A trial of pembrolizumab and chemotherapy for prostate cancer that has spread (KEYNOTE 921)

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 who have prostate cancer that has spread elsewhere in the body despite hormone treatment.

Prostate cancer that has spread to other parts of the body is advanced or metastatic cancer

More about this trial

You might have chemotherapy for advanced prostate cancer if hormone treatment stops working. The usual treatment is a chemotherapy drug called docetaxel. You have this with a steroid drug called prednisolone. 

Doctors are looking for ways to improve treatment. In this trial they are looking at adding a drug called pembrolizumab.

Pembrolizumab is an immunotherapy. It stimulates the body's immune system Open a glossary item to fight cancer cells. 

In this trial some people have docetaxel and pembrolizumab. And some people have docetaxel and a dummy drug (placebo Open a glossary item).

The main aims of the trial are to:

  • see how safe it is to have pembrolizumab with chemotherapy 
  • see if adding pembrolizumab to docetaxel improves treatment
  • learn more about the side effects 
  • see how treatment affects quality of life Open a glossary item

Who can enter

The following bullet points list the entry conditions for this trial. The trial doctor reviews the entry conditions to make sure you are suitable to join the 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:

  • are a man 
  • have adenocarcinoma Open a glossary item of the prostate that has spread elsewhere in the body 
  • have cancer that can be seen on a scan and has spread to the bones or surrounding tissue. You will not be able to join the trial if the cancer has spread only to the lymph nodes  Open a glossary itembetween the hip bones (pelvis Open a glossary item)
  • have prostate cancer that got worse in the last 6 months either while you were having hormone treatment or after you had surgery to remove the testicles  Open a glossary item(the trial team can tell you more about this)
  • had flutamide at least 4 weeks ago or bicalutamide or nilutamide at least last 6 weeks ago, if you had any of these three drugs before joining this trial
  • have had treatment with only 1 of the following drugs such as abiraterone, enzalutamide, apalutamide or darolutamide and the cancer got worse after at least 8 weeks of treatment or you had to stop due to side effects but had treatment for at least 4 weeks
  • have been on a stable dose of bisphosphonates  Open a glossary itemor denosumab for at least 4 weeks if you are taking one of these drugs
  • have a sample of tissue available for the trial team to do some tests on 
  • have satisfactory blood tests results
  • are willing to use a condom during treatment and for 6 months after if there is any chance you can pass your ejaculate to another person of any sex. You should not store any sperm during treatment or for 6 months after 
  • are well enough to carry out all your normal activities but you might not be able to do heavy physical work (performance status of 0 or 1
  • are at least 18 years old 

Who can’t take part

You cannot join this trial if any of these apply. 

Cancer related
You:

  • have cancer in the brain or spinal cord. You might be able to take part if you have cancer spread to your brain that has been successfully treated, has not got any worse in the last 4 weeks and you haven’t taken steroids for at least a week.
  • have cancer spread to the membranes that surround the brain (carcinomatous meningitis)
  • have already had treatment with pembrolizumab or similar drugs. Your doctor will be able to discuss this in more detail with you. 
  • have had docetaxel or another chemotherapy drug in the past for prostate cancer that has spread 
  • have had radioactive medicine for prostate cancer such as radium 223
  • have had abiraterone, enzalutamide, apalutamide or darolutamide within 4 weeks of starting treatment in this trial or you still have moderate to severe side effects from these treatments apart from hair loss
  • have had treatment with hormone drugs such as finasteride, dutasteride or cyproterone within the last 4 weeks
  • have had treatment with a drug called ketoconazole for prostate cancer 
  • had a type of bone scan called a ‘superscan’ bone scan
  • have had any other cancer in the last 3 years that is getting worse or needs treatment apart from basal cell skin cancer Open a glossary item, squamous cell skin cancer Open a glossary item or carcinoma insitu (CIS Open a glossary item) that has been successfully treated with surgery

Medical conditions
You:

  • have a problem with your immune system Open a glossary item or you take a treatment such as steroids that is equal to more than 10mg of prednisolone a day or any another treatment that damps your immune system within 7 days of starting trial treatment 
  • an active autoimmune condition Open a glossary item that needed treatment in the last 2 years apart from treatment to replace hormones Open a glossary item in the body
  • had surgery in the last month and are not yet fully recovered
  • have a problem with your gut (digestive system Open a glossary item) that would affect how you absorb the trial drug
  • can’t swallow tablets or capsules 
  • have an active infection including tuberculosis (TB)
  • have lung inflammation (pneumonitis) Open a glossary item or had lung inflammation in the past which was treated with steroids.
  • have moderate to severe tingling or numbness in your hands or feet unless it was due to an accident not treatment 
  • have a build up of fluid in the tummy (abdomen) or on the lungs
  • have a heart condition called congestive heart failure that is causing symptoms 
  • have had a blood transfusion in the last 120 days or red blood cells  Open a glossary itemor platelets Open a glossary item within the last month 
  • have had treatment to stimulate the bone marrow  Open a glossary itemto make blood cells (growth factors) within 1 month of starting trial treatment 
  • have had monoclonal antibody Open a glossary item treatment within 4 weeks of joining a trial group or you have had one in the past and still have moderate to severe side effects 
  • have had herbal medicines for example ‘saw palmetto’ within 4 weeks of joining a treatment group in this trial 
  • take a medication that blocks an enzyme called CYP3A4 that you can’t stop while you take part in the trial 
  • have had radiotherapy within 2 weeks of starting treatment. Your side effects from radiotherapy must be better and you must not have pneumonitis Open a glossary item.
  • have had treatment in another clinical trial within 4 weeks of starting trial treatment 
  • have had a stem cell transplant Open a glossary item with someone else’s cells or an organ transplant Open a glossary item 
  • have HIV
  • have an active hepatitis B or hepatitis C infection 
  • have any other medical condition, mental health problem or problem with drugs and alcohol that the trial team think would affect you taking part in the trial  

Other

  • You are allergic to pembrolizumab or anything it contains.
  • You are allergic to docetaxel or polysorbate 80.
  • You have had a live vaccination Open a glossary item in the last 30 days. 
  • You and your partner are planning a pregnancy. 

Trial design

This phase 3 trial is taking place worldwide. The researchers need 1,000 men to take part including about 48 men from the UK. 

It is a randomised trial. There are 2 treatment groups. You are put into a treatment group by a computer. Neither you nor your doctor can decide which group you are in. And neither of you know which group you are in. This is a double blind study. 

You have 1 of the following:

  • docetaxel, prednisolone and pembrolizumab
  • docetaxel, prednisolone and a dummy drug (placebo Open a glossary item)


You have docetaxel as a drip into a vein. You have treatment in cycles Open a glossary item. Each cycle of treatment is 3 weeks. You have docetaxel once every 3 weeks. You have up to 10 treatment cycles. 

Prednisolone is a tablet. You take it by mouth during the same period you have docetaxel. The trial team tell you when to take it. 

You have pembrolizumab or the dummy drug as a drip into a vein. You have it once every 3 weeks (on the same day as your docetaxel).  You have it for up to 2 years as long as it is working and the side effects are manageable.

Samples for research
You give a new tissue sample of the cancer if there isn’t one available from a past surgery or biopsy Open a glossary item. You also give some extra blood samples. Where possible, you give these at the same time as your routine blood tests.

The team plan to look at:

  • gene changes (mutations Open a glossary item)
  • substances called biomarkers Open a glossary item to help work out why treatment might work for some men and not for others

Pain questionnaire 
The trial team want to find out if you have pain and if so, how bad it is. You fill in a pain questionnaire on a small electronic device. The device alerts you when you need to complete it. An alarm goes off at the same time every day to remind you to complete it. You complete this until you stop treatment.

You take the device with you to each hospital visit. The team also give you a paper diary to record any pain medication you take. You bring this with you to each visit. 

    Hospital visits

    You see a doctor and have some tests before you join the trial. These include:

    You have treatment at the hospital in the outpatient department. So you shouldn’t need to stay overnight. 

    At each treatment visit you see the doctor for a check up and you have some blood tests.

    When you stop treatment you see the trial team 1 month later. If your cancer has got worse the trial team phone you every 3 months to see how you are getting on. Your doctor will talk to you about other treatment options. 

    If you stop treatment but your cancer hasn’t got worse you see the trial team for a check up every:

    • 9 weeks in the first year 
    • 3 months after that

    You have regular CT scans, MRI scans or bone scans until your cancer gets worse. You have these every:

    • 9 weeks for a year
    • every 3 months after that 

    Side effects

    The trial team monitor you during treatment and afterwards. Having pembrolizumab with docetaxel is a new treatment so there might be some side effects we don’t know about yet. Contact your advice line or tell your doctor or nurse if you have any side effects. 

    Pembrolizumab can affect the immune system. It may cause inflammation in different parts of the body which can cause serious side effects. They could happen during treatment, or some months after treatment has finished. Rarely, these side effects could be life threatening.

    If you have any of these side effects, you should tell the doctor or nurse as soon as possible. You should tell them that you are on, or have been on, an immunotherapy. 

    The most common side effects of pembrolizumab are:

    • joint or back pain 
    • itchy skin or a skin rash
    • loose or watery poo
    • cough
    • fever
    • tummy pain 
    • loss of skin colour
    • low levels of the thyroid hormone so you may feel tired, gain weight, feel cold, or be constipated
    • low levels of salt in the blood that may cause you to feel tired, confused, have a headache, have muscle cramps and feel or be sick 

    The trial doctor talks to you about all the possible side effects of each treatment before you join the trial and during the trial. 

    We have more information about:

    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

    Professor Johann de Bono

    Supported by

    Merck, Sharp & Dohme

    Freephone 0808 800 4040

    Last review date

    CRUK internal database number:

    17101

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

    Over 60,000 cancer patients enrolled on clinical trials in the UK last year.

    Last reviewed:

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