Trial design for evaluation of novel targeted therapies.

Objectives: The vast number of novel targeted therapies available for testing in the United States dictates that a more efficient system aimed at identifying promising agents for phase III testing needs to be developed. Alternatives to traditional phase II trial design including alternative end points, randomized designs, biomarkers, and imaging tools are discussed.

Methods: Novel techniques for phase II trials were researched in the literature. Incorporation of surrogate endpoints and novel approaches were identified.

Results: Phase II trials are traditionally designed evaluating response rates compared to historical controls. In addition to identifying surrogates, novel approaches to phase II study design need to be tested. Incorporation of biomarkers into phase II trial design could allow for more accurate identification of patients who will benefit from targeted therapies. Tumor response as measured by anatomic imaging has been used to measure therapeutic efficacy in the era of cytotoxic drugs. Fluorodeoxyglucose (FDG)-positron emission tomography (PET) however, has been used increasingly in the evaluation of biologic responses.

Conclusions: Alternatives to traditional phase II trial design including alternative end points, randomized designs, biomarkers, and imaging tools should allow ineffective agents to be discarded and promising agents to undergo further investigation.