A trial comparing olaparib with enzalutamide or abiraterone for men with prostate cancer (PROfound)

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

Cancer type:

Prostate cancer

Secondary cancers

Status:

Closed

Phase:

Phase 3

This trial is for men with prostate cancer that has spread to other parts of the body (metastatic).

It is for men who:

have had surgery to remove the testicles (orchidectomy) or are having treatment with hormone therapy
have changes in genes called homologous recombination repair (HRR)

More about this trial

Prostate cancer needs the male sex hormone testosterone to grow. Testosterone is made by the testicles. So, for advanced prostate cancer you might have:

surgery to remove the testicles (orchidectomy)
hormone therapy to reduce the level of testosterone in your body

But after some time, treatment can stop working and prostate cancer might start to grow again. This is called castration resistant prostate cancer.

You usually have hormone therapy such as enzalutamide and abiraterone for castration resistant prostate cancer. But doctors are looking for new ways to help men in this situation. In this trial, they are looking at olaparib.

This trial is in 2 parts. First, doctors test a sample of your cancer for changes (mutations) in the HRR genes. You go to the 2nd part of this trial if doctors find certain gene changes.

Everyone joining the 2nd part of this trial has 1 of the following:

olaparinb (Lynprza)
enzalutamide or abiraterone

Olaparib is a targeted drug called a PARP inhibitor. It blocks an enzyme Open a glossary item

that cancer cells need to repair themselves and grow. Olaparib is already a possible treatment for women with ovarian cancer. Doctors think it can also help men with prostate cancer.

Enzalutamide and abiraterone are 2 types of hormone therapy. Both stop your body from making the hormone testosterone. They are a common treatment for men with prostate cancer.

The main aim of this trial is to find out whether olaparib is better than enzalutamide and abiraterone for men with castration resistant prostate cancer.

Who can enter

The following bullet points list the entry conditions for this trial. Talk to your doctor or the trial 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 prostate cancer that has spread to other parts of the body (metastatic)
you have had surgery to remove the testicles (orchidectomy) or you are having hormone therapy
doctors think that you can have treatment with enzalutamide or abiraterone
your cancer got worse after treatment with hormone therapy such as enzalutamide and abiraterone
you have low levels of testosterone in your body (less than 1.75 nmol/L)
you have had a CT scan, MRI scan or bone scan to confirm that your cancer has spread to other parts of the body
you have certain changes in the HRR genes (your doctor can tell you more about this)
you are willing to have a sample of tissue taken (biopsy ) if there isn’t a suitable sample available that doctors can use to look for changes in the HRR genes
you have satisfactory blood tests results
your heart is working well
you are well enough to be up and about for at least half the day (performance status 0 to 2)
you are at least 18 years old
you are willing to use reliable contraception during treatment and for 3 months afterwards if there is any possibility that your partner could become pregnant

Who can’t take part

You cannot join this trial if any of these apply.

Cancer related

your cancer has spread to the brain
your cancer is causing pressure on the spinal cord or the spinal nerves (spinal cord compression ), unless you have had treatment and it has been stable for the past month
you have had a PARP inhibitor such as olaparib
you have had cancer treatment in the past 3 weeks, unless it was radiotherapy or treatment to reduce the risk of bone fractures such as denosumab and zoledronic acid (Zometa)
you have had treatment with chemotherapy that affects the DNA such as mitoxantrone, cisplatin or carboplatin (your doctor can tell you more about this)
you have had another cancer in the past 5 years, apart from non melanoma skin cancer , lymphoma or any other solid tumour that have been successfully treated
you have, or your doctors think you might have, a condition called myelodysplastic syndrome or acute myeloid leukaemia
you have moderate or severe side effects from previous cancer treatment, apart from hair loss and side effects from hormone therapies

Medical conditions

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

are taking part in another clinical trial, or have taken part in a clinical trial in the past 3 months
are taking, or have taken drugs in the past 2 to 5 weeks that affect the CYP3A enzyme
have had a major surgery in the past 2 weeks and you still have side effects from it
have an active infection
have heart problems such as an irregular heartbeat (arrhythmias) or you have had a heart attack in the last 3 months
have fits (seizures) that aren’t controlled
have lung problems such as interstitial lung disease
have problems with your digestive system that means it may be difficult for you to absorb tablets
have HIV
have hepatitis B or hepatitis C
have had a bone marrow transplant from a donor (allogeneic bone marrow transplant )
have any other serious medical condition or mental health problem that the trial team think might affect you taking part

Other

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

are sensitive to olaparib or anything it contains
have had a whole blood transfusion in the past 4 months

Trial design

This is an international phase 3 trial. Researchers need around 340 men with changes in the homologous recombination repair (HRR) gene to take part.

This trial is in 2 parts:

part 1 is the screening
part 2 is the treatment

Part 1 (screening)

Everyone gives a sample of tissue (archival tumour sample) to check for changes in the HRR genes. You need to have a biopsy if there isn’t a suitable sample available.

The trial doctor will tell you the results of the test when they are available. It usually takes around 2 weeks. You then:

stop the trial if you don’t have changes in the HRR gene
have more tests such as blood tests and scans to find out whether you can join the 2nd part of this trial if you have changes in the HRR gene

Your doctor will tell you which other treatments you might have if you can’t join the 2nd part of this trial.

Part 2 (treatment)

This part of the trial is randomised. Everyone is put into 1 of the following treatment groups by a computer:

olaparib
enzalutamide or abiraterone

Neither you nor your doctor will be able to decide which group you are in. And you are 2 times more likely to have olaparib than enzalutamide or abiraterone.

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You have olaparib as tablets or capsules that you swallow whole, twice a day. You should wait at least 2 hours after eating before taking them. And after you have taken them, don’t eat for an hour afterwards.

You have enzalutamide or abiraterone as tablets that you swallow whole, every day. Your doctor can tell you which treatment you will have.

You continue to take olaparib, enzalutamide or abiraterone for as long as it helps you and the side effects aren’t too bad.

You may be able to cross over to the olaparib group if your cancer gets worse after treatment with enzalutamide or abiraterone. Your doctor can tell you more about this.

Quality of life

Everybody taking part completes quality of life questionnaires before the start of treatment and then:

at set times during the trial
after you finish treatment

The questionnaires ask about how you have been feeling and what side effects you have had.

Blood tests

You have some extra blood tests as part of this trial. Researchers want to:

find out what happens to olaparib in your body
look for substances called biomarkers to see why treatments work better for some people than others
find out whether you have inherited changes in the HRR gene

You have the extra blood tests before the start of treatment and at set times during the trial.

Doctors may also ask you to have a blood test to look at your DNA Open a glossary item

. You don’t have to agree to this if you don’t want to. You can still take part in this trial.

Hospital visits

You see a doctor and have some tests before taking part. The tests might include:

a physical examination
a heart ultrasound (ECHO )
blood tests
urine test
CT scan or MRI scan
bone scan

During treatment, you see the trial team every month for 6 months. You then see them every 2 months. You have blood tests and a physical examination every time you see them.

You have a CT scan or MRI scan and a bone scan every 2 months. This continues for as long the treatment is helping you and the side effects aren’t too bad.

When you finish treatment, you see the trial team after a month. You then see them every 3 months. You see the trial team more often if you stopped treatment for reasons other than your cancer getting worse.

Side effects

The trial team monitor you during treatment and afterwards. You have a phone number to call them if you are worried about anything. The team will tell you about the possible side effects before you start the trial.

The most common side effects of olaparib are: