Phase 0 clinical trials in cancer drug development: from FDA guidance to clinical practice |
| |
Authors: | Kinders Robert Parchment Ralph E Ji Jay Kummar Shivaani Murgo Anthony J Gutierrez Martin Collins Jerry Rubinstein Larry Pickeral Oxana Steinberg Seth M Yang Sherry Hollingshead Melinda Chen Alice Helman Lee Wiltrout Robert Simpson Mel Tomaszewski Joseph E Doroshow James H |
| |
Affiliation: | Laboratory of Human Toxicology and Pharmacology, Applied/Developmental Research Support Directorate, SAIC-Frederick Inc., NCI-Frederick, Frederick, Maryland 21702, USA. |
| |
Abstract: | The Food and Drug Administration (FDA) recently introduced the Exploratory Investigational New Drug Guidance to expedite the clinical evaluation of new therapeutic and imaging agents. Early clinical studies performed under the auspices of this guidance, so-called "Phase 0" trials, have been initiated at the National Cancer Institute to integrate qualified pharmacodynamic biomarker assays into first-in-human cancer clinical trials of molecularly targeted agents. The goal of this integration is to perform molecular proof-of-concept investigations at the earliest stage of cancer drug development. Phase 0 trials do not offer any possibility of patient benefit; instead, intensive, real-time pharmacodynamic and pharmacokinetic analyses of patient tumor samples and/or surrogate tissues are performed to inform subsequent trials. Phase 0 studies do not replace formal Phase I drug safety testing and require a substantial investment of resources in assay development early on; however, they offer the promise of more rational selection of agents for further, large-scale development as well as the molecular identification of potential therapeutic failures early in the development process. |
| |
Keywords: | |
本文献已被 PubMed 等数据库收录! |
|