A study looking at matching treatment to the individual make up of bladder cancer (GUSTO)
Cancer type:
Status:
Phase:
This study is looking at 
in detail to try to match people to treatment for bladder cancer.
It is for people whose cancer has grown into the muscle layer of the bladder. This is called muscle invasive bladder cancer.
More about this trial
The usual treatment for muscle invasive bladder cancer is chemotherapy followed by surgery. A few people might have chemotherapy after surgery. Having chemotherapy doesn’t always work and sometimes the cancer comes back.
Doctors are looking for ways to improve treatment for people with muscle invasive bladder cancer. They hope to be able to provide the best treatment more quickly than the current This could avoid chemotherapy for some people when they think that it won’t work very well but will still cause side effects.
In this study they are matching treatment to the individual make up of the cancer. To do this, they will look at tissue samples (). This helps them to find out more about the make up of each person’s bladder cancer. This is called genetic profiling. They hope this will help doctors decide the best treatment for everyone based on the genetic make up of their cancer. This is called personalised medicine.
We know from research that combinations of genes in bladder cancer cells can be grouped into subtypes. These subtypes help doctors to work out how different treatments work. In this study, the researchers will use the subtypes to guide each person’s treatment.
Everyone in the study has surgery. Some people also have chemotherapy, immunotherapy or both.
Immunotherapy isn’t a standard treatment for muscle invasive bladder cancer. Researchers want to see if having it improves treatment. They are looking at 2 immunotherapies called durvalumab and tremelimumab. Immunotherapy uses the to find and kill cancer cells.
The main aims of this study are to:
- see if enough people join
- identify
gene subtypes and match these to treatment - see how well matched treatments work compared to standard treatment
- find out about side effects
- find out how treatment affects
quality of life
Who can enter
The following bullet points are a summary of 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.
Who can take part
You may be able to join the first part of this study (registration) if all of the following apply.
- Your doctor thinks you may go on to have chemotherapy followed by surgery with the aim to cure. And you are suitable to have any of the treatments in the study including
immunotherapy . - You have muscle invasive bladder cancer that is pure or mixed urothelial (transitional) cell carcinoma. Your doctor will know this.
- You are fit and active but might not be able to do heavy physical work (performance status 0 or 1).
- You are at least 18 years old.
You may be able to join the main part of the study to have treatment if all of the following apply. You:
- joined the registration part of the study
- have muscle invasive cancer that has grown into the muscle wall of the bladder or has spread to the prostate, womb or vagina but no further. This is T2-4a, N0, M0 . Or you have cancer that may have grown into the wall of the bladder and beyond, has spread to only 1
lymph node but hasn’t spread to distant parts of the body. This is T(any), N1, M0 stage cancer. Your doctor will confirm this on a scan to check you are suitable to take part. - weigh more than 30kg
- have satisfactory blood test results.
- are willing to use reliable contraception during the study and for a period after if there is any chance you or your partner could become pregnant
Who can’t take part
Cancer related
You cannot join this study if any of these apply.
- The study team can’t identify the gene subtypes in the cancer cells.
- It takes too long to get the test results from the gene subtype test.
- You have cancer that has spread to distant parts of the body.
- You have cancer that has spread to the tissues that surround the brain.
- You have had durvalumab in the past or have previously taken part in another trial involving durvalumab.
- You are having chemotherapy,
targeted cancer drugs or hormone treatment for cancer. This doesn’t apply to hormone replacement therapy. - You have had radiotherapy to more than a quarter of your body within 4 weeks of starting study treatment.
- You have or had another cancer. You can join if you had successfully treated
non melanoma skin cancer , carcinoma in situ of the cervix or early prostate cancer.
Medical conditions
You cannot join this study if any of these apply. You:
- had a significant
heart problem in the last 6 months or a heart condition that isn’t well controlled with medication. Your doctor checks your heart before you join the study. - have a problem with your heart rhythm
- have a problem with how your kidneys work
- have scarring of the lungs (interstitial lung disease)
- have a serious problem with your
gut that means you have a lot of diarrhoea - have an active
autoimmune condition apart from certain ones or you have an inflammatory disorder such as colitis or Crohn’s disease. Your doctor will know about this. - have had major surgery in the last 28 days
- have moderate to severe side effects from past treatments that aren’t getting better. This doesn’t include hair loss or white patches on the skin (vitiligo).
- have had treatment that damps down the
immune system in the 2 weeks before you are put into a treatment group. This includes steroids within 2 weeks unless it was a low dose. - have a problem with how your immune system works
- have HIV, an active hepatitis B or hepatitis C infection,
tuberculosis or any other severe infection that needs treatment - have had a stem cell transplant with somebody else’s cells (
allogeneic transplant ) in the past - had serious side effects from an immunotherapy or a similar drug that meant you had to stop it. If you had an immunotherapy in the past, all non serious side effects must be completely better.
- have any other medical condition, mental health condition or there is any other reason that could affect you taking part
Other
You cannot join this study if any of these apply. You:
- can’t have cisplatin, gemcitabine, durvalumab or tremelimumab for any reason
- have had a
live vaccine in the 30 days before you are put into a treatment group. This doesn’t apply to the approved COVID-19 vaccines as these aren’t live. - are allergic to any of the study treatments or anything they contain
- are pregnant or breastfeeding
Trial design
This is a phase 2 study The team need to find 320 people to take part in the main part of the study.
To begin with, the researchers identify the gene subtype of each person who joins the study. To do this they look at tissue samples from the bladder.
You won’t be able to join the study if they can’t find the gene subtype in your cancer cells.
The treatment part of the study is randomised. You are put into a group by a computer. Neither you nor your doctor will be able to decide which group you are in.
There are 2 treatment groups. You have 1 of the following:
- standard treatment
- treatment based on the gene subtype in your cancer cells
Everyone has surgery. Not everyone has chemotherapy or immunotherapy. Your doctor will explain which treatment you will have in more detail.
Standard treatment group
In this group you have standard treatment. This is chemotherapy followed by surgery to remove the bladder. Surgery to remove the bladder is called a radical cystectomy.
You have 4 before surgery. Each cycle is 3 weeks, so 12 weeks in total.
You have chemotherapy as a drip into a vein. In each cycle you have:
- gemcitabine and cisplatin chemotherapy on day 1
- gemcitabine chemotherapy on day 8
You then have your surgery as planned.
Gene subtype guided treatment group
In this group, you have treatment based on the gene subtype in the cancer cells. You have 1 of the following:
- chemotherapy and immunotherapy before surgery and immunotherapy after surgery. This is for people who have subtypes that doctors think both chemotherapy and immunotherapy will work for.
- immunotherapy before and after surgery. This is for subtypes that doctors think immunotherapy will work for. But they don’t think chemotherapy will work.
- Surgery only. This is for subtypes that doctors don’t think chemotherapy or immunotherapy will work for. For people with these subtypes getting surgery quicker may work better than chemotherapy.
Everyone has surgery. Not everyone has chemotherapy or immunotherapy. You doctor will explain which treatment you have in more detail.
Chemotherapy
You have 4 cycles of chemotherapy before surgery. Each cycle is 3 weeks, so 12 weeks in total.
You have chemotherapy as a drip into a vein. In each cycle you have:
- gemcitabine and cisplatin chemotherapy on day 1
- gemcitabine chemotherapy on day 8
Immunotherapy
You have 4 cycles of immunotherapy before surgery. This takes 12 weeks. You have 8 cycles of immunotherapy after surgery. This takes 32 weeks. You have it as a drip into a vein.
Before surgery you have:
- durvalumab once every 3 weeks
- tremelimumab once every 6 weeks
After surgery you have durvalumab once every 4 weeks.
Immunotherapy takes about an hour each time.
Surgery
Those not having chemotherapy or immunotherapy have surgery as soon as possible after going into the study. This is within 2 to 6 weeks of being put into a treatment group. You might need treatment after surgery in this group. This isn’t part of the study and the team will talk to you if this applies.
You stop chemotherapy, immunotherapy or both if treatment stops working. Your doctor will talk to you about other treatment options.
Samples for research
The researchers might ask you to give some extra tissue samples () from surgery that you have as part of this study. You don’t have additional surgery or biopsies. They also ask to take some extra blood samples. Where possible, you have these at the same time as your routine blood tests.
They plan to use the samples to see how treatment is working.
They also plan to use them for future research. You can say no to this. It won’t affect you taking part in the rest of the study.
Quality of life
The study team ask everyone to fill out a questionnaire before and after surgery to remove the bladder. You do this at set times online or on a paper questionnaire.
The questionnaire asks about side effects and how you’ve been feeling. This is called a quality of life study.
Hospital visits
You see the doctor for a and have tests before you can take part. These include:
- blood tests
- heart trace (ECG)
- CT scan or MRI scan
During treatment you see the doctor regularly. This is for blood tests and to see how you are. Your doctor will tell you about surgery to remove the bladder, what this involves and how long you stay in hospital for.
You have a CT scan or MRI scan:
- before surgery if you have chemotherapy
- 6 months after surgery
- 1 year after surgery
These are standard scans you would have as part of your routine care.
Follow up appointments
You have a check up with your doctor after surgery at:
- 3 months
- 6 months
- 12 months
These are routine appointments for people who have their bladder removed.
You also have a follow up appointment 3 months after your last dose of chemotherapy or immunotherapy if you have this. You might see the study team at a routine hospital appointment or they may call you to see how you are getting on.
The team might also check your medical notes or catch up with you at other routine hospital appointments.
Side effects
The study 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.
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Durvalumab and tremelimumab can affect the 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. |
The most common side effects of durvalumab include:
- feeling or being sick
- loss of appetite
- diarrhoea or constipation
- stomach pain
- cough
- infection of the nose, throat or upper part of the chest (upper respiratory tract infections)
- joint pain
- hair loss
- feeling tired (fatigue) or weakness
- loss of appetite
- low levels of
thyroid hormone that can cause tiredness or weight gain - a drop in the number of blood cells that can cause an increased risk of infection, bruising and bleeding or breathlessness and tiredness
- skin rash or itchy skin
- high temperatures (fever)
- burning feeling when passing urine
Some of the above side effects may be worse if you have chemotherapy.
The most common side effects of tremelimumab include:
- a low level of thyroid hormone that can cause tiredness or weight gain
- a high level of thyroid hormone that can cause a fast heartbeat or weight loss
- low levels of hormones in the adrenal glands that can cause tiredness
- increased levels of lipase in the blood and inflammation of the
pituitary gland - inflammation of the gut or intestines that can cause symptoms such as tummy pain, diarrhoea and blood in the poo
- inflammation of the liver that can cause you to feel sick or lose your appetite
- skin rash and itchy skin
- cough
- high temperatures (fever)
- swelling in the hands and feet
Your doctor or a member of the study team will talk about the possible side effects of treatment before you agree to take part. You’ll have a chance to ask them any questions you may have.
We have more information about the following treatments and their side effects:
Location
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.
Chief Investigator
Professor James Catto
Supported by
AstraZeneca
National Institute for Health Research (NIHR)
Sheffield Teaching Hospitals NHS Foundation Trust
University of Leeds
If you have questions about the trial please contact our cancer information nurses
Freephone 0808 800 4040
