Nivolumab + Dinutuximab for Neuroblastoma
(MiniVan Trial)
Trial Summary
Will I have to stop taking my current medications?
The trial protocol does not specify if you must stop taking your current medications. However, you cannot participate if you are taking systemic corticosteroids or other immunosuppressive agents within 14 days before the study.
What data supports the effectiveness of the drug combination Nivolumab + Dinutuximab for treating neuroblastoma?
Research shows that the drug dinutuximab beta, when used with other treatments, improves survival in patients with high-risk neuroblastoma. Additionally, combining dinutuximab beta with immune checkpoint inhibitors like Nivolumab has shown promising results in preclinical models, suggesting a potential benefit for patients with neuroblastoma.12345
Is the combination of Nivolumab and Dinutuximab safe for treating neuroblastoma?
Dinutuximab, used in treating high-risk neuroblastoma, is generally safe when managed with supportive care, though it can cause pain, allergic reactions, fever, and capillary leak syndrome (fluid leakage from small blood vessels). Safety data for Nivolumab in this specific combination is not provided, but Dinutuximab has been well-tolerated in clinical settings.46789
How is the drug combination of Nivolumab and Dinutuximab Beta unique for treating neuroblastoma?
This drug combination is unique because it combines Nivolumab, an immune checkpoint inhibitor that helps the immune system attack cancer cells, with Dinutuximab Beta, an antibody that targets neuroblastoma cells, potentially enhancing the immune response against the tumor. This approach is novel as it leverages both immune system activation and direct targeting of cancer cells, which may improve outcomes for patients with high-risk or relapsed neuroblastoma.12345
What is the purpose of this trial?
Neuroblastoma, the most common extra-cranial solid tumour in children, remains one of the major challenges in paediatric oncology. A promising way to further improve outcome in this disease appears to be the development of adjuvant therapeutic strategies. In this research the anti-GD2 antibody, which is a standard treatment, is to be combined with 131-l Metaiodobenzylguanidine (mlBG) and anti-Programmed Cell Death Protein 1 (anti-PD1) antibody Nivolumab - the investigated drugs - with the aim of generating sustained anti-neuroblastoma immunity. In particular it will be determined the safety and tolerability of the novel combination as well as documented any evidence of efficacy in paediatric patients with relapsed and refractory high risk neuroblastoma.This study is sponsored by the University Hospital Southampton and will take place in 4 hospitals in the United Kingdom, Germany and USA. The estimated duration of the study is 2 years, starting in December 2016.This is an "adaptive study". Such design uses accumulating of data from the ongoing trial to modify aspects of the study (e.g. duration, number of treatments) without undermining its validity or integrity. There will be 3 cohorts of patients. As safety of Nivolumab is well established, Cohort 1 will assess its safety and tolerability in combination with 131-l mlBG. Cohort 2 will then add anti-GD2 to the drug combination, assessing safety and tolerability. Cohort 3 will escalate all 3 agents to the full 100% dose level to assure safety for expanded analyses of clinical and laboratory data at that dose level.Patients will initially be recruited into Cohort 1. Patients must have completed at least 12 weeks of trial treatment without reaching a Dose Limiting Toxicity before a patient can be recruited to the next cohort.A minimum of 3 evaluable patients will be treated in cohorts 1-3. Assuming the full dose combination therapy (cohort) is tolerable, 15 evaluable patients will be treated.
Research Team
Juliet Gray
Principal Investigator
Consultant Paediatric Oncologist
Eligibility Criteria
This trial is for children with relapsed/refractory high-risk neuroblastoma. They must have a certain type of active disease visible on imaging, be past specific treatments like myeloablative chemotherapy, and meet health criteria such as adequate organ function and performance status. Children with severe prior reactions to similar therapies or certain medical conditions are excluded.Inclusion Criteria
Exclusion Criteria
Timeline
Screening
Participants are screened for eligibility to participate in the trial
Cohort 1 Treatment
Patients receive 131-I MIBG and Nivolumab to assess safety and tolerability
Cohort 2 Treatment
Patients receive 131-I MIBG, Nivolumab, and anti-GD2 to assess safety and tolerability
Cohort 3 Treatment
Patients receive full dose of 131-I MIBG, Nivolumab, and anti-GD2 for expanded safety analysis
Follow-up
Participants are monitored for safety and effectiveness after treatment
Treatment Details
Interventions
- 131-I mIBG
- Dinutuximab Beta Antibodies
- Nivolumab
Find a Clinic Near You
Who Is Running the Clinical Trial?
University Hospital Southampton NHS Foundation Trust
Lead Sponsor
University College London Hospitals
Collaborator
University of Wisconsin, Madison
Collaborator
University Hospital Greifswald
Collaborator
Solving Kids' Cancer US/EU
Collaborator
Joining Against Cancer in Kids
Collaborator
The Band of Parents
Collaborator