Early clinical trials of chemopreventive and biologic agents: Designs, populations, and endpoints.
The optimal design for initial clinical trials of chemopreventive agents for cancer has not been determined. A single design is unlikely to be the model for chemoprevention of cancer, even for prevention of a single subtype of cancer, because of the heterogeneity of drugs under investigation and the variety of biologic effects being targeted. Factors that are important in designing initial clinical trials include the proposed mechanisms of drug action, the ability and types of assays available to detect that activity or pharmacodynamic effect, and the extent of prior clinical experience. In this article, we present a discussion of the factors to be considered in initial activity studies, followed by a specific example of early clinical assessment of a noncytotoxic agent (R-flurbiprofen, E-7869) as a potential chemopreventive agent for prostate cancer.
Keegan
P
P
Division of Clinical Trials Design and Analysis, Office of Therapeutics, Center for Biologics Evaluation and Research, US Food and Drug Administration, Rockville, Maryland 20852-1445, USA. keegan@cber.fda.gov
Loughman
B E
BE
D016588:Anticarcinogenic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D002986:Clinical Trials as Topic / Q000379:methods*; D017321:Clinical Trials, Phase I as Topic; D017322:Clinical Trials, Phase II as Topic; D004347:Drug Interactions; D004354:Drug Screening Assays, Antitumor / Q000379:methods; D005480:Flurbiprofen / Q000627:therapeutic use*; D006801:Humans; D008297:Male; D011471:Prostatic Neoplasms / Q000517:prevention & control*; D012107:Research Design
D016588:Anticarcinogenic Agents; D005480:Flurbiprofen