title: Challenges Facing Early Phase Trials Sponsored by the National Cancer Institute: An Analysis of Corrective Action Plans to Improve Accrual.
abstract: Accruing patients in a timely manner represents a significant challenge to early phase cancer clinical trials. The NCI Cancer Therapy Evaluation Program analyzed 19 months of corrective action plans (CAP) received for slow-accruing phase I and II trials to identify slow accrual reasons, evaluate whether proposed corrective actions matched these reasons, and assess the CAP impact on trial accrual, duration, and likelihood of meeting primary scientific objectives. Of the 135 CAPs analyzed, 69 were for phase I trials and 66 for phase II trials. Primary reasons cited for slow accrual were safety/toxicity (phase I: 48%), design/protocol concerns (phase I: 42%, phase II: 33%), and eligibility criteria (phase I: 41%, phase II: 35%). The most commonly proposed corrective actions were adding institutions (phase I: 43%, phase II: 85%) and amending the trial to change eligibility or design (phase I: 55%, phase II: 44%). Only 40% of CAPs provided proposed corrective actions that matched the reasons given for slow accrual. Seventy percent of trials were closed to accrual at time of analysis (phase I = 48; phase II = 46). Of these, 67% of phase I and 70% of phase II trials met their primary objectives, but they were active three times longer than projected. Among closed trials, 24% had an accrual rate increase associated with a greater likelihood of meeting their primary scientific objectives. Ultimately, trials receiving CAPs saw improved accrual rates. Future trials may benefit from implementing CAPs early in trial life cycles, but it may be more beneficial to invest in earlier accrual planning. Clin Cancer Res; 22(22); 5408-16. ©2016 AACRSee related commentary by Mileham and Kim, p. 5397.
authors.affiliation: National Cancer Institute, Bethesda, Maryland. massetth@mail.nih.gov.
authors.forename: Holly A
authors.initials: HA
authors.lastname: Massett
authors.affiliation: National Cancer Institute, Bethesda, Maryland.
authors.forename: Grace
authors.initials: G
authors.lastname: Mishkin
authors.affiliation: National Cancer Institute, Bethesda, Maryland.
authors.forename: Larry
authors.initials: L
authors.lastname: Rubinstein
authors.affiliation: National Cancer Institute, Bethesda, Maryland.
authors.forename: S Percy
authors.initials: SP
authors.lastname: Ivy
authors.affiliation: National Cancer Institute, Bethesda, Maryland.
authors.forename: Andrea
authors.initials: A
authors.lastname: Denicoff
authors.affiliation: Emmes Corporation, Rockville, Maryland.
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Godwin
authors.affiliation: Emmes Corporation, Rockville, Maryland.
authors.forename: Kate
authors.initials: K
authors.lastname: DiPiazza
authors.affiliation: Westat, Rockville, Maryland.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Bolognese
authors.affiliation: National Cancer Institute, Bethesda, Maryland.
authors.forename: James A
authors.initials: JA
authors.lastname: Zwiebel
authors.affiliation: National Cancer Institute, Bethesda, Maryland.
authors.forename: Jeffrey S
authors.initials: JS
authors.lastname: Abrams
mesh_terms: D017321:Clinical Trials, Phase I as Topic; D017322:Clinical Trials, Phase II as Topic; D006801:Humans; D054547:National Cancer Institute (U.S.); D009369:Neoplasms / Q000188:drug therapy*; D018579:Patient Selection; D012107:Research Design; D014481:United States