A trial looking at chemotherapy, with or without cetuximab, for bowel cancer that has spread to the liver, but can be removed surgically - New EPOC

This trial is looking at chemotherapy, with or without cetuximab, for advanced bowel cancer. The trial is funded by Cancer Research UK.

Advanced bowel cancer means the cancer has spread from where it started in the bowel or back passage to another part of the body. Your cancer may be advanced when it is first diagnosed. Or it may have come back some time after you were first treated.

If bowel cancer spreads, it often goes to the liver. Sometimes when the secondaries in the liver are small, you can have surgery to remove them. This offers the best chance of keeping the cancer at bay. People who are able to have this type of surgery usually have chemotherapy as well. The drugs most commonly used include 5 fluorouracil (5FU), oxaliplatin and irinotecan.

This trial is looking at giving cetuximab (Erbitux) as well as chemotherapy. Cetuximab is a monoclonal antibody. This drug can already be used for people who have advanced bowel cancer that has not responded to chemotherapy. But this trial will test it in patients who have not yet had treatment for bowel cancer that has spread. (They may have had treatment in the past for the primary cancer in the bowel.)

Some advanced bowel cancers have a genetic change called a K-ras mutation. Recent research has shown that cetuximab doesn't help people who have this mutation. So, the researchers will only ask you to take part in this trial if tests show you have a normal K-ras gene.

The aims of this trial are to

Find out if cetuximab and chemotherapy together work better than chemotherapy alone
Learn more about the side effects

You will have this treatment both before and after surgery to remove secondaries from your liver.

Recruitment

Start 05/02/2007

End 30/09/2012

Phase

Phase 3

Who can enter

You can enter this trial if

You have cancer that started in the large bowel or rectum and has spread to your liver
Your doctors think that the secondary cancer in your liver can be removed if you have an operation
You have a normal K-ras gene (the researchers will test a sample of tissue taken when you had surgery to check for this, but they may also ask you for an extra blood sample)
You are well enough to have treatment - (performance status 0,1 or 2)
You have satisfactory blood test results
You have had a negative pregnancy test and are prepared to use reliable contraception while you are taking part in the trial if there is any chance you or your partner could become pregnant
You have given written informed consent
You are at least 18 years old

You cannot enter this trial if you

Have an altered K-ras gene, or the result of testing your K-ras gene was unclear
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 6 months ago
Have had a combination of chemotherapy and radiotherapy for rectal cancer in the last month
Have damage to the nerves (neuropathy) from earlier chemotherapy - this is most likely to affect your hands or feet
Have cancer that has spread to your brain
Have a blockage in the bowel (bowel obstruction)
Have angina that is not well controlled with medicine
Have had a heart attack in the last 3 months
Have had any other cancer in the past that may affect your treatment or the results of this trial
Have any other serious medical condition or take medication which means you cannot have the treatment in this trial
Are sensitive to any of the drugs being used in the trial
Are breastfeeding

Trial design

This trial will recruit 340 patients. Everybody taking part in this trial will have chemotherapy. You will have one of the following chemotherapy combinations

OxMdG (Oxaliplatin, 5FU and folinic acid)
IrMdG (Irinotecan, 5FU and folinic acid)

Your doctor will talk to you about the drug combination that will be best for you. There is more information about chemotherapy for advanced bowel cancer on CancerHelp UK.

First, you have 12 weeks of chemotherapy. Then you have surgery to remove the secondaries in your liver. When you have recovered from the operation, you will have another 12 weeks of chemotherapy.

As this is a randomised trial, you will be put into one of 2 treatment groups by a computer. Neither you nor your doctor will be able to decide which group you are in.

People in group A have chemotherapy
People in group B have chemotherapy and cetuximab. You have cetuximab as a drip into a vein

If you have OxMdG, you will have 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 oxaliplatin and folinic acid through a drip into a vein over 2 hours. You will then have an injection of 5FU into your vein that takes about 5 minutes. And then 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. But to use a pump, you need to have a central line or a PICC line.

If you have IrMdG, you have chemotherapy in the same way as OxMdG, but you have irinotecan instead of oxaliplatin.

Patients in group B will also have cetuximab on the first day of each chemotherapy cycle. It will take 2 hours and you will then have to wait another hour before having your chemotherapy.

Everyone taking part will fill in a questionnaire before starting chemotherapy, then half way through and at the end of each 12 week course of chemotherapy. This will ask you how you are feeling and about any side effects you have had. It is called a quality of life questionnaire. You will also repeat the questionnaire at the end of your treatment and at follow up appointments after your treatment has finished.

As part of the trial, the researchers will ask your permission to get a sample of tissue that was removed when you had surgery for bowel cancer. And they will ask if they can keep a sample of tissue removed when you have surgery to your liver. They will also ask your permission to take an extra blood sample. The samples will be stored safely and may be used in the future, but only for research purposes. If you do not want to give these samples for research, you don’t have to. You can still take part in the trial.

Hospital visits

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

Physical examination
Blood tests
CT scan

You will have to go to hospital every 2 weeks. After 12 weeks of treatment, you will have another CT scan. This is so the doctors can check that it is still possible to remove the liver secondaries. If it is, you will then have surgery. There is more information about removing secondary cancer on CancerHelp UK.

You will probably be in hospital for between 1 and 3 weeks. You will also need a few weeks to recover from your operation. Within 8 weeks of having surgery, you will start another 12 weeks of chemotherapy. If you are in group B you will also continue to have cetuximab.

You will have a physical examination each time you go to hospital. And blood tests at the beginning of each chemotherapy cycle. At the end of the treatment, you will have another CT scan.

After you finish the treatment, you will see the trial doctors every 3 months for the first 2 years and then every 6 months for the next 3 years. At these visits, you may have more blood tests and scans.

Side effects

All treatments have some side effects. The most common side effects of cetuximab are

A skin rash on the back, chest or face
Soreness around the nails, especially thumb and big toe

The most common side effects of oxaliplatin, 5FU and irinotecan are

A drop in blood cells causing an increased risk of infection, bleeding or bruising, tiredness and shortness of breath
Diarrhoea
Feeling or being sick
Redness and soreness on hands and feet
Sore mouth
Numbness and tingling in hands and feet (peripheral neuropathy) with oxaliplatin

Irinotecan can also cause increased sweating and saliva production, watery eyes and stomach cramps.

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