A trial looking at AZD5305 and darolutamide before surgery for prostate cancer (ASCERTAIN)

Cancer type:

Prostate cancer




Phase 1

This trial is looking at having AZD5305 or darolutamide before surgery to remove prostate cancer. It is also looking at the combination of AZD5305 and darolutamide before surgery.

This trial is for men whose prostate cancer:

  • is recently diagnosed 
  • hasn’t spread outside the prostate gland Open a glossary item (localised prostate cancer) and 
  • has a higher risk of spreading

More about this trial

Localised prostate cancer is cancer that is completely inside the prostate gland. It hasn’t spread outside the prostate or to any other part of the body. 

Radiotherapy or surgery to remove the prostate is standard treatment Open a glossary item for localised prostate cancer. Some people have a higher risk of the cancer coming back after treatment. So doctors are looking at ways to improve treatment for this group of people.

In this trial they are looking at 2 drugs called darolutamide and AZD5305. Darolutamide is a type of hormone therapy Open a glossary item. It is already a treatment for prostate cancer that has stopped responding to previous hormone therapies Open a glossary item.

AZD5305 is a new drug. It is a type of targeted cancer drug called a PARP inhibitor Open a glossary item. PARP is a protein (enzyme) found in our cells. It stands for poly-ADP ribose polymerase. It helps damaged cells to repair themselves. As a cancer treatment, PARP inhibitors stop the PARP from doing its repair work in cancer cells and the cells die.

In this trial some people have AZD5305, darolutamide or both before surgery. And some people have only surgery (standard treatment).

The main aims of the trial are to find out:

  • how safe AZD5305 and darolutamide are for localised prostate cancer 
  • how treatment before surgery works
  • more about the side effects 

Please note, you might not get any direct benefit from taking part in this trial. It may help people with localised prostate cancer in the future.

Who can enter

The following bullet points are a summary of 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 recently been diagnosed
  • have prostate cancer that has a higher risk of coming back after treatment. Your doctor will know this. 
  • are suitable to have surgery to remove the prostate 
  • can switch to a medication called heparin if you are taking a medication called warfarin to thin your blood. Your doctor will know this. 
  • have a sample of tissue available (biopsy Open a glossary item)  that the trial team can access or you are willing to give a new sample 
  • have satisfactory blood test results 
  • are at least 18 years old 

As well as the above, the following must also apply if you are having AZD5305, darolutamide or both. You: 

  • are willing to use reliable contraception during the trial and for a period after if there is any chance your partner could become pregnant 
  • are willing not to donate sperm during the trial and for a period after 

Who can’t take part

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

  • have already had treatment for localised prostate cancer 
  • have myelodysplastic syndromes Open a glossary item or acute myeloid leukaemia Open a glossary item or your doctor suspects you have this 
  • have had another cancer in the last 3 years that could affect you taking part in the trial. Or you have had treatment for another cancer in the last 3 years. You can take part if you had surgery for a local cancer and this treatment was successful. 
  • are taking an experimental drug or using a device as part of another clinical trial. This is if it is within 3 weeks of starting trial treatment. 

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

  • have had a heart attack in the last 6 months or a significant heart problem Open a glossary item that needs treatment. The trial team check if you have a heart condition before you join the trial. 
  • are taking medication that can affect your heartbeat
  • have high blood pressure that isn’t controlled with medication or low blood pressure that is causing symptoms 
  • have had a stroke in the last 6 months 
  • are feeling or being sick and this isn’t well controlled with medication, you have a long term problem with your gut or you can’t swallow or absorb medication 
  • have had treatment that stimulates or damps down the immune system Open a glossary item within 4 weeks of starting trial treatment. You can take part if you are having low dose steroid treatment Open a glossary item.
  • have an active bleeding problem or are at risk of having a bleed. Your doctor will know this. 
  • have HIV, an active hepatitis B or hepatitis C infection or any other infection that needs treatment 
  • are taking medication that affects substances in the body called CYP enzymes. This doesn’t apply if you are in the surgery group. 

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

  • can’t have darolutamide or AZD5305 for any reason 
  • are allergic to AZD5305 and darolutamide or anything they contain
  • would like to have children in the future

Trial design

This is a phase 1 trial. The team need 120 people to take part. Of those, 20 people have surgery only. And 100 people have AZD5305, darolutamide or both before surgery.

You and your doctor decide whether you should have surgery alone or trial treatment before surgery. 

Surgery only (standard treatment group)
You have surgery as planned to remove the prostate gland. Your doctor can tell you more about this and what it involves. 

Trial treatment followed by surgery group
This part of the trial is randomised. 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 before surgery:

  • AZD5305 only 
  • darolutamide only 
  • AZD5305 and darolutamide

AZD5305 and darolutamide are tablets. You have them for 21 days in total before surgery. You take:

  • AZD5305 once a day, every day
  • darolutamide twice a day, every day

You have surgery to remove the prostate gland the day after you finish trial treatment. 

The team give you a diary to fill in when you take your tablets. 

Samples and scans for research 
The team ask to take some extra blood samples. Where possible, you have these at the same time as your routine blood tests.

They plan to use the samples to:

  • look for substances called biomarkers Open a glossary item to help work out why treatment might work for some people and not for others
  • look at genes Open a glossary item to understand more about prostate cancer
  • look for small pieces of DNA from cancer cells in the blood (ctDNA Open a glossary item)

You can say no to giving the samples for genetic research. It won’t affect you taking part in the rest of the trial. 

The team also collect some samples of tissue when you have surgery. This is to see how treatment worked. 

The trial team might ask to take an extra tissue sample before you start treatment. And to have an MRI scan Open a glossary item the day before surgery. You can say no to this if you would prefer not to. 

Hospital visits

You see the doctor and have tests before you can take part. These include:

Some people may also have an mpMRI scan. Your doctor can tell you more about this. 

You see the trial team for regular check ups if you have AZD5305, darolutamide or both. These take place:

  • on the first day of trial treatment 
  • in week 2
  • the day before surgery
  • on the day you have surgery

Follow up
Everyone has a check up 1 month after surgery. You then see your doctor at routine hospital appointments.

Side effects

The trial 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. 

AZD5305 is a new drug so we don’t know what all the side effects are yet. The most common side effects of AZD5305 we know about so far include:

The most common side effects of darolutamide are:

  • tiredness
  • an increased risk of infection 
  • high blood pressure
  • skin rash
  • liver changes 

There are some other serious side effects of darolutamide to look out for. Let your doctor know straight away if you have any of the following:

  • chest pain or pain in other parts of the body. This can spread from your chest to your arms, jaw, neck, back and tummy. You might feel lightheaded or dizzy, sweat, have shortness of breath and feel sick.
  • breathlessness after activity or at rest, tiredness most of the time, feeling lightheaded or fainting and swelling of the ankles and legs 
  • seizures (fits)

You should not eat Seville oranges or grapefruit, or drink their juices while taking AZD5305. This is because they can affect the way AZD5305 works in your body.  

Your doctor will talk to you about all the possible side effects of treatment. You’ll have a chance to ask any questions you may have. 

We have more information about:


Newcastle upon Tyne

Recruitment start:

Recruitment end:

How to join a clinical trial

Please note: In order to join a trial you will need to discuss it with your doctor, unless otherwise specified.

Please note - unless we state otherwise in the summary, you need to talk to your doctor about joining a trial.

Chief Investigator

Dr Simon Pacey

Supported by


If you have questions about the trial please contact our cancer information nurses

Freephone 0808 800 4040

Last review date

CRUK internal database number:


Please note - unless we state otherwise in the summary, you need to talk to your doctor about joining a trial.

Last reviewed:

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