Text on screen: FOCUS4 - A flagship precision medicine cancer trial
Professor Tim Maughan Chief Investigator of FOCUS4
I'm Tim Maughan and I'm professor of
Clinical Oncology at the University of Oxford,
and I'm one of two chief investigators
of the FOCUS4 trial programme. FOCUS4 aims to
test new therapies for molecular subgroups
within colorectal cancer. Patients with metastatic colorectal cancer, the
prognosis has not changed very greatly
for many patients in this disease. And back in 2011
we had certain amount of information about molecular subgroups,
and we wanted to test new therapies in a comprehensive way that allowed
every patient access to a trial
so we integrated it into this large adaptive platform
within which we were testing novel therapies in different subgroups.
We selected the maintenance setting after first line therapy
because we've previously shown in other trials that it was okay to give patients
a break from chemotherapy after four months
treatment. So at the end of four months treatment,
if they had stable or responding disease, standard of care was for those patients
to have a break from treatment. And we were testing whether novel
therapies could improve the disease control in
that period, following first-line therapy.
To lengthen the time before they needed more treatment. And that was the test bed
in which we operated for FOCUS4. Between January, 2014 and October, 2020
1,434 patients were registered from 88 UK hospitals
three molecularly targeted sub trials were activated
assessing MESA D 8931 and aspirin and Adavosertib,
and we also evaluated Capecitabine monotherapy in the non-stratified group.
Text on screen: The MAMS design enabled the trial to adapt as the science evolved
Our first molecular cohort showed a comprehensive
negative result and we were able to close it after only 32
patients have been accrued to FOCUS4-D that was published back in 2017.
And you'll see in many platform designs that actually a number of negative
results come out and that's important because we're
showing that things don't work, as well as the things that do work.
Secondly, we had good evidence that aspirin might be useful
in another molecular cohort, but when we set this up, we found that because
aspirin is so widely available and so widely trusted
patients were not happy to be randomized to receive aspirin or a placebo.
So that trial only recruited six patients and it was stopped because of feasibility.
Then we went on with a third study, the third molecular study
FOCUS4-C which is completed.
And that has now been analyzed and is being submitted for publication this year.
And because of the pandemic
we have also, we closed the whole trial during 2020 and have analyzed the final results.
So the trial is now completed and we will be reporting
the results of three molecular comparisons and one
non-stratified comparison FOCUS4-N.
Text on screen: For more information visit: www.nihr.ac.uk/innovative-trials