Clinical Trial Design, Biostatistics, Ethics, and Recruitment Clinical Trial Design Anthony J....

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