DESIGNS FOR PHASE-II TRIALS ALLOWING FOR A TRADE-OFF BETWEEN RESPONSEAND TOXICITY

In this paper we propose methods for designing phase II trials that al low for a trade-off between treatment safety and antitumor activity, w here safety and antitumor activity are measured as binary endpoints. T he designs can be carried out either in a single stage or can be condu cted in two stag;es, with an interim analysis to assess whether the tr eatment appears sufficiently safe and effective to warrant continuing. The emphasis is on the derivation of stopping rules for phase II tria ls that require the enrollment of a small number of patients and are b ased on enumerating the exact distribution of the proposed test statis tic. We illustrate the methods with a recent study that required the u se of a group sequential design to monitor antitumor activity and toxi city.