Phase II trials powered to detect tumor subtypes
Cet article présente un concept d'essai clinique de phase II qui, mené en deux étapes, inclut une caractérisation des tumeurs et permet de choisir un sous-type de tumeur pertinent à la conclusion de la première étape
Classical phase II trial designs, including "adaptive" designs, require the prospective characterization of tumors. We propose a two stage phase II design that allows for characterization of tumors and selection of a tumor subtype of interest at the conclusion of stage one. The stage two objective is either a classical estimate of the response rate for either the tumor or a subtype or a formal test of the hypothesis that the response rate for a subtype is greater than the overall response rate. Considering likely scenarios, stage one sample sizes approximately range from 20 to 100 with a usual size of 50. This compares with typical classical stage one sample sizes of 12 to 30. Total sample sizes range from identical to classical designs (tens to scores) to large sizes typical of phase III trials in metastatic disease (hundreds). Our design is more efficient than previous adaptive designs because it allows for the selection of a tumor subtype of interest on the basis of results from stage one. It complements classical phase II and phase III designs, in which different treatments are compared in "similar" patients and tumors, by positioning a treatment as fixed (control) and utilizing tumor subtype as the variable of interest. Conclusions:
Clinical Cancer Research , résumé, 2011