A trial looking at deforolimus (AP23573) for people with soft tissue sarcoma or bone sarcoma that has spread (SUCCEED)

Please note this trial is no longer recruiting patients.

This trial is looking at a new drug called deforolimus (also called AP23573) to find out if it can control the growth of cancer in people with soft tissue sarcoma, osteosarcoma or Ewing’s sarcoma.

This trial is for adults and children over13 years old. We use the term 'you' in this summary, but of course if you are a parent, we are referring to your child.

If you have sarcoma that has spread, you may have chemotherapy to shrink or stop the growth of your cancer. But at some point, the cancer may start to grow again.

Doctors hope that deforolimus can help to delay the growth of sarcoma for longer after treatment with chemotherapy. Deforolimus is a targeted treatment that works by stopping the action of a protein called mTOR. This in turn controls other proteins that are needed for cell growth. Cancer cells also need these proteins to grow and so if mTOR can’t do its job, this will hopefully stop or slow the growth of the cancer.

Deforolimus is already being looked at in phase 1 and 2 trials as a drug into the vein (intravenous) and as a tablet, taken by mouth. It has shown some promise as a cancer treatment for people with different types of advanced cancer, including sarcoma.

Doctors in this trial want to know if it helps people whose sarcoma has been successfully controlled with chemotherapy. It has not been used in this way before. This trial aims to find out if deforolimus can control the growth of cancer and for how long.

Recruitment

Start 25/05/2008

End 31/12/2009

Phase

Phase 3

Who can enter

You can enter this trial if you

Have soft tissue sarcoma or osteosarcoma or Ewing’s sarcoma that has spread (metastatic cancer)
Have had at least 1, 2 or 3 courses of chemotherapy (first, second, or third line treatment) for metastatic sarcoma and your cancer has shrunk or stayed the same since treatment finished. Your course should include at least 4 cycles of chemotherapy
Are able to start treatment in this trial within 8 weeks of finishing chemotherapy
Have had at least 4 cycles of chemotherapy but no more than 12 months of chemotherapy for sarcoma that has spread
Are well enough to take part in this trial (performance status 0 or 1)
Have satisfactory blood test results
Are aged 13 years or older (if you are aged 13 to 17 years you must weigh at least 45.4kg or 7 stone 2lb)
Are willing to use reliable contraception from the start of the trial to 30 days after the last dose of deforolimus, if there is a chance that you or your partner could become pregnant

You cannot enter this trial if you

Have any of the following types of sarcoma - alveolar soft part sarcoma, clear cell sarcoma, chrondosarcoma, chordoma, desmoid tumours, low grade fibrosarcoma, gastrointentinal stomal tumour, low grade hemangioendothelioma, hemangiopericytoma, low grade liposarcoma or embryonal rhabdomyosarcoma
Have sarcoma that has spread to your brain or spinal cord
Have already had treatment with deforolimus or a similar type of drug
Are still having significant side effects as a result of previous treatment
Are pregnant or breastfeeding
Have had any other cancer in the past 3 years (apart from non melanoma skin cancer or cervical cancer)
Are allergic to erythromycin or similar antibiotics
Have uncontrolled heart disease (your doctor will be able to explain if this applies to you)
Have HIV
Have an infection that needs intravenous treatment
Have any serious medical condition that means you cannot have the treatment in this trial

Trial design

This international phase 3 trial will recruit about 650 people across about 100 different hospitals.

There are two treatment groups in this trial which is randomised. The people taking part are put into the different treatment groups by a computer. Neither you nor your doctor will be able to decide which group you are in, or will be told which group you are in. This is common in clinical trials and is called a double blind trial.

You will not know whether you are taking deforolimus tablets or dummy (placebo) tablets. You take your tablets every day, for 5 days each week. You have them with water 2 hours after a light meal at about the same time each day. You record the date and time of each dose in a diary card.

You have treatment for as long as the study doctor feels that it is helping you.

The trial doctors will also ask you to give extra blood samples and to allow them to have a sample of your cancer. This is called the ‘biomarker research sub study’. The blood and cancer samples will be looked at to see what effect deforolimus has on your cancer. This part of the trial is optional. You do not have to agree to these extra tests if you don’t want to. You will still be able to take part in the main trial.

Hospital visits

Before you start your treatment, a doctor will examine you and ask about your medical history. You have various tests, including blood tests and a CT scan or MRI scan of your sarcoma.

In the first week you see a doctor and have blood tests. You have your first dose of the study drug while you are at the outpatient clinic. The study doctor or nurse will keep a close eye on you for about an hour after you have taken your tablets to check for any side effects. This first visit will take about 4 hours in total. You then continue to take your tablets at home for the next 4 days.

In week 2, you will go back to hospital to have blood tests and you have your tablet while at the hospital. The study doctor will ask you about any side effects. This visit will take about 2 hours.

You will then be asked to visit the outpatient clinic every 4 weeks during treatment, then 4 weeks after the end of treatment. A doctor will examine you and you will have blood tests.

You have an ECG (heart trace) in week 1, week 8 and 4 weeks after the end of treatment. You have a CT scan or MRI scan every 8 weeks during treatment to find out if the treatment is working. These visits for a scan will take about 2 hours.

After your treatment has finished, the trial team will collect information about you from your hospital notes and your doctor. You will not have any extra hospital visits as a result of follow up for this trial.

You also fill out a questionnaire at the start of the trial, every 4 weeks during treatment and when you finish treatment. This will ask you how you have been feeling. It is called a ‘quality of life’ study.

Side effects

You cannot eat certain foods or take some medications while having treatment in this trial (or for 2 weeks before you start). This is because they may interfere with the way deforolimus works and may increase side effects. These include

Herbal preparations such as St John’s wort, black cohosh and Estroven
Grapefruit juice
Some antibiotics such as ciprofloxacin, clarithromycin and erythromycin
Indinavir
Ketoconazole
Barbiturates such as phenytoin or phenobarbital
Rifampicin

All treatments have side effects. The most common side effects of deforolimus include

Tiredness and feeling weak
Loss of appetite
Sore mouth and throat
Rash
A drop in blood cells causing an increased risk of infection, bleeding problems, tiredness and breathlessness
Diarrhoea
Feeling or being sick
Taste changes

This drug may increase levels of fat in your blood. This does not usually cause any symptoms but if it stays high for a long time, it may cause heart problems. The trial doctor will keep an eye on your fat levels and you may have treatment for this, or stop treatment if necessary.

The trial doctor will also explain the less common side effects of deforolimus to you.