A trial of idasanutlin with abiraterone or enzalutamide for men with prostate cancer who haven’t had docetaxel (MAdCaP)

Please note - this trial is no longer recruiting patients. We hope to add results when they are available.

Cancer type:

Prostate cancer

Status:

Closed

Phase:

Phase 1/2

This trial is for men with prostate cancer that has spread and whose cancer no longer responds to hormone therapy. It is for men who haven’t had the chemotherapy drug docetaxel.

Cancer Research UK supports this trial.

More about this trial

If prostate cancer has spread to another part of the body, doctors often treat it with hormone therapy. This can work well, but after a period of time the cancer can start to grow again. If this happens, men may have a drug called abiraterone. If you have abiraterone, you also take a steroid called prednisolone.

Sometimes you may also have another type of hormone therapy drug called enzalutamide.

Researchers want to see if having a new drug called idasanutlin (or RO5503781) alongside abiraterone and prednisolone or enzalutamide helps men with prostate cancer that has spread and is no longer responding to hormone therapy.

Cancer cells can switch off a protein called p53 which would normally signal that a faulty cell, such as a cancer cell should die. Idasanutlin is designed to switch this protein back on which means the cancer cells will stop growing and die.

The aims of this trial are to

Find the highest safe dose of idasanutlin you can have alongside abiraterone and prednisolone or enzalutamide
See whether adding idasanutlin improves treatment

Who can enter

You may be able to join this trial if all of the following apply

You have prostate cancer that has spread to another part of your body
Scans or blood tests show that your cancer is getting worse despite having other treatment
You have a very low level of the hormone testosterone as a result of hormone therapy (the trial team will do a blood test to check this)
You are well enough to carry out all your normal activities, apart from heavy physical work (performance status of 0 or 1)
You have satisfactory blood test results
You are able to swallow tablets
You are at least 18 years old
You are willing to use reliable contraception during the trial and for 3 months afterwards if there is any chance your partner could become pregnant

You cannot join this trial if any of these apply. You

Had chemotherapy for prostate cancer when it stopped responding to hormone therapy
Have already had abiraterone, a drug called ketoconazole, or drugs such as enzalutamide or TAK-700 (orteronel)
Have high blood pressure that can’t be controlled with medication
Have had a heart attack in the last 6 months or have certain other heart problems (the trial team can advise you about this)
Have had a drug called bicalutamide in the last 6 weeks
Have had other treatment for prostate cancer in the last 4 weeks apart from drugs to lower the level of testosterone in your body. You can be taking drugs called bisphosphonates or a drug called denosumab as long as you’ve been on a stable dose for at least 6 weeks
Have needed to take strong painkillers called opioids to control your cancer pain in the last 2 weeks (you can take part if you’ve taken the painkillers tramadol or codeine)
Take drugs to thin your blood, or have problems with your blood not clotting properly
Have a medical condition affecting your bone marrow such as myelodysplastic syndrome (the trial team can advise you about this)

Trial design

This trial is in 2 parts called phase 1 and phase 2. The researchers need more than 120 men to take part.

Phase 1

In this phase, the researchers are trying to find the highest dose of RO5503781 that you can have safely alongside abiraterone and prednisolone or enzalutamide. This phase is in 2 parts:

part A
part B

Everybody joining part A has abiraterone, prednisolone and idasanutlin.

The first few men taking part will have a low dose of idasanutlin. If they don’t have any serious side effects, the next few patients will have a higher dose. And so on, until they find the best dose. This is called a dose escalation study.

You take abiraterone and prednisolone tablets every day. You take idasanutlin for 5 days every 4 weeks.

Everybody joining part B has enzalutamide and idasanutlin. You have the dose of idasanutlin found during part A.

You have enzalutamide tablets every day. And take idasanutlin tablets for 5 days every 4 weeks

Phase 2

In the 2nd phase of the trial, the researchers want to compare idasanutlin with a dummy drug (a placebo Open a glossary item ).

This part of the trial is randomised. The men taking part are put into 1 of 2 treatment groups by a computer. Neither you nor your doctor will be able to decide which group you are in. And neither of you will know which group you are in. This is called a double blind trial.

All the men joining this part of the trial have abiraterone and prednisolone or enzalutamide. Half of them will also have idasanutlin. The other half will have a dummy drug.

MAdCaP trial diagram

You take abiraterone and prednisolone or enzalutamide tablets every day. You take idasanutlin (or the dummy drug) for 5 days every 4 weeks.

Whichever phase of the trial you join, you can carry on having treatment until the trial doctors can tell that your cancer is getting worse.

If you join the 2nd phase of the trial and your cancer starts to get worse, the trial team can find out whether you’ve been having idasanutlin or the dummy drug. If you have been having the dummy drug, you may be able to start having idasanutlin.

Hospital visits

You see the trial team and have a number of tests before you start treatment. The tests include

Physical examination
Heart trace (ECG )
Blood tests
CT scan or MRI scan
Bone scan

The trial team need to get a sample of your cancer that was removed when you had surgery or a biopsy Open a glossary item in the past. If there isn’t a stored sample available, they will ask you to have a new biopsy.

They may also ask you to have more biopsies from areas of cancer spread before you start treatment, during treatment and at the end of treatment. They will use these to see how the cancer responds to treatment. But you don’t have to have these biopsies if you don’t want to. You can still take part in the trial.

If you join the 1st part of the trial, you need to have a number of extra blood tests on 3 different days at the beginning of your treatment. On these days, you will be at hospital for a number of hours.

Everybody in the trial goes to hospital at least every 4 weeks during treatment. You have regular blood tests and the trial team will monitor your blood pressure.

You have a CT scan, and possibly a bone scan and MRI scan, every 8 weeks for the first 6 months, and then every 12 weeks for the rest of the time you take the tablets.

When you finish treatment, you will continue to see the trial team every 3 months until any side effects have got better or you start another treatment.

If you stop having the trial treatment for any reason other than your cancer getting worse, the trial team would like to see you every 6 weeks until you start another treatment.

Side effects

As idasanutlin is a new drug, there may be side effects we don’t know about yet. In trials so far, the most common problems have been

Feeling or being sick
Diarrhoea
Loss of appetite
A drop in blood cells causing an increased risk of infection, bleeding problems, tiredness and breathlessness
Headache
Cough
High temperature
Constipation
Back pain
Changes to your sense of taste
A low level of potassium in the blood which can cause muscle weakness if it isn’t corrected
Fluid retention
Dry mouth
Dizziness
Urine infection