Nivolumab + Dinutuximab for Neuroblastoma

(MiniVan Trial)

Recruiting at 2 trial locations

Overseen By Danny Pratt

Age: Any Age

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 1

Waitlist Available

Sponsor: University Hospital Southampton NHS Foundation Trust

Stay on Your Current Meds

No Placebo Group

Breakthrough Therapy

Trial Summary

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

MIBG avid disease on imaging within 4 weeks to study entry.

≥ 3 months since any myeloablative chemotherapy / stem cell rescue

≥ 42 days since any other immunotherapy e.g. tumour vaccines. At least 3 half lives since last dose of any monoclonal antibody therapy.

Exclusion Criteria

Patients who have previously received ch14.18 (CHO or SP2/0) will not be excluded unless they have had severe or life threatening toxicity necessitating withdrawal of treatment previously or if they have a strong/neutralizing Human Antichimeric Antibody (HACA) (≥ 10 μg/ml)

Patients previously treated with Nivolumab or any other PD-1 or PD-L1 targeting antibodies will be excluded from the study

You have symptoms of heart failure or an irregular heartbeat that is not under control.

Treatment Details

Interventions

• 131-I mIBG (Radioactive Agent)
• Dinutuximab Beta Antibodies (Monoclonal Antibodies)
• Nivolumab (Checkpoint Inhibitor)

Trial Overview The study tests the safety and potential effectiveness of combining an anti-GD2 antibody (standard treatment) with two drugs: 131-I mIBG (a radioactive compound) and Nivolumab (an immune system-boosting drug). It's an adaptive trial in three cohorts, gradually increasing doses if safe, across hospitals in the UK, Germany, and USA.

Participant Groups

Group I: Treatment Experimental Treatment 2 Interventions

The dose and schedule of 131-I mIBG will be constant, and the doses of ch14.18/ CHO and Nivolumab determined by cohort: * Cohort I: 3 mg/kg Nivolumab (100% adult dose). No ch14.18/CHO. (3-6 patients) * Cohort II: 50mg/m2/cycle ch14.18/CHO (50% established Long Term Intervention (LTI) dose) and 3 mg/kg Nivolumab (100% adult dose) (3-6 patients) * Cohort III: 100mg/m2/cycle ch14.18/CHO (100% established LTI dose) and 3 mg/kg Nivolumab (100% adult dose) (initial 3-6 patients, expanded to 15 patient cohort if tolerated)

Who Is Running the Clinical Trial?

University Hospital Southampton NHS Foundation Trust

Lead Sponsor

Trials

221

Recruited

411,000+

University College London Hospitals

Collaborator

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1,221,000+

University of Wisconsin, Madison

Collaborator

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University Hospital Greifswald

Collaborator

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5

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Solving Kids' Cancer US/EU

Collaborator

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2

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110+

Joining Against Cancer in Kids

Collaborator

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1

Recruited

40+

The Band of Parents

Collaborator

Trials

2

Recruited

110+