Natacha Omer1, Marie-Cécile Le Deley2, Sophie Piperno-Neumann3, Perrine Marec-Berard4, Antoine Italiano5, Nadège Corradini4, Carine Bellera6, Laurence Brugières1, Nathalie Gaspar7. 1. Department of Oncology for Child and Adolescents, Institut Gustave Roussy, 114 rue Edouard Vaillant, 94805 Villejuif, France. 2. 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. 3. Department of Medical Oncology, Institut Curie, 26 rue d'Ulm, 75005 Paris, France. 4. Department of Paediatric Haematology and Oncology, Centre Léon Bérard, 28 Promenade Léa et Napoléon Bullukian, 69008 Lyon, France. 5. Department of Medical Oncology, Institut Bergonié, 229 Cours de l'Argonne, 33000 Bordeaux, France. 6. Clinical Research and Clinical Epidemiology Unit, Institut Bergonié, 229 Cours de l'Argonne, 33000 Bordeaux, France. 7. Department of Oncology for Child and Adolescents, Institut Gustave Roussy, 114 rue Edouard Vaillant, 94805 Villejuif, France. Electronic address: nathalie.gaspar@gustaveroussy.fr.
Abstract
BACKGROUND: The most appropriate design of Phase-II trials evaluating new therapies in osteosarcoma remains poorly defined. OBJECTIVE: 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. METHODS: 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). RESULTS: 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%. CONCLUSION: 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.
BACKGROUND: The most appropriate design of Phase-II trials evaluating new therapies in osteosarcoma remains poorly defined. OBJECTIVE: 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. METHODS: 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). RESULTS: 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%. CONCLUSION: 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: Olaf Beck; Claudia Paret; Alexandra Russo; Jürgen Burhenne; Margaux Fresnais; Kevin Steimel; Larissa Seidmann; Daniel-Christoph Wagner; Nadine Vewinger; Nadine Lehmann; Maximilian Sprang; Nora Backes; Lea Roth; Marie Astrid Neu; Arthur Wingerter; Nicole Henninger; Khalifa El Malki; Henrike Otto; Francesca Alt; Alexander Desuki; Thomas Kindler; Joerg Faber Journal: Cancers (Basel) Date: 2020-03-26 Impact factor: 6.639
Authors: Elisa Mazzoni; Ilaria Bononi; Maria S Benassi; Piero Picci; Elena Torreggiani; Marika Rossini; Andrea Simioli; Maria V Casali; Paola Rizzo; Mauro Tognon; Fernanda Martini Journal: Front Cell Dev Biol Date: 2018-06-22