“I think it’s really important that people keep signing up to these type of trials to push research forward.”
A trial of more treatment after chemotherapy for advanced urinary tract cancer (urothelial cancer) (ATLANTIS)
Cancer type:
Bladder cancer
Kidney cancer
Status:
Open
Phase:
Phase 2
This trial is testing different treatments for different subtypes of urinary tract cancer. It is for people whose cancer has grown into surrounding tissues or spread elsewhere in the body (advanced cancer).
The urinary tract includes the:
- centre of the kidney (renal pelvis)
- 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)
Cancer Research UK supports this trial.
More about this trial
Chemotherapy is one of the usual treatments for advanced urothelial cancer. After chemotherapy, you have regular monitoring. This means you don’t have treatment straight away. Your doctor keeps a close eye on you to check for any signs that the cancer is growing. If it does, then you and your doctor decide which treatment is best for you.
Researchers are looking at ways to delay the cancer growing again after chemotherapy. We know from research in other cancers that having more treatment (sometimes called maintenance therapy) can increase the time it takes for the cancer to come back. Researchers want to see if this also happens in people with advanced urinary tract cancer.
But not all urinary tract cancers are the same and some new cancer drugs may help people with one type of urinary tract cancer more than another.
To work out the subtype of urinary tract cancer you have, the researchers will test a sample of your cancer (biopsy) to look for changes to certain genes and proteins (biomarkers).
The trial team are testing a number of different treatments. In this trial you have 1 of the following:
- cabozantinib or a dummy drug (placebo)
- rucaparib or a dummy drug
- enzalutamide or a dummy drug
They are all types of targeted cancer drugs.
Cabozantinib works in 2 different ways. It blocks particular proteins on cancer cells. These proteins encourage the cancer to grow. It also stops the cancer cells growing blood vessels, which the cells need to be able to grow. Researchers hope that cabozantinib might delay the cancer growing for a time.
Rucaparib is a type of treatment called a PARP-1 inhibitor. This means it blocks an enzyme called PARP-1 that helps damaged cells to repair themselves. PARP stands for poly ADP-ribose polymerase and is in all cells, including cancer cells.
Enzalutamide is a type of hormone therapy.
The overall aims of this trial are to find out:
- if having additional treatment can increase the time before these cancers come back
- if having more treatment can help people live longer
- what the side effects are
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.
The main entry conditions to join the trial include all of the following.
- You have urothelial cancer that started in the middle of the kidney (the renal pelvis), ureter, bladder or urethra
- Your cancer has spread to the wall of the tummy (abdomen) or between the hips (pelvis) or to the lymph nodes or elsewhere in the body
- You have a type of cancer called transitional cell cancer or squamous cell cancer
- You have had chemotherapy as the first treatment for the cancer spread and you have had between 4 and 8 cycles
- There is a tissue sample available for the trial team to do some tests
- It is possible to start trial treatment within 10 weeks of finishing chemotherapy
- You are well enough to be up and about for at least half the day (performance status 0,1 or 2)
- You are willing to use reliable contraception during treatment if there is any possibility you or your partner could become pregnant
- You have satisfactory blood test results
- You must be willing to use reliable contraception during treatment and for 4 months afterwards if there is any possibility you or your partner could become pregnant
- You must be able to swallow tablets
- You are at least 16 years old
You cannot join this trial if any of these apply.
- A scan showed your cancer got worse during the first chemotherapy you had for advanced cancer
- You have had more than 1 course of chemotherapy for advanced cancer – you might still be able to take part if you had to change to a different type of chemotherapy due to bad side effects
- It has been less than 3 weeks or more than 10 weeks since your last chemotherapy treatment
- The trial doctor thinks further chemotherapy will help you
- You are due to have surgery or radiotherapy after chemotherapy unless you are having radiotherapy to control symptoms – (palliative radiotherapy)
- You have had major surgery or radiotherapy within 3 weeks of joining the trial or palliative radiotherapy within 2 weeks
- You have had any other cancer in the last 2 years apart from carcinoma insitu of the cervix or non melanoma skin cancer that was successfully treated or early prostate cancer and you don’t need hormone treatment
- Your kidneys, liver or other organs in the body aren’t working properly
- You have had any other treatment as part of a clinical trial in the last 28 days
- You have any other serious medical condition or mental health problem that the trial team think could affect you taking part
- You are pregnant or breastfeeding
As well as the above, there are separate entry conditions for:
- cabozantinib or a dummy drug
- rucaparib or a dummy drug
- enzalutamide or a dummy drug
The trial team will check these to see which of the drugs you might be suitable to have.
Trial design
This phase 2 trial is based in the UK. 3 parts of the trial are open. The researchers need 188 people to join.
In:
- ATLANTIS-1 you have a cabozantinib or a dummy drug (placebo)
- ATLANTIS-2 you have rucaparib or a dummy drug
- ATLANTIS-3 you have enzalutamide or a dummy drug
The doctors test a sample of your cancer taken when you had a previous biopsy or surgery. They will try to classify your cancer as a particular subtype. You have treatment according to the biomarker they find. Some people have cabozanitinib, rucaparib or enzalutamide. And some have a dummy drug.
Both 3 parts of the trial are randomised. The people taking part are put into treatment groups by a computer. Neither you nor your doctor will be able to decide which group you are in. And neither of you will you know which group you are in. This is called a double blind trial.
Cabozantinib, rucaparib and the dummy drug are tablets. Enzalutamide and the dummy drug are capsules. The trial team will give you a fresh supply of medication every 4 weeks.
You have treatment as long as it is working and the side effects aren’t too bad. You stop treatment if your cancer gets worse. Your doctor will talk to you about other treatment options.
ATLANTIS-1
If you don’t have a specific biomarker being looked at (you are biomarker negative), you might be suitable to join this part of the trial.
You are put into 1 of 2 groups to have 1 of the following:
- cabozantinib
- dummy drug (placebo)
You take cabozantinib or the dummy drug once a day, everyday.
ATLANTIS-2
This part of the trial is for people who have a biomarker called HRD. This means you are HRD biomarker positive.
You are put into 1 of 2 groups to have 1 of the following:
- rucaparib
- dummy drug (placebo)
You take rucaparib or the dummy drug, twice a day, everyday.
ATLANTIS-3
This part of the trial is for people who have AR positive and HR negative urothelial cancer.
You have 1 of the following:
- enzalutamide
- dummy drug (placebo)
You take enzalutamide or the dummy drug once a day, everyday.
Research samples
The trial team will ask to take some extra blood samples as part of this trial. This is to look for biomarkers. Where possible, you have these at the same time as your routine blood tests.
Biomarkers help to predict who is most likely to benefit from this treatment and also help us to better understand advanced urinary tract cancers.
You don’t have to give these samples if you don’t want to. You can still take part in the trial.
Hospital visits
You see a doctor and have some tests before you can take part. These include:
You see the trial team once a month for a check up and some blood tests. You have a CT scan or MRI scan every 3 months.
When you finish treatment you see the trial team:
- a month later
- every 3 months
Side effects
The most common side effects of cabozantinib include:
- diarrhoea or constipation
- tiredness (fatigue)
- feeling or being sick
- loss of appetite
- redness of the skin on palms of hands and soles of feet (hand foot syndrome)
- high blood pressure
- taste changes
- changes to your voice
- muscle weakness
You should avoid grapefruit and Seville oranges as they might increase the levels of cabozantinib in the body.
The most common side effects of rucaparib include:
- feeling or being sick
- tiredness
- constipation or diarrhoea
- loss of appetite
- taste changes
- kidney or liver damage
- high levels of cholesterol in the blood
- a drop in blood cells causing an increased risk of infection, bleeding problems, tiredness and breathlessness
There is also a small chance it might cause:
- breathlessness
- dizziness
- an increased sensitivity to sunlight – you should apply sunscreen and cover up when outside
The most common side effects of enzalutamide include:
- tiredness (fatigue) and weakness
- hot flushes
- headaches
- high blood pressure
The trial team will talk to you about all the possible side effects before you agree to join.
We have more infromation about:
- cabozanitinib
- enzalutamide
Location
Aberdeen
Blackburn
Bournemouth
Bristol
Cardiff
Derbyshire
Edinburgh
Lancaster
Leeds
Leicester
Liverpool
London
Maidstone
Manchester
Newcastle Under Lyme
Nottingham
Oxford
Plymouth
Portsmouth
Preston
Romford
Shrewsbury
Southampton
Sutton in Ashfield
Taunton
Wakefield
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
Professor Robert Jones
Professor Thomas Powles
Supported by
Cancer Research UK
Clovis Oncology Inc
Exelixis
NHS Greater Glasgow and Clyde
University of Glasgow
Astellas Pharma Europe
Other information
This is Cancer Research UK trial number CRUK/12868.
Freephone 0808 800 4040
Last review date
CRUK internal database number:
12868
Please note - unless we state otherwise in the summary, you need to talk to your doctor about joining a trial.
Charlie took part in a trial to try new treatments
