A trial of chemotherapy with or without radioembolisation for bowel cancer that has spread to the liver (FOXFIRE)

You can enter this trial if you

• Have bowel cancer that has spread to the liver and cannot be completely removed with surgery, or cured with other treatments
• Are likely to benefit from chemotherapy
• Have satisfactory blood test results
• Are well enough to take part in the trial (performance status 0 or 1)
• Are willing to use reliable contraception during chemotherapy and for 2 months afterwards, if there is any chance you or your partner could become pregnant
• Are at least 18 years old

You cannot enter this trial if you

• Have cancer in the liver that can be removed with surgery
• Have already had chemotherapy for advanced bowel cancer (you can take part if you had chemotherapy after surgery for early bowel cancer as long as you finished the chemotherapy at least 6 months ago)
• Have a build up fluid in the abdomen (ascites) or other liver problems such as cirrhosis
• Have cancer (or a blood clot) which is blocking the blood vessel that brings blood from the bowel to the liver (the portal vein)
• Have had radiotherapy to the upper part of your abdomen or spine
• Have damage to the nerves in your hands or feet (peripheral neuropathy) unless it is very mild
• Have had another cancer in the last 5 years apart from non melanoma skin cancer
• Are pregnant or breastfeeding

This is a phase 3 trial. It will recruit nearly 500 people in the UK. It is a randomised trial. The people taking part will be put into 1 of 2 treatment groups by a computer. Neither you nor your doctor can decide which group you are in.

• People in group A have chemotherapy alone
• People in group B have chemotherapy combined with radioembolisation

Everybody taking part will have the chemotherapy drugs oxaliplatin and 5FU (fluorouracil), along with a vitamin called folinic acid. This treatment plan is called OxMdG chemotherapy. Or, you may have a similar type of chemotherapy using the same drugs called FOLFOX.

You have OxMdG chemotherapy in 2 week cycles of treatment. On day 1 of each cycle you have the oxaliplatin and folinic acid through a drip into a vein over 2 hours. You then have a slow injection of 5FU into your vein over about 5 minutes. Finally, you have an infusion of 5FU continuously over 46 hours.

Most hospitals can give you a portable pump so that you can go home during the infusion. To use a pump, you need to have a central line or a PICC line. This will mean that you still have to visit hospital once a fortnight but shouldn’t need to stay in overnight.

People in group B have radioembolisation once during their 2nd cycle of chemotherapy. The doctor makes a small cut in your groin and passes a fine tube (a catheter) from there up into blood vessels in the liver. The doctor then injects the microspheres through the catheter and they get stuck in the small blood vessels in and around the cancer.

If you are in group B, up to 3 weeks before you have radioembolisation, you will have a test to look at the blood supply inside your liver. This is to reduce the risk of the microspheres affecting any other areas of your body. The doctor will inject a dye that shows up the blood vessels on a digital X-ray. Very rarely, people cannot have radioembolisation because they have too much blood flowing from the liver to the lungs.

Everybody taking part will be asked to fill out a questionnaire before starting treatment, when they have the 4th cycle of chemotherapy, and after finishing treatment. The questionnaire will ask about any side effects you have had and about how you have been feeling. This is called a quality of life study.

The trial team will ask your permission to get a sample of tissue which was removed when you had surgery or a biopsy. This is so they can learn more about what causes some cancers to grow or spread more quickly, and which cancers are more likely to respond to chemotherapy or radioembolisation. They will also ask your permission to take an extra blood sample for research. This is so the researchers can look at your DNA to try and find out more about which genes might cause bowel cancer, how they affect the way people respond to the treatments in this trial, and which side effects they have. All samples will be stored safely and used only for research purposes.

You will see the trial doctors and have some tests before you start treatment. The tests include

• Physical examination
• Blood tests
• CT scan

In this trial, you have 12 cycles of chemotherapy taking about 6 months altogether. During treatment, you have blood tests every 2 weeks and CT scans every 2 to 3 months. Most people will be able to have chemotherapy as an outpatient.

If you are in group B, you may have to stay in hospital overnight when you have radioembolisation.

After you finish treatment, you will see the trial doctors every 3 months for up to a year. But the trial team will follow your progress for at least 2 years. This may be in clinic appointments, or by telephone. You will have a scan every 2 months for 18 months and every 3 months after that.

The side effects of OxMdG chemotherapy include

• Diarrhoea or constipation
• Sickness
• Sore mouth or mouth ulcers
• A drop in the number of blood cells causing an increased risk of infection, bleeding problems, tiredness and breathlessness
• Numbness or tingling in the hands or feet (peripheral neuropathy)
• Tiredness (fatigue)
• Loss of appetite
• Dry skin

There is more information about the possible side effects of oxaliplatin and 5FU on CancerHelp UK.

Side effects of radioembolisation include

• A mild fever after the treatment
• Pain in the tummy (abdomen)
• Feeling sick
• Tiredness

It is possible that the microspheres may not reach or stay in the liver. They can then affect other parts of the body such as the stomach, pancreas or lungs. This is very rare, but if it happens, it could cause

• Swelling of the pancreas (pancreatitis)
• Ulcers in the stomach or intestine
• Swelling (inflammation) of the lung

There is also a small risk of having an allergic reaction to the dye used to test the liver’s blood supply, and a small risk of long term damage to healthy parts of the liver.

As microspheres give off a small amount of radiation, you have to take certain precautions for a week after the treatment. You must sleep separately from your partner during this time and you cannot spend long periods of time close to pregnant women or young children. You must wash your hands thoroughly after going to the toilet, and carefully clean up any spills of body fluids such as urine or blood. The trial team will explain the precautions you need to take and give you a leaflet to take home with you to remind you what you must avoid.