When the LANTERN goes out: feasibility studies in a changing clinical environment

Assessing feasibility is crucial before deciding whether to justify the resources required for a phase III trial. The environment can change during the lifetime of a trial making a promising study rapidly unfeasible. The LANTERN phase II screening trial had a modest recruitment target of 130 patients, albeit in a relatively rare subgroup of breast cancer, which was expected to be achievable in the UK. The intervention drug (lapatinib) was not approved for use within the NHS and so it was expected that LANTERN would be the main route for patients to potentially access this treatment. However, shortly following trial set-up, the Cancer Drugs Fund (CDF) was launched in response to the concern that patients were not able to access newly available systemic therapies. Recruitment for LANTERN was consistently behind initial estimates and after two years the trial closed due to poor recruitment, with only 30/130 (23%) randomised participants recruited across sixteen centres. During this time the CDF approved at least 886 applications for lapatinib across England and as lapatinib has a relatively narrow indication it is thought that a substantial proportion of these patients would have been eligible for LANTERN. Study non-registration logs suggested just 3/75 patients considered were not entered due to accessing lapatinib via the CDF, however, anecdotal investigator feedback suggested this was a far more limiting factor. Furthermore, the most successful recruitment was observed in Scotland, where the CDF was not available. We believe that the introduction of CDF had a significant negative effect on recruitment to LANTERN and will pose additional challenges in the conduct of research into rarer cancers in the UK. ‘Future-proofing’ clinical trials is challenging and our experience suggests that trialists need to remain acutely aware of the wider environment during the feasibility assessment stage of a study.