Purpose: To describe a phase II study design to evaluate the activity of novel anti-cancer agents that focuses on molecular pathogenesis rather than tumor histology.
Methods: We propose an enrichment design that enrolls patients across histologies expressing target X and incorporates randomized discontinuation of drug Y after an initial treatment period to evaluate for potential cystostatic activity.
Results: We are currently evaluating the activity of lapatinib in patients with HER-2 amplified solid tumors using the target-specific, histology-independent, randomized discontinuation design. Patients receive treatment with lapatinib for an initial 12-week period. After restaging, patients with disease progression are removed from study, patients achieving an objective response continue treatment, and patients with stable disease are randomized to continue lapatinib versus initiate treatment with placebo. The primary endpoints are to evaluate the objective response rate during the initial treatment period and to evaluate the proportion of patients progression-free 12 weeks post-randomization.
Conclusion: The target-specific, histology-independent, randomized discontinuation design is an attractive alternative to the traditional phase II design for the development of "targeted" therapeutics.