A study looking at quality of life with 3 different treatments in older people with soft tissue sarcoma (TOLERANCE)

Cancer type:

Sarcoma

Soft tissue sarcoma

Status:

Open

Phase:

Phase 3

This study is looking at 3 different chemotherapy Open a glossary item treatments for people with soft tissue sarcoma.

It is for people that are over 65 years old, and have sarcoma that both:

cannot be fully removed with surgery, and
has spread (advanced sarcoma)

More about this trial

Soft tissue sarcomas are cancers that develop in the connective and supporting tissues of the body. These include tissues such as the muscle, nerves, fat, fibrous tissue and blood vessels.

Some people are diagnosed with advanced Open a glossary item soft tissue sarcoma. This means that the cancer has spread, and surgeons cannot fully remove it with surgery.

Doctors treat advanced soft tissue sarcoma with a chemotherapy drug called doxorubicin once every 3 weeks. This is also called palliative chemotherapy. The aim is that the chemotherapy will help people live longer and more comfortably, but not to cure the cancer.

Doxorubicin can have side effects. These side effects might include feeling or being sick or feeling very tired (fatigue). This means chemotherapy might interfere with day to day life (quality of life).

Doctors would like to improve the quality of life of people having treatment for advanced soft tissue sarcoma. They think that giving a smaller amount of doxorubicin more often or using another chemotherapy drug called cyclophosphamide with a steroid might help. But they aren’t sure. The researchers are using this study to try and find out.

The main aims of the trial are to:

look at the quality of life of people taking part
see how well the treatments work for advanced soft tissue sarcoma
learn more about side effects

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 soft tissue sarcoma that can’t be removed with surgery or has spread elsewhere in the body (advanced soft tissue sarcoma).
Your cancer is not stable, which means it is continuing to grow.
You have a sample of tissue (biopsy) available for the trial team to do some tests on.
You are well enough to carry out all your normal activities, but may not be able to do heavy physical work (performance status of 0 or 1).
You have cancer that the doctor can measure on a scan.
You have satisfactory blood test results.
You have normal heart function. You have an ECG and an ECHO (heart ultrasound) or MUGA to check.
You are willing to use reliable contraception for up to 12 months after your last dose of chemotherapy if you are male and your partner can become pregnant.
Your doctor thinks doxorubicin will be a suitable treatment for you. They can explain more.
You are at least 65 years old.

Who can’t take part

Cancer related
You cannot join this study if any of these apply. You:

have a rare type of sarcoma that starts in the digestive system called a gastrointestinal stromal tumour (GIST)
have cancer that has spread to the brain
have had a type of chemotherapy drug called an anthracycline before. Your doctor can tell you more.
have had any treatment that reaches your whole body (systemic treatment) for sarcoma that spread to another part of the body. You might still be able to take part if you have had certain cancer drugs before surgery which aimed to make your surgery be more successful. Your doctor can explain more.
have another cancer at the moment, or have had cancer in the past, and the study team think it make it difficult for you to take part in the study. Your doctor can tell you more.
have had, or are planning to have, radiotherapy to your head and neck, chest (thorax) or liver

Medical conditions
You cannot join this study if any of these apply. You:

have a serious heart problem such as a heart attack or other heart problems that need treatment. The trial team check if you have a heart condition before you join the trial.
have high blood pressure that is not well controlled
are at increased risk of bleeding
have diabetes that is not well controlled
have severe weak bones (osteoporosis)
have a stomach ulcer
have problems with your bone marrow making blood cells
have a mental illness called psychosis. This means you have lost some contact with reality and may see or hear things that are imagined.
have an active or uncontrolled infection which needs treatment that reaches the whole body (systemic treatment)
have a bladder infection (cystitis) or you are finding it hard to wee (pass urine)
have any other serious medical condition, mental health problem or difficulties that the study team think could affect you taking part

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

have recently had a live vaccine
are not able to have an MRI scan
are allergic to doxorubicin, cyclophosphamide or prednisolone or anything they contain

Trial design

This is an international phase 3 study. The researchers need 185 people to take part.

It is a randomised trial. 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 3 treatment groups.

You have 1 of the following:

Group A - doxorubicin at the normal dose (standard treatment )
Group B - doxorubicin at a lower dose
Group C - cyclophosphamide and prednisolone

For every ten people taking part in the study:

two will have standard treatment (Group A)
four will have doxorubicin at a lower dose (Group B)
four will have cyclophosphamide and prednisolone (Group C)

Group A
You have doxorubicin as a drip into your bloodstream.

You have doxorubicin every 3 weeks. You have treatment for up to 18 weeks as long as it is working, and the side effects are not too bad.

Group B
You have doxorubicin as a drip or as a slow injection into your bloodstream.

You have doxorubicin weekly. You have treatment for up to 37 weeks as long as it is working, and the side effects are not too bad.

Group C
You have cyclophosphamide and prednisolone as tablets. You take cyclophosphamide twice a day, in the morning and evening. And you take prednisolone once in the morning. You have your treatment for one week on and then one week off. You have treatment for as long as it is working, and the side effects are not too bad.

Tissue samples
The researchers ask for a sample of your cancer that was removed when you had a biopsy Open a glossary item . You don’t need to give a new sample. The researchers use it to look at your specific type of soft tissue sarcoma.

Quality of life questionnaires
You fill in questionnaires about your wellbeing and quality of life before you start the study. And 3, 6, 9, 12, 24, 36 and 48 weeks after joining the study.

You fill the questionnaires in when you go to your clinic appointments. Each questionnaire takes about 20 minutes to fill in.

Hospital visits

You see the trial doctor to have tests before you can take part. The tests include:

a physical examination
blood tests
urine tests
heart scan (echocardiogram ) or MUGA scan
CT scan or MRI scan

It can take up to 4 weeks to have these tests. It might mean you have to travel to hospital more than once to have them all.

You go to the hospital to have doxorubicin as an outpatient. You do not have to stay in hospital overnight. Your team will let you know how long it takes to have the doxorubicin.

You take your cyclophosphamide and prednisolone tablets at home.

During treatment you have some tests every 3 weeks, these include:

a physical examination, including checking your pulse, blood pressure, temperature and weight
blood tests

You might also have urine tests if your doctor thinks you need them.

You have a heart function test such as a heart scan (ECG) or MUGA scan 12 weeks and 24 weeks after you started treatment. You might have heart tests after this time if your doctor thinks you need them.

You have a scan Open a glossary item every 12 weeks during treatment.

At the end of treatment, around 30 days after you had your last dose, you go to the hospital to see the study team. This is to see how you are getting on. You have some of the same tests as before.

Follow up
You see the study team every 12 weeks after you finish treatment and until your cancer starts growing again. This is to see how you are feeling and you have some tests, these include:

a physical examination, including checking your pulse, blood pressure, temperature, height and weight
blood tests
CT scan or MRI scan

You might have urine tests or heart function tests.

The study team get in touch with you every 6 months until 2 years after treatment if your cancer grows. This is to see how your quality of life is.

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.

The most common side effects of doxorubicin are:

a drop in blood cells causing an increased risk of infection, bleeding problems, tiredness and breathlessness
sore mouth
diarrhoea
feeling or being sick
redness and peeling on the palms of the hands and soles of the feet
hair loss
fever or chills
tiredness (fatigue)
heart problems – changes in the electrical activity in the heart that might change the heart rhythm. This can be serious. The heart might pump blood less well.
problems with your liver
a blood clot
skin rash
nail problems such as the nail separating from the nail bed
skin and eye sensitivity to sunlight