As the use of complex innovative design (CID) trials for new cancer treatments continues, a group of UK professors from the University of Oxford, Birmingham and others, as well as representatives from the UK’s Medicines and Healthcare products Regulatory Agency and Pfizer have offered a series of recommendations on the flexible trials.
Published this week in the British Journal of Cancer, the consensus statement explains how unlike conventional trials in which patients are recruited by tumor of origin, patients enrolled in one kind of CID trial, known as “master protocol” trials, incorporate molecular biomarkers. One type of master protocol trial is known as the basket trial, which involves patients who have different tumor types, but all of whom have a common biomarker relevant to the investigational drug.
“By contrast, in umbrella trials, [which is another type of master protocol trial,] patients with a single-tumour type are stratified into multiple cohorts based on molecular markers defining each treatment arm. These stratifications allow parallel comparison of therapy/ies for an individual disease (or biomarker cohort) or enable overall assessment via a single stratified analysis,” the statement says.
One of the earliest examples of a CID trial was the international PROFILE 1001 non-small cell lung cancer (NSCLC) study designed to investigate crizotinib, which was first approved in the US in 2011. “EU Marketing Authorisation was obtained for crizotinib just 5 years after the discovery of the EML4-ALK fusion gene,” the authors note.
One of the UK group’s recommendations for future CID trials, in addition to meeting with regulators, HTA bodies and other stakeholders as early as possible before or during the trial design, is related to the use of risk-based monitoring, which they said “can lead to improvement in the efficiency of monitoring while preserving data quality. This approach has been endorsed by the EMA, and is particularly suited to CID trials given their complexity.”…