What is the REFINE Trial?

REFINE (Reduced Frequency ImmuNE checkpoint inhibition in cancers) is a clinical trial for patients who are receiving immunotherapy drugs for the treatment of advanced cancers.

What are immunotherapy drugs and how are they given?

We use immunotherapy drugs as a standard treatment option for advanced kidney cancer, melanoma, bladder cancer and some lung cancers. They are usually given by infusion every 3-6 weeks (depending on the specific drug). These drugs work by stimulating the body’s own immune system to fight against cancer cells.

Clinical trials have proven the effectiveness of immunotherapy drugs, such as ipilimumab, nivolumab or pembrolizumab, in the treatment of different cancers. However, the best way to give these drugs is not known.

It is likely that immune checkpoint inhibitors work for a longer period of time than originally thought. This means it may be possible to give the drugs less often and still have the same effect on the cancer.

What is the REFINE trial trying to find out?

The REFINE trial tests whether giving an immunotherapy drug less-often to patients with advanced cancer results in fewer side effects whilst continuing to be an effective treatment. We think that giving the drugs in this way (‘less-often’ schedule) will be just as effective as the current standard schedule and may reduce the amount and severity of the side effects.

REFINE will start by testing this in a group of patients with advanced kidney cancer or melanoma but will then test this approach in patients with a range of other tumour types.

Some side effects of treatment are minor such as skin irritation but others can be serious and require medication like steroids or hospital treatment. Sometimes these side effects continue after treatment has stopped so this trial is investigating whether we can reduce the risks and side effects whilst maintaining the benefits. Our section for Participants gives more information.

What do I need to know about treatment on this trial?

The trial compares less-often treatment with the standard treatment schedule (for example patients receive treatment with the drug every 8 weeks instead of every 4 weeks). The less-often schedule involves giving the same doses of immunotherapy drugs, but less-often (though the time you remain on this treatment will remain the same).

Currently, one way to give immunotherapy for advanced cancer is to give two drugs (called nivolumab and ipilumumab), together every 3 weeks for a total of 4 doses, followed by a scan. If your scan shows that you are gaining benefit from treatment, this is then usually followed by receiving nivolumab on its own every 4 weeks (standard schedule).

Alternatively, a drug called pembrolizumab is administered once every 6 weeks with a scan after 12 weeks total treatment. If you are responding to this, you would continue to receive pembrolizumab every 6 weeks (standard schedule).

In the less-often treatment schedule, you will have received the first 12 weeks of treatment as per the standard schedule, then would go on to receive either nivolumab every 8 weeks, or pembrolizumab every 12 weeks. i.e. less often.

It is hoped that using a less-often schedule will be more convenient for patients by reducing visits to hospital and side effects whilst remaining as effective as more frequent treatment. It will also be more cost effective for health services (with lower treatment costs), providing better use of hospital resources and allowing more patients to be treated.

How long does treatment go on?

We cannot predict the length of time you will stay on the treatment. This will depend on how your cancer responds to the treatment and how well you are while having the treatment. You will receive treatment for 1 year and 9 months in the trial, or until your cancer progresses further, or you are unable to continue treatment because of side effects, or your doctor thinks it best for you to stop, or you no longer wish to continue. If after 1 year and 9 months you are still on treatment, your Doctor will discuss with you whether you should continue on treatment outside the trial, and whether this is on the standard or less-often schedule.

Which group will I be in? 

It is important that the groups receiving each treatment schedule are as similar as possible at the start of the study. To ensure that this happens, a process called randomisation is used to allocate you to one of the groups.

‘Randomisation’ means that you will be allocated randomly (as if by the roll of dice) to receive either the less-often schedule or the standard schedule of treatment. For each patient randomised to receive the standard schedule, another patient will be randomised to receive the less often schedule, so that patient numbers are equal. This allocation is done by a computer.

Neither your doctor nor you will be able to choose which treatment you receive. In this way, an unbiased comparison can be made.

REFINE Protocol

Please find the current REFINE protocol below.


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