A study to determine the feasibility of molecular selection of therapy using KRAS, BRAF and topo-1 in patients with metastatic or locally advanced colorectal cancer
Individualising treatment for patients with advanced bowel cancer – can we do it?
What is this study about?
Over 16,000 people die from bowel cancer in the UK every year. There are now molecular tests that can be done on tumour samples from patients with advanced bowel cancer which may help selection of the best treatment options for an individual patient. FOCUS 3 will look at the feasibility of this approach in the UK NHS setting. 240 patients will be randomised to the trial at 24 centres across the UK.
Two tests will be performed on the tumour before a patient is considered eligible for randomisation: the first will assess the levels of a protein called topo-1 and the second will assess the KRAS and BRAF status. KRAS and BRAF are two genes that are often altered in bowel cancer. About half of patients with bowel cancer have low levels of topo-1 and half have high levels. Similarly, about half of patients with bowel cancer have a change (mutation) in either the KRAS or the BRAF gene and about half do not. When the tests are completed, the cancer will be classed as one of four molecular types, and thus give four sub-groups of patients:
- Type 1: low topo-1, KRAS and BRAF normal
- Type 2: low topo-1, KRAS and BRAF mutation
- Type 3: high topo-1, KRAS and BRAF normal
- Type 4: high topo-1, KRAS and BRAF mutation
Within each subgroup each patient will be randomised to one of 3 arms; a control arm which is common to each of the 4 subgroups and two alternative, research arms, which have been chosen based on results from previous research. The control arm (A) is irinotecan and fluorouracil (IrFU). The two alternative research arms will depend on the molecular type of the tumour and will include the following regimens: (B) fluorouracil (FU), (C) irinotecan, oxaliplatin and fluorouracil (IrOxFU), (D) irinotecan, fluorouracil (IrFU) and cetuximab, and (E) irinotecan, fluorouracil (IrFU) and bevacizumab. The primary aims of the trial are to test the feasibility of testing tumour samples before randomisation and will look at whether results of the tests can be provided within 10 working days to allow randomisation.
Type of study
Who is funding the study?
The trial is being paid for by the Medical Research Council. The pharmaceutical company Merck is providing the drug cetuximab, free of charge. Roche is providing an educational grant for colorectal trials.
When is it taking place?
The trial opened to recruitment in February 2010 and is now closed.
Where is it taking place?
24 hospitals throughout the UK
Who is included?
People with advanced colorectal (bowel) cancer.