A trial looking at adding pembrolizumab to chemoradiotherapy for bladder cancer (KEYNOTE-992)

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

Cancer type:

Bladder cancer

Status:

Closed

This trial is looking at adding a drug called pembrolizumab to chemotherapy and radiotherapy (chemoradiotherapy). It is for people with bladder cancer that has spread into or through the muscle layer of the bladder. This is called muscle invasive bladder cancer, or invasive bladder cancer.

More about this trial

You might have chemotherapy Open a glossary item and radiotherapy together for invasive bladder cancer. This is called chemoradiotherapy. The chemotherapy drugs help the radiotherapy to work better. They are called radiosensitisers.

Researchers are looking for ways to improve invasive bladder cancer treatment. In this trial, they are looking at adding a drug called pembrolizumab. It is a type of immunotherapy Open a glossary item .

Immunotherapy stimulates the body’s immune system Open a glossary item to fight cancer cells. Pembrolizumab targets and blocks a protein called PD-1 on the surface of certain immune cells called T-cells. Blocking PD-1 triggers the T-cells to find and kill cancer cells.

In this trial, everyone taking part has chemoradiotherapy. And some people have pembrolizumab and some don’t.

The main aims of the trial are to find out:

if adding pembrolizumab to usual treatment works better
how safe the treatment is
more about the side effects of treatment
more information about the quality of life of people taking part

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 bladder cancer that has spread into or through the muscle layer of the bladder (this is called muscle invasive bladder cancer, or invasive bladder cancer)
have cancer that started in the cells of the bladder wall (urothelial bladder cancer). If you have a mixed type of bladder cancer you might still be able to take part, if at least half of the bladder cancer cells are urothelial. Your doctor can explain more.
have had your diagnosis based on samples from a trans urethral removal of bladder tumour (TURBT) test within the 90 days before signing the consent form for this trial
have had your test results looked at by an independent team of experts. This is called blinded independent central review (BICR).
have a tumour sample available, so that doctors can look for a type of protein called PDL-1. They will use the sample taken during your diagnosis if it is available.
will be having chemoradiotherapy as part of your treatment plan
are well enough to have chemoradiotherapy
can look after yourself and are up and about for half the day (performance status 0, 1 or 2)
have satisfactory blood test results within the 14 days before randomisation
have had a negative pregnancy test in the 24 hours before the first dose of the study drug, if there is a possibility you could be pregnant
are willing to use reliable contraception during treatment and for around 6 months after if there is any possibility that you or your partner could become pregnant. Your doctor will let you know about suitable contraception.
agree not to donate eggs or sperm, or store eggs, during treatment and for around 6 months after
are at least 18 years old

Who can’t take part

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

have cancer that has spread to your lymph nodes or elsewhere in your body, which has been seen on a chest CT or a CT urogram or MR urogram – these are scans of your kidneys, ureters and bladder
have multiple areas of carcinoma in situ (CIS) throughout your bladder
have small cell or neuroendocrine cancer, even if it is a mixed type of bladder cancer
have had any other type of urothelial cancer apart from bladder cancer in the last 2 years, apart from carcinoma in situ of the upper urinary tract or very small cancers of the upper urinary tract which have been removed with surgery that removed your kidney, ureter and part of your bladder
have had another cancer within the past 3 years that has been getting worse, or needed treatment – apart from treated basal cell skin cancer , squamous cell skin cancer, superficial bladder cancer or another carcinoma in situ (for example breast CIS or cervical CIS). You may be able to take part if you have localised prostate cancer and you are having treatment or surveillance . Your doctor will be able to tell you more.
have had any anti-cancer treatment for your muscle invasive cancer. You may be able to take part if you have had treatment for early bladder cancer with BCG or chemotherapy into the bladder, if it finished more than 28 days before randomisation.
have had radiotherapy to the bladder or pelvis before
have had another trial drug or used a healthcare product as part of another clinical trial or study in the 4 weeks before the first dose of the study drug
have had a drug very similar to pembrolizumab in the past. Your doctor can explain more.

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

have a build up of urine inside both kidneys which causes them to become waterlogged and swollen (bilateral hydronephrosis)
have problems with the function of your bladder, such as passing small amounts of urine frequently, not being able to control when you pass urine, or you have a permanent or an in-and-out catheter
have an immune deficiency . Or you have been taking long term steroids that reach the whole body or any other drugs that lower your immune system, in the 7 days before the first dose of the trial drug.
have an active autoimmune disease which has required systemic treatment in the past 2 years. You can still take part if you take replacement therapy, such as insulin or steroids, if your body does not make enough. Your doctor can explain more.
have inflammation of the lung tissue (pneumonitis) or if you have had pneumonitis which needed steroid treatment before
have an infection needing treatment that reaches the whole body
have HIV
have hepatitis B or active hepatitis C
have had an active tuberculosis infection
have had a transplant with someone else’s tissue or organ
have any other medical problem, mental health condition or are taking any medication that the trial team think would affect you taking part

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

are allergic to pembrolizumab, or any of the chemotherapy drugs you would have as part of the trial. Or you are allergic to anything the drugs contain.
have had a live vaccine within 30 days before the first dose of the study drug
are pregnant or breastfeeding

Trial design

This is a phase 3 trial. The researchers need 636 people to take part from approximately 25 different countries. This includes 18 people from the UK.

It is a randomised trial. You are put into treatment groups by a computer. Neither you nor your doctor will be able to decide which group you are in. And neither you nor your doctor will know which treatment you are having. This is a double blind trial. But during the trial if necessary, your doctor can find out which treatment you are having.

You have 1 of the following:

pembrolizumab and chemoradiotherapy (group 1)
a dummy drug and chemoradiotherapy (group 2)

keynote-992.png

You have pembrolizumab or the dummy drug (placebo) as a drip into a vein. You have it once every 6 weeks. You have it for up to around a year as long as it is working, and the side effects are manageable.

You have chemotherapy as a drip into a vein. Your doctor decides which chemotherapy drugs would be best for you. These are all standard Open a glossary item chemotherapy drugs for bladder cancer.

The chemotherapy drugs you have are either:

You have a planning appointment before starting radiotherapy. This is to work out how much radiation you need and exactly where you need it.

How long your chemoradiotherapy takes depends on which chemotherapy drugs you have and what radiotherapy schedule is best for you. It’s usually between 4 and 7 weeks.

Your hospital care team will let you know:

how often you have each drug
how long each drip takes
on which days you have radiotherapy and how long each session takes

Research samples
You give blood and tissue samples during the trial. The trial team use these to find out:

more about how the trial drugs work
what effect the trial drugs have on the body
more about how well the treatment works for invasive bladder cancer
about substances in the blood (biomarkers ) that might tell them how well treatment is working
about any link between PDL-1 and how well the treatment works

Future research
The trial team will ask if you would like to take part in future research. This would mean that they can use samples that they collect as part of the trial. You don’t have to take part if you don’t want to.

Quality of life
The study team will ask you to fill out questionnaire:

before you start treatment
at set times during treatment
after you finish treatment

The questionnaires will ask about side effects and how you’ve been feeling. This is called a quality of life study.

Hospital visits

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

a physical examination
measuring your height, weight and vital signs (blood pressure, temperature and heart rate)
a cystoscopy - to look at the inside of your bladder and urethra
a trans urethral removal of bladder tumour (TURBT) test, if you have not had one in the last 60 days before signing the consent form. Your study doctor will look at the results if you have had one more recently.
collecting tumour tissue during the TURBT or a tumour biopsy – if you have not had one in the last 60 days
a CT scan or MRI scan
a heart trace (ECG )
blood and urine tests – including a pregnancy test if it is possible you could be pregnant

It’s likely you will go to the hospital a few times for all these tests and scans. Having all the tests and waiting for the results can take up to 6 weeks.

Treatment lasts around a year (54 weeks). You might go to the hospital for treatment up to 35 times in the first 7 weeks. After this you go into hospital for treatment once every 6 weeks.

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

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

Tests and scans during treatment
Around 10 weeks after your chemoradiotherapy you have some tests. These are likely to include:

a cystoscopy
urine tests
a biopsy
scans, such as a CT scan or MRI scan

Follow up
When you stop treatment, you see the trial team 1 or 2 times in the first month. You then see the trial team for tests around every 12 weeks for the year after treatment. Then around every 24 weeks.

Tests you have at these visits might include:

a cystoscopy
urine tests
a biopsy (if needed)
scans, such as a CT scan or MRI scan

If your cancer has got worse, or you start a different cancer drug, the trial team phone you every 3 months to see how you are getting on.

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.

Pembrolizumab can affect the immune system. It may cause inflammation in different parts of the body. This 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 tell your 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:

itchy skin, skin rash and loss of skin colour
diarrhoea
cough
joint pain or back pain
rash
fever
stomach pain
loss of skin colour
thyroid problems that can cause tiredness and feeling cold
low levels of salt in your body that may cause you to feel tired, have headaches and muscle cramps

We have more information about the side effects of pembrolizumab.

Chemoradiotherapy may cause more severe side effects than having radiotherapy or chemotherapy on its own.

Generally, radiotherapy can cause:

tiredness and weakness
reddening or darkening of your skin
passing urine more often
inflammation of your bowel causing diarrhoea
hair loss from your pubic area (this usually returns after you’ve finished treatment)

The most common side effects of chemotherapy include: