FOCUS4 - a clinical trial investigating treatment options for advanced bowel cancer

We asked Consultant Oncologist Professor Richard Adams about the FOCUS4 clinical trial, which is testing different treatment options for patients with bowel cancer that has spread to other parts of the body. Professor Adams gives us an overview of what’s being tested, who the trial is suitable for and how you could take part.

What is FOCUS4?

FOCUS4 is a clinical trial taking place across the UK. It’s aimed at patients who have recently been diagnosed with bowel cancer (either small bowel or large bowel) that has spread to other parts of the body (metastasised).

The trial is split into different parts, known as ‘trial arms’, each testing a treatment in patients with different subtypes of bowel cancer.

At the moment, two trial arms are recruiting new patients - FOCUS4-C and FOCUS4-N - which are each testing a different drug:

• FOCUS4-C is looking at a new drug called AZD1775 (adavocertib)
• FOCUS4-N is looking at a different way of using the chemotherapy drug capecitabine

The trial aims to find out if either of the drugs can increase the length of time between stopping the course of chemotherapy and the cancer starting to regrow.  

Who can take part in the trial? 

There are strict criteria to enter the trial. This is both for patient safety and to ensure the researchers are collecting all the information needed to answer their research question and inform future treatment options. This means we can’t accept every patient with bowel cancer into the trial.

You might be able to take part if you have advanced bowel cancer, which has spread to another part of the body or can’t be surgically removed. Your cancer also needs to have shrunk, or at least not grown, whilst you’re receiving your standard chemotherapy treatment. Some parts of the trial are only suitable for people with changes (mutations) in specific genes in their bowel cancer.

If you’d like to take part in FOCUS4, you should speak with your oncologist who will be able to tell you if you’re eligible to take part.  You might ask to be referred to another centre if your own cancer centre is not taking part in the trial.  You can see a list of the cancer centres that are taking part in the trial on the FOCUS4 website.

What happens during the trial?

Your clinical team will give you a patient information sheet with more detail about the trial. This will help you decide if you’d like to take part. If you agree (consent) to take part, the trials team will arrange to test a sample of your tumour.

This sample has usually already been taken and is stored at a local hospital. The testing of your tumour sample allows the trial team to understand more about what features may be driving how your cancer grows. This is known as biomarker testing.

Which trial arm will I join?

FOCUS4-N

FOCUS4-N is open to anyone who is eligible to take part in the trial. If you’re eligible and agree to take part in FOCUS4-N, you will be randomly allocated to one of two groups. You’ll either enter an observation period with close monitoring or you’ll have the chemotherapy drug capecitabine. Being eligible for FOCUS4-N doesn’t necessarily mean you’re eligible to take part in FOCUS4-C and you can’t take part in C and N at the same time. 

FOCUS4-C

Once you’ve had about 16 weeks of standard chemotherapy treatment and if your cancer has shrunk or at least not grown, the information gained from your tumour sample testing can be used to see whether you’re eligible to take part in FOCUS4-C. FOCUS4-C is only open to people who also have changes in specific genes called RAS and p53. 

If you’re eligible and agree to take part in FOCUS4-C, you would also be randomly allocated to one of two groups. Either the observation period with close monitoring or an experimental drug, in tablet form, called AZD1775 (adavocertib). For every three patients who join FOCUS4-C, two of them will take the experimental drug and one of them will have close observation. 

What are the benefits and the risks? 

The potential benefit of receiving the experimental treatment is that it may increase the period of time over which the cancer is controlled without the need to return back to full dose chemotherapy.

Like all treatments, there are risks with the tablets that may result in side effects. Most of these are mild or modest but occasionally severe or life-threatening side effects may occur. Your clinical team can give you more information and answer any questions you have about the trial.

When will these treatments be widely available on the NHS? 

Capecitabine is already available on the NHS but we’re testing whether it can be used in a different way to usual in this trial. We want to find out if using it this different way can benefit patients.

All new treatments in the UK, like AZD1775 (adavocertib), have to be assessed by the National Institute for Health and Care Excellence (NICE) before they can be offered to patients. If trials, like this one, can show the drug is safe and beneficial to patients, the manufacturers may apply for a license and it can then be assessed by NICE. Research such as the FOCUS4 trial are essential to provide the best evidence to help decide who does and who doesn’t benefit from these potential treatments.

• Find out more about the FOCUS4 trial
• If you’d like to read more detailed information about the different arms of the trial, you can read the patient information sheets for registration, FOCUS4-N and FOCUS4-C
• Find out more about clinical trials
• Read more about bowel cancer that has spread to other parts of the body