A trial looking at panitumumab, irinotecan and ciclosporin for advanced bowel cancer (PICCOLO)

This trial is looking at irinotecan alone, irinotecan with panitumumab or irinotecan with ciclosporin for bowel cancer that has come back after one course of chemotherapy.

Doctors usually treat bowel cancer (colorectal cancer) with surgery and chemotherapy. But sometimes the cancer starts to grow again and they need to give another course of chemotherapy (second line treatment). They often give a drug called irinotecan (Campto) in this situation. But irinotecan doesn’t always work very well and it does cause side effects. Researchers want to test 2 new combinations of treatment in this trial.

The first is irinotecan and panitumumab. Panitumumab is a type of immunotherapy called a monoclonal antibody. Doctors hope that irinotecan and panitumumab together will work better than irinotecan alone.

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

The second combination is irinotecan and ciclosporin. Ciclosporin is not an anti cancer drug, but it changes the way the body gets rid of irinotecan. So doctors hope that irinotecan and ciclosporin will work as well as irinotecan alone, but cause fewer side effects.

The aims of this trial are to find out

If irinotecan and panitumumab together are more effective than irinotecan alone for advanced bowel cancer with a normal K-ras gene
If irinotecan and ciclosporin together cause fewer side effects than irinotecan alone
More about the effects these drugs may have on bowel cancer cells

Recruitment

Start 04/12/2006

End 01/01/2010

Phase

Phase 3

Who can enter

You can enter this trial if you

Have advanced bowel cancer
Have an area of cancer that can be measured on a scan
Have had treatment such as 5 fluorouracil (5 FU), with or without oxaliplatin or bevacizumab (Avastin)
Are well enough for treatment (performance status 0, 1 or 2)
Have satisfactory blood test results
Are prepared to use reliable contraception while you are taking part in the trial and for 6 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 bowel cancer that has spread to your brain
Have had irinotecan before
Have had treatment in the last 3 weeks
Have had any experimental treatment or antibody treatment, apart from cetuximab (Erbitux), in the last 6 weeks
Have had a severe allergic reaction to cetuximab in the past
Take ciclosporin regularly for another medical condition
Take diltiazem, verapamil, or amiodarone (all medications for heart conditions) or fluvoxamine - please note, do not stop taking any of your regular medications unless your doctor tells you to do so
Have had any other cancer in the past, apart from non melanoma skin cancer
Have had major chest or abdominal surgery in the last 4 weeks
Have a blocked bowel (bowel obstruction)
Have a condition affecting your bowel such as Crohn’s disease or ulcerative colitis
Have continuing (chronic) diarrhoea
Have a serious and uncontrolled infection
Have a condition such as fluid around the lung (pleural effusion) or your abdomen (ascites), or lung fibrosis that makes you short of breath

Trial design

This is a randomised trial. It will recruit nearly 1,300 people from around the UK. The people taking part will be put into treatment groups by a computer. Neither you nor your doctor will be able to decide which group you are in.

Before you are put into a treatment group, your doctor needs to find out if your cancer has a K-ras gene mutation or not. It is likely that some of the tissue taken when you had a biopsy or surgery to remove your bowel cancer has been safely stored. With your permission, the trial team can arrange to test some of this stored tissue to see if the K-ras gene is normal, or if there is a mutation. As part of this trial, the researchers will ask your permission for any tissue left over after the K-ras gene testing has been done to be stored and used in future bowel cancer research.

At randomisation, if your bowel cancer has a normal K-ras gene, you will be put into either group 1 or group 2. If your cancer has a K-ras gene mutation, you will be put into either group 1 or group 3.

If the researchers cannot successfully test stored tissue, they may ask you to have another biopsy. Or, they may suggest that at randomisation, you can only be put into group 1 or 3.

Group 1 will have standard treatment of irinotecan alone. You have irinotecan through a drip into a vein over about an hour and a half, once every 3 weeks.

Group 2 will have irinotecan and panitumumab. You have panitumumab through a drip into a vein over about an hour, once every 3 weeks. And then you have irinotecan through a drip into a vein over about an hour and a half on the same day.

Group 3 will have irinotecan and ciclosporin. You take ciclosporin as a capsule or liquid for 3 days out of every 3 weeks. And you have irinotecan through a drip into a vein over about 40 minutes, once every 3 weeks. The irinotecan takes less time than for group 1 or 2 because you have a lower dose. This is because you take it with ciclosporin.

Each 3 weeks is one cycle of treatment. Everyone taking part will have 4 cycles over 3 months (12 weeks). You will then see the doctors and have a scan. If there are signs that the treatment is working well and you haven’t had any serious side effects, you may be able to have more treatment. You may have this straight away, or start again after a break. Your doctor will discuss this with you nearer the time.

You will fill out a questionnaire before you start treatment and again at 3 months and 6 months. It will ask you how you have been feeling and about any side effects you have had. This is called a quality of life questionnaire.

The researchers will ask your permission to take an extra blood sample and a urine sample before you start treatment. This is so that they can look at the DNA in these samples to learn more about who benefits most from each treatment.

If you joined the trial when your K-ras status was not known, the trial doctors will go back and check this by looking at some the tissue removed when you had surgery or a biopsy. In this situation, if you are still having treatment as part of the trial, this will continue as originally planned.

Hospital visits

You will see the doctor and have some tests before you can take part in this trial. The tests include

Blood tests
Physical examination
CT scan

You will go to the hospital once every 3 weeks for treatment. If you are in group 3 the doctors will give you a supply of ciclosporin to take at home.

You will have blood tests and a physical examination before each cycle of treatment. And a CT scan every 3 months until there are signs that your cancer has started to grow again.

After you finish treatment you will see the doctors every 3 months for at least a year.

Side effects

As with most treatments, the drugs in this trial cause some side effects.

The most common side effects of irinotecan are

Flushing or sweating while you are having treatment
Diarrhoea
Feeling or being sick
A drop in blood cells causing an increased risk of infection, bleeding or bruising problems, tiredness or shortness of breath
Hair loss

There is more about irinotecan (Campto), including information about less common side effects, on CancerHelp UK.

The most common side effects of panitumumab are

Rash
Sore nails or tips of fingers and toes

Although doctors hope that ciclosporin will help reduce the side effects of irinotecan, it does have side effects of its own. The most common ones are