division of Pediatric Oncology Universitäts-Kinderspital Zürich

    Zurich, CH-8032

    Sabina Kroiss Benninger, MD, 41 44 266 70 57, sabine.kroiss@kispi.uzh.ch

    Recruiting

Other trials in Switzerland

Australia7 sites, 4 recruiting

  • Children's Cancer Centre, Monash Children's Hospital

    Clayton, VIC 3168

    Peter Downie, MD, Peter.Downie@monashhealth.org

    Recruiting

  • Oncology/Haematology Department, Perth Children's Hospital

    Nedlands, WA, 6009

    Suspended

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

    New Lambton Heights, NSW, 2305

    Janis chamberlin, MD, 61 2 4921 3080, Janis.Chamberlain@health.nsw.gov.au

    Recruiting

  • Sydney children Hospital

    Sydney, Randwick, NSW, 2031

    Toby Nicholas Trahair, Phd, MD, 61 2 9382 2970, Toby.Trahair@health.nsw.gov.au

    Recruiting

  • Australian and New Zealand Children's Hematology/oncology Group

    Sydney, NSW, 2031

    Active, not recruiting

  • sydney children Hospital

    Sydney, NSW, 2031

    toby trahair, MD, 61 2 9382 2970, Toby.Trahair@health.nsw.gov.au

    Recruiting

  • Cancer Centre for Children, The Children's Hospital

    Westmead, NSW, 2145,

    Suspended

Other trials in Australia

Greece7 sites, 7 recruiting

  • Children's General Hospital "I AGHIA SOFIA"

    Athens, 11527

    Vassilios papadakis, MD, 0030 210-7452020, 2018, vpapadak@otenet.gr

    Recruiting

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

    Athens, 11527

    Margarita BAKA, MD, 0030 2107452219, margbaka@hotmail.com

    Recruiting

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

    Athens, 15123

    DANA ELENI, MD, 0030 210 6869631, danaeleni@hotmail.gr

    Recruiting

  • Children's General Hospital "AGHIA SOFIA"

    Athens

    ANTONIOS KATTAMIS, MD, 0030 2107452121, ankatt@med.uoa.gr

    Recruiting

  • University General Hospital of Heraklion (UnGHH)

    Heraklion, 71500

    NIKOLAOS KATZILAKIS, MD, 0030 2810 392630, katzilaher@yahoo.gr

    Recruiting

  • University General Hospital of Thessaloniki "AHEPA"

    Thessaloniki, 54621

    EMMANOUEL HATZIPANTELIS, MD, 0030 2310994810, hatzip@auth.gr

    Recruiting

  • General Hospital of Thessaloniki "IPPOKRATIO"

    Thessaloniki, 54642

    EVGENIA PAPAKONSTANTINOU, MD, 0030 2313312430, eugepapa@yahoo.gr

    Recruiting

Other trials in Greece

Sweden6 sites, 6 recruiting

  • Sahlgrenska University Hospital

    Gothenburg

    Torben Ek, MD, Torben.ek@vgregion.se

    Not yet recruiting

  • Linköping University Hospital

    Linköping

    Lisa Törnudd, MD

    Not yet recruiting

  • Skåne University Hospital

    Lund

    Ingrid Øra Ingrid Øra, MD, Ingrid.ora@med.lu.se

    Not yet recruiting

  • Karolinska University Hospital, Stockholm

    Stockholm

    Kleopatra Georgantzi, MD, kleopatra.georgantzi@regionstockholm.se

    Not yet recruiting

  • Norrland University Hospital

    Umeå

    Caroline Björklund, MD, caroline.bjorklund@regionvasterbotten.se

    Not yet recruiting

  • Uppsala University Hospital

    Uppsala

    Träger Träger, MD, catarina.trager@akademiska.se

    Not yet recruiting

Other trials in Sweden

Austria5 sites, 5 recruiting

  • Medical University Graz

    Graz

    Benesch Martin, MD, martin.benesch@klinikum-graz.at

    Recruiting

  • Landeskrankenhaus-Universitätsklinikum Innsbruck

    Innsbruck

    Roman Crazzolara, DR, roman.crazzolara@i-med.ac.at

    Recruiting

  • Kepler Universitatsklinikum Linz

    Linz

    Barbara Winkler, DR, barbara.aistleitner@keplerklinikum.at

    Recruiting

  • Universitastsklinikum Salzburg

    Salzburg

    Neil Jones, n.jones@salk.at

    Recruiting

  • St Anna'S Children Hospital

    Vienna, A-1090

    Ruth Ladenstein, Pr, ruth.ladenstein@ccri.at

    Carina Rajner, carina.rajner@ccri.at

    Recruiting

Other trials in Austria

Belgium5 sites, 5 recruiting

  • Hôpital Universitaire des Enfants Reine Fabiola (ULB)

    Brussels, 1020

    Safiato Diallo, MD, 0032 2 477 26 78, safiatou.diallo@huderf.be

    Recruiting

  • Cliniques Universitaires Saint-Luc (UCL)

    Brussels, 1200

    Benedicte Brichard, MD, 0032 2 764 23 50, benedicte.brichard@saintluc.uclouvain.be

    Recruiting

  • University Hospital Gent

    Ghent, 9000

    Bram De Wilde, MD, 0032 9 332 48 12, bram.dewilde@uzgent.be

    Recruiting

  • University Hospitals Leuven

    Leuven, 3000

    Marleen Renard, MD, 0032 16 34 39 72, marleen.renard@uzleuven.be

    Recruiting

  • CHR Citadelle

    Liège, 4000

    Sophie Gatineau, MD, 0032 4 321 55 18, sophie.gatineau@chrcitadelle.be

    Recruiting

Other trials in Belgium

Finland5 sites, 5 recruiting

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

    Helsinki, 00029

    Minna Koskenvuo, MD, +358 50 427 0424, minna.koskenvuo@hus.fi

    Not yet recruiting

  • Kuopio University Hospital

    Kuopio

    Kaisa Vepsäläinen, MD, +358 44 717 4964, kaisa.vepsalainen@kuh.fi

    Not yet recruiting

  • Oulu University Hospital

    Oulu

    Hanna Juntti, MD, +358 50 579 4440, hanna.juntti@pohde.fi

    Not yet recruiting

  • Tampere University Hospital

    Tampere

    Sauli Palmu, MD, +358 50 353 9956, sauli.palmu@tuni.fi

    Not yet recruiting

  • Turku University Hospital

    Turku

    Marika Grönroos, MD, +358 2 3130646, marika.gronroos@varha.fi

    Not yet recruiting

Other trials in Finland

Norway4 sites, 4 recruiting

  • Haukeland University Hospital

    Haukeland

    Maria Winther Gunnes, MD, maria.gunnes@helse-bergen.no

    Recruiting

  • Oslo University Hospital

    Oslo, 0424

    Maria Winther Gunnes, mawgun@ous-hf.no

    Recruiting

  • University Hospital Northern Norway, Tromsoe

    Tromsø

    Trond Flaegstad, MD, trond.flaegstad@unn.no

    Not yet recruiting

  • St Olavs Hospital,

    Trondheim

    MOE Erling, MD, erling.moe@stolav.no

    Not yet recruiting

Other trials in Norway

Denmark3 sites, 3 recruiting

  • Aarhus University Hospital

    Aarhus, DK-8200

    karin Bækgaard Nissen, karins@rm.dk

    Recruiting

  • Department of Paediatrics and Adolescent Medicine, Rigshospitalet

    Copenhagen, DK-2100

    jesper Sune Brok,, PhD, 0045 35458270, jesper.sune.brok@regionh.dk

    Recruiting

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

    Odense, DK-5000

    Mathias Rathe, PhD, 0045 30296665, mathias.rathe@rsyd.dk

    Recruiting

Other trials in Denmark

Slovakia3 sites, 3 recruiting

  • Children's University Hospital Banská Bystrica

    Banská Bystrica, 974 09

    pavel Bician, MD, 421 907 808 363, pavel.bician@dfnbb.sk

    Not yet recruiting

  • NÚDCH- National Institute of Children's Diseases,

    Bratislava, 833 40

    Achbergerová Monika, MD, monika.achbergerova@fmed.uniba.sk

    Not yet recruiting

  • Children's University Hospital Košice

    Košice, 040 11

    Halušková Viktória, MD, 055 235 3227, viktoria.haluskova@dfnkosice.sk

    Not yet recruiting

Other trials in Slovakia

Czechia2 sites, 2 recruiting

  • Klinika dětské onkologie FN Brno

    Brno, 662 63

    Pavel Pavel, MD, +420 532 234 449, Mazanek.Pavel@fnbrno.cz

    Not yet recruiting

  • University Hospital Motol

    Prague, Prague, 15006

    Josef Malis, MD, +420 224 436 401, josef.malis@fnmotol.cz

    Recruiting

Other trials in Czechia

Germany2 sites, 2 recruiting

  • charite universitatsmedizin Berlin

    Berlin, 13353

    Angelika eggert, Pr, 49 30 450 566 132, angelika.eggert@charite.de

    Recruiting

  • Uniklinik Köln, Klinik und Poliklinik für Kinder und Jugendmedizin

    Cologne, 50937

    Thorsten Simon, MD, +49 221 478 6853, thorsten.simon@uk-koeln.de

    Not yet recruiting

Other trials in Germany

Lithuania2 sites, 2 recruiting

  • Vilnius University Hospital Santaros Klinikos

    Vilnius, 08406

    Jelena Rascon, Pr, +370 5 232 8703, jelena.rascon@santa.lt

    Not yet recruiting

  • National Cancer Institute

    Vilnius, 08660

    Daiva Sendiuliene, MD, +370 5 274 6468, daiva.sendiuliene@nvi.lt

    Not yet recruiting

Other trials in Lithuania

Netherlands2 sites, 1 recruiting

  • Universitair Medisch Centrum Groningen

    Groningen, 9700

    Active, not recruiting

  • Princess Maxima center

    Utrecht, 3584CS

    Lieve TyTGAT, MD, +31 06-55234711, G.A.M.Tytgat@prinsesmaximacentrum.nl

    JAAP MUR, +31 06 5000 66 46, J.Mur@prinsesmaximacentrum.nl

    Recruiting

Other trials in Netherlands

Israel1 site, 1 recruiting

  • RAMBAM Medical Center

    Haifa

    shifra Ash, Pr, S_ash@rmc.gov.il

    Recruiting

Other trials in Israel

Slovenia1 site, 1 recruiting

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

    Ljubljana, 1000

    Cesen maja, MD, : 00 386 41 365 384, maja.cesenmazic@kclj.si

    Recruiting

Other trials in Slovenia

About this study

This is an international multicenter, open-label, randomized phase III trial including three sequential randomizations to assess efficacy of induction and consolidation chemotherapies and radiotherapy for patients with high-risk neuroblastoma.

Read the detailed description

This is an international multicenter, open-label, randomized phase III trial including three sequential randomizations to assess efficacy of induction and consolidation chemotherapies and radiotherapy for patients with high-risk neuroblastoma.

The first randomization (R-I) will compare the efficacy of two induction chemotherapies (RAPID COJEC and GPOH regimens) in a phase III setting. The primary endpoint will be the 3-year EFS from date of randomization . The R-I randomization will be stratified on age, stage, MYCN status and countries.

The second randomization (R-HDC) will compare the efficacy of single HDC with Bu-Mel versus tandem HDC with Thiotepa followed by Bu-Mel. The primary endpoint is 3-year EFS calculated from the date of the R-HDC randomization. The R-HDC randomization will be stratified on the age, stage, MYCN status, induction chemotherapy regimen, response to induction phase and countries.

The impact of local treatment in this phase III setting will be assessed, according to the presence or not of a macroscopic residual disease after surgery and HDC.

In case of macroscopic residual disease, 21.6 Gy radiotherapy to the preoperative tumor bed will be randomized (R-RTx) versus the same treatment plus a sequential boost of additional 14.4 Gy to the residual tumor. The primary endpoint of R-RTx is 3-year EFS from the date of the R-RTx randomization. The R-RTx randomization will be stratified on age, stage, MYCN status, induction chemotherapy regimen, HDC regimen and countries.

In case of no macroscopic residual disease, 21.6 Gy radiotherapy will be delivered to the preoperative tumor bed.

Being tested
Vincristine, Carboplatin, Etoposide, Vindesine, Dacarbazine

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • VincristineDrug

    Also called L01CA02

    1.5 mg/m2 (max dose 2 mg)

  • CarboplatinDrug

    Also called LO1XA02

    750 mg/m2

  • EtoposideDrug

    Also called L01CB01

    175 mg/m2

  • VindesineDrug

    Also called L01CA03

    3 mg/m2/day (max dose 6 mg)

  • DacarbazineDrug

    Also called L01AX04

    200 mg/m2/day

  • IfosfamideDrug

    1500 mg/m2/day

  • DoxorubicinDrug

    Also called L01DB01

    30 mg/m2/dose

  • BusulfanDrug

    Also called L01AB01

    < 9kg: 1.0 mg/kg/dose 9 kg to < 16 kg : 1.2 mg/kg/dose 16 kg to 23 kg : 1.1 mg/kg/dose >23 kg to 34 kg: 0.95 mg/kg/dose >34 kg: 0.8 mg/kg/dose Infusion IV over 2 hours Administration every 6 hours for a total of 16 doses

  • MelphalanDrug

    Also called L01AA03

    140 mg/m2/dose IV short infusion (15'), at least 24 h after the last busulfan dose

  • ThiotepaDrug

    Also called L01AC01

    300 mg/m2/day over 2 hours

  • RadiotherapyRadiation

    21.6 Gy 21.6 Gy + boost de 14.4 Gy

  • Dinutuximab BetaDrug

    Also called L01XC16

    Patients >12 kg are dosed based on the BSA: 10 mg/m^2/day Patients ≤ 12 kg are dosed according to their body weight: 0.33 mg/kg/day

  • CisplatinDrug

    Also called L01XA01

    80 mg/m2/24h

  • Temozolomide 100 MGDrug

    100 mg/m²/Day

  • IrinotecanDrug

    50 mg/m²/jour de J0 à J4

  • CyclophosphamidDrug

    Cyclophosphamide has been demonstrated to have a cytostatic effect in many tumour types. The active metabolites of cyclophosphamide are alkylating agents which transfer alkyl groups to DNA during the process of cell division, thus preventing normal synthesis of DNA.

Study groups in NCT04221035
Study groupRoleWhat they receive
phase induction-R-IExperimentalR-I: induction regimens RAPID COJEC vs GPOH Assuming a baseline 3-year EFS of 40%, with a sample size of 686 patients (343 in each arm) and a two-sided alpha=5% this trial will have 90% power to demonstrate an improvement of 12% in 3-year EFS, within a recruitment period of 3 years and a minimum follow up of 1.5 years. Patients with insufficient metastatic response at the end of induction chemotherapy, defined as SIOPEN score > 3 or less than 50% reduction in mIBG score (or > 3 bone lesions or less 50% reduction in number of FDG-PET-avid bone lesions for mIBG-non avid tumours), have a poorer prognosis. Chemoimmunotherapy arm Metastatic response rate after 4 courses of irinotecan-temozolomide (TEMIRI) combined with dinutuximab beta (DB) in patients with insufficient metastatic response at the end of induction chemotherapy (TEMIRI/DB).
Receives: Drug: Vincristine; Drug: Carboplatin; Drug: Etoposide; Drug: Vindesine; Drug: Dacarbazine; Drug: Ifosfamide; Drug: Doxorubicin; Drug: Dinutuximab Beta; Drug: Cisplatin; Drug: Temozolomide 100 MG; Drug: Irinotecan; Drug: Cyclophosphamid
Phase high dose chemotherapy consolidationExperimentalR-HDC: consolidation regimen Bu-Mel vs Thiotepa + Bu-Mel The 3-year EFS in the Bu-Mel arm (with immunotherapy) is estimated to be 55%. This study aims to show an improvement of 12% for the Thiotepa + Bu-Mel arm (3-year EFS of 67%). With a recruitment of 448 patients (224 in each arm) over a period of 3 years and a minimum follow-up of 2 years, the power to show a 12% difference is 80% (two-sided logrank test and α=5%).
Receives: Drug: Busulfan; Drug: Melphalan; Drug: Thiotepa
Phase of radiotherapyExperimentalR-RTx: 21.6 Gy radiotherapy vs 21.6 Gy + 14.4 Gy boost in patients with macroscopic residual disease
Receives: Radiation: Radiotherapy; Drug: Dinutuximab Beta

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Event free survival (EFS)

    Event free survival

    Measured: Assessed at each end of randomization sequences up to one year

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted9 Jan 2020
  2. Study start5 Nov 2019
  3. Primary completionNov 2026 (estimated)
  4. Study completionNov 2032 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Sequential
Masking
None (open label)
Enrolment
800 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04221035
Sponsor's protocol ID
2019-001068-31
Other IDs
2019/2894, 2024-514917-36-00, 2019
Acronym
HR-NBL2
Status last verified
Jun 2025
First submitted
6 Jan 2020
Last updated
26 Jun 2025
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
Yes

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Vincristine, Carboplatin and Etoposide in people with High-Risk Neuroblastoma and Patient With Insufficient Response Chemoimmunotherapy, run by Gustave Roussy, Cancer Campus, Grand Paris at 142 sites in 20 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 91 inclusion and 0 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: looking for participants now, as of the sponsor's last update on 26 Jun 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 142 sites in France, United Kingdom, Italy, Spain, Switzerland and 15 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

Contact Claudia Pasqualini, MD PhD (+33 (0)1 42 11 42 11, claudia.pasqualini@gustaveroussy.fr), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Event free survival (EFS) (time frame: Assessed at each end of randomization sequences up to one year). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04221035.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 26 Jun 2025.

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