Multi-Institutional Phase I Trials of Anticancer Agents
- 20 April 2008
- journal article
- phase i-and-clinical-pharmacology
- Published by American Society of Clinical Oncology (ASCO) in Journal of Clinical Oncology
- Vol. 26 (12), 1926-1931
- https://doi.org/10.1200/jco.2007.13.3793
Abstract
Purpose Physicians involved in the conduct of phase I studies of novel anticancer agents have raised concerns about the emergence of multi-institutional phase I trials and about using the optimal biologic dose (OBD) as an alternative to the maximum-tolerated dose (MTD) as the primary end point in early drug development. We sought to determine the factors associated with multi-institutional phase I studies and OBD determination. Patients and Methods We reviewed all published phase I trials between January 1998 and June 2006 from two major clinical cancer journals. The following components from each trial were determined: number of participating sites, sponsor, nation where study was conducted, MTD or OBD established, number of patients accrued, mechanism of action of the studied agent, accrual time, and tumor type. Results We identified 463 trials. Fifty-six percent were performed in single institutions. Only 30% reported accrual time. The number of patients enrolled on single institution studies was significantly lower than on multi-institutional studies (P < .05), but there was no difference in accrual time. There was no association between the number of institutions and the sponsor or the mechanism of drug action. National Institutes of Health–sponsored trials enrolled fewer patients per trial than pharmaceutical-sponsored trials (P < .05). Although 99% of trials with cytotoxic agents determined an MTD, only 64% of trials with targeted agents did. Conclusion Multi-institutional phase I studies do not decrease the time to study completion and result in an increase in number of patients per trial. One third of trials with targeted agents failed to determine an MTD.This publication has 4 references indexed in Scilit:
- What Is the Right Dose? The Elusive Optimal Biologic Dose in Phase I Clinical TrialsJournal of Clinical Oncology, 2006
- Novel Phase I Dose De-escalation Design Trial to Determine the Biological Modulatory Dose of the Antiangiogenic Agent SU5416Clinical Cancer Research, 2005
- The Multifunctional, Multi-Institutional, and Sometimes Even Global Phase I Study: A Better Life for Phase I Evaluations or Just “Living Large”?Journal of Clinical Oncology, 2002
- Phase I Clinical Trial Design in Cancer Drug DevelopmentJournal of Clinical Oncology, 2000