A molecularly-stratified randomised controlled trial programme for patients with advanced colorectal (bowel) cancer

Identifying the most effective treatments for patients with different genetic sub-types of colorectal (bowel) cancer

What is this study about?

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 an 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 evaluate how well these new cancer drugs work in different sub-types of bowel cancer.

Patients who decide to join will be started on a course of chemotherapy for up to 16 weeks. During this time a piece of the patient’s tumour will be tested to find out more about the molecular make up of their particular tumour. The results of these tests will be used to classify an individual into the below sub-types of bowel cancer.

  • FOCUS4-A: Patients with BRAF sub-type. an abnormal (mutated) version of the BRAF gene in the cancer
  • FOCUS4-B: Patients with PIK3CA sub-type. An abnormal (mutated) version of the PIK3CA gene
  • FOCUS4-C: P53 + RAS sub-type: an abnormal (mutated) version of the RAS and P53 gene in the cancer
  • FOCUS4-D: No mutation sub-type: no change (mutation) in the BRAF, PIK3CA, RAS or P53 genes in the cancer
  • FOCUS4-N: Non-classified: the tests fail to work so it is not possible to classify the tumour as any one of the specific sub-types 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 sub-type of cancer.

Within each of the cancer sub-types, patients will be allocated randomly to receive either a new treatment or a placebo (dummy treatment) or active monitoring. In some sub-types the new treatment may be given as 2 or 3 new treatments in combination which in previous studies appear to work well together. Within the non-classified sub-type (FOCUS4-N), patients will be allocated randomly to receive either capecitabine or active monitoring.

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

Some of the important design features of the FOCUS4 study have been published in the Journal of Clinical Oncology (Kaplan RK, Maughan TM, Crook AC, Fisher DF, Wilson RW, Brown LC, Parmar MP. Evaluation of many treatments and biomarkers in oncology: a new design. J Clin Oncology 2013; 31 (36):4562-8.)

Read more about the FOCUS4 trial and main results in this article from CRUK: "FOCUS4: Learning from a landmark clinical trial"

Type of study

Randomised trial

Contact details

Who is funding the study?

The study is jointly funded by the UK Government (Medical Research Council (MRC) and National Institute for Health Research (NIHR), Efficacy and Mechanism Evaluation Programme) and the charity, Cancer Research UK.

When is it taking place?

FOCUS4 opened in January 2014. It aims to register 2400 patients and randomise 1500 of these patients over a 5 years. Patients will then be followed up for a further year.

Where is it taking place?

At over 100 participating hospitals across England, Wales, Scotland and Northern Ireland.

Who is included?

Patients who have been recently diagnosed with advanced colorectal cancer.