FOCUS4

What was this study about?

TRIAL NOW CLOSED 

We would like to thank all the patients who took part in FOCUS4 and all the investigators who worked on the trial.

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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 decided to join were started on a course of chemotherapy for up to 16 weeks. During this time a piece of the patient’s tumour was tested to find out more about the molecular makeup of their particular tumour. The results of these tests were 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 failed to work so it was not possible to classify the tumour as any one of the specific sub-types above

Patients were assessed after the 16 weeks of chemotherapy to see how the tumour was responding to standard treatment. If the cancer had shrunk or at least not grown, patients were eligible to enter a clinical trial testing a particular treatment in their sub-type of cancer.

Within each of the cancer sub-types, patients were allocated randomly to receive either a new treatment or a placebo (dummy treatment) or active monitoring. In some sub-types the new treatment was given as 2 or 3 new treatments in combination which in previous studies appeared to work well together. Within the non-classified sub-type (FOCUS4-N), patients were allocated randomly to receive either capecitabine or active monitoring. This randomly allocated treatment continued unless there was evidence that the cancer had grown or the patient or doctor decided to stop it due to side effects. The researchers compared the performance of each drug against the placebo to see if it was better.

The FOCUS4 trial opened in the UK in January 2014 and closed in October 2020. It has now published all the results for the trial; see below for a list of all publications.

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

What difference did this study make?

FOCUS4 publications:

• 2022 FOCUS4 biomarker laboratories: from the benefits to the practical and logistical issues faced during 6 years of centralised testing Journal of Clinical Pathology
• 2022 Experiences of running a stratified medicine adaptive platform trial: Challenges and lessons learned from 10 years of the FOCUS4 trial in metastatic colorectal cancer SAGE Journals
• 2021 Inhibition of WEE1 Is Effective in TP53- and RAS-Mutant Metastatic Colorectal Cancer: A Randomized Trial (FOCUS4-C) Comparing Adavosertib (AZD1775) With Active Monitoring. Journal of Clinical Oncology
• 2021 Capecitabine Versus Active Monitoring in Stable or Responding Metastatic Colorectal Cancer After 16 Weeks of First-Line Therapy: Results of the Randomized FOCUS4-N Trial. Journal of Clinical Oncology
• 2021 Treatment Holidays for Patients With Metastatic Colorectal Cancer. Journal of Clinical Oncology
• 2021 Treatment breaks in first line treatment of advanced colorectal cancer: An individual patient data meta-analysis. Cancer treatment Reviews 
• 2019 This is a platform alteration: a trial management perspective on the operational aspects of adaptive and platform and umbrella protocols BioMed Central
• 2019 Mind the gap? The platform trial as a working environment BioMed Central
• 2019 Changing platforms without stopping the train: experiences of data management and data management systems when adapting platform protocols by adding and closing comparisons BioMed Central
• 2017 Testing many treatments within a single protocol over 10 years at MRC Clinical Trials Unit at UCL: Multi-arm, multi-stage platform, umbrella and basket protocols SAGE Journals
• 2017 Inhibition of EGFR, HER2, and HER3 signalling in patients with colorectal cancer wild-type for BRAF, PIK3CA, KRAS, and NRAS (FOCUS4-D): a phase 2–3 randomised trial. The Lancet. Gastroenterology & hepatology
• 2017 The Promise and the Hype of ‘Personalised Medicine’. The New bioethics 
• 2015 Pre-trial inter-laboratory analytical validation of the FOCUS4 personalised therapy trial. Journal of Clinical Pathology 
• 2013 Evaluating Many Treatments and Biomarkers in Oncology: A New Design. Journal of Clinical Oncology

Type of study

Randomised trial

Contact details

mrcctu.focus4@ucl.ac.uk

Who funded the study?

The study was 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.