ATLANTIS: a randomised multi-arm phase II biomarker-directed umbrella screening trial of maintenance targeted therapy after chemotherapy in patients with advanced or metastatic urothelial cancer

BACKGROUND: Metastatic urothelial cancer (UC) is the eighth most common cause of cancer death in the UK. Standard first-line treatment, for most patients, is cytotoxic chemotherapy. Although UC is initially sensitive to chemotherapy, relapse is almost inevitable and outcomes are poor; median overall survival is 8 months. Therefore, there is an urgent need for novel therapies to improve outcomes for this patient group. METHODS: ATLANTIS is a randomised phase II umbrella-design screening trial of maintenance therapy in biomarker-defined subgroups of patients with advanced UC. The primary end point is progression-free survival, and the study involves over 30 UK cancer centres. DISCUSSION: ATLANTIS is the first study in the UK to employ a precision-medicine approach to patients with UC for maintenance treatment. Agents with a positive efficacy signal will proceed to randomised phase III trials to confirm the activity of novel, biologically stratified therapies in UC. REGISTRATION: ATLANTIS trial EudraCT number 2015–003249-25. ISRCTN25859465.