Around 1 in 5 people diagnosed with cancer in the UK take part in a clinical trial.
A trial of pembrolizumab with radiotherapy for people with advanced bladder cancer (PLUMMB)
This trial is for people with bladder cancer that has spread to the nearby tissues or to another part of the body (advanced bladder cancer).
It is for people going to the Royal Marsden Hospital in Surrey.
More about this trial
Pembrolizumab is already used to help people with other types of cancer such as melanoma and non small cell lung cancer. But doctors want to find out if it can also help people with advanced bladder cancer.
In this trial you have radiotherapy and pembrolizumab. The dose of pembrolizumab you have depends on when you join the trial.
The main aims of this trial are to:
- find out how well pembrolizumab and radiotherapy work as a treatment
- find the highest safe dose of pembrolizumab which can be given with radiotherapy
- learn about the side effects of treatment
- look for certain proteins called PD1 and PDL1
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.
You may be able to join this trial if all of the following apply.
- You have invasive bladder cancer that has spread to the nearby tissues or to another part of the body (T2 to T4, N0 to N3 and M0 to M1)
- You have at least 1 area of cancer that can be seen on a scan or if you have bladder cancer that has grown through the bladder wall or has spread to the lymph nodes but no further on a
- You are not able to have treatment (such as an operation to remove the bladder or chemoradiotherapy) to cure your cancer for any reason
- You are willing to have a sample of your cancer taken (a
biopsy) if there is no suitable sample available (an archival tissue sample)
- You have satisfactory blood tests results
- You are well enough to carry out your normal activities, apart from heavy physical work (performance status of 0 or 1)
- You are at least 18 years old
- You are willing to use reliable contraception during the trial and for 4 months afterwards if there is any chance you or your partner could become pregnant
You cannot join this trial if any of these apply.
- Your cancer has spread to your brain, tissues surrounding your brain or your
spinal cord. You might still be able to take part if you have had treatment, it hasn’t got worse in the past 4 weeks and you haven’t taken steroids in the past 7 days
- You have had radiotherapy to the area between your hip bones (pelvis)
- You have had surgery, chemotherapy, radiotherapy or a targeted therapy (biological therapy) in the past 4 weeks and you still have moderate to severe side effects (apart from hair loss (alopecia) and mild changes to your nails or 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 such as ipilimumab
- You have had another cancer apart from successfully treated early cancer (
carcinoma in situ) of the cervix or non-melanoma skin cancer
- 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 a weakened immune system or you have taken drugs that damp down your immune system (immunosuppressants) such as steroids in the past 7 days
- You have or have had an
autoimmune diseasethat needed systemic treatment in the past 3 months, apart from vitiligo, childhood asthma that has resolved, thyroid problems that are controlled by medications or you need drugs to make you breathe easier (bronchodilators) or steroid injections
- You have lung problems such as interstitial lung disease or inflammation of the lung (pneumonitis)
- You have bowel problems such as inflammatory bowel disease or any other problem that your doctor thinks could affect you having radiotherapy to the pelvis
- 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
- You have had a live
vaccinationin the past 30 days
- You take drugs or drink large amounts of alcohol
- You are pregnant or breastfeeding
This is a phase 1 trial. The researchers need around 28 people who are going to The Royal Marsden Hospital to take part.
You have pembrolizumab and radiotherapy.
You have pembrolizumab as a drip into a vein. It takes about 30 minutes each time.
The first few people taking part have a low dose of pembrolizumab. If they don’t have any serious side effects, the next few people have a higher dose. And so on, until doctors find the best dose.
You have pembrolizumab:
- 2 weeks before the start of radiotherapy
- 1 week after the start of radiotherapy
- then every 3 weeks
This continues for as long as it helps you and the side effects aren’t too bad. You can have it for up to 1 year.
You have a radiotherapy planning scan. The scan helps doctors know how much radiation you need and exactly where you need it. Then you start radiotherapy.
You have radiotherapy once a week, for 6 weeks.
You have 4 extra blood tests as part of this trial. The researchers want to:
- look for cancer
DNAin your bloodstream (circulating DNA)
- look for changes in genes that can help to tell why treatment works better for some people than others
You have the extra blood samples at the same time you have routine blood tests.
Sample of tissue
Researchers will ask to use a sample of your cancer taken either when you were diagnosed or during any treatment you’ve had. They want to look for substances (markers) that affect how cancer develops and how treatment works.
If there isn’t a suitable sample available, you might have a new sample taken (a biopsy).
The research team might also ask you to have a new tissue sample taken 18 weeks (around 4 ½ months) after the start of treatment. This is only if you have bladder cancer that has spread to the nearby tissues.
You see a doctor and have some tests before taking part. These tests might include:
- a physical examination
- blood tests
- a CT scan
- a camera test to look inside your bladder (cystoscopy)
During treatment, you see the doctor for blood tests and a physical examination before each pembrolizumab treatment.
You have a CT scan 12 weeks after the start of treatment and then:
- after 2 months
- every 3 months
This continues for as long as your cancer stays the same and does not get worse. If your cancer gets worse you stop having treatment.
When you finish treatment you see the trial doctor after a month. You have blood tests and a physical examination. After this, you see the doctor as part of your regular follow up.
The trial 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.
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:
- low red blood cells (
anaemia) causing tiredness or shortness of breath
- tiredness (fatigue)
- inflammation of the lungs that can cause shortness of breath
- pneumonia (swelling of lung tissue, usually caused by infection)
- high temperature
We have more information about pembrolizumab.
We also have information about radiotherapy side effects.
How to join a clinical trial
Prof Robbert Huddart
Biomedical Research Centre (BRC)
Institute of Cancer Research (ICR)
Merck Sharp and Dohme (MSD)
National Institute for Health Research (NIHR)
The Royal Marsden NHS Foundation Trust