Target validation using Phase 0 clinical trialsPromises and pitfalls

摘要

Phase 0 clinical trials are a relatively new concept, and were developed in response to the low approval rate of new oncology drugs, and the need to shorten the length of time investigational new drugs (IND) spend in development. Moving an oncology drug from a Phase I to a Phase III clinical trial sometimes takes more than a decade (www.cancer.govewscenter/ pressreleases/PhaseZeroNExTQandA), and the challenges related to assessing target modulation need to be addressed. The U.S. Food and Drug Administration (FDA) developed the exploratory IND Guidance to help expedite the clinical evaluation of new molecular agents. The objectives of Phase 0 trials include obtaining pharmacokinetic (PK) data, examining pharmacodynamic (PD) endpoints that reflect drug activity, examining relationships between PK and PD end-points, showing evidence of early target modulation in humans, optimizing target assay methodology using human samples, and determining whether further clinical development of an agent should be pursued.1 Phase 0 studies are conducted with a small number of patients, with no clinical benefit expected. Sub-therapeutic doses are used in these trials, and only a few time points are analyzed.