A trial of atezolizumab before surgery for urothelial cancer of the bladder (INVEST)

Cancer type:

Bladder cancer
Transitional cell cancer

Status:

Open

Phase:

Phase 1

This trial is looking at having atezolizumab directly into the bladder followed by surgery. 

It is for people who are due to have surgery to remove their bladder (a radical cystectomy). Open a glossary item

More about this trial

Urothelial cancer is a type of bladder cancer. It can start in the:

  • kidneys
  • tube that takes urine from the kidney to the bladder (ureter)
  • bladder
  • tube that drains urine from the bladder and out of the body (urethra) 

The lining of the urinary tract is called the urothelium. So cancer of the urinary tract can also be called urothelial cancer.

Treatment into the bladder and surgery to remove it are common treatments for bladder cancer. 

Doctors are looking at ways to improve treatment for bladder cancer to reduce the need for surgery. In this trial they are looking at a drug called atezolizumab. It is an immunotherapy. It helps the immune system Open a glossary item to find and kill cancer cells.

Atezolizumab is already a treatment for bladder cancer that has spread elsewhere in the body. The usual way to have this is as a drip into the bloodstream.  

Doctors think that for bladder cancer, it might be better to have atezolizumab directly into the bladder. This is rather than having it in the usual way as a drip into the bloodstream.

In this trial you have atezolizumab into the bladder before having surgery to remove it. 

The team plan to give atezolizumab using 2 different methods:

  • giving it into the bladder (passive installation)
  • injecting it into the tumour and the bladder wall (direct injection)

This is the first time people are having atezolizumab in these ways. 

The main aims of the trial are to find out:

  • if having atezolizumab into the bladder is safe
  • the best dose of atezolizumab to have as a treatment into the bladder
  • the best way of giving atezolizumab into the bladder 
  • how well atezolizumab into the bladder works 
  • what happens to atezolizumab in the body 
  • what the side effects are

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 urothelial (urinary tract) cancer of the bladder 
  • have non muscle invasive bladder cancer that has a high risk of coming back or muscle invasive bladder cancer that hasn’t spread to the lymph nodes Open a glossary item or elsewhere in the body  
  • are due to have surgery to remove the bladder (a radical cystectomy Open a glossary item) for urothelial (urinary tract) bladder cancer. And the surgery is going to take place at least 6 weeks after the confirmation you are suitable to take part in this trial. 
  • are not suitable to have cisplatin before surgery if you have muscle invasive bladder cancer or you don’t want to have this
  • have a cancer tissue sample (biopsy Open a glossary item) available that the trial team can access
  • are well enough to be up and about for at least half a day but might not be able to work (performance status 0, 1 or 2)
  • are willing to use reliable contraception during the trial and for a period after if there is any chance you or your partner could become pregnant
  • have satisfactory blood test results
  • 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 the tissues that surround the brain and spinal cord (leptomeningeal disease)
  • have had another treatment into the bladder within 2 weeks of doctors checking if you are suitable to take part in this trial
  • have had radiotherapy to the bladder or you are due to have this
  • have had a drug called a checkpoint inhibitor Open a glossary item in the past. You can take part if you have had BCG Open a glossary item into the bladder in the past.
  • have pain caused by cancer that isn’t well controlled 

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

  • have had a heart attack in the last 3 months or another significant heart problem Open a glossary item that needs treatment
  • have had a stroke in the last 3 months
  • have a tube in your bladder (stent) that helps the urine drain or you have a condition which means the urine flows back up the tube connecting the kidneys to the bladder
  • have had a urine infection in the 2 weeks before doctors check if you are suitable to take part in this trial
  • had a severe infection within 4 weeks of starting trial treatment or you have any other infection that the trial team think could affect you taking part 
  • have had antibiotics to treat an infection within 2 weeks of having trial treatment
  • can’t hold on for a wee for at least an hour
  • have an autoimmune condition Open a glossary item apart from certain ones. Your doctor will know this.
  • have taken medication that damps down the immune system Open a glossary item within 2 weeks of starting trial treatment or you might need to have this during the trial. You might be able to take part if you are having a low dose of steroids. Your doctor will know about this. 
  • have HIV, an active hepatitis B or hepatitis C infection, an active COVID-19 infection, or active tuberculosis (TB)
  • have had a stem cell transplant with someone else’s cells (allogeneic transplant Open a glossary item) or an organ transplant Open a glossary item 
  • have scarring or inflammation of the lungs that means you can’t take part 
  • have had major surgery other than surgery to diagnose your bladder cancer. You had TURBT within 4 weeks of joining the trial or you might need major surgery during the trial.
  • have high levels of calcium in the blood
  • have a collection of fluid on the lung, around the heart or tummy that needs to be drained quickly 
  • have any other medical condition or mental health problem that the trial team think could affect you taking part 

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

  • have had a live vaccine Open a glossary item within 4 weeks of starting treatment or you might need to have one during the trial or for a period of time after
  • are sensitive to atezolizumab, similar drugs or anything they contain 
  • are pregnant or breastfeeding or planning to become pregnant 

Trial design

This phase 1 trial is taking place in Sheffield. 

Everyone has atezolizumab into the bladder in 1 of the following ways by:

  • giving it directly into the bladder (passive installation)
  • injecting it into the tumour in the bladder (direct injection)

The method you have depends on when you join the trial. Your doctor will tell you more about the method you will have. 

Atezolizumab into the bladder (passive instillation)
You have atezolizumab into your bladder through a thin tube (catheter). The catheter goes into your bladder through the urethra. The urethra is the tube that carries wee (urine) from the bladder out of the body. The doctor or nurse puts in the catheter on the day unit. You have this done under local anaesthetic Open a glossary item. You must not pass urine for at least an hour after the procedure.

This is the usual way to have other standard of care drugs into the bladder such as  BCG.

Atezolizumab as injections into the bladder (direct injection)
This involves injecting the atezolizumab directly into the tumour. To do this the doctor uses a narrow telescope (called a cystoscope). This goes into your bladder through the urethra. The drug is then injected into the tumours and the bladder wall. You have this done under local anaesthetic. 

Finding the best dose and schedule of atezolizumab
For both methods, the first few people have a low dose of atezolizumab. The next few people have a higher dose if they don’t have any side effects. This helps the doctors to confirm the best dose. Between 6 and 42 people join this part. 

When they find this dose, they test it in more people. About 20 people join this part.   

Some people have one dose of atezolizumab. And some people have more than one dose. Those having more than one dose have it once a week for 3 to 6 weeks. 

The dose you have and how many depends on when you join the trial. The team can tell you more about this. 

When this treatment is finished you have your surgery as planned. 

Surgery
Trial treatment will fit in before your planned surgery. This means your surgery won’t be delayed by taking part in this trial. Everyone has surgery within 1 to 4 weeks after the last dose of atezolizumab. 

Your doctor will tell you what surgery to remove the bladder involves and how long you’ll be in hospital for. 

Samples for research 
The researchers might ask to take some extra blood samples. Where possible, you have these at the same time as your routine blood tests. They also ask you to give extra urine samples. And they take samples of cancer tissue when your bladder is removed.

They plan to use the samples to:

  • see how well the treatment is working
  • look at genes Open a glossary item to understand more about bladder cancer
  • see what happens to atezolizumab in the body 

Hospital visits

You see a doctor and have some tests before you can take part in this trial. These include: 

The team might also ask you to have an MRI-PET scan. 

One week after you finish trial treatment and before surgery you have:

  • blood tests
  • urine tests
  • a check up with your doctor
  • a CT scan 

You see the doctor for regular blood tests and check ups. This is part of your routine care after bladder cancer surgery. 

One month after surgery, you have a test that looks at the whole of your urinary system. This is called an intravenous urogram (IVU). You have another CT scan 3 months after surgery. These are standard tests that you have after bladder surgery. You would have them even if you weren’t in the trial. 

You have a final check up with the doctor about 3 months after surgery. The team then continue to see how you are getting on. They do this by checking your hospital notes. You won’t have to go to the hospital for extra visits. 

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. 

Having atezolizumab into the bladder might affect the immune system Open a glossary item. This is because small amounts of atezolizumab will be absorbed into the bloodstream. There is a small risk this may cause inflammation Open a glossary item and other reactions in different parts of the body. These are similar to the immune side effects of atezolizumab into a vein. 

These side effects could happen during treatment or months after treatment has finished. Rarely, these side effects could be life threatening. Your doctor or nurse can explain what these side effects are, the risk of them happening and what to look out for.
 
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.

 

Having atezolizumab directly into the bladder is a new way of having it. This is the first time people are having it in this way. The doctors doing this trial think it is safe to have it into the bladder. 

Giving cancer treatment into the bladder does not normally have as many other side effects as having tablets or injections. This is because the drug tends to stay in the bladder and very little gets into the bloodstream. We do not know how much atezolizumab, if any, will get into your bloodstream. If it does you may have side effects in parts of the body other than the bladder. The team will tell you what these are and what to look out for. 

The side effects of other cancer treatments that are given directly into the bladder can include:

  • blood in the urine
  • pain or problems passing urine
  • needing to pass urine more often or urgently
  • bladder spasms or cramps
  • urine infections

These side effects are normally mild and often settle within a day or two. If they go on for longer or are severe your doctor may need to give you other medications to help with your symptoms. 

The team will tell you about all the possible side effects before you start treatment. You’ll have a chance to ask them any questions you may have. 

We have more information the following treatments and their side effects:

Location

Sheffield

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.

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

Chief Investigator

Professor Syed Hussain

Supported by

F. Hoffmann - La Roche, Limited
Leeds Institute of Clinical Trials Research at the University of Leeds and the University of Sheffield
Sheffield Teaching Hospitals NHS Foundation Trust
 

If you have questions about the trial please contact our cancer information nurses

Freephone 0808 800 4040

Last review date

CRUK internal database number:

18863

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

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