Clinical trial designs for the early clinical development of therapeutic cancer vaccines

There are major differences between therapeutic tumor vaccines and chemothe rapeutic agents that have important implications for the design of early cl inical trials. Many vaccines are inherently safe and do not require phase I dose finding trials. patients with advanced cancers and compromised immune systems are not good candidates for assessing either the toxicity or effic acy of therapeutic cancer vaccines. The rapid pace of development of new va ccine candidates and the variety of possible adjuvants and modifications in method of administration makes it important to use efficient designs for c linical screening and evaluation of vaccine regimens. We review the potenti al advantages of a wide range of clinical trial designs for the development of tumor vaccines. We address the role of immunological endpoints in early clinical trials of tumor vaccines, investigate the design implications of attempting to use disease stabilization as an end point and discuss the dif ficulties of reliably utilizing historical control data. Several conclusion s for expediting the clinical development of effective cancer vaccines are proposed. (C) 2001 by American Society of Clinical Oncology.