Phase I Study of 131-I mIBG Followed by Nivolumab & Dinutuximab Beta Antibodies in Children With Relapsed/Refractory Neuroblastoma

Summary

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.

Conditions

• Neuroblastoma

Interventions

DRUG

Nivolumab

Nivolumab is a soluble protein consisting of 4 polypeptide chains, which include 2 identical heavy chains consisting of 440 amino acids and 2 identical light chains. Molecular weight is 146,221 daltons.

DRUG

Ch14.18/CHO

APN311 (ch14.18/CHO) is manufactured in a Good Manufacturing Practice (GMP) compliant facility of Polymun Scientific, Austria according to a state of the art aseptic manufacturing process based on a characterized and stable Chinese Hamster Ovary (CHO) cell line. After propagation of the working cell bank (WCB) in small volume vessels/bioreactors, manufacture is carried out in a 2500 L stirred tank reactor utilizing components which are free of material of animal or human origin.

Sponsors & Collaborators

• University College London Hospitals

  collaborator OTHER

• University of Wisconsin, Madison

  collaborator OTHER

• University Hospital Greifswald

  collaborator OTHER

• Solving Kids' Cancer US/EU

  collaborator UNKNOWN

• Joining Against Cancer in Kids

  collaborator UNKNOWN

• The Band of Parents

  collaborator UNKNOWN

• University Hospital Southampton NHS Foundation Trust

  lead OTHER

Principal Investigators

• Juliet Gray · Consultant Paediatric Oncologist

Study Design

Allocation

NA

Purpose

TREATMENT

Masking

NONE

Model

SINGLE_GROUP

Eligibility

Min Age

1 Year

Max Age

99 Years

Sex

ALL

Healthy Volunteers

Yes

Timeline & Regulatory

Start

2018-05-24

Primary Completion

2025-06-30

Completion

2026-09-30

FDA Drug

Yes

Countries

• United States
• United Kingdom

Study Locations