A trial of abiraterone with either BEZ235 or BKM120 for prostate cancer that is no longer responding to hormone therapy

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

This trial is looking at abiraterone with one of 2 new drugs for prostate cancer that has spread and is not responding to hormone therapy. The new drugs are called BEZ235 and BKM120.

If prostate cancer spreads to other parts of the body, doctors often treat it with hormone therapy. But after a while, this can stop working. If this happens, you may have a drug called abiraterone. But prostate cancer may get worse despite having abiraterone. In this trial, researchers are looking at 2 drugs called BEZ235 and BKM120. They want to find out if having one of these drugs alongside abiraterone helps men in this situation.

BKM120 is a type of biological therapy that bocks the activity of a group of proteins called PI3K. BEZ235 is another biological therapy drug that blocks the activity of both PI3K and a protein called mTOR. Both PI3K and mTOR are involved in cell growth. Blocking them may help stop cancer cells growing.

The aims of the trial are to

Find the highest doses of BEZ235 and BKM120 that you can have safely with abiraterone
Learn more about the side effects and what happens to these drugs in your body
See if the combination of abiraterone and either BEZ235 or BKM120 helps men with advanced prostate cancer that is no longer responding to hormone therapy and has got worse despite having abiraterone

Who can enter

You may be able to enter this trial if you

Have prostate cancer that is no longer responding to hormone therapy and has got worse despite having abiraterone
Are well enough to be up and about for at least half the day (performance status 0, 1 or 2)
Have had surgery to remove your testicles, or have been taking drugs to lower the level of testosterone in your body (luteinising hormone agonists) and you have a low level of testosterone – the trial doctors will do a blood test to check this
Have other satisfactory blood test results
Finished any other anti cancer drug treatment at least 4 weeks ago (6 weeks if you were having a drug called bicalutamide) – you can join the trial if you are taking drugs called bisphosphonates as long as you have been on the same dose for at least 4 weeks
Have recovered from the side effects of any other treatment (apart from hair loss) unless they are very mild
Are able to swallow tablets
Are at least 18 years old
Are willing to use reliable contraception during the trial and for 4 months afterwards if there is any chance your partner could become pregnant

As well as the above, to join the 2nd part of the trial

Your PSA level must have gone down when you started taking abiraterone, but has now started to go up again
You haven’t had any other treatment for prostate cancer since having abiraterone

You cannot enter this trial if you

Have cancer that has spread to your brain and is causing symptoms – you can take part if cancer spread to your brain was treated at least 4 weeks ago and you don’t take steroids
Have had radiotherapy to a large area of your body in the last 4 weeks, radiotherapy to a small area of your body to treat symptoms in the last 2 weeks, or you haven’t recovered from the side effects of earlier treatment
Have had major surgery in the last 2 weeks or have not fully recovered from surgery
Have had more than 2 types of chemotherapy for prostate cancer
Are currently having any other type of anti cancer treatment, including experimental drugs
Have already had a drug called MDV100, drugs that target PI3K, mTOR or a protein called AKT - your doctor can advise you about this
Are taking drugs that affect body proteins called cytochrome P (CYP) enzymes – your doctor can advise you about this
Stopped taking abiraterone because of bad side effects (or you had to have the dose reduced)
Have had any other cancer in the last 3 years apart from non melanoma skin cancer that was successfully treated
Have high blood pressure that can’t be controlled with medication
Have had a heart attack in the last 6 months, have certain other heart problems or take drugs that can affect your heart rhythm
Have problems with your digestive system that could affect how you absorb drugs
Take steroids or other drugs that can affect your immune system (steroid inhalers, creams and eye drops are allowed)
Take warfarin (or a similar drug) to thin your blood
Have had mental health problems in the past, or have moderate to severe depression or severe anxiety – doctors use questionnaires to assess this
Have any other serious medical condition that the trial team think could affect you taking part
Are known to be very sensitive to any of the trial drugs or anything in them
Are known to be HIV positive

Trial design

This phase 1 trial will recruit up to 130 men in different countries. The trial is in 2 parts. In the 1st part, the researchers are trying to find the highest doses of BEZ235 or BKM120 that you can have safely with abiraterone. Everybody taking part has abiraterone. The other drug you have will depend on when you join the trial.

The first few patients taking part will have a low dose of either BEZ235 or BKM120. If they don’t have any serious side effects, the next patients will have a higher dose. And so on, until they find the best doses to give. This is called a dose escalation study.

If you have BEZ235, you take it twice a day. If you have BKM120, you have it once a day. And you take abiraterone once a day.

As well as taking abiraterone and 1 of the trial drugs, you also take a steroid called prednisolone to help reduce some of the side effects. You take all the drugs by mouth. The trial team will tell you exactly how and when to take them.

In the 2nd part of the trial, researchers will compare the 2 drug combinations. They want to learn more about the side effects and whether the treatment helps men with advanced prostate cancer.

This part of the trial is randomised. The men 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.

Half the men have abiraterone and the highest safe dose of BKM120 found in part 1. The other half have abiraterone and the highest safe dose of BEZ235.

Whichever part of the trial you join, you can carry on having the trial treatment as long as your cancer doesn’t get worse and you don’t have bad side effects.

The trial team will ask you to fill out questionnaires before you start treatment, every 2 weeks for the first 3 months and then every month after that. The questionnaires will ask about how you’re feeling (your mood) including whether you are anxious or depressed.

People joining the 2nd part of the trial will also be asked to keep a diary to note down if they have any pain and details of any painkillers they take.

Hospital visits

You see the trial team and have some tests before you start treatment. The tests include

Physical examination
Blood tests
Urine test
Heart trace (ECG )
CT scan or MRI scan
Heart scan (echocardiogram ) or MUGA scan
Bone scan

If you have any cancer on your skin, your trial doctor may take a photograph. This will only show the cancer and the surrounding area. Your face will not be in the photograph and it will not be possible to identify you.

The trial team will try to get a sample of tissue removed when you had surgery or a biopsy Open a glossary item in the past. If there is not a sample available, they may ask you to have a biopsy at this point.

You go to hospital

Each week in the 1st month of treatment
Every 2 weeks for the next 2 months
Once a month after that

Each visit will last a few hours. At some visits, you may need to stay in hospital overnight.

You have regular blood tests and heart traces. You also have a heart scan and a CT or MRI scan every 3 months.

When you finish the treatment, you see the trial team again within the next 2 weeks. You have a physical examination, blood tests, a heart trace and a heart scan. You also have a CT or MRI scan if you haven’t had one recently. If you have any abnormal blood test results, the trial team may ask to see you again a couple of weeks later.

If you stop the treatment because your cancer gets worse, a member of the trial team will contact you by phone every 3 months to see how you are.

If you stop the treatment for any reason other than your cancer getting worse, you will see the trial team every 3 months until your cancer does start to get worse.