title: The design of phase II clinical trials testing cancer therapeutics: consensus recommendations from the clinical trial design task force of the national cancer institute investigational drug steering committee.
abstract: The optimal design of phase II studies continues to be the subject of vigorous debate, especially studies of newer molecularly targeted agents. The observations that many new therapeutics "fail" in definitive phase III studies, coupled with the numbers of new agents to be tested as well as the increasing costs and complexity of clinical trials, further emphasize the critical importance of robust and efficient phase II design. The Clinical Trial Design Task Force (CTD-TF) of the National Cancer Institute (NCI) Investigational Drug Steering Committee (IDSC) has published a series of discussion papers on phase II trial design in Clinical Cancer Research. The IDSC has developed formal recommendations about aspects of phase II trial design that are the subject of frequent debate, such as endpoints (response versus progression-free survival), randomization (single-arm designs versus randomization), inclusion of biomarkers, biomarker-based patient enrichment strategies, and statistical design (e.g., two-stage designs versus multiple-group adaptive designs). Although these recommendations in general encourage the use of progression-free survival as the primary endpoint, randomization, inclusion of biomarkers, and incorporation of newer designs, we acknowledge that objective response as an endpoint and single-arm designs remain relevant in certain situations. The design of any clinical trial should always be carefully evaluated and justified based on characteristic specific to the situation.
authors.affiliation: NCIC Clinical Trials Group, Kingston, Ontario, Canada. lseymour@ctg.queensu.ca
authors.forename: Lesley
authors.initials: L
authors.lastname: Seymour
authors.forename: S Percy
authors.initials: SP
authors.lastname: Ivy
authors.forename: Daniel
authors.initials: D
authors.lastname: Sargent
authors.forename: David
authors.initials: D
authors.lastname: Spriggs
authors.forename: Laurence
authors.initials: L
authors.lastname: Baker
authors.forename: Larry
authors.initials: L
authors.lastname: Rubinstein
authors.forename: Mark J
authors.initials: MJ
authors.lastname: Ratain
authors.forename: Michael
authors.initials: M
authors.lastname: Le Blanc
authors.forename: David
authors.initials: D
authors.lastname: Stewart
authors.forename: John
authors.initials: J
authors.lastname: Crowley
authors.forename: Susan
authors.initials: S
authors.lastname: Groshen
authors.forename: Jeffrey S
authors.initials: JS
authors.lastname: Humphrey
authors.forename: Pamela
authors.initials: P
authors.lastname: West
authors.forename: Donald
authors.initials: D
authors.lastname: Berry
mesh_terms: D014408:Biomarkers, Tumor / Q000032:analysis; D017322:Clinical Trials, Phase II as Topic / Q000379:methods* / Q000592:standards*; D015507:Drugs, Investigational / Q000592:standards*; D023381:Endpoint Determination; D006801:Humans; D054547:National Cancer Institute (U.S.); D009369:Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D018579:Patient Selection; D010606:Pharmacy and Therapeutics Committee / Q000458:organization & administration*; D017410:Practice Guidelines as Topic; D012107:Research Design; D014481:United States
chemical_list: D014408:Biomarkers, Tumor; D015507:Drugs, Investigational