About ARIEL

About ARIEL

When a bowel (also called ‘colon’) cancer has spread to other areas of the body, and it is not possible to remove all of the areas of cancer by surgery, the standard treatment is to offer chemotherapy. Chemotherapy is offered with the aim of controlling the cancer for a longer period of time, although unfortunately not to cure it.

A group of medications called anti-EGFR drugs can be used alongside chemotherapy with the intention of better controlling the bowel cancer. There are two drugs in this group, cetuximab and panitumumab. Both these drugs are already used in the UK and abroad. The doctor advising you about your cancer treatment will be familiar with these drugs and will have prescribed them as part of standard care for other patients in the past. The side effects of these drugs are well understood.

We know that anti-EGFR drugs do not help control bowel cancers in all cases. This means that some people are exposed to their side effects without getting any benefit from them. Researchers have been trying to find out if we can predict who does and who does not benefit from anti-EGFR drugs before they are given to patients.

We can already identify some people who don’t benefit from anti-EGFR drugs. Patients who have a genetic mutation in their cancer in a gene called RAS do not benefit from anti-EGFR drugs. Your doctor already checks for this mutation in the cancers of all patients they are thinking of offering an anti-EGFR drug to. If this mutation were present in your cancer, we know an anti-EGFR drug would not be helpful to you and so your doctor would not offer you one of these drugs.

We also know that anti-EGFR drugs often do not help control bowel cancer in people where the cancer began on the right side of the abdomen (tummy). This might sound odd but makes more sense when we consider that the right and left sides of the bowel develop differently when humans are growing in the womb. Right-sided cancers have different biology when tested by scientists so it is not surprising that they would also respond differently to some treatments.

Although anti-EGFR drugs often do not help control bowel cancers that began on the right side of the abdomen, sometimes they do. The ARIEL trial is looking into two markers found in bowel cancer called AREG and EREG. We know from earlier work that anti-EGFR drugs are more likely to help control bowel cancer in patients with high levels of these markers in their cancer; and that patients with low levels of AREG and EREG in their cancer do not benefit from anti-EGFR drugs. The main aim of the ARIEL trial is to see if we can use the AREG and EREG markers to identify the patients with right-sided bowel cancer who do benefit from anti-EGFR drugs.

Who Can Take Part?

There are two stages to getting involved in the ARIEL trial. In the first stage, any patient with bowel cancer that has spread to other parts of their body, and that started on the right side of their abdomen, can consider taking part in the trial. If they agree, samples of their cancer taken during previous operations or procedures will be used to confirm that:

1. The RAS gene is not affected by a mutation (also known as wild-type) – this is a standard test performed on the cancers of all patients with advanced bowel cancer.
2. The AREG/EREG markers are produced in high levels by their cancer – this is a new test that will be performed as part of the trial.

In the second stage, patients confirmed as having cancers that fulfil these criteria can then consider participating in the main part of the trial.

Patients with a cancer that has a mutation in the RAS gene, or whose cancer produces low levels of the AREG and EREG markers, will be offered treatment by their doctor outside the ARIEL trial. We are very grateful to these patients for considering the trial and would still like to learn something about how their cancer responds to treatment. With their permission, one year after we have tested their cancer for the AREG and EREG markers, we will ask their doctor how their cancer treatment has been going. This will be done using their medical notes and won’t require any special appointments.

What treatments are given in the trial?

Patients whose cancers fit the above criteria and who are willing to take part in the trial will be randomly allocated into one of two trial groups (sometimes called arms).

• Group 1 will receive the standard chemotherapy for patients with right-sided bowel cancer that has spread to other areas of the body.
• Group 2 will receive the standard chemotherapy given to group 1 AND an anti-EGFR drug (either cetuximab or panitumumab)

There are different options for the standard chemotherapy that can be given. If you are thinking about taking part in the trial, your doctor will talk to you about these.

Cetuximab and panitumumab are similar medications and patients can receive treatment with either drug within the ARIEL trial. If you are allocated to Group 2 of the trial, your doctor will talk to you about which drug might be right for you.

For both Group 1 and Group 2, treatment will be given for a total of 16 weeks within the trial.

How will we know if the treatment has been effective?

All patients taking part in the trial will have a CT scan of their body before (or very shortly after) they are allocated into one of the treatment groups. CT scans will be repeated after 8 weeks and 16 weeks of treatment.

We will compare the size of each patient’s tumours on each scan to see if they shrink with treatment. We are looking to see if the tumours of patients in Group 2 shrink more than those of patients in Group 1. If they do, this would confirm that AREG and EREG can be used to identify patients with advanced, right-sided bowel cancer who benefit from anti-EGFR therapy.

After 16 weeks of treatment, your doctor will review your scans with you so you know how your own cancer has responded to treatment. You can then decide together about whether you would like to have more treatment and what that treatment will consist of, or if you would like to have a break from treatment. It is important to note that only the initial 16 weeks of treatment is considered part of the trial.

Will there be any other assessments after 16 weeks?

Treatment after the initial 16 week study period will be the standard treatment your doctor would usually give to a person in your situation. While the trial team will not monitor your treatment closely after the first 16 weeks, we would like to ask your permission for your doctor to tell us how your cancer treatment has been going one year after you finish treatment within the trial, and again one year after we have finished recruiting patients to the trial. This will be done by your doctor reporting information from your medical notes and will not require you to attend any special appointments.