What are the possible benefits of taking part?

We already know that immunotherapy is a helpful treatment in some patients with advanced cancers. All patients will receive immunotherapy treatment in this trial. The best schedule to   give these drugs is not currently known. We hope that the less-often schedule, with less frequent doses of immunotherapy, will prove as effective as the standard schedule but with fewer side-effects and a better quality of life overall. However, we do not know whether this will be the case. This is the reason we are doing the trial. So your participation may not be of direct benefit to you personally, but it is possible that it may be of benefit to future cancer patients because it will help us learn more about the best way to use immunotherapy drugs as a treatment for cancer.

What are the possible disadvantages and risks of taking part?

We don’t know before the trial whether less frequent infusions might increase the risk of disease progression – it is possible that the less often schedule might be less good at controlling your cancer. If this happens you will have the chance to have your treatment increased back to the normal ‘more-often’ schedule. Although we hope that the less-often schedule of immunotherapy drug used in this trial will make treatment easier, i.e. less severe side effects, we do not know this for certain. Potential side-effects you may experience whilst receiving trial treatment have been listed above. The frequency of clinic appointments may be less often than if you received this or another treatment outside of this trial, although some patients may view this as an advantage of being in a trial.

What are the possible side‑effects of immunotherapy drugs?

You will already have received 12 weeks of treatment with immune checkpoint inhibitor drugs at the point at which you enter the trial.  As with all cancer treatments, you may have some side effects. These differ from person to person and they may be mild or more serious; rarely, some may be life-threatening. It is important that you contact your doctor or nurse straight away if you have any side effects that trouble you. The immunotherapy drugs used in REFINE are the same as the ones you will have already received (and the ones that you would receive even if you were not taking part of the trial).

Because of the way immunotherapy drugs work to fight cancer, they can sometimes cause your immune system to attack your normal organs in any area of your body. This can cause inflammation and sometimes can affect the way your organs work. These problems may happen anytime during treatment or even after your treatment has ended. Below is a list of side effects that have been seen in other patients who have had immunotherapy drugs.

The most common side effects (experienced by equal to or greater than 1 in 10 patients) of the immunotherapy drugs are:

• Decreased appetite
• Nausea
• Feeling fatigued, tired or weak
• Pain in the muscles, bones and joints
• Fevers, chills
• Thyroid gland – this may become underactive and work less well. Your doctor will regularly monitor this using blood tests and you may require thyroid replacement tablets.
• Skin problems – this most commonly causes a rash and/or itching. Vitiligo (loss of pigment in the skin) may also occur
• Bowel problems (colitis) – this can cause diarrhoea and abdominal pain. Severe symptoms have been seen in less than 5% of patients
• Liver problems (hepatitis) – symptoms include fatigue, nausea or vomiting, dark urine, yellowing of the whites of your eyes or skin. Your doctor will regularly monitor your liver function using blood tests. Severe inflammation has been seen in less than 5% of patients

Rarer side effects (less than 1 in 10 patients):

• Constipation
• Vomiting
• Kidney problems (nephritis) – Your doctor will carefully monitor your kidney function using blood tests.
• Hormone gland problems (particularly the pituitary, adrenal and pancreas glands) - Symptoms may include: headaches; extreme tiredness; weight gain or weight loss; dizziness or fainting; feeling cold; constipation. You doctor will monitor the function of your glands using regular blood tests
• Lung problems (pneumonitis) – this may cause shortness of breath, a new or worsening cough or chest pain. Severe symptoms are very rare (in less than 1% of patients)
• Eye problems – this can include blurred or double vision, or other visual problems; also eye pain or redness
• In very rare cases the heart, the blood vessels and the nerves may be affected.
• Infusion-related reactions - reactions to the treatment may occur during the infusion itself. This may manifest in a number of ways including fever, chills, pain, headache, rash or low blood pressure. If this occurs, you may need simple medications to control your symptoms and the infusion may need to be slowed down. Very rarely, if the reaction is severe, treatment may need to be permanently discontinued.

What happens if I get side-effects?

If you get side-effects your doctor may interrupt, delay or stop your treatment with immunotherapy just as would happen if you were not involved in the trial. In addition, we may give you other medicines (such as steroids or other immunosuppressive medication) to reduce or treat any side-effects that you may experience.

Do I have to take part in the study?

No, it is up to you if you want to take part. If you decide not to take part this will not affect the standard of care you receive.

What is the MRC CTU and what does it do?

You can find out more about the MRC CTU here: https://www.ctu.mrc.ac.uk/

Do I have to take part in the study?

No, it is up to you if you want to take part. If you decide not to take part this will not affect the standard of care you receive.