A study looking at pembrolizumab for bladder cancer (KEYNOTE-057)

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

Cancer type:

Bladder cancer

Status:

Closed

Phase:

Phase 2

This study is for people with early (non muscle invasive) bladder cancer, who have had BCG treatment that was not successful. They must also be at high risk of their cancer coming back or spreading into the deeper layers of the bladder.

More about this trial

BCG into the bladder is the usual treatment for people with high risk non muscle invasive bladder cancer. This works well for most people. But in some people the treatment either doesn’t work or the cancer comes back within a short period.

Pembrolizumab (Keytruda) is a type of immunotherapy. This type of treatment 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.

Pembrolizumab is already used to help people with other types of cancer such as melanoma and non small cell lung cancer. The aim of this study is to see if it can also help people with early bladder cancer.

Who can enter

The following bullet points list the entry conditions for this study. Talk to your doctor or the study team if you are unsure about any of these. They will be able to advise you.

You may be able to join this study if you have high risk transitional cell (or mainly transitional cell) bladder cancer (stage T1, high grade Ta, CIS).

If you have Ta or T1 disease you must not have any cancer that can be removed by a cystoscopy Open a glossary item or trans urethral removal (TURBT). You must have already had at least 2 of these procedures.

You must have been treated with BCG and your cancer has been unresponsive to this treatment. This means that you must have had BCG at least 5 times once a week (induction therapy) and then twice as maintenance therapy. Or you must have had BCG at least 5 times as a second induction therapy within 6 months of your diagnosis. And your cancer has either not got any better, got worse or come back within 6 months.

As well as the above, all of the following must apply. You:

Are not able, or have decided not, to have your bladder removed (a radical cystectomy)
Have a suitable tissue sample available from a recent cystoscopy or TURBT for testing (the doctors will check this)
Are well enough to be up and about for at least half the day (performance status 0, 1 or 2)
Have satisfactory blood test results
Are willing to use reliable contraception during treatment trial and for 4 months afterwards if there is any chance that you or your partner could become pregnant
Are aged 18 years or older

You cannot join this study if any of these apply.

Cancer related

You have muscle invasive locally advanced bladder cancer and can’t have an operation to remove it or your bladder cancer has spread elsewhere in your body (metastatic bladder cancer)
As well as bladder cancer you have cancer of your urethra, ureter or renal pelvis (transitional cell carcinoma of the urothelium )
You had chemotherapy or immunotherapy into your bladder (intravesical therapy) between your most recent cystoscopy or TURBT and starting treatment in this trial
You have had chemotherapy, radiotherapy or a targeted therapy (biological therapy) in the past 2 weeks and you still have moderate to severe side effects. You might still be able to take part if you only have hair loss (alopecia) and mild problems with your nerves (neuropathy)
You have had the drug pembrolizumab or any other drug that affects a protein called PD-1 or certain immune cells called T-cells
You have had another cancer apart from successfully treated early cancer (carcinoma in situ ) of the cervix, non-melanoma skin cancer or early stage prostate cancer where you have not had hormone therapy for 5 years and your PSA has been undetectable during this time

Medical conditions

You have had an experimental drug or used an experimental device as part of another clinical trial in the past 4 weeks
You have an infection that needs treatment that reaches your whole body (systemic treatment)
You have an autoimmune disease that needed systemic treatment in the past 2 years. You might still be able to take part if the treatment was to replace something the body usually produces such as thyroxine or insulin
You have lung problems such as interstitial lung disease or inflammation of the lung (pneumonitis)
You have hepatitis B or hepatitis C
You have HIV
You have any other serious medical condition or mental health problem that the trial team think could affect you taking part

Other

You have had a live vaccination in the past 30 days
You are pregnant or breastfeeding

Trial design

This is an international phase 2 study. Doctors need about 260 people to take part worldwide and need about 8 people in the UK.

Everyone has pembrolizumab. You have it as a drip into a vein. You have treatment once every 3 weeks.

You have pembrolizumab for up to 2 years as long as it works and the side effects aren’t too bad.

If your cancer comes back or gets worse, you stop having pembrolizumab. Your doctor will discuss other treatment options with you.

Questionnaires
You complete a questionnaire every time you have treatment and when you see the doctor the first time after you finish treatment.

The questionnaires ask about how you’re feeling and about any side effects you have had. This is called a quality of life study.

Samples for research
You need to have a sample of your cancer (a biopsy Open a glossary item ) taken before starting in the trial. This sample along with some blood samples will be used to look for substances called biomarkers. The researchers use these to learn more about how pembrolizumab works on bladder cancer and why treatment works for some people and not others.

You will also need to give some additional blood samples for research. These will be used:

to measure the amount of pembrolizumab in your body- you may hear this called pharmacokinetics
to look for natural antibodies made by the body that attach to pembrolizumab in your blood

Hospital visits

You see the doctors and have some tests before you start treatment. The tests include:

physical examination
heart trace (ECG )
blood and urine tests
cystoscopy
CT or MRI scan

Instead of a CT or MRI scan you might have a CT urogram or MR urogram.

You go to hospital to have your pembrolizumab. You shouldn’t need to stay overnight.

You see the doctor and have regular blood tests during the time you have treatment. You also have a:

cystoscopy every 3 months
CT scan every 6 months

When you finish treatment you see the doctor about a month later. You then see them every 3 months for a year. You have a cystoscopy every 6 months and a CT scan every year. You then see the doctors every 3 months.

If you stop having pembrolizumab for any reason or start a new cancer treatment the doctor will telephone you every 3 months for a year to see how you are.

Side effects

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

The most common side effects of pembrolizumab are: