A Multi-Arm, Platform Trial For Relapsed Neuroblastoma

NCT07334301 | Recruiting Phase 1 DMC

• 1 other identifier: RG_22-136
• Study Type: interventional
• Target: 160
• Locations: 4 countries
• Sites: 22

Brief Summary

Neuroblastoma is one of the most common solid childhood tumours, and a major cause of cancer-related death in children. More than 1200 children/young adults a year are diagnosed in USA and Europe. Around 600 of these cases are considered high-risk, which means the cancer is more difficult to treat successfully. Despite improvements in survival over recent decades, a significant proportion of patients with high-risk neuroblastoma have disease that does not respond to standard treatments (refractory neuroblastoma) or comes back after completion of standard frontline treatment (relapsed neuroblastoma). Therefore, there is a need to develop new treatment strategies and test new drugs to improve outcomes for children with neuroblastoma. Aims Of The BEACON2 Trial

• To improve survival for patients with relapsed neuroblastoma by developing new treatment combinations
• To evaluate new treatment combinations in relapsed neuroblastoma, within a phase I/II trial that can impact clinical practice, while also allowing dose confirmation for new promising combinations
• To evaluate the safety, activity, efficacy and impact on quality of life of these new treatment combinations in relapsed neuroblastoma patients
• To improve our understanding of relapsed neuroblastoma biology and advance the development of targeted therapies using biomarkers, by conducting a comprehensive biomarker sample collection. Trial Design BEACON2 is a randomised phase I/phase II, open label, international trial. The trial will have two tiers: Tier 1 will be the main randomisation for two treatment arms initially. Participants will be randomised at trial entry to receive one of the available regimens, treatment A or treatment B. Tier 2 will include smaller dose expansion/confirmation cohorts for more novel experimental treatment combinations (Arm C and future arms), with the potential for them to be moved to Tier 1. Current Tier 1 (Randomisation Tier) Treatment Arms in the BEACON2 Trial: Arm A: dbIT Treatment with dinutuximab beta, irinotecan, and temozolomide, 3 weekly x12 cycles Arm B: BIT Treatment with bevacizumab, irinotecan, and temozolomide, 3 weekly x12 cycles Current Tier 2 (Registration Only Tier) Treatment Arms in the BEACON2 Trial: Arm C: dbBIT Treatment with dinutuximab beta, bevacizumab, irinotecan, and temozolomide, 3 weekly x12 cycles Patient Population and Sample Size Patients aged ≥1 years of age with relapsed neuroblastoma. For each arm in Tier 1, up to 75 patients will be recruited to complete phase 2 investigations. For each arm in Tier 2, 10 patients will be recruited to complete phase I investigations. Approximately 160 participants are initially planned, 75 in each arm of Tier 1 and 10 participants for one dose-confirmation cohort in Tier 2. The study is expected to recruit patients for 3 years, and then finish patient follow-up after an additional 5 years. Translational Sub-study / Biological Studies It is standard of care for patients diagnosed with relapsed neuroblastoma to:
• Have had a tumour sample collected at point of initial diagnosis (either during biopsy or surgery)
• Have bloods collected before they start and during treatment for their relapsed neuroblastoma
• Have a bone aspirate/trephine procedure in order to help confirm relapse. These samples provide very important opportunities for further research, and the study investigators would like to make full use of these opportunities by collecting the analysis already performed on these samples and collect some additional samples (at the same time as the standard ones) to learn and understand more about neuroblastoma and its treatment. Samples will undergo research analysis at the national SIOPEN reference laboratories.

Conditions

Relapsed Neuroblastoma

Keywords

Neuroblastoma

Outcome Measures

Primary Outcomes (2)

• Progression-Free Survival time

  • Progression-Free Survival time (as per International Neuroblastoma Response Criteria (PD Progressive disease, SD Stable disease, MR Minor response, PR Partial response, CR Complete response) INRC 2017) - for Tier 1 (randomised comparison)

  From date of randomization until the date of first documented failure event (progression or death), assessed up to 60 months.

• Occurrence of dose-limiting toxicities to definition of a safe and tolerable combination regimen

  Tier 2 (dose expansion-confirmation cohorts): Definition of a safe and tolerable (i.e. \</= 3 dose-limiting toxicities) combination regimen

  From date of randomization until the date of first documented failure event (progression or death), assessed up to 60 months.

Secondary Outcomes (6)

• Best objective response

  At the end of the last treatment cycle, up to 12 cycles (each cycle is 21 days)

• Clinical benefit

  At the end of the last treatment cycle, up to 12 cycles (each cycle is 21 days)

• Time response to progression

  From date of response (Complete Response, Partial Response or Minor Response as per INRC) until the date of first documented failure event (progression or death), assessed up to 60 months.

• Overall Survival time

  From date of trial entry until the date of first documented failure event (progression or death), assessed up to 60 months.

• Quality of life of patients measured by Peds-QL questionnaires

  At the end of the last treatment cycle, up to 12 cycles (each cycle is 21 days)

Other Outcomes (3)

• Quality of life of caregivers measured by Peds-QL questionnaires

  At the end of the last treatment cycle, up to 12 cycles (each cycle is 21 days)

• Correlation between objective response using INRC 2017 and PFS/OS

  At the end of the last treatment cycle, up to 12 cycles (each cycle is 21 days)

• Changes in circulating biomarkers and tumour molecular profiles in tumour and blood

  At the end of the last treatment cycle, up to 12 cycles (each cycle is 21 days)

Study Arms (3)

Arm A: dinutuximab, irinotecan and temozolomide (dbIT)

ACTIVE COMPARATOR

Drug: Dinutuximab beta; Drug: Irinotecan (drug); Drug: Topotecan; Drug: Temozolomide (TMZ)

Arm B: bevacizumab, irinotecan and temozolomide (BIT)

EXPERIMENTAL

Drug: Bevacizumab; Drug: Irinotecan (drug); Drug: Topotecan; Drug: Temozolomide (TMZ)

Arm C: dinutuximab, bevacizumab, irinotecan and temozolomide (dbBIT)

EXPERIMENTAL

Drug: Bevacizumab; Drug: Dinutuximab beta; Drug: Irinotecan (drug); Drug: Topotecan; Drug: Temozolomide (TMZ)

Interventions

Bevacizumab DRUG

Bevacizumab

Arm B: bevacizumab, irinotecan and temozolomide (BIT); Arm C: dinutuximab, bevacizumab, irinotecan and temozolomide (dbBIT)

Dinutuximab beta DRUG

Dinutuximab beta

Arm A: dinutuximab, irinotecan and temozolomide (dbIT); Arm C: dinutuximab, bevacizumab, irinotecan and temozolomide (dbBIT)

Irinotecan (drug) DRUG

Irinotecan

Arm A: dinutuximab, irinotecan and temozolomide (dbIT); Arm B: bevacizumab, irinotecan and temozolomide (BIT); Arm C: dinutuximab, bevacizumab, irinotecan and temozolomide (dbBIT)

Topotecan DRUG

Topotecan

Arm A: dinutuximab, irinotecan and temozolomide (dbIT); Arm B: bevacizumab, irinotecan and temozolomide (BIT); Arm C: dinutuximab, bevacizumab, irinotecan and temozolomide (dbBIT)

Temozolomide (TMZ) DRUG

Temozolomide capsule

Arm A: dinutuximab, irinotecan and temozolomide (dbIT); Arm B: bevacizumab, irinotecan and temozolomide (BIT); Arm C: dinutuximab, bevacizumab, irinotecan and temozolomide (dbBIT)

Eligibility Criteria

• Age: 1 Year+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Disease specific
• Histologically proven neuroblastoma as per International Neuroblastoma Staging System (INSS)\[1\] definition
• High risk relapsed neuroblastoma (relapsed or progressed after being defined as High Risk at any time following diagnosis or progressed/relapsed as high-risk neuroblastoma)
• Measurable disease by cross sectional imaging or evaluable disease (uptake on MIBG scan with or without bone marrow histology), as per INRC \[2, 3\]. Participants with only bone marrow detectable disease (bone marrow aspirate or trephine) are NOT eligible for the study General
• Age ≥1 year
• Signed informed consent from participant, parent or guardian Performance and organ function
• Performance Status
• o Lansky (for patients ≤12 years of age) or Karnofsky (for those \>12) ≥ 50%, (Participants who are unable to walk because of paralysis, but who are able to sit upright unassisted in a wheelchair, will be considered ambulatory for the purpose of assessing performance score)
• Life expectancy of ≥12 weeks
• Bone marrow function (within 72 hours prior to randomisation):
• Platelets ≥ 50 x 109/L (unsupported for 72 hours)
• ANC ≥ 0.50 x 109/L (no G-CSF support for 72 hours)
• Haemoglobin \> 8 g/dL (transfusions allowed)
• Renal function (within 72 hours prior to randomisation):
• Absence of clinically significant proteinuria (either early morning urine dipstick ≤ 2+) or if dipstick urinalysis shows \> 2+ proteinuria, protein: creatinine (Pr/Cr) ratio must be \< 0.5 or a 24 hour protein excretion must be \< 0.5g

You may not qualify if:

• Known contraindication or hypersensitivity to:
• Any study drug or component of the formulation
• Chinese hamster ovary products or other recombinant human or humanised antibodies.
• Participants with mild previous hypersensitivity reactions to anti-GD2 antibodies may be included, but those with severe (or G4) hypersensitivity reactions to anti-GD2 antibodies will be excluded.
• Clinically significant neurological toxicity, uncontrolled seizures or objective peripheral neuropathy (\> grade 2). (Unresolved neurological deficits from previous spinal cord compression or surgeries are acceptable). Participants with previous ≥ Grade 3 motor neurotoxicity secondary to anti-GD2 are excluded, even if recovered
• Prior severe arterial thrombo-embolic events (e.g. cardiac ischemia, cerebral vascular accident, peripheral arterial thrombosis) or any ongoing arterial thrombo-embolic events
• A history of (noninfectious) pneumonitis requiring steroids, or current pneumonitis.
• Patients that are allergic to all therapies for Pnemocystis jirovecii pneumonia and can thus not receive prophylaxis for PJP
• Uncontrolled infection
• Inadequate recovery from prior surgery with ongoing ≥ Grade 3 surgical complications. Grade ≥ 2 wound dehiscence.
• Recent surgical procedures (at start of trial treatment). Patient can be randomised up to 48hr prior to these periods being completed provided that trial treatment only starts after complying with all of them:
• Core biopsies within previous 24hr
• Open excisional biopsies within previous 48hr
• Major surgery within previous 2 weeks
• Bone marrow aspirates/trephines, within previous 48hr

Sponsors & Collaborators

• University of Birmingham: lead

Study Sites (23)

Sydney Children's Hospital (SCH)

Sydney, Australia

NOT YET RECRUITING

St. Anna Children´s Hospital

Vienna, Austria

NOT YET RECRUITING

Cliniques Universitaires Saint-Luc (CUSL)

Brussels, Belgium

NOT YET RECRUITING

Starship Children's Hospital (SSH)

Auckland, New Zealand

NOT YET RECRUITING

Royal Aberdeen Children's Hospital

Aberdeen, United Kingdom

RECRUITING

Royal Belfast Hospital for Sick Children

Belfast, United Kingdom

NOT YET RECRUITING

Birmingham Children's Hospital

Birmingham, United Kingdom

RECRUITING

Bristol Royal Hospital for Children

Bristol, United Kingdom

RECRUITING

Addenbrookes Hospital

Cambridge, United Kingdom

RECRUITING

Children's Hospital for Wales

Cardiff, United Kingdom

RECRUITING

Royal Hospital for Sick Children

Edinburgh, United Kingdom

NOT YET RECRUITING

Royal Hospital for Children

Glasgow, United Kingdom

NOT YET RECRUITING

Leeds General Infirmary

Leeds, United Kingdom

RECRUITING

Alder Hey Hospital

Liverpool, United Kingdom

RECRUITING

Great Ormond Street Hospital

London, United Kingdom

RECRUITING

University College London Hospital

London, United Kingdom

NOT YET RECRUITING

Royal Manchester Children's Hospital

Manchester, United Kingdom

RECRUITING

Royal Victoria Infirmary

Newcastle upon Tyne, United Kingdom

RECRUITING

Nottingham Children's Hospital

Nottingham, United Kingdom

NOT YET RECRUITING

John Radcliffe Hospital

Oxford, United Kingdom

NOT YET RECRUITING

Sheffield Children's Hospital

Sheffield, United Kingdom

RECRUITING

Southampton General Hospital

Southampton, United Kingdom

RECRUITING

Royal Marsden Hospital

Sutton, United Kingdom

RECRUITING

Related Publications (1)

• Brodeur GM, Pritchard J, Berthold F, Carlsen NL, Castel V, Castelberry RP, De Bernardi B, Evans AE, Favrot M, Hedborg F, et al. Revisions of the international criteria for neuroblastoma diagnosis, staging, and response to treatment. J Clin Oncol. 1993 Aug;11(8):1466-77. doi: 10.1200/JCO.1993.11.8.1466.

  PMID: 8336186 BACKGROUND

MeSH Terms

Conditions

Neuroblastoma

Interventions

Bevacizumab; dinutuximab; Irinotecan; Pharmaceutical Preparations; Topotecan; Temozolomide

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)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Camptothecin; Alkaloids; Heterocyclic Compounds; Dacarbazine; Triazenes; Organic Chemicals; Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring

Central Study Contacts

Trial Coordinator

CONTACT

44 (0) 121 4143799; beacon2@trials.bham.ac.uk

Study Design

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

Model Details: Multi Arm Multi Stage (MAMS) design

Study Record Dates

• First Submitted: September 12, 2025
• First Posted: January 12, 2026
• Study Start: November 11, 2024
• Primary Completion (Estimated): December 31, 2030
• Study Completion (Estimated): December 31, 2030
• Last Updated: January 12, 2026

Record last verified: 2026-01

Locations

GB (19); NZ (1); BE (1); AU (1)