The Ethics of Phase 0 Oncology Trials

Abstract

Recent guidance from the Food and Drug Administration supports the conduct of a new type of exploratory clinical trial, commonly called phase 0 clinical trials. Proponents argue that phase 0 clinical trials have the potential to expedite the development of new oncology drugs while exposing fewer research subjects to the risks of experimental treatments. At the same time, phase 0 oncology trials raise important ethical concerns that have received little attention. In particular, there is a question of whether it is ethical to enroll individuals in research that offers them no potential for clinical benefit. Further concern focuses on the inclusion of terminally ill and consequently vulnerable cancer patients in these trials. To evaluate these concerns, this article considers relevant empirical data from phase 1 oncology trials and develops several recommendations regarding the conduct of phase 0 clinical trials in oncology.

Requirements to Assess Feasibility of Phase 0 Trials during Major Abdominal Surgery: Variability of PARP Activity

“…The abundance of available tumor tissue during surgery is one further great advantage of the presented approach. Ethical concerns with respect to phase 0 trials have been described, whereas one important aspect was the limited access to tumor tissue via transcutan biopsies, which is solved using this approach (14).…”

Patient Perspectives on Phase 0 Clinical Trials

“…This is discussed extensively in Abdoler et al (2) in this issue of CCR Focus. When asked, a phase I trial participant tends to believe they understand the trial objectives, but the majority are unable to correctly state the purpose of the study.…”

Human Micro Dosing Studies (Phase 0): A Novel Approach in Clinical Research

“…Phase 0 for oncology trials in development is uniquely challenged by the need to identify widely acceptable, minimally toxic compounds that favorably affect carcinogenesis when measured against surrogate biomarkers, rather than direct cancer endpoints. An example for a well-established phase 0 trial is of ABT-888, a poly ADP-ribose polymerase (PARP) inhibitor, because of which the drug was able to move quickly into combination studies, bypassing the traditional phases of clinical trial 9 .…”