title: Challenges of phase III trial design for novel treatments in diseases with no standard treatment: the AZA-001 myelodysplasia study model.
abstract: For cancers lacking standard treatments, comparing new agents with existing treatments is problematic. Here we discuss the study design from the AZA-001 trial, which compared azacitidine with 3 frequently used conventional care regimens (CCR) for higher-risk myelodysplastic syndromes. Before randomization, physicians preselected the most appropriate of 3 CCR for each patient, after thorough examination. Patients were then randomized to azacitidine or CCR. Patients randomized to CCR received their preselected treatment, thus including patients otherwise excluded as poor candidates for a single comparator. This design may serve as a template in other cancers lacking standard therapy.
authors.affiliation: Hôpital St Louis, Paris 7 University, Paris, France. Electronic address: pierre.fenaux@sls.aphp.fr.
authors.forename: Pierre
authors.initials: P
authors.lastname: Fenaux
authors.affiliation: Peter MacCallum Cancer Centre, East Melbourne, & University of Melbourne, Australia.
authors.forename: John F
authors.initials: JF
authors.lastname: Seymour
authors.affiliation: University of Florence, Florence, Italy.
authors.forename: Valeria
authors.initials: V
authors.lastname: Santini
authors.affiliation: Mount Sinai School of Medicine, New York, NY, USA.
authors.forename: Lew
authors.initials: L
authors.lastname: Silverman
authors.affiliation: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, MD, USA.
authors.forename: Steven
authors.initials: S
authors.lastname: Gore
authors.affiliation: H Lee Moffitt Cancer Center and Research Institute, Tampa, FL, USA.
authors.forename: Alan
authors.initials: A
authors.lastname: List
authors.affiliation: Hospital Universitario y Politecnico La Fe, Valencia, Spain.
authors.forename: Guillermo
authors.initials: G
authors.lastname: Sanz
authors.affiliation: King's College London, London, UK.
authors.forename: Ghulam J
authors.initials: GJ
authors.lastname: Mufti
authors.affiliation: Division of Hematology, University of Washington School of Medicine, Seattle, WA, USA.
authors.forename: Eli
authors.initials: E
authors.lastname: Estey
authors.affiliation: Celgene Corporation, Summit, NJ, USA.
authors.forename: Arlene S
authors.initials: AS
authors.lastname: Swern
authors.affiliation: Celgene Corporation, Summit, NJ, USA.
authors.forename: C L
authors.initials: CL
authors.lastname: Beach
authors.affiliation: Karolinska Institute, Department of Hematology, Karolinska University Hospital, Stockholm, Sweden.
authors.forename: Eva
authors.initials: E
authors.lastname: Hellstrom-Lindberg
mesh_terms: D000964:Antimetabolites, Antineoplastic / Q000627:therapeutic use*; D001374:Azacitidine / Q000627:therapeutic use*; D017326:Clinical Trials, Phase III as Topic / Q000379:methods* / Q000592:standards; D015507:Drugs, Investigational / Q000627:therapeutic use*; D006801:Humans; D015337:Multicenter Studies as Topic / Q000379:methods; D009190:Myelodysplastic Syndromes / Q000188:drug therapy*; D018579:Patient Selection; D016032:Randomized Controlled Trials as Topic / Q000379:methods / Q000592:standards; D012107:Research Design; D059039:Standard of Care
chemical_list: D000964:Antimetabolites, Antineoplastic; D015507:Drugs, Investigational; D001374:Azacitidine
keywords: Azacitidine; CCR; Heterogenous; Novel treatment; Standard; Study design