FOCUS4 Summary

Not all bowel cancers are the same and tests can be done on tumour samples from patients with bowel cancer that may help select the best treatment for that individual patient. There are a number of new cancer drugs that may be more beneficial in one type of bowel cancer than another. The FOCUS4 trial programme aims to recruit over 1500 patients at centres across the UK to evaluate how well these new cancer drugs work in different types of bowel cancer.

Patients diagnosed with bowel cancer which is not removable by surgery or has spread to elsewhere in their body will be invited to join this programme of trials. Patients who decide to join will be started on a course of chemotherapy (a form of drug treatment aimed to kill the cancer cells) for up to 16 weeks. During this time a piece of the patient's tumour will be analysed to find out more about the molecular make up of their particular tumour. Two sorts of tests will be performed on the tumour. The first test looks at some of the genes which are often altered in colorectal cancer (the genes are called RAS, BRAF and PIK3CA). The second test detects complex molecules that the cancer is producing, including some proteins. The results of these tests will be used to classify an individual into the following subtypes of colorectal cancer:

A- BRAF subtype: an abnormal (mutated) version of the BRAF gene in the cancer.
B- PIK3CA subtype: an abnormal (mutated) version of the PIK3CA gene.
C- RAS subtype: an abnormal (mutated) version of the KRAS or NRAS genes in the cancer.
D- No mutation subtype: no change (mutation) in the BRAF, PIK3CA, KRAS and NRAS genes in the cancer.
N- Non-classified: the tests fail to work so it is not possible to classify the tumour as any one of the specific subtypes above.

Patients will be assessed after the 16 weeks of chemotherapy to see how the tumour is responding to standard treatment. If the cancer has shrunk or at least not grown, patients will be eligible to enter a clinical trial testing a particular treatment in their subtype of cancer.

Within each of the 5 cancer subtype trials, patients will be allocated randomly to receive either a new treatment or a placebo (dummy treatment). In some subtypes the new treatment may be given as 2 new treatments in combination which in previous studies appears to work well together.

This randomly allocated treatment will continue unless there is evidence that the cancer has grown or the patient or doctor decides to stop it due to side effects. The researchers will compare the performance of each drug against the placebo to see if it is better.



MRC Clinical Trials Unit at UCL
Institute of Clinical Trials & Methodology

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