clinical trial design, biostatistics, ethics, and recruitment clinical trial design anthony j....
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Clinical Trial Design, Biostatistics, Ethics, and Recruitment
Clinical Trial DesignAnthony J. Murgo, MD.,MS; NCI/DCTD
BiostatisticsLarry Rubinstein, PhD; NCI/DCTD/BRB
Ethical Considerations
Holly Taylor, PhD,MPH; JHU Berman Bioethics Instit. David Wendler, PhD; NIH Clinical Center
Phase 0 and patientsDeborah Collyar; Pres. Patient Advocates In Research
Recruitment
Martin Gutierrez, MD; NCI/CCR
Phase 0 Trial DesignsHow do They Differ From First-in-Human Phase 1
TrialsAnthony J. Murgo, MD, MS
Division of Cancer Treatment and DiagnosisNational Cancer Institute
Sept. 5, 2007
Mark O. Hatfield Clinical Research Center
Building 10, Warren Grant Magnuson Clinical Center
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 PeriodUsually at least 4 weeks
May be 2 weeks or less
Number of patients
Usually >20 10-15
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
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
The Next Speaker is:
Dr. Larry Rubinstein