A study looking at treatment for high risk neuroblastoma (HR/NBL2/SIOPEN)
Cancer type:
Status:
Phase:
This study is looking at chemotherapy, radiotherapy and stem cell transplants for people with high risk neuroblastoma.
It is open to children and young people with a high risk 
that:
- is newly diagnosed, and
- you are about to start chemotherapy
Please note, we use the term ‘you’ in this summary, but of course if you are a parent of a child with cancer, we are referring to your child.
More about this trial
Doctors can treat high risk neuroblastoma with:
- induction chemotherapy to shrink the tumour
- followed by
surgery to remove the main tumour - then
high dose chemotherapy and a stem cell transplant - then
radiotherapy to remove any tumour left - then an
immunotherapy as maintenance treatment
In this study you have all parts of the treatment. The study team are looking at the following parts of treatment:
- induction chemotherapy
- high dose chemotherapy and stem cell transplant
- radiotherapy
Induction chemotherapy
The is a combination of drugs called RAPID COJEC. Researchers think that another combination of chemotherapy called GOPH might be better. Doctors in Germany already use GOPH.
In this part of the study half the children have RAPID COJEC. The other half have GOPH.
High dose chemotherapy and stem cell transplant
High dose chemotherapy can damage the which makes your blood cells. So to help with this, before having high dose chemotherapy the doctor takes blood to get stem cells (). You have a stem cell transplant after you have the high dose chemotherapy.
The standard treatment is to give one treatment of high dose chemotherapy and a stem cell transplant. Researchers think that giving an extra treatment of high dose chemotherapy with 2 stem cell transplants might be better.
In this part of the study half the children have the standard treatment. The other half have an extra treatment of high dose chemotherapy and 2 stem cell transplants.
Radiotherapy
Researchers are also looking at adding an extra treatment of radiotherapy to the standard treatment. This is a booster dose. They think it might be better than the standard treatment.
In this part of the study half the children have the standard radiotherapy. The other half have the standard radiotherapy and a booster dose.
The aims of this study are to find out whether:
- GOPH is better than RAPID COJEC as induction chemotherapy
- 2 treatments of high dose chemotherapy and 2 stem cell transplants are better than one of each
- a booster dose added to standard radiotherapy is better than standard radiotherapy
Who can enter
The following bullet points are a summary of the entry conditions for this study. Talk to your doctor or the study team if you are unsure about any of these. They will be able to advise you.
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There are a number of parts in this study. To go into each part there are different entry conditions. At each part your doctor will know what the entry conditions are. They will go through them with you to see if you are able to join that part. The entry conditions below are for when you join the study from the start. |
Who can take part
You may be able to join this study if have high risk neuroblastoma that has spread to nearby tissue or to another part of the body. One of the following apply, you are:
- over 1 year old if you have stage 4 (M)
or
- between 1 year old and 1 ½ years old if you have stage 4s (Ms)
or
- any age with stage 3 (L2), stage 4 (M), stage 4s (Ms) and your neuroblastoma has a large number of the
gene MYCN
And both of the following apply. You:
- have satisfactory blood test results
- are willing to use contraception during treatment and for a time after if you or your partner could become pregnant. That is if you are at an age where you are sexually active.
Who can’t take part
Cancer related
You cannot join this study if any of these apply. You:
- have had chemotherapy. This is apart from 1
treatment cycle of etoposide and carboplatin - are taking part in another clinical trial
Medical conditions
You cannot join this study if any of these apply. You:
- are unable to pass urine due to a blockage
- have major
heart problems such as heart failure - have a lot of damage to the nerves in your hands and feet (
peripheral neuropathy ) - have an
inherited disease that affects your nerves (Demyelinating form of Charcot-Marie-Tooth syndrome) - have a hearing problem
- are having medicine called phenytoin to prevent seizures (fits)
- have a problem with your heart and lung that means you are not able to have a lot of fluid in your body
- are short of breath when resting or the result of a test that shows how much
oxygen there is in the blood is less than 95%. Your doctor will test for this. - have an ongoing problem with inflammation of the bowel and or you have a blockage in the bowel
- are taking St John’s Wort
- have any other medical condition, mental health problem or a social situation that can affect you taking part
Other
You cannot join this study if any of these apply. You are:
- allergic to peanuts or soya
- allergic to any of the treatments used or any of their ingredients
- having the yellow fever vaccines or any
live vaccine - pregnant or breastfeeding
Trial design
This is an international phase 3 study. The team need 800 people worldwide to take part with 206 people in the UK.
There are 5 parts to the study. After each part your doctor will examine you again. This is to make sure you are able to go on to the next part.
Part 1 – Induction
In this part a computer puts you into a treatment group. This is randomisation. Neither you nor your doctor chooses which group you are in. The 2 chemotherapy treatment groups are:
- RAPID COJEC
- GPOH
RAPID COJEC
In this group you have the following chemotherapy:
- vincristine
- carboplatin
- etoposide
- cisplatin
- cyclophosphamide
GPOH
In this group you have the following chemotherapy:
- vindesine
- cisplatin
- etoposide
- vincristine
- dacarbazine
- ifosfamide
- doxorubicin
In each group you have all the chemotherapy as a drip into a vein through a or a .
Everyone has as an injection under the skin. This is a growth factor that helps your bone marrow make blood cells.
Your doctor will tell you when and how often you have the treatment.
Everyone has stem cells collected through a drip into a vein. This can be either during or just after this treatment. Your doctor will talk to you about this before you have the stem cells taken.
TEMIRI with DB
If the induction treatment did not work well enough you have further treatment. You have temozolomide, irinotecan and dinutuximab beta. Temozolomide is a capsule. Your doctor will tell you how many capsules to take and how often to take them. You have irinotecan and dinutuximab beta as a drip into a vein. Your doctor will tell you when and how often you have it.
You then have:
- thiotepa
- busulfan and melphalan
- stem cell transplant
Your doctor can tell you more about the treatments, how long they take and how often you have them.
Part 2 - Surgery
Whether you take part in the study or not you will probably have surgery to remove the neuroblastoma after chemotherapy. You will be in hospital for 1 to 3 weeks. Your doctor will tell more about the surgery.
Part 3 – High dose chemotherapy and stem cell transplant
In this part a computer puts you into a treatment group. This is randomisation. Neither you nor your doctor chooses which group you are in. The 2 high dose chemotherapy treatment groups are:
- thiotepa, busulfan and melphalan
- busulfan and melphalan
After the high dose chemotherapy everyone has their own stem cells put back into their blood stream.
You have all these treatments as a drip into a vein through a central line or a PICC line.
Your doctor can tell you more about the treatments, how long they take and how often you have them.
Part 4 – Radiotherapy
Everyone has radiotherapy.
The 2 radiotherapy treatment groups are:
- standard radiotherapy
- standard radiotherapy with an extra dose of radiotherapy (a booster)
A computer puts you into a treatment group. Your doctor will talk to you about this.
Before your radiotherapy you have a planning appointment. This is to make sure the radiotherapy goes exactly where it is needed.
You have radiotherapy once a day Monday to Friday for 2½ weeks.
Part 5 – Maintenance treatment
After radiotherapy everyone has treatment to prevent the neuroblastoma coming back. This is a standard treatment.
Your doctor will tell about:
- what the treatment is
- how often you have it
- when you have it
- the side effects
Hospital visits
You see the doctor to have tests before taking part. These include:
- a
physical examination - blood tests
- urine test
- heart scan (
ECHO ) - scans such as a CT scan, an MRI scan, an ultrasound, a mIBG scan or PET-CT scan. Your doctor chooses which scans are best for you.
- bone marrow test
- hearing test
You are in hospital for most of your treatment.
Your doctor sees your regularly during treatment.
After treatment you see the doctor:
- every 3 months for a year
- every 4 months for years 2 and 3
- every 6 months for years 4 and 5
Your doctor will then tell you how often they want to see you.
Side effects
The study team monitor you during treatment and afterwards. Contact your advice line or tell your doctor or nurse if any side effects are bad or not getting better.
The side effects of dinutuximab beta include:
- temporary changes to your eyesight and vision
- cough
- fast heartbeat
- drop in blood pressure
- feeling or being sick
- constipation or diarrhoea
- swelling
- too much fluid in your body if this is severe it can cause low blood pressure and difficulty breathing
- pain
- nerve problems
- a drop in blood cells causing an increased risk of infection, bruising and bleeding
We have information about the side effects of:
- vincristine
- carboplatin
- cyclophosphamide
- vindesine
- cisplatin
- etoposide
- dacarbazine
- ifosfamide
- doxorubicin
- thiotepa
- busulfan
- melphalan
- G-CSF
- temozolomide
- irinotecan
We also have information about the side effects of radiotherapy.
Your doctor will talk to you about the possible side effects of all the treatments before you agree to take part.
Location
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.
Chief Investigator
Professor Martin Elliot
Supported by
Cancer Research UK Clinical Trials Unit, Birmingham
International Society of Paediatric Oncology (SIOP)
Solving Kids Cancer (SKC)
Gustave Roussy
SIOPEN
Neuroblastoma UK
If you have questions about the trial please contact our cancer information nurses
Freephone 0808 800 4040
