Clinical Trial Designs for the Early Clinical Development of Therapeutic Cancer Vaccines

• Published in: Journal of clinical oncology Vol. 19; no. 6; pp. 1848 - 1854
• Main Authors: SIMON, Richard M, STEINBERG, Seth M, HAMILTON, Michael, HILDESHEIM, Allan, KHLEIF, Samir, KWAK, Larry W, MACKALL, Crystal L, SCHLOM, Jeffrey, TOPALIAN, Suzanne L, BERZOFSKY, Jay A
• Format: Journal Article
• Language: English
• Published: Baltimore, MD American Society of Clinical Oncology 15.03.2001; Lippincott Williams & Wilkins
• Subjects: Adjuvants, Immunologic - therapeutic use; Antineoplastic agents; Antineoplastic Agents - therapeutic use; Biological and medical sciences; Cancer Vaccines - therapeutic use; Cohort Studies; Endpoint Determination; Humans; Immunocompromised Host; Immunotherapy; Medical sciences; Neoplasms - drug therapy; Neoplasms - virology; Pharmacology. Drug treatments; Randomized Controlled Trials as Topic; Research Design; Treatment Outcome; Antineoplastic agent; Human; Randomization; Treatment; Immunotherapy; Clinical trial; Vaccine; Review; Malignant tumor; Comparative study
• DOI: 10.1200/jco.2001.19.6.1848
• ISSN: 0732-183X

There are major differences between therapeutic tumor vaccines and chemotherapeutic agents that have important implications for the design of early clinical 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 efficacy of therapeutic cancer vaccines. The rapid pace of development of new vaccine candidates and the variety of possible adjuvants and modifications in method of administration makes it important to use efficient designs for clinical screening and evaluation of vaccine regimens. We review the potential 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 difficulties of reliably utilizing historical control data. Several conclusions for expediting the clinical development of effective cancer vaccines are proposed.