Clinical Trial Design, Biostatistics, Ethics, and Recruitment

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Clinical Trial Design, Biostatistics, Ethics, and
Recruitment

• Clinical Trial Design
• Anthony J. Murgo, MD.,MS NCI/DCTD
• Biostatistics
• Larry Rubinstein, PhD NCI/DCTD/BRB
• Ethical Considerations
• Holly Taylor, PhD,MPH JHU Berman Bioethics
  Instit.
• David Wendler, PhD NIH Clinical Center
• Phase 0 and patients
• Deborah Collyar Pres. Patient Advocates In
  Research
• Recruitment
• Martin Gutierrez, MD NCI/CCR

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Phase 0 Trial DesignsHow do They Differ From
First-in-Human Phase 1 Trials

• Anthony J. Murgo, MD, MS
• Division of Cancer Treatment and Diagnosis
• National Cancer Institute

Building 10, Warren Grant Magnuson Clinical
Center
Mark O. Hatfield Clinical Research Center
Sept. 5, 2007
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Differences Between Phase 0 Phase 1 Trials
Phase 1 Trial Phase 0 Trial
Primary Endpoint Establish dose-limiting toxicities and maximum tolerated dose Establish a safe dose-range that modulates (or images) target for use in subsequent definitive trials
Patient Population Advanced incurable malignancy, after failure of standard therapy May include patients with indolent disease not requiring treatment
Washout Period Usually at least 4 weeks May be 2 weeks or less
Number of patients Usually gt20 10-15
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Differences Between Phase 0 Phase 1 Trials
Phase 1 Trial Phase 0 Trial
Dose Escalation Guided primarily by toxicity Intended to achieve desired drug exposure and/or target modulation
Duration of Dosing Multiple cycles until disease progression or unacceptable toxicity Limited dosing (1-7 days) (one cycle only)
Evaluation for Therapeutic benefit Yes No
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Differences Between Phase 0 Phase 1 Trials
Phase 1 Trial Phase 0 Trial
Biomarker Assays Not consistently performed. Most Phase 1 trials do not emphasize PD markers Biomarker assays and/or imaging studies are integrated to establish MOA in patient samples
Tumor Biopsies Usually optional Serial tumor biopsies required to evaluate drug effect on target
Pharmacokinetic/Pharmacodynamic analysis Samples are usually batched and analyzed at a later time point Real time
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The Next Speaker isDr. Larry Rubinstein