A study looking at using gene mutations and an enzyme to decide the best treatment for advanced bowel cancer (FOCUS 3)

Who can enter

You can enter this trial if you

• Have stage 3 bowel cancer (locally advanced cancer) or stage 4 bowel cancer that has spread to another part of your body, apart from the brain
• Are not able to have surgery to remove your cancer
• Have bowel cancer that can be measured on a CT scan
• Have completed chemotherapy 6 months before being asked to take part in this trial
• Have finished having bevacizumab as a part of the QUASAR 2 trial
• Have completed chemoradiation at least 1 month before being asked to take part in this trial
• Have satisfactory blood test results
• Are well enough to take part in this trial (performance status 0,1 or 2)
• Are willing to use reliable contraception if there is any chance you or your partner could become pregnant
• Are at least 18 years old

You cannot enter this trial if you

• Can have surgery to remove your bowel cancer, after having had chemotherapy
• Have bowel cancer that has spread to your brain
• Have had chemotherapy for bowel cancer that has spread to another part of your body (metastatic bowel cancer)
• Had surgery up to 4 weeks before starting treatment as a part of this trial
• Are allergic to the drugs used in this trial
• Are not able to have the chemotherapy drugs used in this trial
• Are on medication that could affect you taking part in this trial
• Have, or had, another cancer that could affect you taking part in this trial
• Have another serious medical condition that could affect you taking part in this trial
• Are pregnant or breastfeeding

Trial design

This is a feasibility study. The researchers will use the results of this study to see if they can set up a bigger trial. This feasibility study will recruit 240 people in the UK.

There are 2 parts in this feasibility study.

In the 1st part your doctor needs to find out if your cancer has the

• K-ras gene mutation
• B-raf gene mutation
• Both gene mutations
• Neither gene mutation

The doctor also needs to know the level of the enzyme topo-1 in your bowel cancer. To do this, they will ask your permission to take a piece of the bowel cancer tissue removed when you had your biopsy, or surgery. This will be tested for the enzyme and the gene mutations.

For some people these tests do not give a plain answer. If this happens, you may not be able to take part in this trial. The doctor will then talk to you about other treatment options.

In the 2nd part when you agree to continue in the trial, you will be put into a treatment group by a computer. This is called randomisation. Neither you nor your doctor will be able to decide which group you are in.

If you have a low level of the enzyme topo-1and neither gene mutation, the treatment groups are

• Irinotecan, Fluorouracil (5FU) and folinic acid
• 5FU and folinic acid
• Irinotecan, 5FU, folinic acid and cetuximab

If you have a low level of the enzyme topo-1 and a gene mutation (either K-ras or B-raf), the treatment groups are

• Irinotecan, 5FU and folinic acid
• 5FU and folinic acid
• Irinotecan, 5FU, folinic acid and bevacizumab

If you have a high level of the enzyme topo-1 and neither gene mutation, the treatment groups are

• Irinotecan, 5FU and folinic acid
• Irinotecan, 5FU, folinic acid and cetuximab
• Irinotecan, 5FU, folinic acid and oxaliplatin

If you have a high level of the enzyme topo-1 and a gene mutation (either K-ras or B-raf), the treatment groups are

• Irinotecan, 5FU and folinic acid
• Irinotecan, 5FU, folinic acid and bevacizumab
• Irinotecan, 5FU, folinic acid and oxaliplatin

You have treatment every 2 weeks. This is one cycle of treatment.

You can continue to have treatment until your

• Cancer starts to grow
• Or the side effects of chemotherapy are too much
• Or if you, or your doctor, decides to stop the treatment

You have treatment through a drip into a vein (intravenous infusion). Or you may have a central line or PICC line put in. You can have all your chemotherapy through this, so you don’t have to have repeated injections or drips. Your doctor will discuss this with you.

If you take part in this trial, the researchers will ask your permission to take an extra blood sample. This sample will be stored safely and may be used in the future for research purposes only. Studying these samples may help researchers learn more about bowel cancer.

If you don’t wish to give permission for this blood sample, you don’t have to. You can still take part in the trial.

Hospital visits

You will see the doctor and have some tests before you start treatment. These tests include

• Physical examination
• Blood tests
• CT scan
• 24 hour urine test (for people having bevacizumab)

During treatment you see the doctor every 2 weeks to have a physical examination and blood tests.

Every 12 weeks you will have a CT scan.

Side effects

The most common side effects of 5FU, irinotecan, oxaliplatin, cetuximab and bevacizumab are

• Tiredness (fatigue)
• Feeling, or being sick (nausea)
• Diarrhoea
• Sore mouth
• Changes to taste
• Hair loss
• Sore hands and feet (plantar palmar syndrome)
• Skin rash
• High blood pressure

You can find more about fluorouracil (5FU), irinotecan, oxaliplatin, cetuximab and bevacizumab on CancerHelp UK.