A trial looking at treatment for children and young people with neuroblastoma (HR-NBL-I/ESIOP NB 2002 06)

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Cancer type:

Children's cancers
Neuroblastoma

Status:

Results

Phase:

Phase 2/3

This trial looked at treatment for children and young people with a rare type of cancer called neuroblastoma that was high risk. 

High risk means the cancer would continue to grow or come back (recur) after treatment.

Cancer Research UK supported this trial.

More about this trial

Neuroblastoma develops in specialised nerve cells and most commonly starts in the nerve cells of the adrenal glands.
 
Children with neuroblastoma usually have a combination of treatments including:
  • surgery
  • chemotherapy
  • radiotherapy 
They may also have a stem cell transplant.
 
In this trial, researchers looked at many different treatments for high risk neuroblastoma.
 
The main aim was to find the best treatment.

Summary of results

Researchers were looking at several different treatments. As the results of each treatment is made available we will update this summary.

This trial was open for children and young people to join between 2002 and 2017. 

These results for interleukin 2 and dinutuximab were published in 2018.

About this trial
This was a phase 3 trial. It was a randomised trial. Everyone who took part was put into 1 of 2 treatment groups. 

Everyone who took part had already had induction treatment and consolidation treatment. This means they had chemotherapy to shrink the cancer followed by high dose chemotherapy and a stem cell transplant.  And this treatment had worked.

Everyone also had isotretinoin which is a standard treatment Open a glossary item to keep the cancer under control for longer. This is called maintenance treatment. Isotretinoin is a man made form of vitamin A.

406 children and young people joined this trial.

Of the 200 children and young people in the isotretinoin and dinutuximab group, 188 had treatment.

Of the 206 children and young people in the isotretinoin, dinutuximab and interleukin 2 group, 192 had treatment.

Results of immunotherapy treatment
In this part of the trial, researchers looked at 2 immunotherapy drugs called dinutuximab and interleukin 2 (IL-2). They work in slightly different ways. They stimulate the immune system to find and kill cancer cells.
 
They compared:
  • isotretinoin and dinutuximab 
  • isotretinoin, dinutuximab and interleukin 2
Interleukin 2 was given as an injection under the skin (subcutaneous injection). Dinutuximab was given as a drip into a vein (infusion) over 8 hours. 
They found that adding dinutuximab and interleukin 2 to isotretinoin didn’t increase the length of time the children and young people were free of their neuroblastoma. 
 
The average follow up after treatment in this trial was just under 5 years (4.7 years). 
 
3 years after treatment
The trial team looked at the percentage of children and young people who were alive and didn’t have a sign of neuroblastoma (event free survival). They found it was:
  • 56 out of every 100 children and young people (56%) in the isotretinoin and dinutuximab group
  • 60 out of every 100 children and young people (60%) in the isotretinoin, dinutuximab and interleukin 2 group

They also looked at the overall percentage of children and young people who were alive (overall survival) at 3 years after treatment. They found it was:
  • 69 out of every 100 children and young people (69%) in the isotretinoin and dinutuximab group 
  • 70 out of every 100 children and young people (70%) in the isotretinoin, dinutuximab and interleukin 2 group 
5 years after treatment
The team looked at the percentage of children and young people who were alive and had no sign of their neuroblastoma. They found it was:
  • 53 out of every 100 children and young people (53%) in the isotretinoin and dinutuximab group
  • 57 out of every 100 children and young people (57%) in the isotretinoin, dinutuximab and interleukin 2 group

The also looked at the overall percentage who were alive. They found it was:
  • 63 out of every 100 children and young people (63%) in the isotretinoin and dinutuximab group
  • 62 out of every 100 children and young people (62%) in the isotretinoin, dinutuximab and interleukin 2 group 
Side effects
The worst side effects in the isotretinoin and dinutuximab group were:
  • infection
  • a change to the way the liver works
  • a decline in general health
  • pain when having treatment
  • high temperature (fever)
  • an allergic reaction
The worst side effects in the isotretinoin, dinutuximab and interleukin 2 group were:
  • a decline in general health
  • high temperature (fever)
  • infection
  • pain when having treatment
  • a change to the way the liver works
  • diarrhoea
  • an allergic reaction
  • low blood pressure
  • blood leaking out of the smallest blood vessels (capillaries) 
  • hives
4 children and young people died due to side effects of treatment (2 in each group):
  • 1 from heart and lung problems
  • 1 from breathing problems caused by an infection
  • 1 from lung problems caused by a build up of scar tissue
  • 1 from a fungal infection 
Conclusion
The team concluded that adding interleukin 2 to isotretinoin and dinutuximab given over 8 hours didn’t improve treatment. It didn’t increase the length of time children and young people were free of their neuroblastoma. So it was no better than dinutuximab and isotretinoin. 
 
The side effects of this combination were also much worse than isotretinoin and dinutuximab only. 
 
Further research is ongoing with the combination of isotretinoin, interleukin 2 and dinutuximab. Researchers are looking at giving dinutuximab over a much longer period of time. And halving the dose of interleukin 2. The hope is that this will reduce the side effects.  
 
Until these results are available, the researchers say that isotretinoin and dinutuximab should be the standard treatment Open a glossary item for neuroblastoma after induction and consolidation treatment. 
 
Where this information comes from
We have based this summary on information from the research team. The information they sent us has been reviewed by independent specialists (peer reviewed Open a glossary item) and published in a medical journal. The figures we quote above were provided by the trial team who did the research. We have not analysed the data ourselves.

Recruitment start:

Recruitment end:

How to join a clinical trial

Please note: In order to join a trial you will need to discuss it with your doctor, unless otherwise specified.

Please note - unless we state otherwise in the summary, you need to talk to your doctor about joining a trial.

Chief Investigator

Dr Martin Elliot

Supported by

Cancer Research UK
Experimental Cancer Medicine Centre (ECMC)
NIHR Clinical Research Network: Cancer
Cancer Research UK Children's Cancer Trials Team, University of Birmingham

 

Other information

This is Cancer Research UK trial number CRUK/02/013.

Questions about cancer? Contact our information nurses

Freephone 0808 800 4040

Last review date

CRUK internal database number:

239

Please note - unless we state otherwise in the summary, you need to talk to your doctor about joining a trial.

Around 1 in 5 people take part in clinical trials

3 phases of trials

Around 1 in 5 people diagnosed with cancer in the UK take part in a clinical trial.

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