Last year in the UK over 60,000 cancer patients enrolled on clinical trials aimed at improving cancer treatments and making them available to all.
A trial looking at different treatments for different types of bowel cancer (FOCUS4)
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 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 open. These are called FOCUS4-B and FOCUS4-N.
Who can enter
The following bullet points list the entry conditions for this. Talk to your doctor or the trial team if you are unsure about any of these. They will be able to advise you.
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 scan, and a sample of your cancer taken before you started chemotherapy 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
- Have satisfactory blood test results
- 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 the comparison called FOCUS4-B
- You must have a change to a gene called PIK3CA
- You have finished treatment with chemotherapy or a biological therapy at least 3 weeks before starting treatment in this trial
- 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
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.
You cannot join any part of the trial if you
- Have cancer that has spread to your brain
- Have had chemotherapy for advanced bowel cancer in the past
- Have had chemotherapy after surgery to try to stop your cancer coming back (adjuvant treatment) in the last 6 months
- Are pregnant or breastfeeding
As well as this, you can’t enter FOCUS4-B if you
- Have had any major surgery, radiotherapy or immunotherapy in the 4 weeks before starting treatment in this trial
- Have had more than 1 anti cancer treatment for advanced bowel cancer unless this was treatment after surgery
- Have had any experimental anti cancer treatment for your advanced bowel cancer
- Have any serious side effects from your previous cancer treatment apart from hair loss
- Have had any other type of cancer apart from any that have been successfully treated and there have been no signs of the cancer for at least 5 years, or a non melanoma skin cancer that has been completely removed or successfully treated very early cancers (carcinoma in situ)
- Are currently taking aspirin regularly (for example, more than twice a week for more than 4 consecutive weeks)
- Take any type of non steroidal anti inflammatory such as ibuprofen, naproxen, diclofenac, celecoxib, mefenamic acid, etoricoxib or indometacin for more than 1 week in the month before starting in this trial
- Have drugs to prevent blood clots such as warfarin or heparin
- Are taking
- Are allergic or sensitive to aspirin, non steroidal anti inflammatories or any similar drug
- Are lactose intolerant
- Have a liver or biliary disease that is causing symptoms
- Have or have had a peptic ulcer unless this has been well controlled by medication for at least 6 months or you have had successful treatment and have no signs of it
- Have had bleeding into your gut, unless the cause of the bleeding has been surgically removed
- Have any disease or condition that means that your body would have problems absorbing, processing or getting rid of drugs
- Have or have had inflammatory bowel disease
- Have serious problems with your kidneys
- Have diabetes or high blood pressure that aren’t well controlled
- Have G6PD deficiency
- Have HIV, hepatitis B or hepatitis C
- Have any medical or mental health problem that the trial team think could affect you taking part
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 if 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 FOCUS4-N
The researchers aim to recruit more than 1,500 people at hospitals across the UK. To start with, you have up to 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
At the moment, the trial aims to test treatments in 4 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, NRAS, or H3K36me3
- 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
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-B and FOCUS4-N. FOCUS4-D has now closed.
Comparison FOCUS4-B is looking at aspirin. Some research has suggested that bowel cancer grows more slowly in people who take regular aspirin. And this benefit is higher in people who have the PIK3CA gene change. But doctors need to know this for sure.
FOCUS4-B has 2 treatment groups.
- One group has a dummy drug (
placebo) and active monitoring (Treatment Plan B1)
- The other group has aspirin and active monitoring (Treatment Plan B2)
You have a 2 out of 3 chance of being in the group having aspirin.
The dummy tablet looks the same as aspirin. You take the tablets once a day. The trial team will give you a diary card so you can record each time you take a tablet.
Neither you nor your doctor will know which tablet you are having. This is called a double blind trial.
If there are any signs that your cancer is starting to grow again, the trial doctor will talk to you about restarting 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:
- no further treatment until scans show your cancer is beginning to grow again (active monitoring)
- capecitabine tablets twice each day for 2 weeks out of every 3
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.
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.
When you join the trial, the researchers will test a sample of your cancer that had already been removed. But they will ask you to consider having 2 new
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 group you are in.
If you are in FOCUS4-B you see the doctors 4 weeks after starting the tablets. You then see them every 8 weeks. You have a CT scan every 8 weeks.
If you are in FOCUS4-N, you see the trial team every 3 to 4 weeks and have a CT scan every 8 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.
The most common side effects of aspirin include:
- irritation of the stomach
- bruising more easily
The side effects of capecitabine include:
- sore hands and feet
- feeling sick
Occasionally, it can also cause some chest pain.
We have more information about side effects of capecitabine.
How to join a clinical trial
Professor Tim Maughan
Professor Richard Wilson
Cancer Research UK
Experimental Cancer Medicine Centre (ECMC)
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
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.