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

This trial is looking at treatment for children and young people with a rare type of cancer called neuroblastoma.

This trial is for children and young people up to and including the age of 20. We use the term 'you' in this summary, but of course if you are a parent, we are referring to your child. Neuroblastoma develops in specialised nerve cells and most commonly starts in the nerve cells of the adrenal glands.

This trial is looking at the treatment of children with ‘high risk’ neuroblastoma. This means that there is a high risk that your cancer will continue to grow or come back (recur) after treatment.

Children with neuroblastoma usually have a combination of treatments including surgery, chemotherapy and radiotherapy. They may also have a stem cell transplant. Doctors want to try and improve these treatments. This trial aims to find out which combination of chemotherapy drugs are better at stopping your cancer from growing or coming back.

Recruitment

Start 01/12/2002

End 30/11/2011

Phase

Phase 3

Who can enter

You can enter this trial if you

Have been diagnosed with neuroblastoma
Have stage 4 neuroblastoma, or stage 2 or 3 neuroblastoma with MycN amplification - your doctor would be able to tell you if this applies to you (children under 1 year old should be stage 2, 3 or 4 with MycN amplification)
Are aged between 0 and 20 years old (inclusive)
Have satisfactory blood tests
Are well enough to take part

You cannot enter this trial if you

Have had previous chemotherapy, except your first cycle of chemotherapy
Have stage 1 neuroblastoma, or stage 2 or 3 neuroblastoma without MycN amplification

Trial design

This European trial aims to recruit about 1,000 patients over 5 to 6 years. There are five different parts to the treatment in this trial.

Before your treatment begins, you have a central line or long line put in. This is also sometimes called a ‘wiggly line’. It makes it easier to give chemotherapy and take blood samples.

Part 1 - Induction chemotherapy

Everyone will have induction chemotherapy (called COJEC) to shrink the primary cancer and try to get rid of cancer cells that have spread.

COJEC includes the drugs vincristine, carboplatin, etoposide, cisplatin and cyclophosphamide. You have 2 or 3 of these drugs every 10 days. One 10 day course is called a cycle of chemotherapy. You will have 8 cycles of induction chemotherapy.

You also have a growth factor called G-CSF. You have this as an injection just under the skin (subcutaneously). You have these injections daily for several days between chemotherapy cycles to lower the risk of infection. You then have G-CSF after your chemotherapy has finished. This helps the bone marrow make extra stem cells in preparation for your stem cell collection.

You will then have your stem cells collected and stored.

Part 2 - Surgery

You will have an operation to remove as much of the neuroblastoma as possible.

Part 3 - High dose chemotherapy and stem cell transplant

When you have recovered from surgery, you have high dose chemotherapy. You will be put into one of two treatment groups by a computer. This is called randomisation. You have either

Carboplatin, etoposide and melphalan (called CEM) OR
Busulfan and melphalan (called Bu/Mel)

You have chemotherapy through a drip into your central line.

You then have your stem cells through a drip into your central line.

Part 4 - Radiotherapy

After the stem cell transplant, you have radiotherapy to your operation site. You have this every day from Monday to Friday for about 3 weeks.

Part 5 - Differentiation treatment

After radiotherapy, you have a tablet called ‘13-cis retinoic acid’ or isotretinoin. This is a man made form of vitamin A. You have this tablet twice a day for 2 weeks, followed by 2 weeks with no tablets. You will have this 6 times, so treatment in part 5 will take about 6 months.

Hospital visits

Your will see a doctor and have various tests before you start treatment. These tests include

Taking a sample (biopsy) of your cancer
Ultrasound and MRI or CT scan of the cancer
Bone marrow test
Blood tests
Tests to check your heart function
Hearing test (audio gram)
Urine tests

You may have some of these tests again during and after your treatment.

Your treatment for neuroblastoma is very intensive, whether you take part in this trial or not. You will be in hospital on and off for about a year.

Side effects

The combination of treatments for this type of cancer can cause severe side effects. If you take part, you will have a detailed information sheet explaining the side effects. Below is a brief outline.

The most common side effects of chemotherapy and a stem cell transplant are

Hair loss
A drop in blood cells causing an increased risk of infection, bleeding problems, tiredness and breathlessness
Feeling or being sick
Loss of appetite
Dry and sore mouth

There is more information about the side effects of vincristine, etoposide, cisplatin, cyclophosphamide, carboplatin, melphalan and busulphan on CancerHelp UK. The side effects you have will depend on the combination of drugs used. Your doctor will discuss this with you.

The side effects of having an operation include the risk of infection and pain.

The most common side effects of radiotherapy are