A trial looking at how often to give immunotherapy for cancer that has spread (REFINE)
Cancer type:
Status:
Phase:
This trial is looking at whether it is possible to give 
less often for cancer that has spread.
The trial is open to people who have:
- renal cell kidney cancer or
- melanoma
More about this trial
Doctors treat some types of cancer with an immunotherapy. This is the for advanced kidney cancer, melanoma and some bowel cancers. The immunotherapy drugs you might have include ipilimumab and nivolumab or pembrolizumab.
Immunotherapy works by helping the body’s to kill cancer cells. How often you have this depends on the specific drug you are having. Research suggests that this may be too often. You might be able to have treatment less often without affecting how well it works. The benefits of this could be:
- fewer side effects
- fewer hospital visits
- improved
quality of life
Everyone joining this trial will have had or be having 12 weeks of immunotherapy. As part of this trial you then have more immunotherapy:
- on the usual schedule or
- less often than usual on the newer schedule
The main aims of this trial are to find out:
- whether giving immunotherapy less often is as good as the standard schedule
- what the side effects are when you have immunotherapy less often
- how having immunotherapy less often affects quality of life
Who can enter
Please note, there are different treatment groups in this trial. Each group has specific entry conditions and we haven’t listed them all.
The following bullet points are a summary of the main entry conditions. 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 melanoma or renal cell kidney cancer
- have cancer that has grown into surrounding tissue or spread elsewhere in the body. This is
locally advanced or advanced cancer . - are having immunotherapy because this is a standard treatment for your cancer type.
- are suitable to have immunotherapy as part of this trial
- are fully active but 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 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 trial if any of these apply. You:
- have cancer that has spread to the brain or spinal cord and it hasn’t been treated or has only been treated with radiotherapy. The cancer must be stable and not causing symptoms.
- have cancer that got worse after the initial 12 weeks of immunotherapy
- have had immunotherapy in the past
- have already had treatment for cancer that has grown into surrounding tissues or elsewhere in the body. You can join if you have had a
targeted cancer drug for melanoma that included a BRAF or MEK inhibitor. - are having your 12 weeks of immunotherapy in combination with a
targeted drug - are taking part in another clinical trial where you have treatment as part of the trial
- have had another cancer in the last 5 years. You can take part if you have
non melanoma skin cancer or carcinoma in situ (CIS) that has been successfully treated or you have bladder cancer that hasn’t grown into the muscle wall.
Medical conditions
You cannot join this trial if any of these apply. You:
- are having or have had treatment to dampen down the
immune system within 7 days of starting trial treatment unless it is a low dose - have an active infection including tuberculosis, hepatitis B, hepatitis C or HIV
- have a problem with how your
adrenal glands work which is not controlled by treatment - have any other medical condition or mental health problem that would affect you taking part
Other
You cannot join this trial if any of these apply. You:
- have had a
live vaccine within 30 days of starting treatment in this trial - are allergic to immunotherapy drugs
- are pregnant or breastfeeding
Trial design
This is a phase 2 trial. The team need 160 people in each group (cohort) to take part.
Everyone has or will have had 12 weeks of immunotherapy. This isn’t part of the trial. This is part of your routine treatment. You may have already had this when you join the trial. The 12 weeks of immunotherapy is:
- ipilimumab and nivolumab for renal cell kidney cancer
- ipilimumab and nivolumab for melanoma
- pembrolizumab for melanoma
You have a or after you finish the 12 weeks of immunotherapy. This is before you join the trial. It is to check how well the immunotherapy worked. You can join this trial if your cancer hasn’t got worse and you fulfil all the .
Trial treatment
You have nivolumab or pembrolizumab. You have nivolumab if you have renal cell cancer. If you have melanoma you have whichever treatment you had for the 12 weeks before starting on the trial. So you have either nivolumab or pembrolizumab.
You have nivolumab or pembrolizumab as a drip into a vein. Nivolumab takes about 60 minutes each time. Pembrolizumab takes about 60 minutes each time. You will be at the hospital for longer than this.
You have treatment for just under 2 years. You stop treatment if your cancer gets worse. Your doctor will talk to you about other treatment options.
Part 1
Renal cell kidney cancer group (part one)
This group is randomised. There are 2 treatment groups. Neither you nor your doctor can choose which group you are in.
You have one of the following:
- nivolumab once every 4 weeks (standard schedule)
- nivolumab once every 8 weeks (new schedule)
Melanoma group (part one)
This group is randomised. There are 2 treatment groups. Neither you nor your doctor can choose which group you are in.
You have one of the following:
- nivolumab every 4 weeks or pembrolizumab every 6 weeks (standard schedule)
- nivolumab every 8 weeks or pembrolizumab every 12 weeks (new schedule)
Part 2
When there are about 80 people in each group the team compare the schedules. This is to make sure that having the new schedule is working just as well as the standard one. When they are sure of this, they will go onto part 2.
In part 2 the team hope to test different schedules of nivolumab and pembrolizumab in more people. We will add more information about this when part 2 opens.
Samples for research
The researchers ask for a sample of cancer tissue () from when you were first diagnosed. 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 what happens to immunotherapy in the body
- look at
genes to understand more about cancer - look for substances called
biomarkers to help work out why treatment might work for some people and not for others
Quality of life
The trial team ask you to fill out a questionnaire:
- before you start treatment
- at set times during treatment
The questionnaire asks about side effects and how you’ve been feeling. This is called a quality of life study.
Hospital visits
You see a doctor and have some tests before you join a trial. These include:
You have treatment at the hospital on the day care ward. During treatment you have regular blood tests and check ups with your doctor.
You have a CT scan or PET scan every 12 weeks.
You see the doctor 8 weeks after you finish treatment.
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.
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Nivolumab and pembrolizumab 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 immunotherapy include:
- loss of appetite
- feeling sick
- tiredness (fatigue)
- pain in the muscles, bones and joints
- high temperatures (fevers)
- problems with how the
thyroid gland works - skin rash, itching or loss of pigment in the skin
- diarrhoea and tummy pain
- liver problems
The trial team will talk to you about all the possible side effects of treatment. You will have a chance to ask any questions you may have.
We have more information about:
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
Dr Duncan Gilbert
Supported by
Medical Research Council
Jon Moulton Charity Trust
University College London (UCL)
If you have questions about the trial please contact our cancer information nurses
Freephone 0808 800 4040
