Trial Design: This is an adaptive, open-label, randomised phase II trial that aims to evaluate the impact of 3 vs 6 cycles of first-line platinum-based chemotherapy followed by maintenance avelumab in the quality of life (QoL) of patients with locally advanced or metastatic urothelial cancer (UC). Initially, 224 eligible and evaluable patients (112 in each arm) will receive 3 cycles vs 6 cycles of 3-weekly gemcitabine plus cisplatin/carboplatin, followed by 2-weekly maintenance avelumab until disease progression or intolerable toxicities. Avelumab treatment will be given up to a maximum of 2 years from the end of chemotherapy. Patients who continue to derive benefit at the end of the 2-year avelumab period can be switched to local supply as per standard of care and at the discretion of the local investigator. On completion of treatment or sooner if disease progression or toxicities occur, patients will be contacted 12-weekly to collect survival and disease status data. All patients will be followed up until the end of avelumab treatment or for 2 years from completion of chemotherapy, whichever is longer. The primary endpoint of the study is QoL as measured by the change from baseline in EORTC QLQ-C30 questionnaire GHS/QoL scale scores from baseline to the completion of 6 cycles of treatment. The study also includes extensive biomarker analysis using archival tissue samples as well as translational blood collection including but not limited to circulating tumour DNA (ctDNA) analysis before and on treatment. Sequential urine samples will be collected for urinary microbiome and urinary ctDNA analysis.
Chief Investigator: Prof T. Powles
Trial contact: firstname.lastname@example.org
Sponsor: Queen Mary University of London
Participating countries: UK, Spain, France
Source of funding: Merck Healthcare KGaA (funding and study drug)
Key partner: Pfizer Inc.