A trial looking at V940 and pembrolizumab for urothelial (urinary tract) cancer after surgery
Cancer type:
Status:
Phase:
This trial is looking at the combination of a treatment called V940 and pembrolizumab for urothelial cancer. It is comparing this to having pembrolizumab on its own.
It is for people whose cancer:
- had grown into the muscle layer of the bladder or upper urinary tract and they have had surgery with the aim to cure
- has a higher chance of coming back
More about this trial
The urinary tract includes the:
- centre of the kidney (renal pelvis)
- tube that takes urine from the kidney to the bladder (ureter)
- tube that drains urine from the bladder and out of the body (urethra)
The lining of the urinary tract is called the urothelium, so cancer of the urinary tract can also be called urothelial cancer.
Removing the bladder or the kidney and ureter is the usual treatment for invasive urothelial cancer. You are then followed up to see if there are any signs of the cancer coming back. Some people have a higher risk of this happening. So researchers are looking at treatments for this group of people.
In this trial they are comparing the combination of pembrolizumab and V940 with pembrolizumab on its own.
Pembrolizumab is an immunotherapy. It helps the 
to find and kill cancer cells. It is already a treatment for some other types of bladder cancer.
V940 is another type of immunotherapy. It is a new treatment. It is also called mRNA-4157. To make it, doctors analyse tissue and blood samples from each person's cancer. This is to see which proteins in your cancer cells contain gene changes (). Using this information, the researchers make the cancer treatment for each person. This teaches your immune system to find and target the cancer at its earliest stages.
In this trial, some people have pembrolizumab and a dummy drug (). And some people have V940 and pembrolizumab.
The main aims of the trial are to find out:
- how safe it is to have the combination of V940 and pembrolizumab
- if V940 and pembrolizumab work better than pembrolizumab on its own to stop or slow the cancer growing again
- what the side effects of treatment are
Who can enter
The following bullet points are a summary of 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.
Who can take part
You may be able to join this trial if all of the following apply. You:
- have cancer that started in the layer of cells that line most of the
urinary system (urothelial cancer). If you have a mixed type of cancer you might still be able to take part if most of the cancer cells are urothelial. Your doctor can explain more. - have had surgery with the aim to cure your cancer. You must have had surgery less than 8 weeks before you agree to join the trial.
- have a higher risk of your cancer coming back. Your doctor will know this.
- have a sample of tissue (
biopsy ) from surgery that the team can use to do some tests on. There must be enough of the tissue sample and a blood sample so that the trial team can do some tests on it called next generation sequencing. Your doctor can tell you more. - are willing to have frequent blood samples taken
- have no signs of cancer on a scan within 4 weeks of being put into a treatment group
- may or may not have had chemotherapy or BCG
treatment into the bladder for non muscle invasive bladder cancer - are willing to use reliable contraception during the trial and for a time after if there is any chance you could become pregnant
- are fit and active but might not be able to do heavy physical work (performance status 0 or 1)
- have satisfactory blood test results
- are at least 18 years old
Who can’t take part
Cancer related
You cannot join this trial if any of these apply. You:
- have had
immunotherapy or certain checkpoint inhibitors in the past. You might be able to take part if you have had a checkpoint inhibitor for non muscle invasive bladder cancer that came back and this was at least 12 months ago. Your doctor will know this. - have had V940 (mRNA-4157) in the past. Your doctor will know this.
- have had
systemic treatment including experimental treatment after surgery to remove all the cancer - have had treatment before surgery. Cisplatin chemotherapy before surgery is allowed.
- haven’t had standard cisplatin chemotherapy to treat your
stage of cancer unless you weren’t suitable to have it. Your doctor will know what these reasons are. - had radiotherapy after surgery to remove all the cancer
- have moderate to severe side effects from past cancer treatments that aren’t getting better. This doesn’t apply if the side effects include tingling in your hands or feet or if you are taking hormones to treat them.
- have had another cancer that has got worse or needed treatment in the past 3 years. You can join if you had successfully treated
non melanoma skin cancer , carcinoma in situ (CIS ) or early prostate cancer. You can’t join if you had CIS of the bladder. - are taking an experimental drug or using a device as part of another clinical trial. This is if it is within 28 days of being put in a treatment group for this trial.
Medical conditions
You cannot join this trial if any of these apply. You:
- have had treatment that damps down the
immune system . This includes steroids within 1 week of starting trial treatments unless it was a low dose. - have an
autoimmune condition that needed treatment in the last 2 years apart from certain ones. Your doctor will know about this. - have HIV that isn’t well controlled with medication, an active hepatitis B or hepatitis C infection or any other severe infection that needs treatment
- have both hepatitis B and hepatitis C
- have or had scarring on the lungs or active inflammation of the lungs (
pneumonitis ) that needed treatment - have had a
stem cell transplant with somebody else’s cells or you have had an organ transplant - have side effects from surgery that aren’t getting better
- have had recent treatment to encourage white blood cells or clotting blood cells to grow. This includes
G-CSF or GM-CSF - have another medical condition, mental health condition or is there is any reason that could affect you taking part in the trial
Other
You cannot join this trial if any of these apply. You:
- have had a
live vaccine within 30 days of the start of treatment. Please note that the approved COVID-19 vaccines are allowed as they aren’t live. - are severely allergic to pembrolizumab, V940 or anything they contain
- are pregnant or breastfeeding
- have a problem with drugs or alcohol
Trial design
This phase 2 trial is taking place worldwide. The team need 200 people to take part including 15 from the UK.
It is a randomised trial. A computer puts you into a treatment group. 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:
- pembrolizumab and V940
- pembrolizumab and a dummy drug (
placebo )
Treatment
You have V940 or the dummy drug as an injection. You have them into a muscle in the upper arm, thigh, or buttock. You have an injection once every 3 weeks. You have up to 9 injections and this takes about 6 months in total.
You have pembrolizumab as a drip into a vein. You have it once every 6 weeks. You have up to 9 doses. This takes about a year.
Samples for research
The researchers would like to use a tissue sample from your surgery. This is stored at your hospital.
The team also ask to take some extra blood and urine samples. Where possible, you have the blood samples taken when you have 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
If there are any remaining samples the team will ask to store this away for future research. You do not have to agree to your samples being stored. You can still take part in the trial.
Hospital visits
You see the doctor for a and tests before you can take part. The tests include:
- blood tests
- a heart trace (ECG)
- a cystoscopy
- a CT scan or MRI scan
You might also have a bone scan.
You have all your treatment at the hospital in the outpatient department.
During treatment you see the doctor regularly. This is for blood tests and to see how you are.
Trial scans and tests
You have a CT scan or MRI scan:
- every 3 months during treatment and then
- every 3 months for up to 2 years and then
- every 6 months until the cancer gets worse
You might also need to have regular cystoscopies. The trial team can tell you more about this.
You stop having the scans and cystoscopies as part of the trial if your cancer comes back.
Follow up
When you stop treatment, the team check to see how you are getting on. You see them 1 month after you stop treatment.
If your cancer doesn’t get worse, you see the trial doctor for a check up:
- every 3 months for a year and then
- every 6 months after that
When you stop having follow up visits, a member of the trial team will call you every 3 months. This is to see how you.
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.
V940 is a new treatment and only a few people have had it. Having the combination of V940 with pembrolizumab is also a new combination of treatment. We don’t know what all the side effects are.
The most common side effects of V940 we know about so far include:
- tiredness (fatigue)
- high temperatures (fever)
- chills, a cough and body aches (flu-like illness)
- feeling sick
- joint and muscle pain
- headache
- skin rash, warmth, swelling, redness and pain at the site of injection
- loss of appetite
- diarrhoea
There may be a small risk that you could have a serious allergic reaction to V940. This could cause a change in blood pressure, difficulty breathing or severe hives.
The trial doctor or nurse will monitor you very closely during and after you have V940. You will have medication to treat any allergic reaction that might happen.
|
Pembrolizumab can affect the
. This may cause 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 common side effects of pembrolizumab include:
- itchy skin or skin rash
- diarrhoea
- cough
- high temperatures
- back, joint or tummy (abdominal) pain
- loss of skin colour
- not enough
thyroid hormone. This can cause tiredness, weight gain, feeling cold, or constipation. - low levels of salt in the blood. This can cause tiredness, confusion, headache, muscle cramps, and feeling or being sick.
We have more information about pembrolizumab and its 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 Tom Powles
Supported by
If you have questions about the trial please contact our cancer information nurses
Freephone 0808 800 4040
