A trial of pembrolizumab with radiotherapy for people with advanced bladder cancer (PLUMMB)

Cancer type:

Bladder cancer

Status:

Open

Phase:

Phase 1

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

Advanced bladder cancer is often treated with radiotherapy. This uses high energy waves similar to x-rays to shrink the cancer and help to control the symptoms. 

Pembrolizumab (Keytruda) is a type of targeted therapy called a monoclonal antibody. It helps the immune system  Open a glossary itemto attack the cancer and stops it from growing.

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 cystoscopy Open a glossary item
  • 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 Open a glossary item) 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.

Cancer related

  • Your cancer has spread to your brain, tissues surrounding your brain or your spinal cord Open a glossary item. 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 Open a glossary item) of the cervix or non-melanoma skin cancer

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 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 disease Open a glossary item that 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

Other

  • You have had a live vaccination Open a glossary item in the past 30 days
  • You take drugs or drink large amounts of alcohol
  • You are pregnant or breastfeeding

Trial design

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. 

Pembrolizumab
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. 

Radiotherapy
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.  

Blood tests 
You have 4 extra blood tests as part of this trial. The researchers want to:

  • look for cancer DNA  Open a glossary itemin 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.

Hospital visits

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. 

Side effects

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.

The most common side effects of pembrolizumab are:

We have more information about pembrolizumab

We also have information about radiotherapy side effects

Location

London

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

Prof Robbert Huddart

Supported by

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

Freephone 0808 800 4040

Last review date

CRUK internal database number:

14560

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

Wendy took part in a new trial studying the possible side effect of hearing loss

A picture of Wendy

"I was delighted to take part in a clinical trial as it has the potential to really help others in the future.”

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