A trial looking at treatment for children and young adults with an ependymoma (SIOP Ependymoma Program II) Pathway 3

Cancer type:

Brain (and spinal cord) tumours
Children's cancers




Phase 2

This trial is looking at adding valproic acid to chemotherapy after surgery to treat ependymoma. It is open to children younger than 1 year old and those with an ependymoma who can’t have radiotherapy after surgery to remove their tumour. Cancer Research UK supports this trial.

There are 2 parts to this trial. In the 1st part the trial committee looks at the results of your tests and scans. The 2nd part is looking at treatment pathways. 

There are 3 treatment pathways in this trial. This information is about pathway 3. We have information on pathway 1 and pathway 2.

More about this trial

Ependymoma is a type of brain tumour that mostly affects children and young people. We use the term ‘you’ in this summary, but if you are a parent, we are referring to your child. 

Doctors usually treat ependymoma by removing it with surgery. After surgery if you can’t have radiotherapy you have chemotherapy instead.

In this pathway researchers want to find out if adding a drug called valproic acid to chemotherapy improves treatment. 

Valproic acid is a drug that blocks substances (enzymes) in the body called histone deacetylases (pronounced dee-as-et-isle-azes). Cells need these to grow and divide. Blocking them may stop cancer growing. Drugs that block these enzymes are called histone deacetylase inhibitors or HDAC inhibitors.

We know from research that valproic acid can help people with other types of brain tumours. 

The aims of this pathway are to find 

  • how well chemotherapy with valproic acid works for young children and those who can’t have radiotherapy to treat ependymoma
  • what the side effects of valproic acid and chemotherapy are
  • how safe it is to give valproic acid with chemotherapy

Who can enter

The following bullet points list the entry conditions for this trial. Talk to your doctor or the trial team if you are unsure about any of these. They will be able to advise you. 

You may be able to join this trial if all of the following apply. You

  • Have been diagnosed with an ependymoma in the brain that is grade 2 or 3 
  • Have satisfactory blood test results 
  • Are able to have chemotherapy
  • Are under 1 year old or you are older but not able to have radiotherapy

You cannot join this trial if any of these apply

  • You have been diagnosed with an ependymoma called a subependymoma, ependymomablastoma or myoxopapillary ependymoma
  • Your ependymoma started in the spine 
  • You have already had chemotherapy 
  • You have already had radiotherapy
  • You are already having treatment with another anti tumour drug
  • You are already taking part in another clinical trial looking at treatment for ependymoma
  • You have severe damage to your liver or kidneys 
  • There is a family history of severe epilepsy
  • You are unable to have any of the drugs used in the trial for any reason 
  • There is a medical or other reason why you can’t have the amounts of fluids you need as part of the treatment in this trial
  • You have another medical problem that the trial team think could affect you taking part

Trial design

There are 2 parts to the SIOP Ependymoma Program II. 

Part A
In part A you have all the tests and scans that are normally done to diagnose your tumour. A national committee looks at the results of the tests and scans. This is to confirm your diagnosis and consider the most appropriate pathway for you. 

The team want to find out more about ependymoma and its treatment. With your permission you will be entered on to a national registry even if you aren’t offered a treatment pathway. They will look at your hospital records to find out what treatment you have.  

The trial team need 480 children and young people from the UK and Europe to join part A.

Part B
This is an international phase 2 trial. The researchers need 100 children and young people from the UK and Europe to take part.

It is a randomised trial. After your surgery you are put into 1 of 2 treatment groups by a computer. Neither you nor your doctor will be able to decide which group you are in

  • vincristine, carboplatin, methotrexate, cyclophosphamide and cisplatin (standard chemotherapy)
  • standard chemotherapy and valproic acid

Diagram for trial design pathway 3

Before starting chemotherapy you will have a central line put in. You have all your chemotherapy as a drip through the central line. All blood samples will be taken through the central line. 

  • Week 1 you have vincristine and carboplatin on 1 day
  • Week 2 you have no chemotherapy
  • Week 3 you have vincristine and methotrexate. You have methotrexate over 24 hours through a pump (syringe driver) attached to the central line. After methotrexate you have folinic acid for 2 to 4 days afterwards. You have it at regular times as a drip through your central line. Folinic acid helps reduce the side effects of methotrexate.
  • Week 4 you have no chemotherapy
  • Week 5 you have vincristine and cyclophosphamide on 2 days
  • Week 6 you have no chemotherapy
  • Week 7 you have cisplatin on 2 days
  • Week 8 you have no chemotherapy

Each 8 week period is called a cycle of treatment. You have 8 cycles of treatment. 

Valproic acid is a liquid you take every day. Your doctor will tell you how much to take. After 2 weeks your doctor might need to change the dose. To check the dose the doctor will take blood samples

  • before having valproic acid
  • 1 hour 
  • 2 hours 
  • 4 hours
  • 6 hours after

Depending on the amount of valproic acid in your blood the dose might be increased. It is gradually increased over 3 weeks if needed. Your doctor will talk to you about this. 

For your safety every time the dose is increased blood samples are taken. This is to measure how much valproic acid is in the blood. 

With your permission the team will use the blood samples to 

  • test how valproic acid works
  • what effect it has on the body
  • what happens to it in the body

After finishing chemotherapy, as long as your tumour hasn’t got worse, you can continue taking valproic acid for another year.

You keep a diary while taking valproic acid. In the diary you write down the daily dose and any side effects or symptoms you have.  

Quality of life studies
Depending on how old you are, the trial team will ask you to fill out a few questionnaires 

•    before you start treatment
•    2 years after your diagnosis
•    5 years after your diagnosis

The questionnaires ask about side effects and how you’ve been feeling. This is called a quality of life study

For children and teenagers diagnosed under the age of 18 they will ask you to do the same questionnaires again when you are 18 years old.

Tissue and blood samples
With your permission the researchers will ask for a sample of your cancer that was removed when you had surgery. They will also ask to take extra blood and CSF samples. They will use these samples to find out more about ependymoma. You don’t have to agree to give these samples if you don’t want to. You can still take part in the trial. 

Hospital visits

You see the doctor to have some tests before taking part. These tests include

  • A physical examination
  • Blood tests
  • Urine test
  • Lumbar puncture
  • MRI scan of the head and spine
  • Hearing test
  • Tests to see how your brain works (neurological tests)

You might need to stay in hospital for 1 night when the central line is put in.

On the days you have chemotherapy you stay in hospital. Blood tests will be taken regularly. The doctor will see you regularly to see how you are doing.

You have an MRI scan after cycles 2, 4, 6 and at the end of chemotherapy. 

After treatment you see the doctor 

  • every 3 months for 2 years
  • every 4 months for 3 years
  • then at least once a year up to 18 years old

You have a physical examination and an MRI scan at every visit for 5 years. You have a hearing test every 6 months for 2 years. Then another 5 years after you finish treatment. 

After the age of 18 your doctor will tell you how often they want to see you.

Side effects

A side effect of valproic acid can be liver damage. You will have a blood test done regularly while taking valproic acid to check how well your liver is working. 

The most common side effects of the chemotherapy drugs used in this trial are

Vincristine can also cause 

Cisplatin can also cause changes to the way the kidneys work and changes to hearing.  

We have more information about the side effects of 

We have information about the side effects of radiotherapy to the brain


Newcastle upon Tyne

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

Professor R Grundy 

Supported by

Cancer Research UK
Centre Léon Bérard
University of Birmingham

Other information

This is Cancer Research UK trial number CRUK/12/036.

Freephone 0808 800 4040

Last review date

CRUK internal database number:


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

Wendy took part in a new trial studying the possible side effect of hearing loss

A picture of Wendy

"I was delighted to take part in a clinical trial as it has the potential to really help others in the future.”

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