Phase I trials

The primary purpose of most phase I trials is to study safety and tolerability of an experimental intervention, one aim being to determine the maximum tolerated dose. Such trials may or may not be randomised, often depending upon disease area and the intervention being studied. They are often conducted in healthy volunteers, but again this depends upon the intervention with a notable exception being in cancer trials. In trials of pharmaceuticals additional outcomes are likely to include pharmacokinetics and pharmacodynamics and include single and multiple ascending dose studies, and food and drug interaction studies.

Phase II trials

The aim of phase II trials is to obtain an early indication of efficacy and explore different doses and frequencies of administration. Safety and tolerability will also be a consideration particularly when the relevant phase I trials are conducted in healthy volunteers. Such trials are often randomised but that is not always the case, with the decision to randomise being based on both the disease and nature of the intervention. Phase II trials are seldom fully powered for effect as the focus is on gaining sufficient evidence to justify the investment in Phase III trials.

Examples

• Robert Z. Orlowski, Peter M. Voorhees, Reynaldo A. Garcia, Melissa D. Hall, Fred J. Kudrik, Tammy Allred, Anandhi R. Johri, Paul E. Jones, Anastasia Ivanova, Hendrik W. Van Deventer, Don A. Gabriel, Thomas C. Shea, Beverly S. Mitchell, Julian Adams, Dixie-Lee Esseltine, Elizabeth G. Trehu, Marie Green, Mary Jo Lehman, Susan Natoli, Jason M. Collins, Celeste M. Lindley, and E. Claire Dees. Phase 1 trial of the proteasome inhibitor bortezomib and pegylated liposomal doxorubicin in patients with advanced hematologic malignancies.Blood, 2005, 105(8), 3058-3065.

• Douglas W. Losordo, Peter R. Vale, Robert C. Hendel, Charles E. Milliken, F. David Fortuin, Nancie Cummings, Richard A. Schatz, Takayuki Asahara, Jeffrey M. Isner, ichard E. Kuntz. Phase 1/2 Placebo-Controlled, Double-Blind, Dose-Escalating Trial of Myocardial Vascular Endothelial Growth Factor 2 Gene Transfer by Catheter Delivery in Patients With Chronic Myocardial Ischemia. Circulation. 2002, 105, 2012-2018

• Masahiro Fukuoka, Seiji Yano, Giuseppe Giaccone, Tomohide Tamura, Kazuhiko Nakagawa, Jean-Yves Douillard, Yutaka Nishiwaki, Johan Vansteenkiste, Shinzoh Kudoh, Danny Rischin, Richard Eek, Takeshi Horai, Kazumasa Noda, Ichiro Takata, Egbert Smit, Steven Averbuch, Angela Macleod, Andrea Feyereislova, Rui-Ping Dong, and Jose´ Baselga. Multi-Institutional Randomized Phase II Trial of Gefitinib for Previously Treated Patients With Advanced Non–Small-Cell Lung Cancer. Journal of Clinical Oncology, 2003, 21(12), 2237-2246