A trial looking at treatment after surgery for people with osteosarcoma (Euramos 1 trial)

Please note this trial is no longer recruiting patients.

This trial is looking at treatment for people who have had an operation to remove their osteosarcoma.

The trial is for children and young people up to the age of 40. We use the term ‘you’, but of course if you are a parent, we are referring to your child.

Osteosarcoma is a type of bone cancer. Doctors often treat it with chemotherapy both before and after surgery. The chemotherapy drugs usually used are methotrexate, doxorubicin (Adriamycin) and cisplatin. This combination of drugs is often called MAP.

MAP chemotherapy helps stop the osteosarcoma coming back after surgery. Doctors think that adding other treatments to MAP after surgery may be even better. But they are not sure how well the new combinations of treatment will work. All treatments have side effects, so it is important that patients do not have treatments they don’t need.

In this trial, some patients will have MAP after surgery as normal (the ‘control group’). Some patients will have MAP plus ifosfamide and etoposide, called MAPIE. And some patients will have MAP plus interferon, called MAPifn. There is more information about the different groups in the ‘trial design’ section below.

Recruitment

Start 19/09/2005

End 30/06/2011

Phase

Phase 3

Who can enter

You can enter this trial if you

Have recently been diagnosed with high grade osteosarcoma in a bone in your arm, leg, ribs, spine or breastbone (sternum)
Have not had any treatment for your osteosarcoma yet
Are due to have surgery to remove your osteosarcoma
Have satisfactory blood test results
Are well enough for treatment (performance status 0, 1 or 2)
Are aged 40 or under

You cannot enter this trial if you

Have low grade osteosarcoma
Have osteosarcoma that cannot be removed with an operation
Have osteosarcoma in the fibrous tissue covering the bones (juxtacortical osteosarcoma), or in a bone in your face or skull (craniofacial osteosarcoma)
Have already had treatment for your osteosarcoma
Have had chemotherapy in the past
Have any other serious medical condition
Are pregnant or breastfeeding
Are over 40 years old

Trial design

In the first part of this trial, everyone taking part will have MAP chemotherapy before surgery. You will have 2 cycles of chemotherapy. Each cycle is 5 weeks, so you will have 10 weeks of treatment in total.

In week 1 of each cycle of MAP, you have doxorubicin and cisplatin over 2 or 3 days. You don’t have any treatment in week 2 or 3. Then in weeks 4 and 5 you have methotrexate on one day in each week.

After 2 cycles of MAP you will have an operation to remove your osteosarcoma. The doctors will look at some of the sarcoma they have removed in the lab to see how well the chemotherapy has worked. People taking part are then split into 2 groups - those whose cancer responded well to chemotherapy, and those whose cancer responded less well.

The next part of the trial is randomised. This means that the people taking part are put into treatment groups by a computer. Neither you nor your doctor will be able to decide which group you are in.

If tests showed that your cancer responded well to chemotherapy, you will either have more MAP chemotherapy (standard treatment), or MAP with interferon (MAPifn). And if tests showed that your cancer responded less well to chemotherapy, you will either have more MAP chemotherapy (standard treatment), or MAP with ifosfamide and etoposide (MAPIE).

MAP

If you are in the standard chemotherapy group, you will have a further 4 cycles of MAP after your surgery (see above).

MAPifn

If you are in this group, you will have 4 cycles of MAP (see above). After that you have interferon once a week for up to 17 months. You have interferon as an injection into the skin (subcutaneous injection).

MAPIE

If you are in this group, you will have 7 cycles of MAPIE chemotherapy. The first 6 cycles take 4 weeks each, and the last cycle takes 5 weeks. In week 1 of each cycle you have 2 out of these 4 drugs - doxorubicin, cisplatin, ifosfamide and etoposide. You have treatment over 3 to 5 days. The 2 drugs you have vary from cycle to cycle. The exact regime is too complicated to go into detail here but your doctors will tell you more about it. You don’t have any treatment in weeks 2 or 3. In week 4 (and also in week 5 of the last cycle) you have methotrexate on one day. You have all 5 drugs through a drip into a vein.

Hospital visits

You will see the doctors and have some tests before you take part in this trial. The tests include

Physical examination
Blood tests
Urine tests
MRI scan or CT scan
Chest X-ray and other X-rays
Heart ultrasound (echocardiogram, or echo)
Hearing test

You may also have a bone scan and a PET scan.

You will go to the hospital to have chemotherapy on several days during each cycle of chemotherapy. How long you stay in hospital will depend on which group you are in.

If you are in the group that has MAPifn, you won’t have to go to the hospital each week for your interferon injection. You (or a family member) will be taught how to do this at home. Or, if this is not possible, a district nurse will come to your home to give you the injections.

You will have regular scans and blood tests during and after treatment. After you finish treatment you will see the doctors

Every 6 to 12 weeks for 2 years, then
Every 2 to 4 months for another 2 years, then
Every 6 months until 10 years, and
Every 6 to 12 months after that

You will fill out a questionnaire before you have surgery, and then at 3 months, 18 months and 3 years. This will ask you how you have been feeling and about any side effects you have had. It is called a quality of life questionnaire.

Side effects

The most common side effects of methotrexate, doxorubicin and cisplatin (MAP) are

A drop in blood cells causing an increased risk of infection, bleeding or bruising problems, tiredness and shortness of breath
Hair loss
Feeling or being sick
Sore mouth
Reduced kidney function with cisplatin (you will have lots of fluids to stop this happening)
Reduced hearing of high pitched sounds with cisplatin
Diarrhoea
Loss of fertility

The most common side effects of ifosfamide and etoposide are

A drop in blood cells causing an increased risk of infection, bleeding or bruising problems, tiredness and shortness of breath
Hair loss
Feeling or being sick
Irritation to bladder and kidneys with ifosfamide
Loss of fertility
Taste changes

The most common side effects of interferon are