A trial of sacituzumab govitecan for urothelial cancer (urinary tract cancer) that has spread (TROPHY U-01)

Cancer type:

Bladder cancer

Kidney cancer

Secondary cancers

Status:

Open

Phase:

Phase 2

This trial is looking at a new drug called sacituzumab govitecan on its own or in combination with other cancer treatments for urinary tract cancer.

It is for people who have urinary tract cancer that:

has grown into nearby tissues and you can’t have surgery to remove it or
has spread to another part of the body (metastatic cancer)

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

More about this trial

Urothelial cancer is a type of bladder cancer. Urinary tract cancer 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)

Doctors are looking for ways to improve treatment for people with urinary tract cancer that has spread. In this trial they are looking at adding sacituzumab govitecan to other cancer drugs.

Sacituzumab govitecan is a new drug for urinary tract cancer. It is a combination of 2 drugs:

sacituzumab - a monoclonal antibody
SN-38 - a chemotherapy drug

The other cancer drugs in this trial include:

cisplatin – a standard chemotherapy drug
zimberelimab – an immunotherapy
domvanalimab – an immunotherapy
avelumab – an immunotherapy
carboplatin and gemcitabine – standard chemotherapy drugs

Immunotherapies stimulate the immune system Open a glossary item to find and kill cancer cells. This can slow down or stop the growth of the cancer. You might have avelumab for urinary tract cancer. Both zimberelimab and domvanalimab are currently being looked at for urinary tract cancer.

There are 3 treatment groups open in the UK. The group you join depends on the treatments you have had in the past. And which treatment you might be suitable for in this trial.

The main aims of the trial are to find out:

if sacituzumab govitecan on its own or in combination with other cancer drugs improves treatment for urinary tract cancer
what happens to sacituzumab govitecan in the body
more about the side effects of treatment

Who can enter

Please note, there are several treatment groups so the entry conditions for this trial are complex. Each group has specific entry conditions and we haven’t listed them all.

The trial team check if you are suitable to take part in the trial and which group you might join. The group you take part in depends on:

treatment you have had in the past
whether you are suitable to have cisplatin or not

The following bullet points summarise some of the main entry conditions Open a glossary item . 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 the trial if all of the following apply. You:

have confirmed urinary tract bladder cancer that has spread to the wall of the tummy (abdomen), or to at least 2 lymph nodes or elsewhere in the body
have a sample of cancer tissue (biopsy ) that the trial team can access for them to do some tests on
are fully active but you might not be able to do heavy physical work (performance status 0 or 1)
have satisfactory blood test results
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
are at least 18 years old

As well as the above there are specific entry conditions for each treatment group. Speak to your doctor or research nurse if you want to find out more about the entry conditions for this trial.

Who cannot take part

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

have had chemotherapy, a targeted cancer drug or radiotherapy within 2 weeks of starting treatment or you have side effects from cancer treatment that aren’t getting better. You may be able to take part if you have moderate numbness or tingling in your hands or feet or hair loss.
have cancer that has spread to the brain, spinal cord, or the tissues that surround the brain unless it has been treated, it has been stable for at least 1 month and you aren’t on a high dose of steroids
have had a monoclonal antibody drug within 4 weeks of starting trial treatment or you have side effects from these treatments. You can take part if these side effects are mild.
have had a chemotherapy drug called irinotecan in the past
have another cancer unless it has been treated and there have been no signs of it for at least 3 years
are taking part in another clinical trial that involves an experimental drug or device within 4 weeks of starting trial treatment

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

have had a heart attack within 6 months of starting treatment or another significant heart problem that needs treatment. Your doctor checks your heart before you join the trial.
have inflammation of the bowel and you had a blockage or a hole (perforation) in the bowel in the past
have a condition called Gilbert’s disease
have had a significant bleed, a blocked bowel or you had a hole in the bowel within 6 months of joining the trial
have an active hepatitis B or hepatitis C infection, an infection that needs treatment or you have HIV that isn’t well controlled with medication. If you are taking medication to treat HIV that could interfere with trial treatment you might not be able to take part.
have a problem with how your immune system works or you have had treatment that damps down the immune system within 3 years of starting trial treatment
have had high doses of steroids within 2 weeks of joining the trial
have scarring of the lung or inflammation of the lung (pneumonitis ) caused by cancer treatment
take medication that interferes with a protein called the ABCA1 transporter or an enzyme called UGT1A1. This can affect how your body breaks down drugs. Your doctor will know what this means.
have an autoimmune condition that needs treatment apart from certain ones. Your doctor will know about this.
have any other medical condition or mental health problem that could affect you taking part

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

are allergic to sacituzumab govitecan, checkpoint inhibitors , any other treatment in the trial or you can’t have these treatments for any reason
have had a live vaccine in the 30 days before you start treatment. This doesn’t include the seasonal flu or approved COVID-19 vaccines as these aren’t live.
are pregnant or breastfeeding

As well as the above there are specific entry conditions and exclusion criteria for each treatment group. Speak to your doctor or research nurse if you want to find out more about the entry conditions for this trial.

Trial design

This phase 2 trial is taking place worldwide. The trial team need 643 people to take part.

There are 6 groups in this trial. 3 groups are open in the UK, and we have included only information about these groups. Your doctor will tell you about the treatment group you might be suitable to join.

Depending on your treatment group, you may have a certain number of treatments. If this is the case, the number of treatments are described below. With all the other groups, you have treatment for as long as it is working, and the side effects aren’t too bad.

You have treatment in cycles Open a glossary item . Each cycle lasts for 3 weeks.

You stop treatment if your cancer gets worse. The trial doctor will talk to you about other treatment options.

Group 4
This group is open to people who haven’t yet had chemotherapy that included a platinum drug Open a glossary item such as cisplatin.

To begin with, you have 4 to 6 cycles of cisplatin and sacituzumab govitecan. This is called induction treatment Open a glossary item .

If your cancer doesn’t get worse after induction treatment you have maintenance treatment Open a glossary item . The aim is to keep the cancer under control. Some people have:

sacituzumab govitecan and
avelumab

And some people have:

sacituzumab govitecan and
zimberelimab

Maintenance treatment starts about 4 to 6 weeks after the last dose of induction treatment.

Group 5
Group 5 is open to people who have had 4 to 6 cycles of gemcitabine and cisplatin chemotherapy before joining this trial and:

their cancer didn’t get worse after this and
they haven’t had any other type of chemotherapy

To begin with, the first 6 to 8 people have sacituzumab govitecan and zimberelimab.

Once this part of the trial is finished and the team think it is safe to continue, the next part is randomised. A computer puts those taking part into a treatment group. There are 3 groups.

You have one of the following:

sacituzumab govitecan and zimberelimab (arm 1)
avelumab (arm 2)
zimberelimab (arm 3)

Group 6
This group is open to people who can’t have cisplatin chemotherapy.

To begin with 6 to 8 people have sacituzumab govitecan and zimberelimab.

The next 6 to 8 people have sacituzumab govitecan, zimberelimab, and domvanalimab.

Once these parts of the trial are finished and the team think it is safe to continue, the next part of the trial is randomised. A computer puts those joining the randomised part into a treatment group. There are 4 groups.

You have one of the following:

sacituzumab govitecan (arm 1)
sacituzumab govitecan and zimberelimab (arm 2)
sacituzumab govitecan, zimberelimab, and domvanalimab (arm 3)
carboplatin and gemcitabine chemotherapy for 4 to 6 cycles. If your cancer doesn’t get worse you then have avelumab (arm 4).

Samples for research
The researchers might ask you to give a sample of cancer tissue if there isn’t already a suitable one they can access. 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 well the treatment is working
look at genes to understand more about urinary tract cancer
look for substances called biomarkers to help work out why treatment might work for some people and not for others
see what happens to sacituzumab govitecan in the body

Hospital visits

You see the doctor and have tests before you can take part. These include:

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

Treatment and how you have it
You have all your treatment at the hospital in the outpatient department.

Everyone taking part has cycles of treatment that last 3 weeks. The first day of each cycle is called day 1. You have all your treatment as a drip into a vein.

You have:

sacituzumab govitecan on day 1 and day 8 of each treatment cycle
zimberelimab once every 3 weeks
domvanalimab once every 3 weeks
avelumab once every 2 weeks

Check ups and trial scans
You see the trial doctor for regular check ups and blood tests.

You have a CT scan or MRI scan every 6 weeks for the first 3 months and then every 9 weeks. You have the trial scans until your cancer gets worse.

Follow up
You see the team one month after you stop treatment. After that they contact you every 3 months for up to 2 years. This might be at a routine hospital appointment, or they may call you to see how you are getting on.

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.

Zimberelimab, domvanalimab, and avelumab can affect the immune system Open a glossary item . This may cause inflammation and other reactions in different parts of the body. For many people the inflammation and reactions are not too bad. For some people they can cause serious side effects.

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.

The most common side effects of zimberelimab include:

a drop in blood cells causing an increased risk of infection, bruising and bleeding, breathlessness and tiredness
tummy pain
constipation or diarrhoea
cough
loss of appetite
dizziness
tiredness (fatigue)
high temperatures (fever)
feeling or being sick
shortness of breath
skin rash
swelling in the body

The common side effects of domvanalimab include:

back or joint pain
constipation or diarrhoea
tiredness or lack of energy
high temperatures (fever)
headache
a reaction to the drug. This can cause chills, hives, or both.
itchy skin or skin rash
liver damage due to inflammation
loss of appetite
feeling sick
high levels of thyroid hormone. This can cause weight loss, heart rate changes and sweating.
low levels of thyroid hormone. This can cause weight gain, heart problems or constipation.
pain
inflammation of the lungs (pneumonitis) that can cause shortness of breath and difficulty breathing
sudden growth in the cancer or worsening of problems that the cancer can cause

The most common side effects of sacituzumab govitecan include:

an allergic reaction . This could cause a skin rash or hives, breathing problems, wheezing, feeling dizzy or lightheaded, fast pulse, sweating or swelling around the mouth, throat or eyes.
a drop in the number of blood cells causing an increased risk of infection, tiredness, and breathlessness
feeling or being sick
diarrhoea or constipation
pain in the tummy (abdomen) or joint pain
tiredness (fatigue)
urine infections
weight loss, loss of appetite or both
low levels of magnesium, potassium, or phosphate in the blood
lack of fluids in the body (dehydration)
headache
dizziness
shortness of breath with or without exercise
cough
skin rash or itchy skin
hair loss

You might have more severe side effects with combinations and your doctor will talk to you about this. You’ll have a chance to ask any questions you may have.

We have more information about the following drugs and their side effects: