A trial of more treatment after chemotherapy for advanced urinary tract cancer (urothelial cancer) (ATLANTIS)

Please note - this trial is no longer recruiting patients. We hope to add results when they are available.

Cancer type:

Bladder cancer

Kidney cancer

Status:

Closed

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.

Please note, there are no groups open for people to join at the moment. The research team hope to open another group in the future.

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 (not currently open for people to join)
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)

ATLANTIS Trial Diagram

You take cabozantinib or the dummy drug once a day, everyday.

ATLANTIS-2 (not currently open for people to join)
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)

Atlantis-2 randomisation trial diagram

You take rucaparib or the dummy drug, twice a day, everyday.

ATLANTIS-3 (not currently open for people to join)

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)

12868-atlantis-3-randomisation.png

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:

physical examination
heart trace (ECG)
blood tests
urine tests
MRI scan or CT scan

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

Early results

In 2022 the research team presented the first results for the ATLANTIS trial. The results were for the people in group 2 who had a dummy drug (placebo Open a glossary item ) or rucaparib.

We don’t have results for the other groups in the trial yet. We plan to update this page once more results are available.

Results for group 2 (rucaparib)
A total of 40 people joined this part of the trial. They all had a urinary tract cancer and a biomarker called HRD.

They were put into a treatment group at random:

20 had rucaparib
20 had a dummy drug (placebo)

The research team looked at how long it was before people’s cancer started to grow again. They found that on average it was:

35 weeks for those who had rucaparib
15 weeks for those who had the placebo

ATLANTIS trial bar chart showing how long it was before people’s cancer started to grow again

When they analysed the trial they also looked at how many people were living. They found it was:

11 out of 20 people (55%) who had rucaparib
6 out of 20 people (30%) who had the placebo

ATLANTIS trial bar chart showing how many people were living after 95 weeks

Side effects
Many people taking part had at least one side effect. But most were mild or didn’t last long.

The team looked at the more common side effects of people in both groups.

For the people who had rucaparib they were:

tiredness (fatigue)
feeling sick
rash
an increase in a protein in the liver called ALT

Conclusion
The research team concluded that rucaparib could be a useful treatment for urinary tract cancers. And that it didn’t cause too many side effects.

They suggest doing a larger phase 3 trial Open a glossary item to confirm the results of this trial. So that it might support the use of rucaparib in this way.

Where this information comes from
We have based this summary on information from the research team. The information they sent us has been reviewed by independent specialists (peer reviewed Open a glossary item ) but may not have been published in a medical journal. The figures we quote above were provided by the research team. We have not analysed the data ourselves.