A trial looking at different treatments for different types of bowel cancer (FOCUS4)

Cancer type:

Bowel (colorectal) cancer
Colon cancer
Rectal cancer

Status:

Open

Phase:

Phase 2/3

This trial is testing different treatments for different subtypes of bowel cancer. The trial is for bowel cancer that cannot be removed with surgery or has spread to another part of your body.

More about this trial

If bowel cancer cannot be completely removed with surgery, or has spread to another part of your body, you are likely to have chemotherapy. We know from research that for most people it is safe to have a break from chemotherapy after a few months.

In this trial, researchers want to see if having other treatment during this chemotherapy break helps to extend the time before bowel cancer starts growing again. Not all bowel cancers are the same and some new cancer drugs may help people with one type of bowel cancer more than another.

To work out the subtype of bowel cancer you have, the researchers will test a sample of your cancer to look for changes to certain genes and proteins that your tumour produces. 

If you agree to have a sample of your cancer tested, and your cancer doesn’t get any bigger during chemotherapy, you can enter the part of the trial testing new treatments. The researchers will look at a number of different treatments. They call these comparisons.

Please note – at present, only 2 of the comparisons are recruiting people. These are called FOCUS4-C and FOCUS4-N.

Who can enter

The following bullet points list the entry conditions for this study. Talk to your doctor or the study if you are unsure about any of these. They will be able to advise you. 
 
Who can take part
You may be able to join this trial if all of the following apply. You:
  • have a type of cancer called adenocarcinoma that started in the large bowel (colon) or back passage (rectum)
  • have cancer that cannot be removed with surgery or has spread to another part of your body
  • have cancer that can be measured on a CT scan, and a sample of your cancer taken before you started chemotherapy that can be tested to look for proteins and gene changes
  • are well enough to be up and about for at least half the day (performance status 0, 1 or 2)
  • had a CT scan in the 6 weeks before you started chemotherapy and the results of the scan are available electronically
  • are at least 18 years old
  • are willing to use reliable contraception during the trial if there is any chance you or your partner could become pregnant
As well as the above. 
 
To enter comparison FOCUS4-C:
  • you must have a change to genes called KRAS/NRAS and p53 or loss of the H3K36me3 protein (your doctor can tell you more about this)
  • your cancer has stayed the same size or got smaller after having 16 weeks of chemotherapy 
  • you have had a CT scan in the last 4 weeks that confirms this
  • have satisfactory blood test results and organ function
To enter comparison FOCUS4-N:
  • your cancer must have stayed the same size or got smaller after having 16 weeks of chemotherapy
  • you have had a CT scan in the last 4 weeks that confirms this
  • have satisfactory blood test results
 
Who can’t take part
You cannot join this study if any of these apply. You:
  • have cancer that has spread to your brain
  • have previously had chemotherapy for advanced bowel cancer
  • have had chemotherapy after surgery to try to stop your cancer coming back (adjuvant treatment Open a glossary item) in the last 6 months
  • are pregnant or breastfeeding
  • have HIV
  • have hepatitis B or hepatitis C
You can’t enter FOCUS4-C if you:
  • still have moderate or severe side effects from previous treatments, apart from hair loss (alopecia) and loss of appetite
  • can’t swallow tablets
  • have a serious infection or any other medical problem that the trial team think could affect you taking part
  • have heart problems such high blood pressure, angina that isn’t controlled, congestive heart failure or a condition called Torsades de pointes
  • have stomach problems such as an ulcer, unless you have had an operation to remove it or it has been stable for the past 6 months
  • have had bleeding in your gut unless this has been surgically removed
  • have had a major operation in the last month, or a small surgery in the past week
  • are taking drugs called CYP3A4 such as erythromycin, verapamil or nefazodone and you can’t stop it during this trial
  • are taking certain drugs such as aprepitant, atorvastatin or simvastatin and are not able to stop or substitute these 2 weeks before starting trial treatment
  • are taking herbal remedies and are not able to stop or substitute these 1 week before starting trial treatment
  • are taking St John’s Wort and are not able to stop or substitute this 3 weeks prior to starting trial treatment
And you can’t enter FOCUS4-N if you:
  • can’t take capecitabine for any reason
  • have had any other chemotherapy treatment for your bowel cancer apart from the 16 weeks of chemotherapy you have just had
  • are going to have a combination of chemotherapy and radiotherapy for rectal cancer (you can take part in you’re having radiotherapy for symptoms)
  • have high blood pressure that can’t be well controlled or certain heart problems
  • are taking part in any other trial looking at treatment for people in your situation, if this would cause problems with you taking part in the FOCUS4-N

Trial design

The researchers aim to recruit more than 1,500 people at hospitals across the UK. To start with, you have 16 weeks of chemotherapy. If you have already started chemotherapy, you can join the trial up until the 12th week of your chemotherapy treatment.
 
While you are having chemotherapy, the researchers will test a sample of cancer that was taken when you had surgery or a biopsy Open a glossary item to diagnose it. They will try to classify your cancer as a particular subtype. In about 2 out of 100 people (2%), it is not possible to classify the tumour as a specific bowel cancer subtype.
 
At the moment, the trial aims to test treatments in different subtypes of bowel cancer:
  • the comparison called FOCUS4-A is for cancer with a change (mutation) to a gene called BRAF
  • the comparison called FOCUS4-B is for cancer with a change to a gene called PIK3CA or that only produces a small amount of a protein called PTEN
  • the comparison called FOCUS4-C is for cancer with a change to genes called KRAS or NRAS in combination with a change to the gene called p53 OR there is a loss of the H3K36me3 protein in the cancer
  • the comparison called FOCUS4-D is for cancer that doesn’t have changes to any of these genes
  • the comparison called FOCUS4-N is for cancer that cannot be classified as any of the subtypes above or for people that do not wish to enter any of the comparisons above 
Each comparison is randomised. You are put into treatment groups by a computer. Neither you nor your doctor can decide which group you are in.
 
 
Please note – at the moment, people are only being recruited into the comparisons called FOCUS4-C and FOCUS4-N. 
 
Comparison FOCUS4-C is looking at a new drug called AZD1775. Everyone who joins this group has 1 of the following:
  • AZD1775
  • no further treatment until scans show that your cancer is growing again (active monitoring)
You are 2 times more likely to have AZD1775 than active monitoring. 
 
If you are in the AZD1775 group, you take AZD1775 tablets once a day, for 5 days during week 1 and week 2. You then have a break of 1 week. Each 3 week period is called a cycle of treatment. 
 
If you are having AZD1775 and there are signs that your cancer is starting to grow again, you stop taking the tablets. The trial doctor will talk to you about restarting chemotherapy or starting a different treatment.
 
If you are in the active monitoring group and there are signs that your cancer is starting to grow again the trial doctor will talk to you about having chemotherapy or starting a different treatment. 
 
Comparison FOCUS4-N is looking at the chemotherapy drug capecitabine. If you join this comparison, you will have 1 of the following:
  • capecitabine tablets twice each day for 2 weeks out of every 3
  • no further treatment until scans show your cancer is beginning to grow again (active monitoring)
If you are having capecitabine and there are signs that your cancer is starting to grow again, you stop taking the tablets. The trial doctor will talk to you about restarting chemotherapy or starting a different treatment.
 
If you are in the active monitoring group and there are signs that your cancer is starting to grow again, the trial doctor will talk to you about restarting chemotherapy or starting a different treatment. 

Hospital visits

When you join the trial, the researchers will test a sample of your cancer that had already been removed. If you enter the FOCUS4-C comparison they will ask you to consider having 2 new biopsies Open a glossary item to compare with the sample that has already been tested. 

They will want to get a new biopsy sample before you start one of the trial treatments and another one at the end of the trial treatment. These biopsies are optional. If you don’t want to give these samples for research, you don’t have to. You can still take part in the main trial.

You see the trial team and have blood tests regularly during the trial. How often you go to hospital, and the tests you need to have depends on which comparison you are in.
 
If you are in FOCUS4-C you see the trial doctor every 3 weeks for blood tests and a physical examination. You also have a CT scan every 7 to 9 weeks.

If you are in FOCUS4-N, you see the trial doctor every 3 to 4 weeks and have a CT scan every 7 to 9 weeks. 

The trial team will ask people who join FOCUS4-N to fill out a questionnaire before they start treatment, every 8 weeks during treatment and after they finish treatment. The questionnaire will ask about side effects and how you’ve been feeling.  This is called a quality of life study.

Whichever comparison you join, when you finish the trial treatment, you see the trial team again within 4 weeks, then after 3 months and then every 6 months after that.

Side effects

The side effects of capecitabine include:
Occasionally, it can also cause some chest pain.
 
We have more information about side effects of capecitabine.
 
AZD1775 is a new treatment and there might be side effects we don’t know about yet. So far, the most common side effects of AZD1775 are:

Location

Aberdeen
Airdrie
Ashford
Bangor
Barrow in Furness
Basingstoke
Bath
Bedford
Birmingham
Blackpool
Boston
Bournemouth
Brighton
Bristol
Burton on Trent
Cambridge
Canterbury
Cardiff
Carlisle
Carmarthen
Cheltenham
Chesterfield
Cottingham
Crewe
Dorchester
Dudley
Dundee
East Kilbride
Edinburgh
Exeter
Forth Valley
Glasgow
Gloucester
Greenock
Guildford
Halifax
Harlow
Hartlepool
Haverfordwest
Huddersfield
Huntingdon
Inverness
Ipswich
Kendal
Kilmarnock
Kirkcaldy
Knowsley
Lancaster
Leeds
Leicester
Lincoln
London
Macclesfield
Maidstone
Manchester
Margate
Middlesbrough
Milton Keynes
Newcastle upon Tyne
Northampton
Northwood
Nottingham
Oxford
Peterborough
Plymouth
Poole
Portsmouth
Preston
Rhyl
Rotherham
Sheffield
South Shields
Southampton
Stockton-on-Tees
Sunderland
Sutton
Swansea
Swindon
Taunton
Torquay
Truro
Wakefield
Warrington
Weston Super Mare
Wigan
Winchester
Wirral
Wolverhampton
Worthing
Wrexham
Yeovil

Recruitment start:

Recruitment end:

How to join a clinical trial

Please note: In order to join a trial you will need to discuss it with your doctor, unless otherwise specified.

Please note - unless we state otherwise in the summary, you need to talk to your doctor about joining a trial.

Chief Investigator

Professor Tim Maughan
Professor Richard Wilson

Supported by

AstraZeneca
Bayer
Cardiff University 
Cancer Research UK
Medical Research Council (MRC)
NIHR Clinical Research Network: Cancer
NIHR Efficacy and Mechanism Evaluation (EME) Programme
University College London (UCL)
University of Belfast
University of Leeds
University of Oxford

Other information

The Trial is funded jointly by Cancer Research UK and the Medical Research Council (MRC)/National Institute for Health Research (NIHR) Efficacy and Mechanism Evaluation (EME) Programme.

This is Cancer Research UK trial number CRUK/11/054.

Questions about cancer? Contact our information nurses

Freephone 0808 800 4040

Last review date

CRUK internal database number:

9181

Please note - unless we state otherwise in the summary, you need to talk to your doctor about joining a trial.

Wendy took part in a new trial studying the possible side effect of hearing loss

A picture of Wendy

"I was delighted to take part in a clinical trial as it has the potential to really help others in the future.”

Last reviewed:

Rate this page:

Currently rated: 4.5 out of 5 based on 8 votes
Thank you!
We've recently made some changes to the site, tell us what you think