A trial looking at chemotherapy and cetuximab for advanced bowel cancer (COIN-B)

Who can enter

You can enter this trial if you

• Have stage 3 bowel cancer (locally advanced cancer) or stage 4 bowel cancer that has spread to another part of your body, apart from your brain
• Are not able to have surgery to remove your cancer
• Give your permission for the trial team to test your cancer to find out if you have a normal K-ras gene or not
• Are well enough to have chemotherapy (performance status 0, 1 or 2)
• Have satisfactory blood test results
• Are prepared to use effective contraception 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 that has spread to your brain
• Have already had chemotherapy for bowel cancer that has spread - you can join if you’ve had chemotherapy for your primary cancer in the bowel, as long as it was more than a month ago
• Have had chemoradiation for rectal cancer in the last month
• Have had oxaliplatin before
• Have had any other cancer that may affect your treatment or the results of this trial
• Have any other serious medical condition
• Are known to be sensitive to any of the drugs in this trial
• Are having any other drugs that are not allowed in this trial - your doctor will advise you about this
• Are pregnant

Trial design

Before you have treatment as part of this trial, your doctor needs to find out if your cancer has a K-ras gene mutation. With your permission, the trial team will arrange to test some of the tissue that was taken when you had a biopsy or surgery to remove your bowel cancer.

If your cancer has a K-ras gene mutation, you will not be able to carry on in the trial. Your doctor will talk to you about other treatment options.

If you have a normal K-ras gene, and you agree to continue in the trial, you will be put into one of 2 treatment groups by computer. This is called randomisation. Neither you nor your doctor will be able to decide which group you are in.

Everybody has 12 weeks of chemotherapy in 2 week cycles of treatment. You will have oxaliplatin and 5FU, along with a vitamin called folinic acid. On day 1 of each cycle you will have the oxilaplatin and folinic acid through a drip into a vein over 2 hours. You will have an injection of 5FU into your vein which takes about 5 minutes. And then you have an infusion of 5FU into a vein continuously over 46 hours. Most hospitals can give you a portable pump so that you can go home during the infusion. You will also have cetuximab through a drip into a vein once a week during this first 12 weeks of treatment.

After 12 weeks of treatment, you have a CT scan. If the scan shows that your cancer has got bigger, you will have another 12 weeks of the same treatment. If it shows that your cancer has stayed the same size or got smaller, your treatment will depend on which group you are in.

If you are in group 1, you stop both the chemotherapy and the cetuximab. You have a CT scan every 12 weeks. If your cancer starts to grow again, you may have another 12 weeks of chemotherapy and cetuximab.

If you are in group 2, you stop the chemotherapy, but continue to have cetuximab every week. This is called maintenance cetuximab. You have a CT scan every 12 weeks. If your cancer starts to grow again, you may have another 12 weeks of chemotherapy. And you also continue to have the cetuximab.

As part of the trial, the researchers will ask your permission for any tissue left over after the K-ras gene testing to be stored and used in future bowel cancer research. The researchers will also ask your permission to take an extra blood sample. This is so they can look at the DNA in your blood. If you do not want to give these samples for research, you don’t have to. You can still take part in the trial. The blood and tissue samples will be stored safely and may be used in the future, but only for research purposes.

If you joined the trial earlier, when your K-ras status was not checked before treatment, the trial team will go back and check this by looking at some of the tissue removed when you had surgery or a biopsy. This will help them to learn more about how bowel cancer responds to treatment.

Hospital visits

You will go to hospital to see the doctor and have some tests before you take part in the trial. These include

• Physical examination
• Blood tests
• CT scan

Everybody taking part will go to hospital at least once a week for the first 12 weeks of treatment.

If you are in group 1, you will then stop having treatment, but you will go to see the doctors every 6 weeks. You will have a CT scan every 12 weeks to see if the cancer has started to grow again.

If you are in group 2, you will continue to go to hospital once a week to have cetuximab. You will have a CT scan every 12 weeks to see if the cancer has started to grow again.

If you have another 12 weeks of chemotherapy and cetuximab, you will go to the hospital at least once a week during this time.

After you finish your treatment, you will go to the hospital once every 3 months to see the trial doctors.

Side effects

The most common side effects of oxaliplatin and 5FU are

• A drop in blood cells causing an increased risk of infection, bleeding or bruising, tiredness and shortness of breath
• Feeling or being sick
• Diarrhoea
• Sore mouth
• Redness and soreness of the skin on hands and feet (plantar palmar or hand foot syndrome)
• Numbness and tingling in hands and feet (peripheral neuropathy)

The most common side effects of cetuximab are

• Skin rash on back, chest and face
• Dry skin
• Soreness around nails, especially the thumb and big toe

Cetuximab may also cause a drop in magnesium levels in your blood, which can cause weakness.

There is more information about oxaliplatin, 5FU and cetuximab on CancerHelp UK.