A study looking at improving treatment for children and young people with medulloblastoma (PNET5 MB)

Please note - this trial is no longer recruiting patients. We hope to add results when they are available.

Cancer type:

Brain (and spinal cord) tumours

Status:

Closed

Phase:

Phase 2/3

This study is looking at using the results of laboratory tests on a sample of your medulloblastoma to decide which type of treatment is best.

It is for children and young people aged from 3 years old to younger than 22. We use the term ‘you’ in this summary, but if you are a parent, we are referring to your child.

More about this trial

Medulloblastoma is a type of brain tumour called a primitive neuro-ectodermal tumour (PNET). It is usually treated with surgery, radiotherapy and chemotherapy.

Following surgery the doctors take into account various things such as:

your age
whether the surgeon was able to remove all, or nearly all, of the tumour
whether the cancer has spread anywhere
what the tumour (cancer) cells look like under the microscope

They then decide if you are standard or high risk. Knowing the risk group helps the doctors to come up with the best treatment plan for you. To be considered for this study you must have a standard risk medulloblastoma.

The first part of the study is called screening. Results from MRI scans you have had are looked at by the researchers. They will also look at a sample of your medulloblastoma. They do this to check if you are suitable for the treatment part of the study. From looking at your scans and checking your brain tumour sample the researchers decide if you are:

low biological risk
standard biological risk

The treatment part of the study is in 2 phases. Phase 2 is for children and young people who are low biological risk and phase 3 is for children and young people who are standard biological risk

Doctors want to change existing treatment by:

seeing if using carboplatin with radiotherapy improves this treatment for people in the standard risk group
not using vincristine during radiotherapy as there is no evidence this improves treatment
reducing the amount of a chemotherapy drug called cisplatin by replacing it with cyclophosphamide for some of your chemotherapy treatment after your radiotherapy (maintenance chemotherapy)
giving a lower dose of radiotherapy to the brain and spine and shorter course of chemotherapy to children who are low risk

They aim to improve the chances of curing your medulloblastoma and hope to reduce the severity of the long term side effects that can happen after treatment. They also want to look at how treatment affects your quality of life to see how to improve future treatments.

Who can enter

The following bullet points list 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.

You may be able to join this study if you first have the results from your MRI scans and a sample of your medulloblastoma looked at (screening) and have been told by your doctor you have either low biological risk or standard biological risk medulloblastoma.

And if all of the following apply:

You have had surgery to remove your medulloblastoma and there are no signs that the cancer has spread anywhere else in your brain or spine
You have not had any other treatment for your medulloblastoma other than surgery
Your surgeon was able to send a suitable sample of your medulloblastoma for tests in the laboratory
You are able to have radiotherapy and chemotherapy
You are able to start radiotherapy within 28 days of your operation
You have satisfactory liver and kidney function
You have no significant hearing loss
If you are female and sexually active, you need to use reliable contraception during the time you are on the trial
You are aged between 3 and up to age 22. The doctors will use the age you are when you have your surgery

You cannot join this study if any of these apply. You

Have a high risk medulloblastoma or the doctors are not able to tell from your cancer what risk group you are
Have 1 of the following types of tumours
- brainstem or supratentorial primitive neuro ectodermal tumour
- atypical teratoid rhabdoid tumour
- medulloepithelioma
- ependymoblastoma
- large cell medulloblastoma
- anaplastic medulloblastoma
- medulloblastoma with extensive nodularity (MBEN)
Have had treatment for any other type of brain tumour or cancer in the past
Have a condition which could affect you having chemotherapy or radiotherapy such as Fanconi anaemia, Nijmegen breakage syndrome, or Gorlin’s syndrome
Have Turcot syndrome or Li-Fraumeni syndrome
Are pregnant
Have any other condition that the trial team think could affect you taking part

Trial design

This is an international phase2/3 trial. Researchers need 60 children and young people for phase 2 and 300 for phase 3. They need about 150 children and young people in the UK to take part.

You will be in either the low risk (phase 2) or standard risk (phase 3) treatment group.

Low risk group
You have radiotherapy followed by maintenance chemotherapy. Radiotherapy starts around 4 to 6 weeks after your surgery. You have it once a day, Monday to Friday for 30 days.

Usually you would have vincristine alongside your radiotherapy but this is not being used in this study because the doctors don’t think it helps.

Your radiotherapy is carefully targeted so you have the standard dose (53.4GY) to where the tumour was and a lower dose (18GY) to the rest of your brain and spine. Doctors hope that using a lower dose of radiotherapy will help to reduce the side effects, without affecting your chances of cure.

Six weeks after you finish your radiotherapy you start your maintenance chemotherapy.

To have your chemotherapy you have a long tube that goes into your chest. You might hear it called a Hickman line or a central line. You have this put in the operating theatre. It means your doctors and nurses can take blood and give your treatment through this line.

You have two different combinations of chemotherapy that your doctors call Regimen A and Regimen B. You alternate between A and B.

PNET5 MB diagram

The following chemotherapy drugs make up Regimen A:

cisplatin given as a drip into your central line
lomustine capsules
vincristine given as an injection into your central line

With Regimen A you have treatment over 2 weeks followed by 4 weeks rest.

Regimen B consists of 2 chemotherapy drugs:

cyclophosphamide given as a drip into your central line
vincristine given as an injection into your central line

You have treatment over 2 days followed by 3 weeks rest.

Each treatment period is called a cycle. You have 6 cycles in total. This takes about 27 weeks (standard maintenance chemotherapy usually lasts 48 weeks).

Standard risk group
You have radiotherapy followed by maintenance chemotherapy.

Your radiotherapy is also targeted. You have the standard dose (53.4GY) to the area where the tumour was and the standard dose (23.4GY) to the rest of the brain and spine.

Alongside the radiotherapy you might have carboplatin.

Carboplatin is already used for children and young people with high risk medulloblastoma. Now doctors want to see if it is useful for people with standard risk disease.

To test this, everyone in the standard risk group is randomised. This means you are put into one of two treatment groups by a computer. You have either:

radiotherapy
radiotherapy and carboplatin

Neither you nor your doctor will be able to decide which group you are in.

PNET5 MB Diagram

Your radiotherapy starts around 4 to 6 weeks after surgery. You have it once a day, Monday to Friday for 30 days. Like the low risk group, vincristine will not be given alongside radiotherapy for anyone in the standard risk group.

If you are having carboplatin, you have this every day you have radiotherapy. You have it 1 to 4 hours before radiotherapy. You have carboplatin as a drip into your central line. It takes about 1 hour to have.

Six weeks after you finish radiotherapy, you start maintenance chemotherapy.

You have two different combinations of chemotherapy that your doctors call Regimen A and Regimen B. You alternate between A and B.

PNET5 MB Diagram

The following chemotherapy drugs make up Regimen A:

cisplatin given as a drip into your central line
lomustine capsules
vincristine given as an injection into your central line

With Regimen A you have treatment over 2 weeks followed by 4 weeks rest.

Regimen B consists of 2 chemotherapy drugs:

cyclophosphamide given as a drip into your central line
vincristine given as an injection into your central line

You have treatment over 2 days followed by 3 weeks rest.

Each treatment period is called a cycle. You have 8 cycles in total. This takes about 36 weeks (standard maintenance chemotherapy usually lasts about 48 weeks).

Questionnaires
Everyone taking part in the trial will be asked to complete some questionnaires. You complete a questionnaire that looks at your brain (neurological and intellectual) function. You also complete other questionnaires for a Quality of life study. These have questions about:

how you’re feeling (your emotions)
your physical health
how treatment is affecting your everyday life

You complete these:

before you start radiotherapy
2 and then 5 years after you were diagnosed with medulloblastoma
when you’re 18

Hospital visits

You see the doctors and have some tests before starting in the trial. These include:

a physical examination
hearing test
blood tests
a lumbar puncture
a CT scan and an MRI scan of your head and spine

During both your radiotherapy and chemotherapy you have regular checks and tests. As well as repeating some of the tests above you also have:

tests to see how well your kidneys are working (kidney function tests)

You usually have your radiotherapy as a day patient. You will need to be in hospital for some of the time you have your maintenance chemotherapy.

Once you complete all your treatment you continue to be seen regularly by the doctors. They will check how you are and see if the treatment you had has affected your growth and development. The doctors will explain how often they’ll see you.

Side effects

Radiotherapy to your head can cause short term and long term side effects.

Short term side effects include:

hair loss – this usually grows back after treatment but sometimes you have permanent hair loss in the area that had the highest dose of radiation
red and sore skin
tiredness – you might sleep a lot more than usual

Long term side effects include:

a decrease in your ability to learn – you might need extra help at school
an effect on your growth - this is because the radiotherapy can affect your growth hormones
an increase in the risk of another cancer in the place where you had radiotherapy (this is not common)

We have more information on the side effects of radiotherapy to your brain.

The side effects from chemotherapy can vary according to the drugs you have but the most common general side effects include:

hair loss
a drop in blood cells causing an increased risk of infection, bleeding problems, tiredness and breathlessness
feeling or being sick
sore mouth
diarrhoea
constipation
loss of appetite
weight loss
numbness and tingling in your hands and feet (peripheral neuropathy)
tiredness (fatigue)
tummy ache
problems with your hearing
problems with the way your kidneys work
reduced fertility (for boys)