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Phase I and II clinical trial design for targeted agents

Phase I and II clinical trial design for targeted agents Challenges presented in the development of targeted agents include selection of the optimal dose, particularly when dose-limiting toxicity does not occur or cannot be easily distinguished from adverse events related to the underlying disease; description of the safety profile when the signs and symptoms of drug toxicity may be similar to those of the underlying disease or of co-morbid conditions; and assessment of antitumor activity if tumor shrinkage is not expected or does not occur when the drug is administered. In such cases, time to progression (TTP) rather than response rate has become a commonly used endpoint, although, with the use of TTP, a reliable estimate of drug effect can only be made in the setting of a randomized trial, thereby increasing the number of patients typically required for phase II testing. Another confounding issue in the clinical development of targeted therapies is whether or not assessment of the target in tumor tissue should be incorporated in the clinical development plan. While doing so has potential advantages such as increasing the likelihood of observing a drug effect and reducing the sample size necessary for clinical trials, there are considerable risks associated with this strategy that stem from incomplete understanding of the target, inadequate assays for target expression or activity and the requirement to develop a molecular diagnostic alongside the therapeutic agent to be used for patient selection. This paper will briefly review the trial designs employed for the phase I and II development of four recently developed angiogenesis inhibitors—bevacizumab, sorafenib, sunitinib and vatalanib—three of which have received marketing approval in one or more tumor types. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Targeted Oncology Springer Journals

Phase I and II clinical trial design for targeted agents

Targeted Oncology , Volume 1 (4) – Oct 3, 2006

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References (26)

Publisher
Springer Journals
Copyright
Copyright © 2006 by Springer-Verlag
Subject
Medicine & Public Health; Biomedicine general; Oncology
ISSN
1776-2596
eISSN
1776-260X
DOI
10.1007/s11523-006-0030-5
Publisher site
See Article on Publisher Site

Abstract

Challenges presented in the development of targeted agents include selection of the optimal dose, particularly when dose-limiting toxicity does not occur or cannot be easily distinguished from adverse events related to the underlying disease; description of the safety profile when the signs and symptoms of drug toxicity may be similar to those of the underlying disease or of co-morbid conditions; and assessment of antitumor activity if tumor shrinkage is not expected or does not occur when the drug is administered. In such cases, time to progression (TTP) rather than response rate has become a commonly used endpoint, although, with the use of TTP, a reliable estimate of drug effect can only be made in the setting of a randomized trial, thereby increasing the number of patients typically required for phase II testing. Another confounding issue in the clinical development of targeted therapies is whether or not assessment of the target in tumor tissue should be incorporated in the clinical development plan. While doing so has potential advantages such as increasing the likelihood of observing a drug effect and reducing the sample size necessary for clinical trials, there are considerable risks associated with this strategy that stem from incomplete understanding of the target, inadequate assays for target expression or activity and the requirement to develop a molecular diagnostic alongside the therapeutic agent to be used for patient selection. This paper will briefly review the trial designs employed for the phase I and II development of four recently developed angiogenesis inhibitors—bevacizumab, sorafenib, sunitinib and vatalanib—three of which have received marketing approval in one or more tumor types.

Journal

Targeted OncologySpringer Journals

Published: Oct 3, 2006

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