title: Phase I and Phase II Objective Response Rates are Correlated in Pediatric Cancer Trials: An Argument for Better Clinical Trial Efficiency.
abstract: Although many phase I trials report tumor response, formal analysis of efficacy is deferred to phase II. We reviewed paired phase I and II pediatric oncology trials to ascertain the relationship between phase I and II objective response rate (OR%). Single-agent phase I trials were paired with corresponding phase II trials (comparable study drug, dosing schedule, and population). Phase I trials without efficacy data or a matching phase II trial were excluded. OR% was tabulated for all trials, and phase II authors' subjective conclusions regarding efficacy were documented; 35 pairs of trials were analyzed. The correlation between phase I and II OR% was 0.93. Between phase II studies with a "positive" conclusion versus a "negative" one, there was a statistically significant difference in mean phase I OR% (32.0% vs. 4.5%, P<0.001). Thirteen phase II studies were undertaken despite phase I OR% of 0%; only 1 had a "positive" conclusion, and none exceeded OR% of 15%. OR% are highly correlated between phase I and II pediatric oncology trials. Although not a formal measure of drug efficacy, phase I OR% may provide an estimate of phase II response, inform phase II study design, and should be given greater consideration.
authors.affiliation: *Johns Hopkins School of Medicine †The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, MD.
authors.forename: Jonathan C
authors.initials: JC
authors.lastname: Yeh
authors.forename: Peng
authors.initials: P
authors.lastname: Huang
authors.forename: Kenneth J
authors.initials: KJ
authors.lastname: Cohen
mesh_terms: D024221:Antineoplastic Protocols; D002648:Child; D002986:Clinical Trials as Topic / Q000379:methods* / Q000592:standards; D017321:Clinical Trials, Phase I as Topic / Q000592:standards*; D017322:Clinical Trials, Phase II as Topic / Q000592:standards*; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy; D016017:Odds Ratio; D010372:Pediatrics / Q000379:methods; D016896:Treatment Outcome