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Oncologic phase 0 trials incorporating clinical pharmacodynamics: from concept to patient

James H Doroshow1, Ralph E Parchment

  • 1Division of Cancer Treatment and Diagnosis, and the Laboratory of Molecular Pharmacology, Center for Cancer Research, National Cancer Institute, Bethesda, Maryland 20892, USA. doroshoj@mail.nih.gov

Clinical Cancer Research : an Official Journal of the American Association for Cancer Research
|June 19, 2008
PubMed

Insights

The U.S. Food and Drug Administration

Area of Science:

  • Oncology
  • Pharmacology
  • Clinical Trial Design

Background:

  • The U.S. Food and Drug Administration (FDA) has introduced new guidance for Exploratory Investigational New Drug (IND) applications.
  • This guidance facilitates early-phase clinical trials for targeted anticancer agents.
  • It allows for evaluation of target modulation, pharmacokinetics, and molecular imaging potential.

Purpose of the Study:

  • To examine the development and implications of the new Exploratory IND mechanism.
  • To discuss its impact on clinical trial design and pharmacodynamics.
  • To explore ethical considerations and industry perspectives on non-therapeutic clinical investigations.

Main Methods:

  • Review of the FDA's Exploratory IND guidance.
  • Analysis of the effects on early-phase clinical trial design.
  • Examination of clinical pharmacodynamics and molecular imaging.
  • Discussion of ethical implications and industry viewpoints.

Main Results:

  • The Exploratory IND streamlines early evaluation of novel anticancer drugs.
  • It reduces manufacturing and toxicologic assessment requirements for initial trials.
  • These trials lack therapeutic intent, focusing on feasibility and preliminary data.
  • The guidance impacts clinical trial design, pharmacodynamics, and ethical considerations.

Conclusions:

  • The Exploratory IND offers a valuable platform for assessing new anticancer agents early in development.
  • This approach enables proof-of-principle target modulation and preliminary pharmacokinetic/imaging studies.
  • Understanding the ethical and practical implications is crucial for successful implementation.

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