A study looking at proton beam therapy for people with a brain tumour called oligodendroglioma (APPROACH)
Cancer type:
Status:
Phase:
This study is comparing standard radiotherapy with 
for adults with oligodendroglioma. The researchers aim to improve long term side effects of treatment.
More about this trial
The main treatments for oligodendroglioma are:
- surgery to remove as much tumour as possible
- radiotherapy, which uses high energy x-rays to destroy cancer cells
- chemotherapy, which uses anti cancer (
cytotoxic ) drugs to destroy cancer cells
The standard for oligodendroglioma uses x-rays also known as photons. This is the most targeted radiotherapy available for this cancer type at the moment. But there are possible long term side effects of radiotherapy. These can develop many years after the treatment. They might include memory problems or difficulties processing information. These are called neurocognitive problems.
Proton beam therapy is a type of radiotherapy that uses high energy protons. Doctors can target the oligodendroglioma with proton beam therapy so that lower doses reach the healthy brain tissue around the cancer. This may include lower doses to parts of the brain involved in memory and information processing.
Researchers think that people having proton beam therapy may have fewer long term neurocognitive side effects than those having standard radiotherapy. But they aren’t sure. They are doing this study to try and find out.
In this study half the people will have standard radiotherapy and chemotherapy and the other half will have proton beam therapy and chemotherapy. The researchers will compare the 2 groups.
The main aims of the study are to:
- find out if using proton beam therapy means there are fewer long term neurocognitive side effects compared with standard radiotherapy
- find out if people are willing to be part of a trial comparing these two treatments
- find out more about how the two treatments affect quality of life
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.
Who can take part
You may be able to join this trial if all of the following apply. You:
- have a type of brain tumour called an oligodendroglioma
- have a change (
mutation ) in the IDH (isocitrate dehydrogenase) gene. And you are missing parts of chromosome 1 and chromosome 19 – this is called 1p/19q co-deletion. Your will doctor will know if you have these changes. - have had an
MRI scan in the 28 days before randomisation . This scan must show doctors that radiotherapy would be a good treatment for you at the moment. You have another MRI scan if there is not a scan available for the study team to look at. - can care for yourself even if you can’t carry on with all your normal activities or do active work (Karnofsky performance status of 70 or above)
- have surgical wounds that are healing well if you have had surgery recently
- are able to complete tests to check how well your brain and nervous system are working. Your doctor will know this.
- are willing to use reliable contraception during the study and for 6 months after the end of chemotherapy study treatment if you, or your partner, are able to become pregnant. Your doctor can advise you on suitable contraception.
- are able to swallow tablets
- are aged at least 25 years when you start radiotherapy or proton beam therapy during the study
- have satisfactory blood test results which mean you are able to have PCV chemotherapy
Who can’t take part
Cancer related
You cannot join this trial if any of these apply. You:
- have cancer in your spinal cord or in the lower back part of the brain (infratentorial). Your doctor can tell you more.
- have cancer cells that have spread to the thin tissue layers covering the brain and spinal cord (the leptomeninges)
- have had radiotherapy to the brain or your head and neck before
- have had chemotherapy to treat your oligodendroglioma before. You might be able to take part if you have had a
targeted cancer drug called vorasidenib or similar drugs before having radiotherapy. Your doctor can explain more. - have another cancer at the moment or have had another cancer within the last 3 years
Medical conditions
You cannot join this trial if any of these apply. You:
- have any other illnesses which affect the cells of your nervous system (neurodegenerative disease) which are causing you memory problems or difficulty processing information
- have any serious medical condition which could affect you having radiotherapy or chemotherapy. Your doctor can tell you more.
- have a
genetic syndrome which would make you very sensitive to radiotherapy. Your doctor will know this. - have
coeliac disease - have problems absorbing sugars such as
hereditary problems of galactose intolerance, total lactase deficiency or glucose-galactose malabsorption
Other
You cannot join this trial if any of these apply. You:
- are unable to have an MRI scan or are unable to have the dye used in MRI scans
- are unable to have the chemotherapy drugs procarbazine, vincristine or lomustine
- are taking part in any other studies that involve having treatment for your oligodendroglioma
- are pregnant or breastfeeding
Trial design
The study team need around 246 people to take part.
It is a randomised study. A computer will put you into 1 of 2 treatment groups. The 2 groups are:
- radiotherapy and chemotherapy – standard treatment
- proton beam therapy and chemotherapy
Everyone taking part
Everyone has a planning appointment before starting treatment. This appointment includes a . This is to work out your dose of radiotherapy and the exact treatment area. You have a mask made before you start your treatment.
You also have an MRI scan before starting treatment.
Both groups have either standard radiotherapy or proton beam treatment every day Monday to Friday, for around 6 weeks. Each treatment will take about three to four minutes although you are in the department for a bit longer than this. Ask the study team how long they think you are likely to be in the hospital for each day.
You don’t feel anything while having treatment.
Everyone has chemotherapy about one or two months after their standard radiotherapy or proton beam treatment has finished. This is standard treatment for oligodendroglioma. It is the same whether you take part in the study or not.
Standard radiotherapy group
You have radiotherapy treatment at your local radiotherapy centre.
Proton beam therapy group
You have treatment at either The Christie NHS Foundation Trust in Manchester or the University College Hospital in London. The NHS can arrange accommodation for you and your partner or carer during your treatment. Someone from the team at the hospital where you have treatment will give you information about this.
You do not have to stay in the accommodation if, for example, you live close to the NHS proton centre. You might prefer to return home every day following your treatment.
Chemotherapy
Everyone has PCV chemotherapy about one or two months after their radiotherapy or proton beam treatment has finished. This is standard treatment for oligodendroglioma.
PCV chemotherapy includes the drugs:
- procarbazine
- lomustine (also known as CCNU)
- vincristine
You have vincristine as a drip into your vein over about 15 minutes. You have lomustine as capsules on the same day as the vincristine. You have procarbazine as capsules over 10 days. You start procarbazine the same day, or the day after. the vincristine.
You have chemotherapy as . This means you have treatment and then a rest to allow your body to recover. Each cycle takes around 6 weeks.
You have up to 6 cycles of chemotherapy treatment as long as it is working, and the side effects are not too bad.
You have chemotherapy as an outpatient at your local hospital.
Neurocognitive tests
Everyone has tests to try and find out how well their brain is working. These are called neurocognitive tests. It takes around an hour each time. An example of one of the tests is tapping numbered dots in the right order as quickly as possible.
You have the neurocognitive tests:
- before starting radiotherapy or proton beam treatment
- one month after the end of your radiotherapy or proton beam treatment
- then once a year for five years
Quality of life
You fill in questionnaires:
- before starting radiotherapy or proton beam treatment
- during your last week of radiotherapy or proton beam treatment
- one month after your radiotherapy or proton beam treatment has finished
- 3 months after your radiotherapy or proton beam treatment has finished
- 6 months after your radiotherapy or proton beam treatment has finished
- then once a year for 4 years
The questions ask about:
- your general health and wellbeing
- what you are able to do at work or at home
- side effects
- using other health services such as your GP
- any financial costs you’ve had from having oligodendroglioma
These are quality of life questionnaires.
The trial team will ask your care giver to fill in a questionnaire around the same time as yours. This questionnaire asks about their:
- quality of life
- what they are able to do at work or at home
- using other health services such as the GP
- any financial costs they have had from being a care giver
Hormone blood tests for research
Radiotherapy to the brain can affect hormone levels. The study team would like to find out if proton beam therapy has the same effect.
The study team ask you to have blood tests to look at your hormone levels. You have these tests:
- before you start radiotherapy
- 6 months after your radiotherapy is finished
- 12 months after your radiotherapy is finished
- then once a year for 4 years
You need to be at the hospital for several hours on the day of the blood tests. And you will be asked not to have anything to eat or drink from midnight before the blood tests. The trial team can explain more about this.
It’s likely that you would have your hormone levels checked even if you were not taking part in the study.
Future research
The study team will ask if they can use your radiotherapy data and MRI data for future research. This is to learn more about radiotherapy and brain function. You don’t have to agree to this. You can say no and still take part in the study.
The results of your neurocognitive tests and quality of life questionnaires may be used in future research. This is to try and understand more about the effect of treatment on people with brain tumours. You can ask the study team more about this.
Hospital visits
You see the study doctor and have some tests before taking part. These include:
- a
physical examination - blood tests
- a pregnancy test if you are able to become pregnant
You see a member of the healthcare team at each of your hospital visits for treatment. This is to check how you are getting on and if you have any side effects.
You will see the study doctor in your local hospital about one month after finishing your radiotherapy and before starting chemotherapy. You then see them once every 6 weeks during the chemotherapy. The study doctor checks how you are feeling and how you are getting on with the treatment.
You have a blood test before each cycle of chemotherapy. This is usually at the same time as your appointment in clinic.
MRI scans
You have an MRI scan when you join the study and before you start radiotherapy or proton beam treatment.
You then have them once your treatment has finished at:
- 3 months
- 6 months
- a year
- then once a year for the next 4 years
It is likely that you would have had your oligodendroglioma monitored in this way if you were not part of the study.
Follow up appointments
You see your study doctors at least once a year for five years after you have finished your radiotherapy.
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.
Possible side effects of radiotherapy for brain tumours include:
- tiredness (fatigue)
- some hair loss, which can be permanent
- headaches
- dizziness
- swelling in your brain (oedema)
- feeling or being sick
- skin redness or irritation on your scalp
- crustiness or a blockage in your ear canal – this may make it harder to hear temporarily
- seizures (fits)
- dry mouth or taste changes
- temporary worsening of existing symptoms such as weakness
- some damage to the normal brain tissue (radionecrosis)
Possible long term side effects of radiotherapy include:
- memory problems or difficulties processing information (neurocognitive problems)
- hormone level changes – this might make it more difficult to become pregnant
cataracts or dry eyes- an increased risk of
stroke - a very small increased risk of a second cancer
- permanent damage to your eyesight or hearing – this is very rare
Possible side effects of chemotherapy include:
- an increased risk of getting an infection due to a drop in white blood cells. Symptoms include a change in temperature, aching muscles, headaches, feeling cold and shivery and generally unwell.
- bruising, bleeding gums or nosebleeds. This is due to a drop in the number of platelets in your blood.
- tiredness (fatigue)
- feeling or being sick
- taste changes
- sore mouth or mouth ulcers
- loss of appetite
- hair thinning
- diarrhoea or constipation
- tummy (abdominal pain)
- changes to the way your liver and kidneys work
- breathlessness and looking pale due to a drop in red blood cells
- skin changes including a rash
- fertility changes
- an allergic reaction
- flu-like symptoms
- difficulty sleeping, bad dreams and hallucinations
- numbness or tingling in your fingers and toes
- jaw or back pain
- damage to the lungs or eyes – this is rare
We have more information about:
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
Dr Louise Murray
Supported by
University of Leeds
If you have questions about the trial please contact our cancer information nurses
Freephone 0808 800 4040
