Study Combining Dinutuximab Beta With Two Chemotherapy Regimens in Neuroblastoma

NCT06485947 | Recruiting Phase 1 DMC

• 2 other identifiers: SIOPEN-Pilot01.2023-509673-22-00
• Study Type: interventional
• Target: 38
• Locations: 1 country
• Sites: 1

Brief Summary

The goal of this clinical trial is to to assess the dose level of dinutuximab Beta (DB) when combined with 2 different induction chemotherapy regimens (named GPOH or rapid COJEC) in newly diagnosed high-risk neuroblastoma patients. The main question is:

• to assess the safety and tolerability and identifying the recommended phase II dose and/or the maximum tolerable dose of dinutiximab Beta when combined with 2 standard induction chemotherapy regimens Participants will receive:
• GPOH + dinutuximab beta infusion duration = 10 mg/m2 × 5 days (50 mg/m2/course) in 21-day treatment intervals.
• Rapid COJEC + dinutuximab beta infusion duration = 10 mg/m2 × 3 days (30 mg/m2/course) in 10-day treatment intervals.

Conditions

Neuroblastoma

Outcome Measures

Primary Outcomes (2)

• the incidence of dose limiting toxicities (DLTs) associated with the combination of Dinituximab Beta with GPOH chemotherapy regimen

  Number of DLT's per dose level of Dinituximab Beta

  Within first 63 days of treatment

• the incidence of dose limiting toxicities (DLTs) associated with the combination of Dinituximab Beta with rapid COJEC chemotherapy regimen

  Number of DLT's per dose level of Dinituximab Beta

  Within first 50 days of treatment

Secondary Outcomes (4)

• overall response rate during after Dinituximab Beta with GPOH chemotherapy regimen

  126 days

• metastatic response rate after Dinituximab Beta with GPOH chemotherapy regimen

  126 days

• overall response rate during after Dinituximab Beta with rapid COJEC chemotherapy regimen

  80 days

• metastatic response rate after Dinituximab Beta with rapid COJEC chemotherapy regimen

  80 days

Other Outcomes (2)

• event free survival (EFS) from the date of enrollment

  5 years

• overall survival (OS) from the date of enrollment

  5 years

Study Arms (2)

Dinutuximab Beta with chemotherapy treatment called GPOH

EXPERIMENTAL

Dinutuximab Beta will be administered at a fixed daily dose of 10 mg/m2 given as a 24-hour continuous infusion for a scheduled number of days within each treatment cycle of chemotherapy.

Biological: Dinutuximab beta; Drug: chemotherapy treatment called GPOH

Dinutuximab Beta with chemotherapy treatment called rapid COJEC

EXPERIMENTAL

Dinutuximab Beta will be administered at a fixed daily dose of 10 mg/m2 given as a 24-hour continuous infusion for a scheduled number of days within each treatment cycle of chemotherapy.

Biological: Dinutuximab beta; Drug: chemotherapy treatment called rapid COJEC

Interventions

Dinutuximab beta BIOLOGICAL

Combination of immunotherapy with standard chemotherapy

Also known as: Immunotherapy

Dinutuximab Beta with chemotherapy treatment called GPOH; Dinutuximab Beta with chemotherapy treatment called rapid COJEC

chemotherapy treatment called GPOH DRUG

chemotherapy treatment called GPOH

Dinutuximab Beta with chemotherapy treatment called GPOH

chemotherapy treatment called rapid COJEC DRUG

chemotherapy treatment called rapid COJEC

Dinutuximab Beta with chemotherapy treatment called rapid COJEC

Eligibility Criteria

• Age: 18 Months - 18 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Established diagnosis of neuroblastoma Stage M, according to the SIOPEN modified International Neuroblastoma Risk Group (INRG) and to the INSS criteria (Appendix 1).
• Age ≥18 months and \<18 years.
• Body weight \>12 kg.
• Alanine transaminase and aspartate aminotransferase \<10 × upper limit of normal (ULN), total bilirubin \<1.5 × ULN based on age specific reference ranges.
• Calculated glomerular filtration rate \> 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.

You may not qualify if:

• Previous cancer-specific treatment for neuroblastoma.
• Current use of a prohibited medication or requires any of these medications during the study:
• Treatment with corticosteroids is not allowed within 2 weeks prior to the first block of chemotherapy and until 1 week after the last treatment course with dinutuximab beta, except for life-threatening conditions.
• Vaccinations (including seasonal influenza) are not allowed during administration of dinutuximab beta and until 10 weeks after last treatment course.
• Concomitant use of intravenous (IV) immunoglobulins is not allowed.
• Concomitant use of cardioprotectant dexrazoxane is not allowed.
• Pregnancy or positive pregnancy test in females of childbearing potential.
• Breast feeding.
• Sexually active participants not willing to use highly effective contraceptive method
• Major surgery within 21 days prior to the first treatment dose
• History or documented evidence of severe acute or chronic infection or infectious illness requiring parenteral therapy unless fully healed
• Patients with spinal cord involvement
• 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
• Have a known immediate or delayed hypersensitivity reaction to study drugs

Sponsors & Collaborators

• Princess Maxima Center for Pediatric Oncology: lead
• EUSA Pharma, Inc.: collaborator

Study Sites (1)

Princess Maxima center for pediatric oncology

Utrecht, Utrecht, 3584 CS, Netherlands

RECRUITING

MeSH Terms

Conditions

Neuroblastoma

Interventions

dinutuximab; Immunotherapy

Condition Hierarchy (Ancestors)

Neuroectodermal Tumors, Primitive, Peripheral; Neuroectodermal Tumors, Primitive; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue

Intervention Hierarchy (Ancestors)

Immunomodulation; Biological Therapy; Therapeutics

Study Officials

• Holger Lode, MD, PhD

  Princess Maxima Center for Pediatric Oncology

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Jorden Veeneman, PhD

CONTACT

+31650173417; trialmanagement@prinsesmaximacentrum.nl

Paco Bautista, MD, PhD

CONTACT

0031650006606; f.j.bautista@prinsesmaximacentrum.nl

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 15, 2024
• First Posted: July 3, 2024
• Study Start: January 28, 2025
• Primary Completion (Estimated): July 1, 2030
• Study Completion (Estimated): December 1, 2031
• Last Updated: July 8, 2025

Record last verified: 2025-07

Data Sharing

• IPD Sharing: Will share
• Shared Documents: CSR
• Time Frame: Within 6 months from study end.

Locations

NL (1)