A trial looking at improving treatment for children and adults with newly diagnosed Ewing’s sarcoma (INTER-EWING-1)
Cancer type:
Status:
Phase:
This trial is looking at different ways to improve treatment for Ewing’s sarcoma. It’s mainly looking at changes to chemotherapy and radiotherapy.
Ewing’s sarcoma is a type of bone cancer. It can also affect the soft tissues in the body.
Ewing’s sarcoma is a type of cancer that mainly affects teenagers, young adults and children. This trial is for adults and children. We use the term 'you', but if you are a parent, we are referring to your child.
Cancer Research UK supports this trial.
More about this trial
The main treatments for Ewing’s sarcoma include chemotherapy, surgery and radiotherapy. Often you have a combination of these.
Researchers would like to improve treatment for people with Ewing’s sarcoma. To do this they are looking at whether changes to chemotherapy and radiotherapy can improve treatment outcomes.
They are also looking at Ewing’s sarcoma cells closely to learn more about:
genes 
involved in Ewing’s sarcoma- what might make the cancer more difficult to treat
The researchers will also look at to see if they are able to use them to predict how well the cancer will respond to treatment.
This trial is trying to answer a number of questions about the treatment of Ewing’s sarcoma. These include looking at:
- adding a
targeted cancer drug to chemotherapy as initial treatment (induction and consolidation) - changing the amount of radiotherapy you have
- giving chemotherapy to keep the cancer under control after initial chemotherapy. This is called maintenance treatment.
The aim of the trial is to improve treatment outcomes and .
Who can enter
The following bullet points are a summary of 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.
The trial team check if you are suitable to join the trial and which group you might join. They can tell you more about this.
Who can take part in the main study
You may be able to join this trial if all of the following apply. You:
- have Ewing’s sarcoma of either your bone or soft tissue. Or you have round cell sarcoma which doctors think is similar to Ewing’s sarcoma, but it does not have the changes to a
gene called EWSR1-Fli. - are at least 2 years old
Who can’t take part in the main study
You cannot join this trial if you have had cancer before.
Please note, there are several treatment groups so the entry conditions for this trial are complex. Each group has specific entry conditions, we haven’t listed all of them.
Group A – Induction chemotherapy and targeted cancer drug
This part of the trial is not open to recruitment yet.
You may be able to join this group if all of the following apply. You:
- have cancer that has spread to another part of the body
- are female and willing to use reliable contraception during treatment and for 12 months afterwards if there is any chance you could become pregnant. Or you are male and willing to use reliable contraception during treatment and for 6 months afterwards if there is any chance your partner could become pregnant.
You cannot join this group if you are pregnant or breastfeeding.
Group B1 and Group B2 joint entry conditions – Radiotherapy
This part of the trial is not open to recruitment yet.
You may be able to join one of these groups if all of the following apply. You:
- have had your first (induction) or later (consolidation) chemotherapy with certain chemotherapy drugs. Your doctor will know which ones they are and when you had them.
- are well enough to have
radiotherapy - are female and willing to use reliable contraception during treatment and for 12 months afterwards if there is any chance you could become pregnant. Or you are male and willing to use reliable contraception during treatment and for 6 months afterwards if there is any chance your partner could become pregnant.
Who can’t take part
You cannot join one of these groups if any of the following apply. You:
- have had radiotherapy to the same area before
- have had
high dose chemotherapy with busulphan and melphalan in the 10 weeks before joining the trial - are pregnant or breastfeeding
Group B1 – Radiotherapy without surgery or after surgery that cannot remove all the cancer
This part of the trial is not open to recruitment yet.
As well as the above (joint criteria for B1 and B2), you may be able to join group B1 if either of the following apply:
- your treatment team think that radiotherapy to the area of your
primary tumour is the best treatment option and you’re not going to have any other treatment that reaches the primary tumour itself - you have had surgery to the primary tumour and some cancer remains that the surgeon can see
Some people may not be able to join this group if they have had high dose busulphan chemotherapy. It depends on how much you have had overall. Your doctor will know this.
Group B2 – Radiotherapy after surgery where there are some cancer cells left
This part of the trial is not open to recruitment yet.
As well as the joint criteria for B1 and B2, you may be able to join group B2 if:
- your treatment team think you should have radiotherapy after your operation
You are not able to join this group if any of the following apply:
- you have had surgery to the primary tumour and some cancer remains that the surgeon can see without the need for a microscope
- you’ve had surgery to remove the cancer and an area around it which had no signs of cancer. All the cancer was removed during the operation.
Group C – Maintenance chemotherapy
This part of the trial is open to recruitment.
You may be able to join this group if all of the following apply:
- you have had your first (induction) or later (consolidation) chemotherapy with certain chemotherapy drugs. Your doctor will know which ones they are and when you had them.
- your first chemotherapy treatment worked well, and your cancer has not got worse
- you are well enough to have chemotherapy
- you have satisfactory blood test results
- are female and willing to use reliable contraception during treatment and for 12 months afterwards if there is any chance you could become pregnant. Or you are male and willing to use reliable contraception during treatment and for 6 months afterwards if there is any chance your partner could become pregnant.
You may not be able to join this group if any of the following apply. You:
- have severe damage to your nerves after having vincristine chemotherapy. And you have stopped having vincristine because of this.
- have problems passing urine because of a blockage and this cannot be unblocked before starting treatment
- have bladder inflammation (
cystitis ) - have another serious illness or have an active infection
- are allergic to any of the chemotherapy treatments used in the trial or anything they contain. Or you’re not able to safely have the treatments. Your doctor will know this.
- are pregnant or breastfeeding
Trial design
This is an international phase 3 trial. The researchers need around 900 people to take part worldwide.
There are 3 treatment groups. Only group C is open to recruitment at the moment.
Group A – Induction chemotherapy and regorafenib
This part of the trial is not open to recruitment yet.
This part of the trial is for people who have newly diagnosed Ewing’s sarcoma that has spread elsewhere in the body. This is also called advanced, or metastatic Ewing’s sarcoma.
Induction therapy is the first treatment you have to try to control the growth of your cancer. The standard induction treatment for Ewing’s sarcoma that has spread is a combination of chemotherapy drugs.
The researchers think that adding a called regorafenib to chemotherapy might improve treatment. But they aren’t sure. They are doing this part of the trial to find out.
Regorafenib is a type of targeted drug called a cancer growth blocker. It stops signals that the cancer cells use to divide and grow. It also stops them from forming new blood vessels that they need to divide and grow.
This part of the trial is . You are put into a group by a computer. Neither you nor your doctor will be able to decide which group you are in. There are 2 treatment groups.
You have 1 of the following:
- VDC/IE chemotherapy (this is standard treatment)
- VDC/IE chemotherapy and regorafenib
You have the chemotherapy drugs through a central line. This is a long plastic tube that gives the drugs into a large vein, either in your chest or through a vein in your arm. It stays in while you’re having treatment, which may be for a few months.
You have regorafenib as a tablet or granules.
You have . The trial team will explain how and when you have your drugs.
Group B1 – Radiotherapy without surgery or after surgery that cannot remove all the cancer
This part of the trial is not open to recruitment yet.
This part of the trial is for people who:
- have Ewing’s sarcoma that cannot be fully removed with surgery and
- are having radiotherapy as part of their treatment
Radiotherapy is a common treatment for people with Ewing’s sarcoma that cannot fully be removed with surgery.
The researchers think that giving a higher dose of radiotherapy to the cancer could work better than the current standard dose. But they aren’t sure. So, they are doing this part of the trial to try and find out.
This part of the trial is randomised. You are put into a group by a computer. Neither you nor your doctor will be able to decide which group you are in. There are 2 treatment groups.
You have 1 of the following:
- the standard dose of radiotherapy
- a higher dose of radiotherapy
Standard dose radiotherapy
You have 30 sessions of radiotherapy over around 6 weeks.
Higher dose radiotherapy
You have either:
- 36 sessions of radiotherapy over around 7 weeks or
- 30 sessions of radiotherapy over around 6 weeks
The aim is to see if having a higher dose of radiotherapy works better for people who can’t have their sarcoma fully removed with surgery. And to look at the side effects of this treatment.
You have radiotherapy once a day from Monday to Friday. It takes about 10 to 20 minutes each time.
Group B2 – Radiotherapy after surgery where there are some cancer cells left
This part of the trial is not open to recruitment yet.
This part of the trial is for people who:
- have Ewing’s sarcoma and have had surgery to remove all their cancer
- are having radiotherapy after surgery as part of their treatment
At the moment, there is no standard dose of radiotherapy for treating Ewing’s sarcoma after surgery to remove the cancer. There are generally 2 different doses used worldwide, and the doctor decides which dose you should have. The researchers would like to find out which dose is best. They are doing this part of the trial to find out.
This part of the trial is randomised. You are put into a group by a computer. Neither you nor your doctor will be able to decide which group you are in. There are 2 treatment groups.
You have 1 of the following:
- the higher dose of radiotherapy
- the lower dose of radiotherapy
Higher dose of radiotherapy
You usually have 30 sessions of radiotherapy over 6 weeks.
Lower dose of radiotherapy
You usually have 25 sessions of radiotherapy over 5 weeks.
You have radiotherapy once a day from Monday to Friday. It takes about 10 to 20 minutes each time.
Group C - Maintenance chemotherapy
This part of the trial is open to recruitment.
This part of the trial is for people who are coming towards the end of their sarcoma treatment.
Consolidation treatment aims to kill any cancer cells left in the body.
Maintenance treatment aims to:
- get rid of any traces of cancer that might be left after previous treatment
- stop the cancer from coming back
The trial team want to find out if maintenance chemotherapy would benefit people with Ewing’s sarcoma. At the moment, maintenance chemotherapy is not . The researchers are comparing maintenance chemotherapy with no further treatment after consolidation chemotherapy.
This part of the trial is randomised. You are put into a group by a computer. Neither you nor your doctor will be able to decide which group you are in. There are 2 treatment groups.
You have 1 of the following:
- no treatment after consolidation chemotherapy (standard treatment)
- maintenance chemotherapy
If you have maintenance chemotherapy this is up to 6 with vinorelbine and cyclophosphamide. Each cycle lasts around 4 weeks.
You have the chemotherapy drugs by mouth. You might have them as:
- a tablet
- a capsule
- oral liquid
You might also have vinorelbine as a drip into a vein. The trial team will explain how and when you have your drugs.
Samples for research
The researchers ask for a sample of cancer that is removed when you have a for any reason. For example, at diagnosis or at any time during or after treatment.
You don’t have to have biopsies as part of this trial.
The researchers would also like to collect extra blood samples for research. You have a research blood test:
- before you start treatment - if you’ve not already had chemotherapy
- up to 4 times during treatment
- if your cancer is not responding well to treatment
You don’t have to have these blood samples taken if you don’t want to. You can still take part in the trial.
The researchers use these samples to look at:
genes involved in Ewing’s sarcomabiomarkers
Scans
As part of standard care, you have several scans to see how treatment is working.
These can include:
The researchers look at these scans to see:
- how big the cancer is and whether it has spread before treatment
- if they can predict how well treatment will work
The researchers are also looking at different types of scans in the trial. These are:
- diffusion weighted MRI scan – this means having extra pictures taken at the same time as a usual MRI scan
- whole body MRI scan
- FDG-PET scan – active cancer cells take up a substance called FDG which then shows up brighter on the scan
They use the results of the scans to try and find out if:
- having further scans during treatment can help doctors predict how well treatment will work in the long term
- a whole body MRI scan is better than a FDG-PET scan at seeing how big the sarcoma is and whether it has spread before treatment
- a FDG-PET scan is better than having a bone marrow test to check if the sarcoma has spread to the
bone marrow
These extra scans are optional. You can say no and still take part in the trial.
Quality of life
The trial team ask you to fill out a questionnaire before you start treatment and at set times during the trial. The questionnaire asks about side effects and how you’ve been feeling. This is called a quality of life study.
Hospital visits
You see the doctor and have some tests before taking part in the trial. These include:
- a
physical examination - a pregnancy test if there is any chance you could become pregnant
You have other tests before you join a treatment group. These include:
- an MRI scan or CT scan. Some people have both.
- blood tests
Hospital visits and appointments will depend on what treatment group you are in. You may have some chemotherapy treatment as a day patient, though sometimes you may need to stay overnight.
You usually have radiotherapy as an .
Follow up
When you finish treatment, you have regular check ups with your doctor. They repeat some of the tests you had when you joined the trial. How often you have check ups depends on the routine follow up care at your hospital. The team will tell you more about this.
Side effects
The trial 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 most common side effects of radiotherapy include:
- tiredness
- feeling and being sick
- diarrhoea
- sore skin or rash in the area where you have radiotherapy
- hair loss to the treated area
- lack of appetite
- a drop in blood cells causing an increased risk of infection, bleeding problems, tiredness and breathlessness
- sore throat or pain when swallowing
The symptoms are usually worse at the end of treatment and start to improve a few weeks after treatment has finished.
Some possible side effects may develop many years after radiotherapy. These include:
- developing another cancer
- problems with puberty and fertility
- other problems in the body for example it may affect the muscles, bones, heart and lungs
The most common side effects of chemotherapy include:
- hair loss
- feeling and being sick
- tiredness (fatigue)
- raised temperature (fever)
- a drop in blood cells causing an increased risk of infection, bleeding problems, tiredness and breathlessness
- constipation
- nerve changes
- allergic reactions
- changes in how the liver works
- muscle and bone pain
Your doctor will talk to you about all the possible side effects of chemotherapy treatment.
The most common side effects of regorafenib include:
- soreness, redness and peeling on palms or soles of feet
- skin rash
- bleeding
- problems with wound healing
- low levels of the
thyroid hormone. This might cause muscle cramps and tiredness. - diarrhoea
- loss of appetite and taste changes
- voice changes such as hoarseness
- kidney problems
- mouth sores and ulcers
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
Professor Bernadette Brennan
Supported by
Cancer Research UK
Cancer Research UK Clinical Trials Unit, Birmingham
University of Birmingham
Other information
This is Cancer Research UK trial number CRUK/21/018
If you have questions about the trial please contact our cancer information nurses
Freephone 0808 800 4040
