title: Phase-II trials in osteosarcoma recurrences: A systematic review of past experience.
abstract: The most appropriate design of Phase-II trials evaluating new therapies in osteosarcoma remains poorly defined.
  
  
  
  To study consistency in phase-II clinical trials evaluating new therapies for osteosarcoma recurrences with respect to eligibility criteria, response assessment, end-points, statistical design and reported results.
  
  
  
  Systematic review of clinical trials registered on clinicaltrials.gov, clinicaltrialsregister.eu and French National Cancer Institute website or referenced in PubMed and American Society of Clinical Oncology websites, between 2003 and 2016, using the following criteria: (osteosarcoma OR bone sarcoma) AND (Phase-II).
  
  
  
  Among the 99 trials identified, 80 were Phase-II, 17 I/II and 2 II/III, evaluating mostly targeted therapy (n = 40), and chemotherapy alone (n = 26). Results were fully (n = 28) or partially (abstract, n = 6) published. Twenty-four trials were dedicated to osteosarcoma, 22 had an osteosarcoma stratum. Twenty-eight out of 99 trials refer to the age range observed at recurrence (28%). Overall, 65 trials were run in multicentre settings, including 17 international trials. Only 9 trials were randomised. The primary end-point was tumour response in 71 trials (response rate, n = 40 or best response, n = 31), with various definitions (complete + partial ± minor response and stable disease), mainly evaluated with RECIST criteria (n = 69); it was progression-free survival in 24 trials and OS in 3. In single-arm trials evaluating response rate, the null hypothesis tested (when available, n = 12) varied from 5% to 25%.
  
  
  
  No robust historical data can currently be derived from past efficacy Phase-II trials. There is an urgent need to develop international randomised Phase-II trials across all age ranges with standardised primary end-point.
authors.affiliation: Department of Oncology for Child and Adolescents, Institut Gustave Roussy, 114 rue Edouard Vaillant, 94805 Villejuif, France.
authors.forename: Natacha
authors.initials: N
authors.lastname: Omer
authors.affiliation: Centre Oscar Lambret, 3 rue Frédéric Combemale, 59000 Lille, France; CESP, INSERM, Fac. de médecine - Univ. Paris-Sud, Université Paris-Saclay, F-94805 Villejuif, France.
authors.forename: Marie-Cécile
authors.initials: MC
authors.lastname: Le Deley
authors.affiliation: Department of Medical Oncology, Institut Curie, 26 rue d'Ulm, 75005 Paris, France.
authors.forename: Sophie
authors.initials: S
authors.lastname: Piperno-Neumann
authors.affiliation: Department of Paediatric Haematology and Oncology, Centre Léon Bérard, 28 Promenade Léa et Napoléon Bullukian, 69008 Lyon, France.
authors.forename: Perrine
authors.initials: P
authors.lastname: Marec-Berard
authors.affiliation: Department of Medical Oncology, Institut Bergonié, 229 Cours de l'Argonne, 33000 Bordeaux, France.
authors.forename: Antoine
authors.initials: A
authors.lastname: Italiano
authors.affiliation: Department of Paediatric Haematology and Oncology, Centre Léon Bérard, 28 Promenade Léa et Napoléon Bullukian, 69008 Lyon, France.
authors.forename: Nadège
authors.initials: N
authors.lastname: Corradini
authors.affiliation: Clinical Research and Clinical Epidemiology Unit, Institut Bergonié, 229 Cours de l'Argonne, 33000 Bordeaux, France.
authors.forename: Carine
authors.initials: C
authors.lastname: Bellera
authors.affiliation: Department of Oncology for Child and Adolescents, Institut Gustave Roussy, 114 rue Edouard Vaillant, 94805 Villejuif, France.
authors.forename: Laurence
authors.initials: L
authors.lastname: Brugières
authors.affiliation: Department of Oncology for Child and Adolescents, Institut Gustave Roussy, 114 rue Edouard Vaillant, 94805 Villejuif, France. Electronic address: nathalie.gaspar@gustaveroussy.fr.
authors.forename: Nathalie
authors.initials: N
authors.lastname: Gaspar
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000627:therapeutic use; D001859:Bone Neoplasms / Q000628:therapy*; D002648:Child; D002675:Child, Preschool; D017322:Clinical Trials, Phase II as Topic; D006801:Humans; D007167:Immunotherapy / Q000379:methods; D007223:Infant; D007231:Infant, Newborn; D008875:Middle Aged; D058990:Molecular Targeted Therapy / Q000379:methods; D015337:Multicenter Studies as Topic; D009364:Neoplasm Recurrence, Local / Q000628:therapy*; D012516:Osteosarcoma / Q000628:therapy*; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D000970:Antineoplastic Agents
keywords: Osteosarcoma; Phase-II trial; Trial design