RecruitingPhase IVInterventional

Can extra tests on cancer samples identify more patients with bowel/colon cancer who should be treated with drugs called anti-EGFR agents?

Bowel cancer that starts on the right side of the tummy often behaves differently from cancer on the left side and can be harder to treat. Targeted medicines called anti-EGFR drugs (cetuximab and panitumumab) block signals that tell cancer cells to grow. However, these drugs do not work for everyone with right-sided bowel cancer. The ARIEL trial is testing whether an extra test on existing tumour samples can find people who are most likely to benefit. This test looks for high levels of two proteins, called AREG and EREG. Participants will be placed into one of two groups by chance: one group receives standard chemotherapy alone, and the other receives standard chemotherapy plus an anti-EGFR drug. The aim is to see if matching patients to these targeted drugs helps keep the cancer under control for longer.

At a glance

Status

Recruiting

Phase

Phase IV

Sponsor

University of Leeds

Enrolment target

440

Start

25 Apr 2022

Estimated completion

01 Oct 2027

Advanced colorectal cancer

What is this study about?

Bowel cancer is one of the most common cancers in the UK, but not all bowel cancers are the same. In recent years, doctors have discovered that where the cancer first started makes a big difference. Cancers that begin on the right side of the bowel tend to behave more aggressively and often do not respond as well to certain standard treatments compared to those on the left side.

One important group of treatments is targeted drugs known as anti-EGFR therapies, such as cetuximab and panitumumab. These drugs work by attaching to cancer cells and switching off the signals that tell them to divide and spread. While these drugs can be very effective, doctors usually avoid giving them to patients with right-sided bowel cancer because past studies showed they rarely helped and sometimes caused extra side effects without any real benefit.

However, newer research suggests that some people with right-sided tumours might still benefit after all. Scientists have found two proteins, known as AREG and EREG, inside some tumours. If a tumour has high levels of these proteins, the targeted drugs might actually work well. This trial tests whether using this new protein check can help doctors safely choose the right patients for these powerful medicines.

By taking part, patients help researchers learn whether adding an anti-EGFR drug to standard chemotherapy improves cancer control. If successful, this trial could give future patients with right-sided bowel cancer access to new, personalised treatment options on the NHS.

Key takeaways

The ARIEL trial tests whether targeted drugs help a specific group of people with right-sided advanced bowel cancer.
Your tumour sample is checked for two specific proteins (AREG and EREG) to see if you can take part.
Participants are randomly chosen to receive standard chemotherapy alone or chemotherapy plus a targeted medicine.
Treatment is given every two weeks, with regular scans to monitor how well the cancer is being controlled.
Participation is entirely voluntary and will not affect your right to standard NHS care.

Who may be eligible?

This trial is open to adults aged 18 and over who have been diagnosed with advanced bowel cancer (cancer that has spread or cannot be removed with an operation) that started on the right side of the bowel.

To be considered, you must have an existing tumour sample (a biopsy) that can be sent for extra laboratory testing. The tests must show that your cancer cells have a normal 'RAS' gene and high levels of the AREG and EREG proteins.

You also need to be well enough to manage day-to-day activities and tolerate chemotherapy. Your doctor will check your general fitness, blood counts, and kidney and liver function to make sure it is safe for you to take part.

Could this study suit you?

Answer these quick questions to see if you may be eligible. This is a guide only — the research team makes the final call.

I am aged 18 or over.
I have been diagnosed with advanced or inoperable bowel cancer.
My cancer started on the right side of my bowel.
I have a tumour sample available from an earlier biopsy or surgery.
I am well enough to carry out daily tasks and receive chemotherapy.

Answer every question to see your result.

What does participation involve?

If you join the study, you will first have tests including blood tests, physical checks, and a CT scan to ensure the trial is safe for you. You will then be put into one of two treatment groups by a computer. This process is completely random, like flipping a coin. One group receives standard chemotherapy on its own. The other group receives standard chemotherapy combined with an anti-EGFR targeted drug (either cetuximab or panitumumab).

Treatment is usually given through a drip into a vein once every two weeks at the hospital. You will have regular CT scans, usually around week 8 and week 16, to monitor how your tumour is responding. You can stay on the treatment for as long as it is helping to keep your cancer under control and any side effects remain manageable. The overall trial is scheduled to run until late 2030, but your personal time on the study depends entirely on your health and response to treatment.

Potential risks and benefits

The potential benefit of joining this study is that receiving a targeted drug alongside chemotherapy might help control your cancer for longer than chemotherapy alone. You will also be helping to improve future bowel cancer care. However, there is no guarantee of direct benefit. The targeted drugs can cause side effects such as skin rashes, tiredness, diarrhoea, or allergic reactions, and you might experience these without the drug shrinking your tumour. Taking part is completely voluntary. You are free to leave the trial at any point, and your standard NHS cancer care will continue as normal.

Locations (43)

St James's University Hospital
Approximate
Leeds, England
Velindre NHS Trust
City only
Cardiff, Wales
NHS Greater Glasgow and Clyde
City only
Glasgow, Scotland
NHS Grampian
Approximate
Aberdeen, Scotland
NHS Lothian
Approximate
Edinburgh, Scotland
The Christie Hospital
Unverified
Manchester, England
Calderdale and Huddersfield NHS Foundation Trust
Unverified
Huddersfield, England
Bradford Royal Infirmary
Unverified
Bradford, England
Cambridge Biomedical Campus
Unverified
Cambridge, England
University College London Hospitals NHS Foundation Trust
Unverified
London, England
Southampton General Hospital
Unverified
Southampton, England
St Thomas' Hospital
Unverified
London, England

Common questions

Why does it matter which side of the bowel my cancer started on?

The right and left sides of the bowel develop differently before birth and have different biology. Right-sided tumours often have different genetic features, which means they do not always respond to the same medicines as left-sided tumours.

Can I choose to have the targeted drug?

No. A computer assigns you to a group by chance. This is called randomisation, and it is the fairest way for researchers to clearly compare whether adding the targeted drug works better than standard chemotherapy alone.

Do I need to have a new biopsy taken?

In most cases, the researchers can use tissue samples that were already taken during your earlier surgery or biopsy, provided there is enough sample left to run the protein tests.

How long will I be on the trial?

You will remain on the trial treatment for as long as your scans show the cancer is controlled and the side effects are acceptable to you and your medical team.

What happens if I decide I want to stop?

You can leave the study at any time without giving a reason. Your doctors will simply talk through other standard treatment options available to you on the NHS.

How to find out more

Claire Dimbleby

ariel@leeds.ac.uk - Official trial record

Always speak to your GP or specialist before deciding to take part in a study.