Overview
Sponsor-declared trial summary
Phase
Phase I and Phase II (Integrated) - Other
Status
Ongoing, recruiting
Participants planned
39
Countries
7
Sites
13
Neuroblastoma
• To assess the safety and tolerability and identify the RP2D and MTD of dinutuximab beta when combined with two different induction chemotherapy regimens (GPOH or rapid COJEC) for the treatment of newly diagnosed high-risk neuroblastoma patients as defined by Stage M ≥ 18 months of age and <18 years, according to the …
Key facts
- Sponsor
- Prinses Maxima Centrum voor Kinderoncologie B.V.
- Participant type
- Pediatric, Patients
- Age range
- 0-17 years
- Gender
- Male and Female
- Therapeutic area
- Diseases [C] - Neoplasms [C04]
- Trial duration
- 2 Dec 2024 → ongoing
- Decision date (initial)
- 2025-07-14
- Transition trial
- No
- Low-intervention
- No
- Rare-disease indication
- No
- Vulnerable population
- Yes
- Funding sources
- EUSA Pharma
Trial design
CTIS Part I — objectives, methods, condition coding
Main objective
Scope: Pharmacodynamic, Pharmacokinetic, Safety, Dose response, Therapy
• To assess the safety and tolerability and identify the RP2D and MTD of dinutuximab beta when combined with two different induction chemotherapy regimens (GPOH or rapid COJEC) for the treatment of newly diagnosed high-risk neuroblastoma patients as defined by Stage M ≥ 18 months of age and <18 years, according to the INRGSS.
Secondary objectives 3
- To characterize the toxicity of induction chemotherapy when combined with dinutuximab beta
- To determine the overall response (primary tumor, metastases) during the induction and at the end of induction chemotherapy with dinutuximab beta.
- To determine the metastatic response rate to chemotherapy plus dinutuximab beta.
Conditions and MedDRA coding
Neuroblastoma
| Version | Level | Code | Term | System organ class |
|---|---|---|---|---|
| 21.0 | LLT | 10008126 | Cerebral neuroblastoma | 10029104 |
| 21.1 | PT | 10073130 | Central nervous system neuroblastoma | 100000004864 |
| 20.0 | PT | 10029260 | Neuroblastoma | 100000004864 |
Eligibility criteria
Principal inclusion / exclusion criteria as submitted by sponsor
Inclusion criteria 8
- Established diagnosis of neuroblastoma Stage M, according to the SIOPEN modified International Neuroblastoma Risk Group (INRG) and to the INSS criteria
- Age ≥18 months and <18 years
- Body weight >12 kg.
- Alanine transaminase (ALT) and aspartate aminotransferase (AST) <10 × upper limit of normal (ULN), total bilirubin <1.5 × ULN based on age specific reference ranges
- Calculated glomerular filtration rate (based on Schwartz formula; section 10.4.7) >60 mL/min/1.73 m2 or serum creatinine <1.5 × ULN corrected for age.
- Shortening fraction (SF) ≥27% and/or left ventricular ejection fraction (LVEF) >50% as determined by echocardiography or MUGA.
- Able to comply with scheduled follow-up and study procedures.
- Written informed consent from parents/legal representative, patient, and age-appropriate assent before any study specific screening procedures are conducted, according to local, regional or national law and legislation.
Exclusion criteria 11
- Previous cancer-specific treatment for neuroblastoma
- Have a known immediate or delayed hypersensitivity reaction or idiosyncrasy to the study drugs, or drugs chemically related to study treatment or excipients that contraindicate their participation, including conventional chemotherapeutics and dinutuximab beta.
- Current use of a prohibited medication or requires any of these medications during the study (See Section 8.1.2 for details): a. Treatment with corticosteroids is not allowed within 2 weeks prior to the first treatment course and until 1 week after the last treatment course with dinutuximab beta, except for life-threatening conditions. b. Vaccinations (including seasonal influenza) are not allowed during administration of dinutuximab beta and until 10 weeks after last treatment course. c. Concomitant use of intravenous (IV) immunoglobulins is not allowed. d. Concomitant use of cardioprotectant dexrazoxane is not allowed.
- Pregnancy or positive pregnancy test (urine or serum) in females of childbearing potential. Pregnancy test must be performed within 7 days prior to C1D1
- Breast feeding
- Sexually active participants not willing to use highly effective contraceptive method (pearl index <1) as defined in CTFG HMA 2020 (Appendix 2) during trial participation and until 6 months after end of protocol therapy
- Major surgery within 21 days prior to enrollment of the first treatment dose (open tumor biopsy or central line placement is not considered major surgery).
- History or documented evidence of severe acute or chronic infection or infectious illness requiring parenteral therapy unless fully healed (Grade <1) at least 4 weeks prior to start of treatment
- Patients with spinal cord involvement (symptomatic patients or if identified on imaging done to establish the diagnosis; there is no screening for spinal cord involvement for all patients).
- Any other disease, metabolic or psychological dysfunction, physical examination finding, or clinical laboratory finding giving reasonable suspicion of a disease or condition that contraindicates use of an investigational drug or places the patient at unacceptable risk from treatment complications.
- Patients with pre-existing grade 3-4 neurological toxicity.
Endpoints
Primary and secondary outcome measures (English text)
Primary endpoints 1
- Incidence of dose limiting toxicities (DLTs) associated with the combination of dinutuximab beta with GPOH (2 DLT evaluation cycles: first N6 and second N5 cycles) or rapid COJEC (first C and second B and A cycles) induction chemotherapy regimens.
Secondary endpoints 3
- Type, incidence, severity, seriousness and relationship to study medications for Grade 3 and 4 AEs, including laboratory abnormalities and severe adverse events (SAEs). • Cumulative incidence of treatment-related mortality and of disease-related mortality.
- Overall response during and after induction (primary tumor, metastases).
- mCR after induction treatment. mPR according to eligibility criteria to proceed to consolidation by HDC/ASCT: mPR for bone disease: MIBG uptake (or FDG-PET uptake for MIBG-non avid tumors) 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-non avid tumors). mPR for bone marrow disease: CR and/or MD according to INRC. mPR for other metastatic sites
Investigational products
Investigational medicinal products (IMPs), comparators, placebo, auxiliary
Test 10
Mitoxana 1 g Powder for Sterile Concentrate
PRD7253987 · Product
- Active substance
- Ifosfamide
- Pharmaceutical form
- SOLUTION FOR INJECTION/INFUSION
- Route of administration
- CONCENTRATE FOR SOLUTION FOR INFUSION
- Authorisation status
- Authorised
- ATC code
- L01AA06 — IFOSFAMIDE
- Marketing authorisation
- PA 2299/028/001
- MA holder
- BAXTER HOLDING B.V.
- MA country
- Ireland
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
Carboplatin 10 mg/ml concentrate for solution for infusion
PRD7277959 · Product
- Active substance
- Carboplatin
- Pharmaceutical form
- SOLUTION FOR INFUSION
- Route of administration
- CONCENTRATE FOR SOLUTION FOR INFUSION
- Authorisation status
- Authorised
- ATC code
- L01XA02 — CARBOPLATIN
- Marketing authorisation
- PA 2059/032/001
- MA holder
- FRESENIUS KABI DEUTSCHLAND GMBH
- MA country
- Ireland
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
Qarziba 4.5 mg/mL concentrate for solution for infusion
PRD5240131 · Product
- Active substance
- Dinutuximab Beta
- Pharmaceutical form
- SOLUTION FOR INFUSION
- Route of administration
- CONCENTRATE FOR SOLUTION FOR INFUSION
- Authorisation status
- Authorised
- ATC code
- L01FX06 — -
- Marketing authorisation
- EU/1/17/1191/001
- MA holder
- RECORDATI NETHERLANDS B.V.
- MA country
- EU
- Paediatric formulation
- No
- Orphan designation
- Yes
- Orphan designation number
- EU/3/12/1062
- Modified vs. Marketing Authorisation
- No
Vincristine Sulfate 1 mg/ml Solution for Injection or Infusion
PRD994485 · Product
- Active substance
- Vincristine Sulfate
- Pharmaceutical form
- SOLUTION FOR INJECTION/INFUSION
- Route of administration
- CONCENTRATE FOR SOLUTION FOR INFUSION
- Authorisation status
- Authorised
- ATC code
- L01CA02 — VINCRISTINE
- Marketing authorisation
- PA 0822/232/001
- MA holder
- PFIZER HEALTHCARE IRELAND
- MA country
- Ireland
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
Eldisine Powder for Solution for Injection 5.0 mg
PRD2100912 · Product
- Pharmaceutical form
- POWDER FOR SOLUTION FOR INJECTION
- Route of administration
- CONCENTRATE FOR SOLUTION FOR INFUSION
- Authorisation status
- Authorised
- ATC code
- L01CA03 — VINDESINE
- Marketing authorisation
- PL 06831/0117
- MA holder
- GENUS PHARMACEUTICALS LIMITED
- MA country
- XI
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
Cyclophosphamide 1000 mg Powder for Solution for Injection or Infusion
PRD1649381 · Product
- Active substance
- Cyclophosphamide
- Pharmaceutical form
- SOLUTION FOR INJECTION/INFUSION
- Route of administration
- CONCENTRATE FOR SOLUTION FOR INFUSION
- Authorisation status
- Authorised
- ATC code
- L01AA01 — CYCLOPHOSPHAMIDE
- Marketing authorisation
- PL 04416/1394
- MA holder
- SANDOZ LTD
- MA country
- XI
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
Doxorubicin Teva 2 mg/ml Concentrate for Solution for Infusion
PRD490161 · Product
- Active substance
- Doxorubicin Hydrochloride
- Pharmaceutical form
- SOLUTION FOR INFUSION
- Route of administration
- CONCENTRATE FOR SOLUTION FOR INFUSION
- Authorisation status
- Authorised
- ATC code
- L01DB01 — DOXORUBICIN
- Marketing authorisation
- PA 749/083/1
- MA holder
- TEVA PHARMA B.V.
- MA country
- Ireland
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
Etoposide 20 mg/ml Concentrate for Solution for Infusion
PRD1800135 · Product
- Active substance
- Etoposide
- Pharmaceutical form
- SOLUTION FOR INFUSION
- Route of administration
- CONCENTRATE FOR SOLUTION FOR INFUSION
- Authorisation status
- Authorised
- ATC code
- L01CB01 — ETOPOSIDE
- Marketing authorisation
- PA 2315/201/001
- MA holder
- ACCORD HEALTHCARE IRELAND LIMITED
- MA country
- Ireland
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
Dacarbazine Lipomed 200 mg powder for solution for injection or infusion
PRD994992 · Product
- Active substance
- Dacarbazine
- Substance synonyms
- DIC, DACARBAZINUM
- Pharmaceutical form
- SOLUTION FOR INJECTION/INFUSION
- Route of administration
- CONCENTRATE FOR SOLUTION FOR INFUSION
- Authorisation status
- Authorised
- ATC code
- L01AX04 — DACARBAZINE
- Marketing authorisation
- PA1760/001/001
- MA holder
- LIPOMED GMBH
- MA country
- Ireland
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
Cisplatin 1 mg/ml Concentrate for Solution for Infusion
PRD1168083 · Product
- Active substance
- Cisplatin
- Pharmaceutical form
- SOLUTION FOR INFUSION
- Route of administration
- CONCENTRATE FOR SOLUTION FOR INFUSION
- Authorisation status
- Authorised
- ATC code
- L01XA01 — CISPLATIN
- Marketing authorisation
- PA 0822/199/001
- MA holder
- PFIZER HEALTHCARE IRELAND
- MA country
- Ireland
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
Auxiliary 4
Glucose 5% Intravenous Infusion BP
PRD7577160 · Product
- Active substance
- Glucose
- Pharmaceutical form
- SOLUTION FOR INFUSION
- Route of administration
- INTRAVENIOUS INFUSION
- Authorisation status
- Authorised
- ATC code
- B05BA03 — CARBOHYDRATES
- Marketing authorisation
- PA2299/003/001
- MA holder
- BAXTER HOLDING B.V.
- MA country
- Ireland
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
Human Albumin Baxalta 50 g/l Solution for Infusion
PRD3234497 · Product
- Active substance
- Human Albumin Solution
- Substance synonyms
- ALBUMINE HUMAINE (SOLUTION D’), ALBUMIN SOLUTION, HUMAN
- Pharmaceutical form
- SOLUTION FOR INFUSION
- Route of administration
- INTRAVENIOUS INFUSION
- Authorisation status
- Authorised
- ATC code
- B05AA01 — ALBUMIN
- Marketing authorisation
- PA 2004/4/1
- MA holder
- BAXALTA INNOVATIONS GMBH
- MA country
- Ireland
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
PRD7195290 · Product
- Active substance
- Water for Injection
- Pharmaceutical form
- SOLVENT FOR PARENTERAL USE
- Route of administration
- INTRAVENOUS ADMINISTRATION
- Authorisation status
- Authorised
- ATC code
- V07AB — SOLVENTS AND DILUTING AGENTS, INCL. IRRIGATING SOLUTIONS
- Marketing authorisation
- PA2299/013/001
- MA holder
- BAXTER HOLDING B.V.
- MA country
- Ireland
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
Sodium Chloride 0.9% Intravenous Infusion BP
PRD7372533 · Product
- Active substance
- Sodium Chloride
- Pharmaceutical form
- SOLUTION FOR INFUSION
- Route of administration
- INTRAVENOUS ADMINISTRATION
- Authorisation status
- Authorised
- ATC code
- B05XX — OTHER I.V. SOLUTION ADDITIVES
- Marketing authorisation
- PA2299/002/001
- MA holder
- BAXTER HOLDING B.V.
- MA country
- Ireland
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
Sponsors and contacts
Sponsor organisations, regulatory contacts, third parties
Prinses Maxima Centrum voor Kinderoncologie B.V.
- Sponsor organisation
- Prinses Maxima Centrum voor Kinderoncologie B.V.
- Address
- Heidelberglaan 25
- City
- Utrecht
- Postcode
- 3584 CS
- Country
- Netherlands
Scientific contact point
- Organisation
- Prinses Maxima Centrum voor Kinderoncologie B.V.
- Contact name
- Paco Bautista
Public contact point
- Organisation
- Prinses Maxima Centrum voor Kinderoncologie B.V.
- Contact name
- secretariat TCD
Locations
7 EU/EEA countries · 13 investigational sites
By country
| Country | MS status | Planned subjects | Sites |
|---|---|---|---|
| Austria | Authorised, recruiting | 1 | 1 |
| France | Ongoing, recruiting | 10 | 3 |
| Germany | Authorised, recruitment pending | 10 | 3 |
| Italy | Ongoing, recruiting | 1 | 2 |
| Netherlands | Ongoing, recruiting | 8 | 1 |
| Poland | Authorised, recruitment pending | 1 | 1 |
| Spain | Ongoing, recruiting | 8 | 2 |
| Rest of world | — | 0 | — |
Investigational sites
St. Anna Kinderspital GmbH
Hemato-Oncology Station 2B, Kinderspitalgasse 6, Alsergrund, Vienna
Hopital de la Timone Enfants
Pediatric oncology, 265, Rue Saint-Pierre, Marseille
Institut Gustave Roussy
Children and adolescent oncology, 114 Rue Edouard Vaillant, 94800, Villejuif
Centre Oscar Lambret
Pediatric unit - Oncology, 3 Rue Frederic Combemale, 59000, Lille
Charite Universitaetsmedizin Berlin KöR
Klinik für Pädiatrie m.S. Onkologie und Hämatologie, Augustenburger Platz 1, Wedding, Berlin
University Of Cologne
Department of Pediatric Oncology and Hematology, Kerpener Strasse 34, Lindenthal, Cologne
Universitaetsmedizin Greifswald KöR
Department of Pediatrics, Pediatric Hematology and Oncology/BMT, Ferdinand-Sauerbruch-Strasse, 17489, Greifswald
IRCCS Istituto Giannina Gaslini
UOC Oncologia, Via Gerolamo Gaslini 5, 16147, Genoa
Ospedale Pediatrico Bambino Gesu
UOC Oncoematologia, Trapianto Emopoietico, Terapie Cellulari e Trial, Piazza Di Sant'onofrio 4, 00165, Rome
Prinses Maxima Centrum voor Kinderoncologie B.V.
Specialisten SO, Heidelberglaan 25, 3584 CS, Utrecht
Uniwersytecki Szpital Dzieciecy W Krakowie
Pediatric Oncology and Hematology Department, Ul. Wielicka 265, 30-663, Cracow
Country notifications
Trial-start, recruitment-start, end and early-termination notifications submitted per Member State
| Country | Trial start | Trial end | Recruitment start | Recruitment end | Early termination |
|---|---|---|---|---|---|
| Austria | 2026-04-22 | ||||
| France | 2025-09-08 | 2026-04-17 | |||
| Italy | 2026-01-29 | 2026-02-23 | |||
| Netherlands | 2024-12-02 | 2025-01-27 | |||
| Spain | 2025-08-06 | 2025-11-13 |
Application history
8 submissions — initial application plus substantial / non-substantial modifications
| # | Type | Code | Submitted | Reference MS | Conclusion | Decision date |
|---|---|---|---|---|---|---|
| 1 | INITIAL | IN | 2024-03-01 | Netherlands | Acceptable 2024-06-17
|
2024-06-22 |
| 2 | SUBSEQUENT ADDITION OF MSC | APP-2 | 2025-01-14 | Acceptable 2024-06-17
|
2025-04-10 | |
| 3 | SUBSEQUENT ADDITION OF MSC | APP-3 | 2025-01-14 | Acceptable 2024-06-17
|
2025-04-10 | |
| 4 | SUBSEQUENT ADDITION OF MSC | APP-4 | 2025-01-14 | Acceptable 2024-06-17
|
2025-03-21 | |
| 5 | SUBSEQUENT ADDITION OF MSC | APP-5 | 2025-04-15 | Acceptable 2024-06-17
|
2025-07-14 | |
| 6 | SUBSEQUENT ADDITION OF MSC | APP-6 | 2025-04-15 | 2025-07-10 | ||
| 7 | SUBSEQUENT ADDITION OF MSC | APP-7 | 2025-04-15 | Acceptable 2024-06-17
|
2025-07-14 | |
| 8 | NON SUBSTANTIAL MODIFICATION | NSM-1 | 2025-09-11 | Netherlands | Acceptable 2024-06-17
|
2025-09-11 |