A trial of sacituzumab govitecan for urothelial cancer (urinary tract cancer) that has spread (TROPHY U-01)
Cancer type:
Status:
Phase:
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 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 . 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 . 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 such as cisplatin.
To begin with, you have 4 to 6 cycles of cisplatin and sacituzumab govitecan. This is called .
If your cancer doesn’t get worse after induction treatment you have . 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 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 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:
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 Thomas Powles
Supported by
Gilead
If you have questions about the trial please contact our cancer information nurses
Freephone 0808 800 4040
