TY - JOUR
T1 - Phase 0 clinical trials
T2 - Conceptions and misconceptions
AU - Kummar, Shivaani
AU - Rubinstein, Larry
AU - Kinders, Robert
AU - Parchment, Ralph E.
AU - Gutierrez, Martin E.
AU - Murgo, Anthony J.
AU - Ji, Jay
AU - Mroczkowski, Barbara
AU - Pickeral, Oxana K.
AU - Simpson, Mel
AU - Hollingshead, Melinda
AU - Yang, Sherry X.
AU - Helman, Lee
AU - Wiltrout, Robert
AU - Collins, Jerry
AU - Tomaszewski, Joseph E.
AU - Doroshow, James H.
PY - 2008/5
Y1 - 2008/5
N2 - Phase 0 clinical trials, developed in response to the United States Food and Drug Administration (FDA)s recent exploratory Investigational New Drug (IND) guidance, are intended to expedite the clinical evaluation of new molecular entities. The exploratory IND supports the performance of first-in-human testing of new investigational agents at subtherapeutic doses based on reduced manufacturing and toxicologic requirements, allowing the demonstration of drug-target effects and assessment of pharmacokineticĝ€" pharmacodynamic relationships in humans earlier in clinical development. The objectives of a phase 0 cancer clinical trial are to establish at the very earliest opportunityĝ€"before large numbers of patients have been accrued and exposed to potential drug-associated toxicityĝ€ "whether an agent is modulating its target in a tumor, and consequently whether further clinical development is warranted. We review here the fundamental requirements of clinical studies conducted under an exploratory IND and address some common misconceptions regarding oncologic phase 0 trials.
AB - Phase 0 clinical trials, developed in response to the United States Food and Drug Administration (FDA)s recent exploratory Investigational New Drug (IND) guidance, are intended to expedite the clinical evaluation of new molecular entities. The exploratory IND supports the performance of first-in-human testing of new investigational agents at subtherapeutic doses based on reduced manufacturing and toxicologic requirements, allowing the demonstration of drug-target effects and assessment of pharmacokineticĝ€" pharmacodynamic relationships in humans earlier in clinical development. The objectives of a phase 0 cancer clinical trial are to establish at the very earliest opportunityĝ€"before large numbers of patients have been accrued and exposed to potential drug-associated toxicityĝ€ "whether an agent is modulating its target in a tumor, and consequently whether further clinical development is warranted. We review here the fundamental requirements of clinical studies conducted under an exploratory IND and address some common misconceptions regarding oncologic phase 0 trials.
KW - Clinical trial
KW - Exploratory IND
KW - Oncology
KW - Pharmacodynamics
KW - Phase 0
UR - http://www.scopus.com/inward/record.url?scp=52649181124&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=52649181124&partnerID=8YFLogxK
U2 - 10.1097/PPO.0b013e318172d6f3
DO - 10.1097/PPO.0b013e318172d6f3
M3 - Review article
C2 - 18536551
AN - SCOPUS:52649181124
SN - 1528-9117
VL - 14
SP - 133
EP - 137
JO - Cancer Journal (United States)
JF - Cancer Journal (United States)
IS - 3
ER -