Evaluating Many Treatments and Biomarkers in Oncology: A New Design

摘要: There is a pressing need for more-efficient trial designs biomarker-stratified clinical trials. We suggest new approach to design that links novel treatment evaluation with the concurrent of biomarker within confirmatory phase II/III setting. describe protocol using this in advanced colorectal cancer called FOCUS4. The will ultimately answer three research questions number treatments and biomarkers: (1) After period first-line chemotherapy, do targeted therapies provide signals activity different biomarker-defined populations? (2) If so, these definitively improve outcomes? (3) Is evidence restricted groups? randomizes agents against placebo concurrently across population-enriched cohorts: BRAF mutation; activated AKT pathway: PI3K mutation/absolute PTEN loss tumors; KRAS NRAS mutations; wild type at all mentioned genes. Within each population, uses multistaged flexibility adapt response planned interim analyses lack activity. FOCUS4 first test assigns patients metastatic one parallel population-enriched, randomized Using allows regarding efficacy safety multiple be answered relatively quick efficient manner, while also allowing assessment biomarkers help target treatment.