A study of durvalumab and the vaccine S-488210/S-488211 for bladder cancer (DURANCE)

Cancer type:

Bladder cancer

Status:

Open

Phase:

Phase 1/2

This study is looking at durvalumab in combination with the S-488210/S-488211 vaccine to treat non muscle invasive bladder cancer.

More about this trial

Doctors can treat non muscle invasive bladder cancer with:

surgery to remove the cancer (TURBT)
Bacillus Calmette-Guerin (BCG)

Trans urethral removal of bladder cancer (TURBT) is usually the first treatment for non muscle invasive bladder cancer.

BCG is a type of immunotherapy Open a glossary item . You have this directly into your bladder using a flexible tube (catheter). You usually have BCG if your bladder cancer is at a high risk of coming back or spreading.

When these treatments don’t work or your cancer comes back the standard treatment Open a glossary item is to remove the whole bladder (cystectomy).

Researchers think that other immunotherapies might work after BCG stops working. This is what the DURANCE study is looking at. In this case, doctors could then use these treatments instead of doing a cystectomy.

Durvalumab is an immunotherapy. Durvalumab works by stimulating the body’s immune system Open a glossary item to attack cancer cells. Doctors already use durvalumab to treat non small cell lung cancer. And researchers are also using it in clinical trials for other cancers.

The S-488210/S-488211 vaccine is also an immunotherapy and it works in a similar way to durvalumab. The vaccine is an experimental drug. It isn’t used as a treatment for any cancer.

In this study you have durvalumab and the S-488210/S-488211 vaccine.

The aims of the study are to find out:

how well this treatment combination works for non muscle invasive bladder cancer
how safe the combination is
what the side effects are
how it affects quality of life

Who can enter

The following bullet points are a summary of the entry conditions for this study. Talk to your doctor or the study 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 study if all of the following apply. You:

have non muscle invasive bladder cancer that is mainly transitional cell (more than 50%) and has a high risk of coming back. Your doctor will know about this.
have a previous tissue sample (biopsy ) of your cancer that the study team can assess
have cancer that came back after having BCG treatment or got worse while having BCG treatment. Or you are not able to have BCG treatment.
did not want to have surgery to remove the whole bladder or you weren’t suitable to have the surgery
must have had certain tests and scans within 8 weeks of joining the study. Your doctor will know which tests and scans these are.
have satisfactory blood test results
weigh more than 30kg (4st 7lb)
can take care of yourself but might not be able to do heavy physical work (performance status 0 or 1)
are willing to use contraception during treatment and for a time after if there is any chance you or your partner could become pregnant
are at least 18 years old

Who can’t take part

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

have cancer that spread to the brain and spinal cord
have any other treatment within a month of starting the study treatment
have already had an immunotherapy that targets PD-1 or PD-L1, or you have had a CTLA-4 monoclonal antibody or any new immunotherapy. Your doctor will know if you have had any of these treatments.
have ongoing moderate to severe side effects from previous treatment. This is apart from hair loss, vitiligo, some blood test results and other side effects that might not get any worse. Your doctor will know which side effects these are.
are already taking part in another clinical trial using an experimental drug or device
have had an experimental drug or used a device as part of a clinical trial within a month of starting the study treatment
have already taken part in a trial using durvalumab. This applies whether you had durvalumab or not in the trial.
have had another cancer within the past 2 years apart from non melanoma skin cancer

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

have or had an autoimmune disease or an inflammatory disease. This is apart from any thyroid problems that are controlled by treatment and any skin problems that don’t need corticosteroid treatment that reaches the whole body. You might be able to join if you had an autoimmune disease and it has not been active for the past 5 years.
have had a stem cell transplant from a donor (allogeneic transplant)
have had an organ transplant
have or had lung problems including pulmonary fibrosis, inflammation of the lungs or pneumonia. Your doctor will know more about this.
have heart problems such as heart disease, heart failure or unstable angina
have type 1 diabetes that isn’t controlled by insulin. You could join if you are having a stable dose of insulin that is controlling the diabetes.
have Addison’s disease that isn’t controlled
have AIDS, HIV that isn’t controlled, active hepatitis B, hepatitis C, active tuberculosis (TB) or any other active infection
are taking antibiotics within 2 weeks of starting study treatment or having antibiotics by a drip into a vein (infusion) for an infection within 2 weeks of enrolling onto the study treatment. This is unless it is to prevent an infection.
have an immune system that isn’t working well
have had corticosteroids or similar medication that damps down the immune system within 2 weeks of joining the study. This is apart from inhalers or corticosteroids to replace what the body would make such as taking them for Addison’s disease.
have major surgery within 4 weeks of starting study treatment. This is apart from a rigid cystoscopy, or a TURBT and taking tissue samples (biopsies).
have any other medical condition, mental health problem or social situation that could affect you taking part

Other
You can’t take part if any of the following apply. You:

are allergic or sensitive to the treatments used or any of their ingredients
have a live vaccine within the 4 weeks before starting treatment or you are planning to have a live vaccine during the treatment. The COVID-19 vaccines aren’t live vaccines.
are pregnant or breastfeeding

You are also not able to donate blood while taking part in the study and for at least 3 months after the last dose of study treatment.

Trial design

This is a phase 1/2 study. The team need 64 people to join.

Everyone has durvalumab and the S-488210/S-488211 vaccine. You have durvalumab as a drip into the vein. You have the S-488210/S-488211 vaccine as an injection under the skin.

You have treatment in cycles. Each treatment cycle Open a glossary item is 4 weeks. You have up to 7 cycles of treatment as long as the treatment is helping and the side effects aren’t too bad.

Cycle 1
On the first day you have durvalumab by itself. On day 2 you have the vaccine by itself.

You then have the vaccine by itself once a week for the next 3 weeks.

Cycle 2
On the first day you have durvalumab and the vaccine.

You then have the vaccine once a week for the next 2 weeks.

Cycle 3
On the first day you have durvalumab and the vaccine.

You then have the vaccine by itself again at the start of the 2nd week.

Around 3 months after you start study treatment (around cycle 3) you have a cystoscopy to see how well the treatment is working. You continue to have the study treatment if the treatment is working as expected.

Cycles 4, 5 and 6
On the first day you have durvalumab and the vaccine.

You then have the vaccine by itself again at the start of the 2nd week

Cycle 7
You have durvalumab and the vaccine on the first day.

Samples for research
The study team take blood samples and urine samples during the study. Your doctor will tell you when they take these. Where possible they will take the blood samples at the same time you have blood taken for your routine tests.

You have a cystoscopy when you join the study. As part of your routine care after starting treatment you have a cystoscopy at:

3 months
6 months
9 months
12 months

At 6 months and 12 months you have a tissue sample (biopsy) taken. The study team will ask to use these tissue samples for research.

Quality of life
You fill in a questionnaire:

before starting treatment
at regular times during treatment
at regular times after treatment

Your doctor will tell how often you fill the questionnaire in.

The questions ask about:

your general health
what you are able to do

This is a quality of life questionnaire.

Diary
You have a diary to fill in at home. In this you record any side effects and any medications you take. You need to bring this diary with you whenever you go to the hospital.

Your doctor will tell what you need to record in the diary and how often you need to do so.

Hospital visits

You see the doctor to have tests before taking part. These tests include:

a physical examination
blood tests
urine test
CT urogram or MRI scan
CT scan of the chest or x-ray of the chest
cystoscopy

You see the doctor at regular times during treatment and a month after finishing treatment. You then see them:

every 3 months up to a year after starting treatment
then every year up to at least 5 years after starting treatment

You have a CT urogram or MRI scan:

a year after starting treatment
then at 2 years, 3 years, 4 years and 5 years after starting treatment

You have a cystoscopy every 3 months for a year after starting treatment.

Side effects

The study 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.

Durvalumab and the S-488210/S-488211 vaccine can affect the immune system. They may cause inflammation in different parts of the body. This can cause serious side effects. They could happen during treatment, or some 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 S-488210/S-488211 vaccine is new and has not been tested in a study before. So we don’t know what the side effects of the vaccine are.

Other studies have used similar vaccines to S-488210/S-48211 and the side effects reported were quite minor.

You might have changes to the skin or irritation where you have the injection. You will have the injection in different areas of the body to help with this.

This is the first time that durvalumab and the S-488210/S-488211 vaccine have been used together. So we don’t know what the side effects might be when you have them together.

We have information about durvalumab and its side effects.